Gene Detail

Gene Symbol VHL
Synonyms HRCA1 | pVHL | RCA1 | VHL1
Gene Description VHL, von Hippel-Lindau tumor suppressor, is part of an E3 ubiquitin protein ligase complex, which promotes degradation of HIF-alpha and other protein targets required for cellular growth and angiogenesis (PMID: 24583008, PMID: 30194449). VHL contributes to von Hippel-Lindau disease (PMID: 30194449, PMID: 30006056) and sporadic tumors, including clear cell renal carcinoma (PMID: 24583008, PMID: 30149673).
ACMG Incidental List v2.0:
Yes, Von Hippel-Lindau syndrome (PMID: 27854360)
Entrez Id 7428
Chromosome 3
Map Location 3p25.3
Canonical Transcript NM_000551

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
R161* nonsense unknown VHL R161* results in a premature truncation of the Vhl protein at amino acid 161 of 213 (UniProt.org). R161* has been identified in sequencing studies (PMID: 26111976, PMID: 28757314, PMID: 28178687, PMID: 27617348), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
N131Y missense unknown VHL N131Y lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). N131Y has been identified in the scientific literature (PMID: 24727139, PMID: 29172931, PMID: 26831717), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
Q73E missense unknown VHL Q73E does not lie within any known functional domains of the Vhl1 protein (UniProt.org). Q73E has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
W88C missense unknown VHL W88C does not lie within any known functional domains of the Vhl protein (UniProt.org). W88C has been identified in sequencing studies (PMID: 10567493), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Oct 2018).
R167W missense loss of function - predicted VHL R167W does not lie within any known functional domains of the Vhl protein (UniProt.org). R167W is predicted to confer a loss of function to the Vhl protein, as indicated by impaired binding to Elongin BC complex and Clu-2 in cell culture (PMID: 9122164).
G123W missense unknown VHL G123W lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G123W has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
N131fs frameshift loss of function - predicted VHL N131fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 131 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), N131fs is predicted to lead to a loss of Vhl function.
I180V missense unknown VHL I180V does not lie within any known functional domains of the Vhl protein (UniProt.org). I180V has been identified in sequencing studies (PMID: 23606570), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L101P missense unknown VHL L101P lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). L101P has been identified in the scientific literature (PMID: 19996202), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R161P missense loss of function VHL R161P lies within the Elongin BC complex interaction region of the Vhl protein (UniProt.org). R161P confers a loss of function to the Vhl protein as indicated by loss of binding to the elongin BC complex and destabilization of microtubule in culture (PMID: 10587522, PMID: 20855504).
F136L missense loss of function VHL F136L lies within the CCT complex-binding region and the aromatic tetrahedron core domain of the Vhl protein (UniProt.org, PMID: 23840444). F136L results in decreased Vhl protein stability as compared to wild-type, demonstrating increased misfolding and aggregation of Vhl protein in in-vitro assays (PMID: 23840444), and reduced solubility and decreased binding to Hif1a protein, and overexpression of P136L leads to a lethal phenotype in animal models (PMID: 30194449).
R107G missense unknown VHL R107G lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). R107G has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
W117C missense loss of function VHL W117C lies within the CCT complex binding region of the Vhl protein (UniProt.org). W117C confers a loss of function to the Vhl protein as demonstrated by weak binding with CCT resulting in improper folding of the VHL-elongin BC complex (PMID: 14636579).
E186K missense unknown VHL E186K does not lie within any known functional domains of the Vhl protein (UniProt.org). E186K has been identified in the scientific literature (PMID: 28753842), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L158V missense unknown VHL L158V lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). L158V has been identified in the scientific literature (PMID: 27069690), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
P154L missense loss of function VHL P154L lies within the CCT complex-binding region of the Vhl protein (UniProt.org). P154L results in a loss of Vhl binding to Tbp-1 and failure to mediate hypoxia-induced Hif1a degradation in culture (PMID: 14556007).
Q164R missense no effect - predicted VHL Q164R lies within the Elongin BC complex interaction region of the Vhl protein (UniProt.org). Q164R results in decreased Vhl binding to Elongin C but retains HIF regulation in culture (PMID: 26503325).
S183L missense loss of function VHL S183L does not lie within any known functional domains of the Vhl protein (UniProt.org). S183L confers a loss of function to the Vhl protein as indicated by impaired ability to regulate Hif1a degradation and function in culture (PMID: 21454469).
W88* nonsense loss of function - predicted VHL W88* results in a premature truncation of the Vhl protein at amino acid 88 of 213 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), W88* is predicted to lead to a loss of Vhl protein function.
N78T missense unknown VHL N78T does not lie within any known functional domains of the Vhl protein (UniProt.org). N78T has been identified in the scientific literature (PMID: 22177731, PMID: 25691774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
P25L missense unknown VHL P25L lies within the pentameric repeat region of the Vhl protein (UniProt.org). P25L has been identified in the scientific literature (PMID: 16884327, PMID: 27845047, PMID: 25803323, PMID: 24727139), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
C162F missense loss of function VHL C162F lies within the Elongin BC complex-interacting region of the Vhl protein (UniProt.org). C162F leads to a loss of Vhl function as indicated by failure to bind to Elongin BC complex and inhibition of ubiquitin-dependent proteolysis in cell culture (PMID: 9447969, PMID: 11331612).
V155fs frameshift loss of function - predicted VHL V155fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 155 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), V155fs is predicted to lead to a loss of Vhl function.
L128H missense unknown VHL L128H lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). L128H has been identified in the scientific literature (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L158fs frameshift loss of function - predicted VHL L158fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 158 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), L158fs is predicted to lead to a loss of Vhl protein function.
Q132fs frameshift loss of function - predicted VHL Q132fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 132 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), Q132fs is predicted to lead to a loss of Vhl function.
G39D missense unknown VHL G39D lies within the pentameric repeat region of the Vhl protein (UniProt.org). G39D has been identified in the scientific literature (PMID: 23558940), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
R107P missense unknown VHL R107P lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). R107P has been identified in the scientific literature (PMID: 18836774, PMID: 19996202), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
over exp none no effect VHL over exp indicates an over expression of the Vhl protein. However, the mechanism causing the over expression is unspecified.
P25S missense unknown VHL P25S lies within tandem repeat 3 of the Vhl protein (UniProt.org). P25S has been identified in the scientific literature (PMID: 11536052), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
wild-type none no effect Wild-type VHL indicates that no mutation has been detected within the VHL gene.
C162Y missense unknown VHL C162Y lies within the Elongin BC complex-interacting region of the Vhl protein (UniProt.org). C162Y has been identified in the scientific literature (PMID: 23797736, PMID: 17264095), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
N78Y missense unknown VHL N78Y does not lie within any known functional domains of the Vhl protein (UniProt.org). N78Y has been identified in sequencing studies (PMID: 23036577), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
V130F missense loss of function - predicted VHL V130F lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). V130F is predicted to lead to destabilizing of Vhl by computational modeling (PMID: 19408289).
L89H missense unknown VHL L89H does not lie within any known functional domains of the Vhl protein (UniProt.org). L89H has been identified in the scientific literature (PMID: 25583177, PMID: 24755468), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R205C missense unknown VHL R205C does not lie within any known functional domains of the Vhl protein (UniProt.org). R205C has been identified in the scientific literature (PMID: 22549840), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L158P missense loss of function VHL L158P lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). L158P leads to decreased binding of Vhl to the Elongin BC complex and failure to activate Hif1a ubiquitination in cell culture (PMID: 10973499).
loss unknown loss of function VHL loss indicates loss of the VHL gene, mRNA and protein.
L201P missense unknown VHL L201P does not lie within any known functional domains of the Vhl protein (UniProt.org). L201P has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
F91L missense unknown VHL F91L does not lie within any known functional domains of the Vhl protein (UniProt.org). F91L has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
F76S missense unknown VHL F76S does not lie within any known functional domains of the Vhl protein (UniProt.org). F76S has been identified in the scientific literature (PMID: 18836774, PMID: 24166983), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L184P missense loss of function - predicted VHL L184P does not lie within any known functional domains of the Vhl protein (UniProt.org). L184P is predicted to confer a loss of function to the Vhl protein, as indicated by decreased binding to Elongin C and Cul2 in culture (PMID: 28775317).
L188P missense unknown VHL L188P does not lie within any known functional domains of the Vhl protein (UniProt.org). L188P has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
negative unknown loss of function VHL negative indicates a lack of the VHL gene, mRNA, and/or protein.
E173D missense unknown VHL E173D does not lie within any known functional domains of the Vhl protein (UniProt.org). E173D has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
inact mut unknown loss of function VHL inact mut indicates that this variant results in a loss of function of the Vhl protein. However, the specific amino acid change has not been identified.
N90Y missense unknown VHL N90Y does not lie within any known functional domains of the Vhl protein (UniProt.org). N90Y has been identified in sequencing studies (PMID: 24727139), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
V165D missense unknown VHL V165D lies within the Elongin BC complex-interacting region of the Vhl protein (UniProt.org). V165D has been identified in sequencing studies (PMID: 24727139), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
F119L missense loss of function VHL F119L lies within the CCT complex-binding region and the aromatic tetrahedron core domain of the Vhl protein (UniProt.org, PMID: 23840444). F119L results in decreased Vhl protein stability as compared to wild-type, demonstrating increased misfolding and aggregation of Vhl protein in in-vitro assays (PMID: 23840444), and reduced solubility and decreased binding to Hif1a protein, and overexpression of P119L leads to a lethal phenotype in animal models (PMID: 30194449).
V155A missense no effect - predicted VHL V155A lies within the CCT complex interaction region of the Vhl protein (UniProt.org). V155A results in decreased Vhl binding to Elongin C but retains HIF regulation in culture (PMID: 26503325) and therefore, is predicted to have no effect on Vhl protein function.
C162R missense unknown VHL C162R lies within the Elongin BC complex-interacting region of the Vhl protein (UniProt.org). C162R has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
S111N missense loss of function VHL S111N lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). S111N leads to a loss of Vhl function as indicated by impaired binding to Hif-alpha and inhibition of Hif1a ubiquitination (PMID: 10878807).
H115Y missense unknown VHL H115Y lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). H115Y has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R205H missense unknown VHL R205H does not lie within any known functional domains of the Vhl protein (UniProt.org). R205H has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
S65W missense loss of function VHL S65W lies within the pentameric repeat region of the Vhl protein (UniProt.org). S65W leads to a loss of Vhl function as indicated by impaired binding to Hif1a and failure to target Hif2a for degradation (PMID: 15611064).
G144A missense unknown VHL G144A lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G144A has been identified in the scientific literature (PMID: 9458097), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
L116fs frameshift loss of function - predicted VHL L116fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 116 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), L116fs is predicted to lead to a loss of Vhl protein function.
L184fs frameshift unknown VHL L184fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 184 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). L184fs has been identified in sequencing studies (Cancer Res 2016;76(14 Suppl):Abstract nr 4503), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R82P missense loss of function VHL R82P does not lie within any known functional domains of the Vhl protein (UniProt.org). R82P leads to a loss of Vhl function as indicated by impaired binding to hVdu1 and inhibition of hVdu1 ubiquitination in cell culture (PMID: 11739384).
N90I missense loss of function - predicted VHL N90I does not lie within any known functional domains of the Vhl protein (UniProt.org). N90I is predicted to confer a loss of function to the Vhl protein, as indicated by failure to regulate Hif1a ubiquitination in cell culture (PMID: 10823831).
A149D missense unknown VHL A149D lies within the CCT complex-binding region of the Vhl protein (UniProt.org). A149D has been identified in the scientific literature (PMID: 19996202), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
R161G missense loss of function - predicted VHL R161G lies within the Elongin BC complex interaction region of the Vhl protein (UniProt.org). R161G is predicted to confer a loss of function to the Vhl protein, as indicated by failure to bind to the elongin BC complex in an in vitro assay (PMID: 10587522).
Y175* nonsense unknown VHL Y175* results in a premature truncation of the Vhl protein at amino acid 175 of 213 (UniProt.org). Y175* has been identified in sequencing studies (PMID: 25583177, PMID: 27422173), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
D121Y missense unknown VHL D121Y lies within the CCT complex-binding region of the Vhl protein (UniProt.org). D121Y has been identified in sequencing studies (PMID: 24504440), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
I151T missense unknown VHL I151T lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). I151T has been identified in sequencing studies (PMID: 24504440), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
mutant unknown unknown VHL mutant indicates an unspecified mutation in the VHL gene.
del none loss of function VHL del indicates a deletion of the VHL gene.
L184R missense unknown VHL L184R does not lie within any known functional domains of the Vhl protein (UniProt.org). L184R has been identified in sequencing studies (PMID: 23036577, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
Y98N missense loss of function VHL Y98N does not lie within any known functional domains of the Vhl protein (UniProt.org). Y98N confers a loss of function to the Vhl protein as demonstrated by failure to completely suppress Glut1 and defects in Hif1-alpha ubiquitination (PMID: 10823831).
L188R missense unknown VHL L188R does not lie within any known functional domains of the Vhl protein (UniProt.org). L188R has been identified in sequencing studies (PMID: 24504440), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
G127V missense unknown VHL G127V lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G127V has been identified in the scientific literature (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
L153P missense unknown VHL L153P lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). L153P has been identified in the scientific literature (PMID: 24504440, PMID: 28431395), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
L89P missense unknown VHL L89P does not lie within any known functional domains of the Vhl protein (UniProt.org). L89P has been identified in the scientific literature (PMID: 18836774, PMID: 28431395), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
C162W missense loss of function - predicted VHL C162W lies within the Elongin BC complex-interaction region of the Vhl protein (UniProt.org). C162W is predicted to confer a loss of function to the Vhl protein, as indicated by failure to induce protein ubiquitination in culture (PMID: 17350623).
H115N missense unknown VHL H115N lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). H115N has been identified in the scientific literature (PMID: 24446253), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
N78S missense loss of function - predicted VHL N78S does not lie within any known functional domains of the Vhl protein (UniProt.org). N78S is predicted to confer a loss of function to the Vhl protein, as indicated by failure to regulate Hif1a ubiquitination in cell culture (PMID: 11331613).
S111R missense loss of function VHL S111R lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). S111R leads to a loss of Vhl function as indicated by impaired binding to Hif1a, p300 and Tip60, and failure to transactivate p53 on DNA damage in cell culture (PMID: 22071692).
V130D missense unknown VHL V130D lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). V130D has been identified in sequencing studies (PMID: 25691774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
V74G missense loss of function - predicted VHL V74G does not lie within any known functional domains of the Vhl protein (UniProt.org). V74G is predicted to lead to a loss of Vhl function by computational modeling (PMID: 18836774).
H115Q missense loss of function - predicted VHL H115Q lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). H115Q is predicted to confer a loss of function to the Vhl protein, as indicated by decreased binding to Hif-1alpha in cell culture (PMID: 28775317).
P86L missense unknown VHL P86L does not lie within any known functional domains of the Vhl protein (UniProt.org). P86L has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R167G missense unknown VHL R167G does not lie within any known functional domains of the Vhl protein (UniProt.org). R167G has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
S65L missense loss of function VHL S65L does not lie within any known functional domains of the Vhl protein (UniProt.org). S65L results in a loss of Vhl binding to Hif1a and failure to mediate Hif2a degradation in culture (PMID: 15611064).
W88L missense unknown VHL W88L does not lie within any known functional domains of the Vhl protein (UniProt.org). W88L has been identified in sequencing studies (PMID: 24727139, PMID: 29118224), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
V155M missense unknown VHL V155M lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). V155M has been identified in sequencing studies (PMID: 24471421), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
P86H missense loss of function VHL P86H does not lie within any known functional domains of the Vhl protein (UniProt.org). P86H confers a loss of function to the Vhl protein as demonstrated by failure to suppress GLUT1 expression and impaired regulatory activity of Hif1-alpha (PMID: 10535940).
Q73H missense unknown VHL Q73H does not lie within any known functional domains of the Vhl1 protein (UniProt.org). Q73H has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
G29D missense unknown VHL G29D lies within the pentameric repeat region of the Vhl protein (UniProt.org). G29D has been identified in the scientific literature (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on VHL protein function is unknown (PubMed, Sep 2018).
L169P missense unknown VHL L169P does not lie within any known functional domains of the Vhl protein (UniProt.org). L169P has been identified in the scientific literature (PMID: 24727139, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
P192S missense unknown VHL P192S does not lie within any known functional domains of the Vhl protein (UniProt.org). P192S has been identified in the scientific literature (PMID: 18836774, PMID: 26957611), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
G106V missense unknown VHL G106V lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G106V has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
S80I missense loss of function - predicted VHL S80I does not lie within any known functional domains of the Vhl protein (UniProt.org). S80I is predicted to lead to a loss of Vhl function by computational modeling (PMID: 18836774).
S38F missense unknown VHL S38F lies within tandem repeat 5 of the Vhl protein (UniProt.org). S38F has been identified in sequencing studies (PMID: 15932632), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R79P missense loss of function - predicted VHL R79P does not lie within any known functional domains of the Vhl protein (UniProt.org). R79P is predicted to lead to a loss of Vhl function by computational modeling (PMID: 18836774).
G114R missense loss of function - predicted VHL G114R lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G114R is predicted to confer a loss of function to the Vhl protein, as indicated by failure to bind to Elongin BC complex and TriC in cell culture (PMID: 14636579).
Q96* nonsense loss of function - predicted VHL Q96* results in a premature truncation of the Vhl protein at amino acid 96 of 213 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), Q96* is predicted to lead to a loss of Vhl protein function.
R161Q missense unknown VHL R161Q lies within the Elongin BC complex interaction region of the Vhl protein (UniProt.org). R161Q has been identified in the scientific literature (PMID: 17102087, PMID: 14767570, PMID: 23842656, PMID: 29752349), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
I151F missense unknown VHL I151F lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). I151F has been identified in the scientific literature (PMID: 10766184, PMID: 22357542), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
F148fs frameshift loss of function - predicted VHL F148fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 148 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the Elongin BC complex-binding region (UniProt.org), F148fs is predicted to lead to a loss of Vhl protein function.
A149T missense unknown VHL A149T lies within the CCT complex-binding region of the Vhl protein (UniProt.org). A149T is conflicting, as it results in defective cell cycle exit in cell culture and increased Cyclin-D and Cyclin-A expression compared to wild-type as demonstrated by in-vitro assay, but forms spheroid growth similar to wild-type Vhl in cell culture (PMID: 17526729), results in reduced binding to Hif1a and ubiquitination (PMID: 11865071), and therefore, its effect on Vhl protein function is unknown (PubMed, Nov 2018).
L158Q missense no effect - predicted VHL L158Q lies within the Elongin BC complex interaction region of the Vhl protein (UniProt.org). L158Q results in decreased Vhl binding to Elongin C but retains HIF regulation in culture (PMID: 26503325).
G114C missense unknown VHL G114C lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G114C has been identified in the scientific literature (PMID: 18836774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
I151N missense unknown VHL I151N lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). I151N has been identified in the scientific literature (PMID: 29941223), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
D121G missense no effect - predicted VHL D121G lies within the CCT complex-binding region of the Vhl protein (UniProt.org). D121G results in decreased binding to Elongin C, but retains Vhl interaction with CUL2, ROC1, and Elongin B, and HIF regulation in culture (PMID: 19030229, PMID: 11865071).
P86R missense unknown VHL P86R does not lie within any known functional domains of the Vhl protein (UniProt.org). P86R has been identified in the scientific literature (PMID: 11257211), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
Y98C missense unknown VHL Y98C does not lie within any known functional domains of the Vhl protein (UniProt.org). Y98C has been identified in the scientific literature (PMID: 22799452), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
H115R missense loss of function - predicted VHL H115R lies within the CCT complex binding region of the Vhl protein (UniProt.org). H115R is predicted to confer a loss of function to the Vhl protein based on computer modeling, demonstrating decreased protein stability and interference with Hif1 binding (PMID: 22105711).
R177fs frameshift unknown VHL R177fs results in a change in the amino acid sequence of the Vhl protein beginning at 177 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). R177fs has been identified in sequencing studies (PMID: 22683710), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
V74D missense unknown VHL V74D does not lie within any known functional domains of the Vhl protein (UniProt.org). V74D has been identified in sequencing studies (PMID: 24446253, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
P81S missense loss of function VHL P81S does not lie within any known functional domains of the Vhl protein (UniProt.org). P81S results in a loss of Vhl binding to Tceb1 and failure to regulate Hif1a degradation in culture, and growth advantage in animal tumor models (PMID: 23990666).
Y98H missense loss of function - predicted VHL Y98H does not lie within any known functional domains of the Vhl protein (UniProt.org). Y98H is predicted to confer a loss of function to the Vhl protein, as indicated by defects in Hif1-alpha ubiquitination (PMID: 11331612).
D126N missense loss of function - predicted VHL D126N lies within the CCT complex-binding region of the Vhl protein (UniProt.org). D126N is predicted to confer a loss of function to the Vhl protein, as indicated by impaired regulation of Hif1a in cell culture (PMID: 21454469).
S80N missense unknown VHL S80N does not lie within any known functional domains of the Vhl protein (UniProt.org). S80N has been identified in the scientific literature (PMID: 22683710, PMID: 23797736, PMID: 26895810), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
G93V missense unknown VHL G93V does not lie within any known functional domains of the Vhl protein (UniProt.org). G93V has been identified in the scientific literature (Journal of Clinical Oncology 28, no. 15_suppl e15024), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
S68* nonsense loss of function - predicted VHL S68* results in a premature truncation of the Vhl protein at amino acid 68 of 213 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), S68* is predicted to lead to a loss of Vhl protein function.
S80R missense loss of function - predicted VHL S80R does not lie within any known functional domains of the Vhl protein (UniProt.org). S80R is predicted to lead to a loss of Vhl function by computational modeling (PMID: 18836774).
P81T missense unknown VHL P81T does not lie within any known functional domains of the Vhl protein (UniProt.org). P81T has been identified in the scientific literature (PMID: 21602815), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
C77* nonsense loss of function - predicted VHL C77* results in a premature truncation of the Vhl protein at amino acid 77 of 213 (UniProt.org). Due to the loss of all known functional domains (PMID: 19878677), C77* is predicted to lead to a loss of Vhl protein function.
V62fs frameshift loss of function - predicted VHL V62fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 62 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), V62fs is predicted to lead to a loss of Vhl protein function.
R79G missense unknown VHL R79G does not lie within any known functional domains of the Vhl protein (UniProt.org). R79G has been identified in the scientific literature (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
R167Q missense loss of function VHL R167Q does not lie within any known functional domains of the Vhl protein (UniProt.org). R167Q leads to a loss of Vhl function as indicated by impaired Enlongin C binding and inhibition of Hif2a expression in cell culture (PMID: 15574766).
R161fs frameshift unknown VHL R161fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 161 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). R161fs has been identified in sequencing studies (PMID: 7881415), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
N78D missense unknown VHL N78D does not lie within any known functional domains of the Vhl protein (UniProt.org). N78D has been identified in the scientific literature (PMID: 23224817), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
G144E missense unknown VHL G144E lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). G144E has been identified in the scientific literature (PMID: 27998968), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
I180N missense unknown VHL I180N does not lie within any known functional domains of the Vhl protein (UniProt.org). I180N has been identified in sequencing studies (PMID: 25691774), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
W88R missense unknown VHL W88R does not lie within any known functional domains of the Vhl protein (UniProt.org). W88R has been identified in sequencing studies (PMID: 23036577), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
H110Q missense unknown VHL H110Q lies within the CCT complex-interacting region of the Vhl protein (UniProt.org). H110Q has been identified in the scientific literature (PMID: 12781449), but has not been biochemically characterized and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
Y112H missense loss of function VHL Y112H lies within the CCT binding complex region of the Vhl protein (UniProt.org). Y112H confers a loss of function to the Vhl protein as demonstrated by decreased stability and impaired regulation of Hif1-alpha activity in culture (PMID: 16261165, PMID: 19030229).
S68fs frameshift loss of function - predicted VHL S68fs results in a change in the amino acid sequence of the Vhl protein beginning at aa 68 of 213, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), S68fs is predicted to lead to a loss of Vhl protein function.
P95Q missense unknown VHL P95Q does not lie within any known functional domains of the Vhl protein (UniProt.org). P95Q has not been characterized in the scientific literature and therefore, its effect on Vhl protein function is unknown (PubMed, Sep 2018).
Molecular Profile Protein Effect Treatment Approaches
VHL R161* unknown
VHL N131Y unknown
VHL Q73E unknown
VHL W88C unknown
VHL R167W loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL G123W unknown
VHL N131fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL I180V unknown
VHL L101P unknown
VHL R161P loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL F136L loss of function
VHL R107G unknown
VHL W117C loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL E186K unknown
VHL L158V unknown
VHL P154L loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Q164R no effect - predicted
VHL S183L loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL W88* loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL N78T unknown
VHL P25L unknown
VHL C162F loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL V155fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L128H unknown
VHL L158fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Q132fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL G39D unknown
VHL R107P unknown
VHL over exp no effect
VHL P25S unknown
VHL wild-type no effect
VHL C162Y unknown
VHL N78Y unknown
VHL V130F loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L89H unknown
VHL R205C unknown
VHL L158P loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
PTEN loss VHL loss
VHL loss loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L201P unknown
VHL F91L unknown
VHL F76S unknown
VHL L184P loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L188P unknown
VHL negative loss of function
VHL E173D unknown
VHL inact mut loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
TP53 R248W VHL inact mut
VHL N90Y unknown
VHL V165D unknown
VHL F119L loss of function
VHL V155A no effect - predicted
VHL C162R unknown
VHL S111N loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL H115Y unknown
VHL R205H unknown
VHL S65W loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL G144A unknown
VHL L116fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L184fs unknown
VHL R82P loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL N90I loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL A149D unknown
VHL R161G loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Y175* unknown
VHL D121Y unknown
VHL I151T unknown
VHL mut unknown
VHL del loss of function
VHL L184R unknown
VHL Y98N loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L188R unknown
VHL G127V unknown
VHL L153P unknown
VHL L89P unknown
VHL C162W loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL H115N unknown
VHL N78S loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL S111R loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL V130D unknown
VHL V74G loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL H115Q loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL P86L unknown
VHL R167G unknown
VHL S65L loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL W88L unknown
VHL V155M unknown
VHL P86H loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Q73H unknown
VHL G29D unknown
VHL L169P unknown
VHL P192S unknown
VHL G106V unknown
VHL S80I loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL S38F unknown
VHL R79P loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL G114R loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Q96* loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL R161Q unknown
VHL I151F unknown
VHL F148fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL L158Q no effect - predicted
VHL G114C unknown
VHL I151N unknown
VHL D121G no effect - predicted
VHL P86R unknown
VHL Y98C unknown
VHL H115R loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL R177fs unknown
VHL V74D unknown
VHL P81S loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Y98H loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL D126N loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL S80N unknown
VHL G93V unknown
VHL S68* loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL S80R loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL P81T unknown
VHL C77* loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL V62fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL R79G unknown
VHL R167Q loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL R161fs unknown
VHL N78D unknown
VHL G144E unknown
VHL I180N unknown
VHL W88R unknown
VHL H110Q unknown mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL Y112H loss of function mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL S68fs loss of function - predicted mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor
VHL P95Q unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
VHL V155fs kidney cancer predicted - sensitive Sunitinib + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination of Mekinist (trametinib) and Sutent (sunitinib) inhibited tumor growth in patient-derived xenograft models of renal cancer harboring VHL V155fs (referred to as V155fs*4) (PMID: 26487278). 26487278
VHL over exp clear cell renal cell carcinoma no benefit Cediranib + Saracatinib Phase II Actionable In a Phase II clinical study, baseline expression of VHL was not predictive for response to Saracatinib (AZD0530) and Recentin (cediranib) relative to Recentin (cediranib) in patients with metastatic clear-cell renal cell carcinoma (PMID: 26802156). 26802156
PTEN loss VHL loss renal carcinoma decreased response Gedatolisib Preclinical Actionable In a preclinical study, human renal carcinoma cells with PTEN loss and VHL loss had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073). 21325073
VHL loss renal cell carcinoma sensitive BPTES + Olaparib Preclinical - Cell culture Actionable In a preclinical study, the combination of BPTES and Lynparza (olaparib) resulted in a synergistic effect, demonstrating growth inhbition of VHL-deficient renal cell carcinoma cells in culture (PMID: 28346230). 28346230
VHL loss renal cell carcinoma sensitive ELR510444 Preclinical - Cell line xenograft Actionable In a preclinical study, renal cell carcinoma cells deficient for VHL were sensitive to ELR510444 both in culture and in cell line xenograft models (PMID: 22295124). 22295124
VHL loss renal cell carcinoma sensitive Bevacizumab Preclinical Actionable In a preclinical study, clear cell renal cell carcinoma xenograft models with VHL loss demonstrated sensitivity to Avastin (bevacizumab) (PMID: 22931246). 22931246
VHL loss renal cell carcinoma sensitive CB-839 Preclinical - Cell culture Actionable In a preclinical study, VHL-deficient renal cell carcinoma cells demonstrated growth inhibition in culture when treated with CB-839 (PMID: 28346230). 28346230
VHL loss renal cell carcinoma sensitive CB-839 + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CB-839 and Lynparza (olaparib) resulted in a synergistic effect, demonstrating greater reduction in tumor volume compared to either agent alone in renal carcinoma cell xenograft models deficient for VHL (PMID: 28346230). 28346230
VHL loss renal cell carcinoma sensitive BPTES Preclinical - Cell culture Actionable In a preclinical study, VHL-deficient renal cell carcinoma cells demonstrated growth inhibition and suppression of DNA synthesis in culture when treated with BPTES (PMID: 28346230). 28346230
VHL negative renal cell carcinoma sensitive STF-62247 Preclinical Actionable In a preclinical study, STF-62247 induced selective cytotoxicity and inhibited tumor growth of renal cell carcinoma cells lacking VHL (PMID: 18769110, PMID: 18598947). 18769110 18598947
VHL inact mut renal cell carcinoma no benefit GDC-0980 Phase II Actionable In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression free survival when stratified by the presence (n=5) or absence (n=17) of deleterious VHL mutations (PMID: 26951309). 26951309
VHL inact mut renal cell carcinoma predicted - sensitive Everolimus Phase II Actionable In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had a trend towards improved in progression free survival when stratified by the presence (median PFS=8.6 months, n=15) or absence (median PFS=5.5 months, n=16) of deleterious VHL mutations (PMID: 26951309). 26951309
VHL inact mut renal cell carcinoma predicted - sensitive Bevacizumab + Alpha 2 Interferon Clinical Study Actionable In a retrospective analysis, VHL alterations did not impact overall survival or objective response in renal cell carcinoma patients treated with a VEGF-targeted therapy,including Avastin (bevacizumab) and Alpha 2 Interferon combination therapy, but were associated with a prolonged time to progression (PMID: 16827904). 16827904
VHL inact mut clear cell renal cell carcinoma conflicting PT2399 Preclinical - Pdx Actionable In a preclinical study, PT2399 had variable impact on tumor growth in clear cell renal cell carcinoma (ccRCC) cell line and patient-derived xenograft (PDX) models with defective VHL, with decreased tumor growth in a VHL-defective ccRCC PDX model and some VHL-defective ccRCC cell line xenograft models, and no tumor suppression in other cell line xenograft models (PMID: 27595393). 27595393
TP53 R248W VHL inact mut clear cell renal cell carcinoma resistant PT2399 Preclinical - Cell culture Actionable In a preclinical study, TP53 R248W was associated with resistance to PT2399 in VHL-defective clear cell renal cell carcinoma cell lines in culture (PMID: 27595393). 27595393
VHL mut renal cell carcinoma sensitive Sunitinib Phase I Actionable In a Phase I study, 33% (6/18) of renal cell carcinoma archived patient samples with VHL mutations demonstrated partial response when treated with Sutent (sunitinib) (PMID: 22105611). 22105611
VHL mut renal cell carcinoma no benefit N/A Clinical Study Prognostic In a meta-analysis of 6 clinical studies, VHL mutation status was not associated with overall response rate (relative risk=1.47, p=0.20), progression-free survival (HR=1.02, p=0.91), or overall survival (HR=0.80, p=0.21) in a total of 633 patients with renal cell carcinoma who received anti-VEGF therapy (PMID: 28103578). 28103578
VHL mut renal cell carcinoma sensitive Everolimus Phase I Actionable In a Phase I study, Afinitor (everolimus), as compared to Apitolisib (GDC-0980), resulted in a greater progression free survival and overall survival in patients with renal cell carcinoma harboring VHL mutations (J Clin Oncol 32:5s, 2014 (suppl; abstr 4525)). detail...
VHL del renal cell carcinoma predicted - sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited angiogenesis and tumor growth in cell line xenograft models of renal cell carcinoma harboring VHL gene deletion (PMID: 21170960). 21170960