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Gene Symbol HRAS
Synonyms C-BAS/HAS | C-H-RAS | C-HA-RAS1 | CTLO | H-RASIDX | HAMSV | HRAS1 | p21ras | RASH1
Gene Description HRAS, HRas proto-oncogene, GTPase, is a member of the small GTPase family that upon activation by growth factors stimulates multiple downstream pathways such as RAF and PI3K to promote cell proliferation and survival (PMID: 21779504). HRAS activating mutations are commonly found in tumors, including dermatological, head and neck, thyroid, kidney, and bladder cancers (PMID: 29524560).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A11D missense unknown HRAS A11D lies within a GTP binding region of the Hras protein (UniProt.org). A11D has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Mar 2020).
A11S missense unknown HRAS A11S lies within a GTP binding region of the Hras protein (UniProt.org). A11S has been identified in the scientific literature (PMID: 22683711), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
A130T missense unknown HRAS A130T does not lie within any known functional domains of the Hras protein (UniProt.org). A130T has been identified in the scientific literature (PMID: 30348504), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jan 2020).
A134S missense unknown HRAS A134S does not lie within any known functional domains of the Hras protein (UniProt.org). A134S has been identified in sequencing studies (PMID: 26870252), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
A134T missense unknown HRAS A134T does not lie within any known functional domains of the Hras protein (UniProt.org). A134T has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
A146T missense gain of function HRAS A146T lies within the SAK motif of the Hras protein (PMID: 24224811). A146T does not affect Hras intrinsic GTPase activity, but results in increased nucleotide exchange rates, which leads to increase GTP-bound Hras, activation of downstream signaling, and senescence of cultured cells (PMID: 24224811, PMID: 21850009).
A146V missense gain of function HRAS A146V lies within the SAK motif of the Hras protein (PMID: 24224811). A146V does not affect Hras intrinsic GTPase activity, but results in increased nucleotide exchange rates, which leads to increase GTP-bound Hras, activation of downstream signaling, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 3043178).
A59D missense unknown HRAS A59D lies within a GTP binding region of the Hras protein (UniProt.org). A59D has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
A59Rfs*32 frameshift loss of function - predicted HRAS A59Rfs*32 indicates a shift in the reading frame starting at amino acid 59 and terminating 32 residues downstream causing a premature truncation of the 189 amino acid Hras protein (UniProt.org). Due to the loss of the GTP binding domain (UniProt.org), A59Rfs*32 is predicted to confer loss of function on the Hras protein.
A59T missense gain of function HRAS A59T lies within the GTP binding domain of the Hras protein (UniProt.org). A59T does not affect Hras GTPase activity, but increases nucleotide exchange rate, resulting in increase GTP-bound Hras and transformation of cultured cells (PMID: 21779495, PMID: 3004741).
A66T missense unknown HRAS A66T does not lie within any known functional domains of the Hras protein (UniProt.org). A66T has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
act mut unknown unknown HRAS act mut indicates that the variant results in activation of HRAS downstream signaling. The mechanism causing the activation can include either loss of GTP hydrolysis activity (loss of function) or increased nucleotide exchange rate (gain of function).
amp none no effect HRAS amplification indicates an increased number of copies of the HRAS gene. However, the mechanism causing the increase is unspecified.
D33N missense loss of function HRAS D33N lies within the effector region of the Hras protein (UniProt.org). D33N demonstrates decreased binding affinity for effector protein Raf compared to wild-type Hras, and is not transforming in cell culture (PMID: 28686159, PMID: 8035810).
D47E missense unknown HRAS D47E does not lie within any known functional domains of the Hras protein (UniProt.org). D47E has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
E143K missense unknown HRAS E143K does not lie within any known functional domains of the Hras protein (UniProt.org). E143K has not been characterized in the scientific literature and therefore, its effect on Hras function is unknown (PubMed, Nov 2019).
E162G missense unknown HRAS E162G does not lie within any known functional domains of the Hras protein (UniProt.org). E162G has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
E162K missense unknown HRAS E162K does not lie within any known functional domains of the Hras protein (UniProt.org). E162K has been identified in the scientific literature (PMID: 22932669), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
E62G missense unknown HRAS E62G lies within the GTP binding domain of the Hras protein (PMID: 21779495). E62G has been identified in the scientific literature (PMID: 19628422), but has not been biochemically characterized, and therefore its effect on Hras protein function is unknown (PubMed, Nov 2019).
E91K missense unknown HRAS E91K does not lie within any known functional domains of the Hras protein (UniProt.org). E91K has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
F82L missense unknown HRAS F82L does not lie within any known functional domains of the Hras protein (UniProt.org). F82L has been identified in the scientific literature (PMID: 28939558, PMID: 25360634), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
G10S missense unknown HRAS G10S lies within a GTP nucleotide binding region of the Hras protein (UniProt.org). G10S has been identified in sequencing studies (PMID: 27713118), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
G12A missense loss of function HRAS G12A is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12A results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, leading to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12C missense loss of function HRAS G12C is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12C results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, thus leads to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12D missense loss of function HRAS G12D is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12D results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, thus leads to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12E missense loss of function HRAS G12E is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12E results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, and is transforming in cultured (PMID: 24224811, PMID: 6092966).
G12F missense loss of function - predicted HRAS G12F is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12F has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12H missense loss of function - predicted HRAS G12H is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12H has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12I missense loss of function - predicted HRAS G12I is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12I has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12K missense loss of function - predicted HRAS G12K is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12K has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12L missense loss of function - predicted HRAS G12L is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12L has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12M missense loss of function - predicted HRAS G12M is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12M has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12N missense loss of function - predicted HRAS G12N is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12N has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12Q missense loss of function - predicted HRAS G12Q is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12Q has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12R missense loss of function HRAS G12R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12R results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3042780, PMID: 6092966).
G12S missense loss of function HRAS G12S is hotspot mutation that lies within a GTP nucleotide binding region of the Hras protein (UniProt.org). G12S results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729).
G12T missense loss of function - predicted HRAS G12T is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12T has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12V missense loss of function HRAS G12V is hotspot mutation that lies within a GTP nucleotide binding region of the Hras protein (UniProt.org). G12V results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729).
G12W missense loss of function - predicted HRAS G12W is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12W has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G12X missense unknown HRAS G12X indicates any HRAS missense mutation that results in replacement of the glycine (G) at amino acid 12 by a different amino acid. HRAS codon 12 mutations are "hotspot" mutations that often result in decreased Hras GTPase activity and transformation of cultured cells (PMID: 6092966, PMID: 24224811, PMID: 26985062).
G12Y missense loss of function - predicted HRAS G12Y is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G12Y has not been biochemically characterized, but demonstrates transforming ability in cultured cells (PMID: 6092966) and therefore, is predicted to result in a loss of Hras protein function.
G13C missense loss of function HRAS G13C is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13C results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, leading to activation of downstream signaling and cell senescence in culture (PMID: 24224811, PMID: 21850009).
G13D missense loss of function HRAS G13D is hotspot mutation that lies within the GTP nucleotide binding region of the Hras protein (UniProt.org). G13D results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, leading to activation of downstream signaling and senescence in cell culture (PMID: 24224811, PMID: 21850009).
G13I missense unknown HRAS G13I is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13I has been identified in the scientific literature (PMID: 26974156, PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
G13R missense loss of function HRAS G13R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13R confers a loss of function on Hras protein as indicated by activation of Mapk and Pi3k signaling, increased cell proliferation in culture (PMID: 22683711).
G13S missense loss of function HRAS G13S is hotspot mutation that lies within the GTP-binding domain of the Hras protein (UniProt.org). G13S results in increased Hras GTPase activity, but loss of response to GTPase-activating proteins, leading to transformation in Xenopus oocytes (PMID: 8430333).
G13T missense loss of function HRAS G13T is hotspot mutation that lies within the GTP-binding domain of the Hras protein (UniProt.org). G13T results in increased Hras GTPase activity, but loss of response to GTPase-activating proteins, leading to transformation in Xenopus oocytes (PMID: 8430333).
G13V missense loss of function HRAS G13V is a hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13V does not affect Hras GTPase activity, but results in a loss of response to GTPase-activating proteins, leading to increased GTP-bound Hras in culture (PMID: 24224811).
G13X missense unknown HRAS G13X indicates any HRAS missense mutation that results in replacement of the glycine (G) at amino acid 13 by a different amino acid. HRAS codon 13 mutations are "hotspot" mutations that often result in decreased Hras GTPase activity and transformation of cultured cells (PMID: 8430333, PMID: 21850009, PMID: 24224811, PMID: 26985062).
G151E missense unknown HRAS G151E does not lie within any known functional domains of the Hras protein (UniProt.org). G151E has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
G15S missense unknown HRAS G15S lies within a GTP-binding region of the Hras protein (UniProt.org). G15S has been identified in sequencing studies (PMID: 29844865, PMID: 9528840), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jan 2020).
G48R missense no effect - predicted HRAS G48R does not lie within any known functional domains of the Hras protein (UniProt.org). G48R demonstrates GTP affinity and GTP hydrolysis activity similar to wild-type Hras, and enhances effector recruitment in combination with HRAS G12V in culture (PMID: 26274561), and therefore, is predicted to have no effect on Hras protein function.
inact mut unknown loss of function HRAS inact mut indicates that the variant results in failure to activate HRAS downstream signaling. However, the specific amino acid change has not been identified.
K117E missense loss of function HRAS K117E lies within the GTP binding domain of the Hras protein (UniProt.org). K117E confers a loss of function on Hras protein as indicated by increased GTP-bound Hras, activation of downstream signaling, and transformation of cultured cells (PMID: 12569357).
K117N missense loss of function HRAS K117N lies within the GTP binding domain of the Hras protein (UniProt.org). K117N results in decreased nucleotide binding affinity and activation of Hras in culture (PMID: 24247240).
K117R missense gain of function HRAS K117R lies within the GTP binding region of the Hras protein (UniProt.org). K117R does not affect Hras intrinsic GTPase activity, but increases nucleotide exchange rates, resulting in increased GTP-boud Hras, activation of downstream signaling, and cell senescence in culture (PMID: 24224811, PMID: 17979197, PMID: 21850009).
L120V missense unknown HRAS L120V does not lie within any known functional domains of the Hras protein (UniProt.org). L120V has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
L133R missense unknown HRAS L133R does not lie within any known functional domains of the Hras protein (UniProt.org). L133R has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
mutant unknown unknown HRAS mutant indicates an unspecified mutation in the HRAS gene.
N116H missense gain of function - predicted HRAS N116H lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116H results in increased nucleotide exchange rate in in vitro assays, and is transforming in cell culture (PMID: 3043178, PMID: 1549350).
N116I missense loss of function HRAS N116I lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116I results in a loss of intrinsic and GEF-stimulated GTPase activity, and is transforming in cell culture (PMID: 3487832, PMID: 8227029).
N116Q missense no effect - predicted HRAS N116Q lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116I results in GTPase activity similar to wild-type Hras, and is not transforming in cell culture (PMID: 3487832), therefore, is predicted to have no effect on Hras protein function.
N26S missense unknown HRAS N26S does not lie within any known functional domains of the Hras protein (UniProt.org). N26S has been identified in sequencing studies (PMID: 28229982, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
P174S missense unknown HRAS P174S lies within the hypervariable region of the Hras protein (UniProt.org). P174S has been identified in sequencing studies (PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
Q61A missense loss of function HRAS Q61A is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61A results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61C missense loss of function HRAS Q61C is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61C results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61E missense loss of function HRAS Q61E is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61E results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61F missense loss of function HRAS Q61F is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61F results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61G missense loss of function HRAS Q61G is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61G results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61H missense loss of function HRAS Q61H is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61H results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61I missense loss of function HRAS Q61I is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61I results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61K missense loss of function HRAS Q61K is a hotspot mutation that lies within the GTP nucleotide binding region of the Hras protein (UniProt.org). Q61K results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61L missense loss of function HRAS Q61L is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61L results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 23487764, PMID: 3510078).
Q61M missense loss of function HRAS Q61M is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61M results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61N missense loss of function HRAS Q61N is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61N results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61P missense loss of function HRAS Q61P is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61P results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61R missense loss of function HRAS Q61R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61R results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61T missense loss of function HRAS Q61T is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61T results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61V missense loss of function HRAS Q61V is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61V results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61W missense loss of function HRAS Q61W is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61W results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61X missense unknown HRAS Q61X indicates any HRAS missense mutation that results in replacement of the glutamine (Q) at amino acid 61 by a different amino acid. HRAS codon 61 mutations are hotspot mutations that often result in decreased Hras GTPase activity and transformation of cultured cells (PMID: 3510078, PMID: 26985062).
Q61Y missense loss of function HRAS Q61Y is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). Q61Y results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
R123C missense unknown HRAS R123C does not lie within any known functional domains of the Hras protein (UniProt.org). R123C has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
R123H missense unknown HRAS R123H does not lie within any known functional domains of the Hras protein (UniProt.org). R123H has been identified in sequencing studies (PMID: 25303977), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
R128L missense unknown HRAS R128L does not lie within any known functional domains of the Hras protein (UniProt.org). R128L has been identified in sequencing studies (PMID: 22941189), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
R128W missense unknown HRAS R128W does not lie within any known functional domains of the Hras protein (UniProt.org). R128W has been identified in sequencing studies (PMID: 27499925), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
R149Gfs*23 frameshift unknown HRAS R149Gfs*23 indicates a shift in the reading frame starting at amino acid 149 and terminating 23 residues downstream causing a premature truncation of the 189 amino acid Hras protein (UniProt.org). R149Gfs*23 has been identified in sequencing studies (PMID: 27713118), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2019).
R73C missense unknown HRAS R73C does not lie within any known functional domains of the Hras protein (UniProt.org). R73C has been identified in sequencing studies (PMID: 22185227, PMID: 15861495), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
R73H missense unknown HRAS R73H does not lie within any known functional domains of the Hras protein (UniProt.org). R73H has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
T58I missense loss of function HRAS T58I does not lie within any known functional domains of the Hras protein (UniProt.org). T58I confers a loss of function on the Hras protein as indicated by decreased GTP hydrolysis and binding to GEF proteins, leading to constitutive activation of Hras signaling in culture (PMID: 26888048).
V81M missense unknown HRAS V81M does not lie within any known functional domains of the Hras protein (UniProt.org). V81M has been identified in sequencing studies (PMID: 27612322, PMID: 24997986, PMID: 14616967), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Sep 2019).
wild-type none no effect Wild-type HRAS indicates that no mutation has been detected within the HRAS gene.
Y32* nonsense loss of function - predicted HRAS Y32* results in the premature truncation of the Hras protein at amino acid 32 of 189 (UniProt.org). Due to the loss of the GTP binding domain of Hras (UniProt.org), Y32* is predicted to confer loss of function to the Hras protein.
Y32S missense unknown HRAS Y32S lies within the switch I region of the Hras protein (PMID: 11333268). Y32S results in a moderate increase of nucleotide exchange rate, but decreased binding to Sos and reduced sensitivity to Sos-mediated nucleotide exchange, and therefore, its effect on Hras protein function is unknown (PMID: 11333268).
Y40A missense gain of function - predicted HRAS Y40A lies within the swtich I region of the Kras protein (PMID: 11333268). Y40A results in decreased binding to Sos1 but response to Sos-mediated nucleotide exchange, and demonstrates increased intrinsic GDP/GTP exchange rate in in vitro assays, and therefore, is predicted to lead to a gain of Hras protein function (PMID: 11333268).