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Gene Symbol NTRK2
Synonyms DEE58 | EIEE58 | GP145-TrkB | OBHD | trk-B | TRKB
Gene Description NTRK2, neurotrophic receptor tyrosine kinase 2, is membrane receptor tyrosine kinase that binds neurotrophins, initiating signaling cascades that lead to cell growth and differentiation (PMID: 17008023). Inappropriately regulated NTRK2 may be involved in initiation and metastasis of some cancers (PMID: 17008023) and NTRK2 fusions, with multiple gene partners, have been commonly observed in solid tumors (PMID: 32319699), including glioma (PMID: 28512244, PMID: 24705251), while NTRK2 missense mutations may confer resistance to TRK inhibition (PMID: 21242122).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A268V missense unknown NTRK2 A268V lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). A268V has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
act mut unknown gain of function NTRK2 act mut indicates that this variant results in a gain of function in the Ntrk2 protein. However, the specific amino acid change has not been identified.
amp none no effect NTRK2 amplification indicates an increased number of copies of the NTRK2 gene. However, the mechanism causing the increase is unspecified.
C45F missense unknown NTRK2 C45F lies within the LRRNT domain of the Ntrk2 protein (UniProt.org). C45F has been identified in sequencing studies (PMID: 25234657), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
C45Y missense unknown NTRK2 C45Y lies within the LRRNT domain of the Ntrk2 protein (UniProt.org). C45Y has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
D386N missense unknown NTRK2 D386N lies within the extracellular domain of the Ntrk2 protein (UniProt.org). D386N has been identified in the scientific literature (PMID: 34290315), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
D676V missense unknown NTRK2 D676V lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). D676V has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
D700N missense unknown NTRK2 D700N lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). D700N has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
dec exp none no effect NTRK2 dec exp indicates decreased expression of the Ntrk2 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
E209D missense unknown NTRK2 E209D lies within the Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). E209D has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
E242K missense unknown NTRK2 E242K lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). E242K has been identified in the scientific literature (J Clin Oncol 33, 2015 (suppl; abstr 1553)), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
E371D missense unknown NTRK2 E371D lies within the extracellular domain of the Ntrk2 protein (UniProt.org). E371D has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
E588D missense unknown NTRK2 E588D lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). E588D has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
E70K missense unknown NTRK2 E70K lies within the extracellular domain of the Ntrk2 protein (UniProt.org). E70K has been identified in sequencing studies (PMID: 28467829), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Mar 2022).
E84K missense unknown NTRK2 E84K lies within the extracellular domain of the Ntrk2 protein (UniProt.org). E84K has been identified in sequencing studies (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
F452L missense unknown NTRK2 F452L lies within the transmembrane domain of the Ntrk2 protein (UniProt.org). F452L has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
fusion fusion unknown NTRK2 fusion indicates a fusion of the NTRK2 gene, but the fusion partner is unknown.
G261R missense unknown NTRK2 G261R lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). G261R has been identified in sequencing studies (PMID: 25234657), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
G357R missense unknown NTRK2 G357R lies within Ig-like C2-type domain 2 of the Ntrk2 protein (UniProt.org). G357R has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
G487W missense unknown NTRK2 G487W lies within the cytoplasmic domain of the Ntrk2 protein (UniProt.org). G487W has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
G623R missense unknown NTRK2 G623R lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). G623R has been identified in the scientific literature (PMID: 26884591), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Jun 2022).
G639R missense unknown NTRK2 G639R (corresponds to G623R in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). G639R is associated with resistance to Trk inhibitors in culture (PMID: 34625502), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Jul 2022). Y
G693C missense unknown NTRK2 G693C lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). G693C has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
G709C missense unknown NTRK2 G709C (corresponds to G693C in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). G709C is associated with resistance to Trk inhibitors in culture (PMID: 34625502), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Jul 2022). Y
G740R missense unknown NTRK2 G740R lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). G740R has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
H482Y missense unknown NTRK2 H482Y lies within the cytoplasmic domain of the Ntrk2 protein (UniProt.org). H482Y has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
I81F missense unknown NTRK2 I81F lies within the extracellular domain of the Ntrk2 protein (UniProt.org). I81F has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Mar 2022).
inact mut unknown loss of function NTRK2 inact mut indicates that this variant results in a loss of function of the Ntrk2 protein. However, the specific amino acid change has not been identified.
K602T missense no effect - predicted NTRK2 K602T lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). K602T is predicted to have no effect on the function of Ntrk2, as the corresponding variant in an alternative isoform (K618T) demonstrates similar transformation ability and levels of autophosphorylation to wild-type Ntrk2 in cell culture (PMID: 30926633).
K618T missense no effect NTRK2 K618T (corresponds to K602T in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). K618T has no effect on Ntrk2 protein function, as demonstrated by similar transformation ability and levels of autophosphorylation to wild-type Ntrk2 in cell culture (PMID: 30926633).
L138F missense no effect NTRK2 L138F lies within the extracellular domain of the Ntrk2 protein (UniProt.org). L138F demonstrates activity similar to wild-type Ntrk2 in ligand-dependent phosphorylation of Ntrk2, activation of Akt and Erk signaling, transformation of cell in culture, and promoting tumor growth in animal models (PMID: 21379385).
L568V missense no effect - predicted NTRK2 L568V lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). L568V is predicted to have no effect on the function of Ntrk2, as the corresponding variant in an alternative isoform (L584V) demonstrates similar transformation ability and levels of autophosphorylation to wild-type Ntrk2 in cell culture (PMID: 30926633).
L584V missense no effect NTRK2 L584V (corresponds to L568V in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). L584V has no effect on Ntrk2 protein function, as demonstrated by similar transformation ability and levels of autophosphorylation to wild-type Ntrk2 in cell culture (PMID: 30926633).
loss unknown loss of function NTRK2 loss indicates loss of the NTRK2 gene, mRNA, and protein.
M354I missense unknown NTRK2 M354I lies within Ig-like C2-type domain 2 of the Ntrk2 protein (UniProt.org). M354I has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
M713I missense loss of function NTRK2 M713I (corresponds to M697I in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). M713I results in loss of Ntrk2 autophosphorylation, decreased phosphorylation of Ntrk2, Akt and Erk upon growth factor stimulation, is not transforming in cell culture, and is associated with resistance to a Trk inhibitor (PMID: 21242122). Y
mutant unknown unknown NTRK2 mutant indicates an unspecified mutation in the NTRK2 gene.
N280S missense unknown NTRK2 N280S lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). N280S has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
N67S missense unknown NTRK2 N67S lies within the extracellular domain of the Ntrk2 protein (UniProt.org). N67S has been identified in the scientific literature (PMID: 34290315), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
over exp none no effect NTRK2 over exp indicates an over expression of the Ntrk2 protein. However, the mechanism causing the over expression is unspecified.
P10H missense unknown NTRK2 P10H does not lie within any known functional domains of the Ntrk2 protein (UniProt.org). P10H has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
positive unknown unknown NTRK2 positive indicates the presence of the NTRK2 gene, mRNA, and/or protein.
Q76H missense unknown NTRK2 Q76H lies within the extracellular domain of the Ntrk2 protein (UniProt.org). Q76H has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
R136H missense unknown NTRK2 R136H lies within LRR repeat 2 of the Ntrk2 protein (UniProt.org). R136H has been identified in sequencing studies (PMID: 34290315), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
R715G missense loss of function NTRK2 R715G (corresponds to R699G in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). R715G demonstrates decreased autophosphorylation and phosphorylation of Ntrk2, Akt and Erk upon growth factor stimulation, does not support anchorage independent growth, and is associated with resistance to a Trk inhibitor in culture (PMID: 21242122). Y
R734C missense loss of function NTRK2 R734C (corresponds to R718C in the canonical isoform) lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). R734C results in loss of Ntrk2 autophosphorylation, decreased phosphorylation of Ntrk2, Akt and Erk upon growth factor stimulation, is not transforming, and is associated with resistance to a Trk inhibitor in cell culture (PMID: 21242122). Y
R770Q missense unknown NTRK2 R770Q lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). R770Q has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
rearrange unknown unknown NTRK2 rearrangement indicates an unspecified rearrangement of the NTRK2 gene.
S167Y missense no effect - predicted NTRK2 S167Y lies within the LRRCT domain of the Ntrk2 protein (UniProt.org). S167Y does not induce Il-3 independent growth in culture cells (PMID: 32315394), and therefore, is predicted to have no effect on Ntrk2 protein function.
S257F missense unknown NTRK2 S257F lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). S257F has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
S35F missense unknown NTRK2 S35F lies within the LRRNT domain of the Ntrk2 protein (UniProt.org). S35F has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
S46G missense unknown NTRK2 S46G lies within the LRRNT domain of the Ntrk2 protein (UniProt.org). S46G has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
S738T missense unknown NTRK2 S738T lies within the protein kinase domain of the Ntrk2 protein (UniProt.org). S738T has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
V422I missense unknown NTRK2 V422I lies within the extracellular domain of the Ntrk2 protein (UniProt.org). V422I has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
V449I missense unknown NTRK2 V449I lies within the transmembrane domain of the Ntrk2 protein (UniProt.org). V449I has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
V87D missense unknown NTRK2 V87D lies within the extracellular domain of the Ntrk2 protein (UniProt.org). V87D has been identified in the scientific literature (PMID: 34290315), but has not been biochemically characterized and therefore, its effect on Ntrk2 protein function is unknown (PubMed, May 2022).
W158* nonsense loss of function - predicted NTRK2 W158* results in a premature truncation of the Ntrk2 protein at amino acid 158 of 822 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W158* is predicted to lead to a loss of Ntrk2 function.
W230L missense unknown NTRK2 W230L lies within Ig-like C2-type domain 1 of the Ntrk2 protein (UniProt.org). W230L has not been characterized in the scientific literature and therefore, its effect on Ntrk2 protein function is unknown (PubMed, Feb 2022).
wild-type none no effect Wild-type NTRK2 indicates that no mutation has been detected within the NTRK2 gene.