NTRK3 (NT-3 growth factor receptor) variants and mutations
NTRK3 (also known as NT-3 growth factor receptor) is a human protein-coding gene encoding a NT-3 growth factor receptor protein. Neurotrophin-3 signaling through this pathway supports neuronal differentiation and survival. Constitutively active NTRK3 fusion kinases, most notably ETV6::NTRK3, drive several otherwise unrelated cancers and are highly actionable with TRK inhibitors. This analysis covers 2,992 NTRK3 variants and mutations. Of these, 45% have computational variant effect predictions. Disease context includes cancer, non-small cell lung carcinoma, and neoplasm. Example NTRK3 variants include D2G, D2V, and S4C.
Variant analysis overview
- Gene: NTRK3
- Protein: NT-3 growth factor receptor
- UniProt accession: Q16288
- Organism: Homo sapiens
- Variants analyzed: 2992
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,861 unspecified-consequence records; 2 stop lost; 1 stop retained variant; 55 synonymous variants; 67 missense variants; 2 splice-region variants; 1 stop-gained variants; 1 frameshift variants; 2 substitution
- Prediction scores: 1,339 variants have prediction scores (45% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cancer, non-small cell lung carcinoma, neoplasm, neurodegenerative disease, keratitis, ovarian neoplasm, thyroid gland papillary carcinoma, congenital fibrosarcoma, pancreatic ductal adenocarcinoma, congenital mesoblastic nephroma, ganglioglioma, lung carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 2 binding sites; 18 post-translational modification sites.
- Structural context: 2,182 variants have structural context.
- PTM context: 51 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable NTRK3 variants
Examples include D2G, D2V, S4C, L5F, L5V, P7Q, P7R, P7S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D2G (p.Asp2Gly), gnomAD rs1397502133
- D2V (p.Asp2Val), gnomAD rs1397502133
- S4C (p.Ser4Cys), cosmic curated COSV58146, REVEL 0.10, CADD 22.90
- L5F (p.Leu5Phe), gnomAD rs1332907152, REVEL 0.11, CADD 22.40
- L5V (p.Leu5Val), cosmic curated COSV58118, REVEL 0.10, CADD 23.30
- P7Q (p.Pro7Gln), ExAC rs776416833, gnomAD rs776416833, REVEL 0.21, CADD 24.90
- P7R (p.Pro7Arg), cosmic curated COSV58149
- P7S (p.Pro7Ser), Ensembl rs2142090681
- A8G (p.Ala8Gly), ExAC rs760529304, gnomAD rs760529304, REVEL 0.11, CADD 23.00
- A8P (p.Ala8Pro), ExAC rs766330065, gnomAD rs766330065, REVEL 0.17, CADD 23.10
- A8S (p.Ala8Ser), ExAC rs766330065, gnomAD rs766330065
- A8T (p.Ala8Thr), ExAC rs766330065, gnomAD rs766330065, REVEL 0.10, CADD 23.00
- A8V (p.Ala8Val), ExAC rs760529304, gnomAD rs760529304
- K9E (p.Lys9Glu), TOPMed rs1368927294, gnomAD rs1368927294, REVEL 0.17, CADD 22.80
- K9N (p.Lys9Asn), cosmic curated COSV58135
- C10Y (p.Cys10Tyr), TOPMed rs2054033029
- F12C (p.Phe12Cys), ExAC rs772820012, TOPMed rs772820012, gnomAD rs772820012, REVEL 0.31, CADD 24.50
- W13C (p.Trp13Cys), gnomAD rs1456468651, REVEL 0.59, CADD 26.70
- R14Q (p.Arg14Gln), rs761609264, ClinGen CA7717433, cosmic curated COSV58115, ClinVar RCV004239425, REVEL 0.34, CADD 24.60, Uncertain significance, not specified
- R14W (p.Arg14Trp), cosmic curated COSV10609, ExAC rs111731219, TOPMed rs111731219, gnomAD rs111731219, REVEL 0.45, CADD 25.00
- L17* (p.Leu17Ter), cosmic curated COSV10044
- L17F (p.Leu17Phe), gnomAD rs1288166921, REVEL 0.09, CADD 21.30
- G19E (p.Gly19Glu), cosmic curated COSV58139, REVEL 0.28, CADD 22.10
- G19V (p.Gly19Val), ExAC rs746157259, gnomAD rs746157259, REVEL 0.20, CADD 22.20
- S20N (p.Ser20Asn), ExAC rs781379782, gnomAD rs781379782, REVEL 0.19, CADD 23.00
- S20R (p.Ser20Arg), ExAC rs771001903, gnomAD rs771001903, REVEL 0.40, CADD 23.10
- V21A (p.Val21Ala), ExAC rs777949397, TOPMed rs777949397, gnomAD rs777949397, REVEL 0.24, CADD 22.70
- V21F (p.Val21Phe), rs200822610, ClinGen CA7717427, cosmic curated COSV58110, ClinVar RCV000892087, REVEL 0.23, CADD 23.00, Likely benign, not provided
- V21I (p.Val21Ile), cosmic curated COSV10044, 1000Genomes rs200822610, ExAC rs200822610, TOPMed rs200822610, REVEL 0.08, CADD 18.10, Likely benign
- V21L (p.Val21Leu), 1000Genomes rs200822610, ExAC rs200822610, TOPMed rs200822610, gnomAD rs200822610, REVEL 0.10, CADD 19.30, Likely benign
- W22C (p.Trp22Cys), gnomAD rs1288150213, REVEL 0.28, CADD 24.10, Uncertain significance, not specified
- W22R (p.Trp22Arg), Ensembl rs2054029908
- L23M (p.Leu23Met), TOPMed rs1229340087, gnomAD rs1229340087, REVEL 0.15, CADD 22.60
- L23P (p.Leu23Pro), Ensembl rs2142089632
- L23V (p.Leu23Val), TOPMed rs1229340087, gnomAD rs1229340087
- Y25C (p.Tyr25Cys), TOPMed rs1169532276, REVEL 0.28, CADD 23.10
- Y25H (p.Tyr25His), gnomAD rs1006732882, REVEL 0.20, CADD 24.20
- G27D (p.Gly27Asp), cosmic curated COSV58112, Ensembl rs139291499
- G27R (p.Gly27Arg), Ensembl rs1392275447
- G27V (p.Gly27Val), Ensembl rs139291499, REVEL 0.21, CADD 19.80
- S28F (p.Ser28Phe), rs201985502, ClinGen CA7717425, ClinVar RCV004183318, 1000Genomes rs201985502, REVEL 0.30, CADD 24.20, Uncertain significance, not specified
- S28Y (p.Ser28Tyr), cosmic curated COSV58145
- V29A (p.Val29Ala), TOPMed rs1044565923, gnomAD rs1044565923
- V29M (p.Val29Met), cosmic curated COSV58117, REVEL 0.09, CADD 22.20
- L30M (p.Leu30Met), cosmic curated COSV58114
- L30P (p.Leu30Pro), ExAC rs754518518, gnomAD rs754518518, REVEL 0.36, CADD 23.00
- A31T (p.Ala31Thr), cosmic curated COSV10588, Ensembl rs2142088987
- A31V (p.Ala31Val), Ensembl rs1598217110
- C32F (p.Cys32Phe), ExAC rs753336841, gnomAD rs753336841
- P33S (p.Pro33Ser), Ensembl rs2142088881
- P33T (p.Pro33Thr), cosmic curated COSV58116
- A34E (p.Ala34Glu), 1000Genomes rs199520545, ExAC rs199520545, TOPMed rs199520545, gnomAD rs199520545, REVEL 0.44, CADD 20.50
- A34T (p.Ala34Thr), ExAC rs766063980, TOPMed rs766063980, gnomAD rs766063980, REVEL 0.35, CADD 21.30
- N35D (p.Asn35Asp), TOPMed rs1381478314, REVEL 0.37, CADD 22.80
- N35I (p.Asn35Ile), TOPMed rs1435203101
- N35S (p.Asn35Ser), TOPMed rs1435203101
- C36W (p.Cys36Trp), cosmic curated COSV58111
- C36Y (p.Cys36Tyr), cosmic curated COSV58119
- V37A (p.Val37Ala), cosmic curated COSV58139
- C38Y (p.Cys38Tyr), Ensembl rs2142088579
- S39I (p.Ser39Ile), TOPMed rs1339674722, REVEL 0.69, CADD 25.80
- S39R (p.Ser39Arg), cosmic curated COSV58124
- S39T (p.Ser39Thr), TOPMed rs1339674722
- T41A (p.Thr41Ala), gnomAD rs1224048634, REVEL 0.67, CADD 21.70
- T41S (p.Thr41Ser), ExAC rs750256958, gnomAD rs750256958, REVEL 0.62, CADD 21.30
- N44S (p.Asn44Ser), rs761851885, ClinGen CA7717416, cosmic curated COSV10588, ClinVar RCV004310411, REVEL 0.23, CADD 15.30, Uncertain significance, not specified
- N44Y (p.Asn44Tyr), Ensembl rs150851656
- R46G (p.Arg46Gly), ExAC rs774269690, gnomAD rs774269690, REVEL 0.40, CADD 20.80
- R46P (p.Arg46Pro), rs769920098, ClinGen CA7717414, ClinVar RCV004148012, ExAC rs769920098, REVEL 0.51, CADD 22.50, Uncertain significance, not specified
- R46Q (p.Arg46Gln), ExAC rs769920098, TOPMed rs769920098, gnomAD rs769920098, REVEL 0.28, CADD 21.10, Uncertain significance
- R46W (p.Arg46Trp), ExAC rs774269690, gnomAD rs774269690, REVEL 0.50, CADD 25.60
- R47G (p.Arg47Gly), ExAC rs771206956, TOPMed rs771206956, gnomAD rs771206956, REVEL 0.33, CADD 24.40
- R47L (p.Arg47Leu), ESP rs373123404, ExAC rs373123404, TOPMed rs373123404, gnomAD rs373123404, REVEL 0.39, CADD 23.10, Uncertain significance
- R47Q (p.Arg47Gln), rs373123404, ClinGen CA7717410, cosmic curated COSV10962, ClinVar RCV004496045, REVEL 0.27, CADD 22.10, Uncertain significance, not specified
- R47W (p.Arg47Trp), cosmic curated COSV58107, ExAC rs771206956, TOPMed rs771206956, gnomAD rs771206956, REVEL 0.56, CADD 29.90
- P48A (p.Pro48Ala), Ensembl rs2142087886
- P48L (p.Pro48Leu), ExAC rs772316369, TOPMed rs772316369, gnomAD rs772316369, REVEL 0.66, CADD 24.00
- P48Q (p.Pro48Gln), cosmic curated COSV10044, ExAC rs772316369, TOPMed rs772316369, gnomAD rs772316369, REVEL 0.68, CADD 22.90
- P48S (p.Pro48Ser), cosmic curated COSV10962, Ensembl rs2142087886
- P48T (p.Pro48Thr), Ensembl rs2142087886
- D49G (p.Asp49Gly), Ensembl rs2142087719
- D50E (p.Asp50Glu), ExAC rs779572834, gnomAD rs779572834, REVEL 0.26, CADD 16.40
- D50G (p.Asp50Gly), ExAC rs748721173, gnomAD rs748721173, REVEL 0.45, CADD 22.30
- D50H (p.Asp50His), TOPMed rs907290552, gnomAD rs907290552, Uncertain significance
- D50N (p.Asp50Asn), TOPMed rs907290552, gnomAD rs907290552, REVEL 0.31, CADD 20.40, Uncertain significance, not specified
- D50Y (p.Asp50Tyr), rs907290552, ClinGen CA275112632, ClinVar RCV004496046, TOPMed rs907290552, REVEL 0.66, CADD 25.00, Uncertain significance, not specified
- G51E (p.Gly51Glu), Ensembl rs141393833
- G51R (p.Gly51Arg), ExAC rs755466103, gnomAD rs755466103, REVEL 0.74, CADD 23.50
- G51W (p.Gly51Trp), ExAC rs755466103, gnomAD rs755466103
- N52D (p.Asn52Asp), Ensembl rs2142087347
- N52K (p.Asn52Lys), cosmic curated COSV10044, TOPMed rs1434105549, gnomAD rs1434105549, REVEL 0.07, CADD 17.00
- L53F (p.Leu53Phe), cosmic curated COSV58120, REVEL 0.30, CADD 20.40
- L53I (p.Leu53Ile), cosmic curated COSV58146, ExAC rs753434646, gnomAD rs753434646, REVEL 0.28, CADD 21.60
- L53P (p.Leu53Pro), Ensembl rs2142087194
- L53V (p.Leu53Val), ExAC rs753434646, gnomAD rs753434646, REVEL 0.30, CADD 20.20
- F54S (p.Phe54Ser), Ensembl rs2142087128
- P55S (p.Pro55Ser), cosmic curated COSV58136
- L56I (p.Leu56Ile), TOPMed rs201878520, gnomAD rs201878520, REVEL 0.57, CADD 22.10
- L56V (p.Leu56Val), TOPMed rs201878520, gnomAD rs201878520, REVEL 0.53, CADD 23.00
- L57P (p.Leu57Pro), ExAC rs779387312, gnomAD rs779387312, REVEL 0.60, CADD 24.70
- E58G (p.Glu58Gly), Ensembl rs2142086946
- E58K (p.Glu58Lys), cosmic curated COSV10044
- G59R (p.Gly59Arg), Ensembl rs2142086890
- G59V (p.Gly59Val), Ensembl rs2142086853
- G59W (p.Gly59Trp), cosmic curated COSV58133, Ensembl rs2142086890
- Q60E (p.Gln60Glu), Ensembl rs2142086778
- Q60H (p.Gln60His), cosmic curated COSV10588, Ensembl rs2142086699
- Q60K (p.Gln60Lys), cosmic curated COSV58136, REVEL 0.34, CADD 22.10
- Q60R (p.Gln60Arg), 1000Genomes rs527991294, ExAC rs527991294, TOPMed rs527991294, gnomAD rs527991294, REVEL 0.12, CADD 22.20
- D61G (p.Asp61Gly), cosmic curated COSV58121, Ensembl rs2142086621
- D61N (p.Asp61Asn), Ensembl rs2054019888
- D61Y (p.Asp61Tyr), Ensembl rs2054019888, REVEL 0.35, CADD 26.50
- S62L (p.Ser62Leu), cosmic curated COSV58139
- G63R (p.Gly63Arg), Ensembl rs2142086466
- G63V (p.Gly63Val), gnomAD rs1489483779, REVEL 0.24, CADD 20.80
- S65N (p.Ser65Asn), cosmic curated COSV58110
- N66H (p.Asn66His), gnomAD rs2054018806, REVEL 0.14, CADD 22.10
- N66K (p.Asn66Lys), Ensembl rs2142086261
- N66S (p.Asn66Ser), ExAC rs767415545, gnomAD rs767415545, REVEL 0.10, CADD 18.90
- G67A (p.Gly67Ala), ExAC rs148728207, TOPMed rs148728207, gnomAD rs148728207
- G67E (p.Gly67Glu), ExAC rs148728207, TOPMed rs148728207, gnomAD rs148728207, REVEL 0.32, CADD 22.70
- G67R (p.Gly67Arg), cosmic curated COSV10044
- G67V (p.Gly67Val), cosmic curated COSV58117
- G67W (p.Gly67Trp), gnomAD rs2054018291, REVEL 0.34, CADD 28.70
- N68D (p.Asn68Asp), Ensembl rs2142086088
- N68H (p.Asn68His), Ensembl rs2142086088
- N68K (p.Asn68Lys), gnomAD rs1220570284, REVEL 0.04, CADD 22.50
- N68S (p.Asn68Ser), gnomAD rs1275957831, REVEL 0.14, CADD 21.60
- A69T (p.Ala69Thr), Ensembl rs2142085965
- S70C (p.Ser70Cys), ExAC rs751297846, gnomAD rs751297846, REVEL 0.20, CADD 24.70
- I71N (p.Ile71Asn), TOPMed rs2054016212, Uncertain significance
- I71V (p.Ile71Val), rs200923715, UniProt VAR 074602, ESP rs200923715, ExAC rs200923715, REVEL 0.06, CADD 14.90, Uncertain significance
- N72H (p.Asn72His), gnomAD rs1397843265, REVEL 0.13, CADD 22.70
- I73M (p.Ile73Met), Ensembl rs2142085726
- T74M (p.Thr74Met), TOPMed rs2054015509, gnomAD rs2054015509, REVEL 0.17, CADD 23.00
- D75G (p.Asp75Gly), cosmic curated COSV58109, REVEL 0.22, CADD 25.00
- D75Y (p.Asp75Tyr), Ensembl rs2142085626
- I76L (p.Ile76Leu), gnomAD rs1298685975, REVEL 0.05, CADD 19.40
- I76T (p.Ile76Thr), Ensembl rs2054014854, REVEL 0.22, CADD 22.90
- I76V (p.Ile76Val), cosmic curated COSV10588
- S77* (p.Ser77Ter), gnomAD rs1598216394, cosmic curated COSV10044, CADD 38.00
- R78K (p.Arg78Lys), cosmic curated COSV10962, ExAC rs776738528, TOPMed rs776738528, gnomAD rs776738528, REVEL 0.27, CADD 22.80, Uncertain significance, not specified
- N79D (p.Asn79Asp), cosmic curated COSV10461
- I80S (p.Ile80Ser), cosmic curated COSV10461
- I80V (p.Ile80Val), gnomAD rs1357478879, REVEL 0.28, CADD 19.70
- T81A (p.Thr81Ala), TOPMed rs1178373735, gnomAD rs1178373735
- T81N (p.Thr81Asn), TOPMed rs1429641565, REVEL 0.45, CADD 23.30
- T81S (p.Thr81Ser), TOPMed rs1178373735, gnomAD rs1178373735, REVEL 0.28, CADD 21.70
- S82F (p.Ser82Phe), cosmic curated COSV58123
- I83L (p.Ile83Leu), cosmic curated COSV58127
- I83V (p.Ile83Val), Ensembl rs2054013531
- H84N (p.His84Asn), cosmic curated COSV58119
- H84Y (p.His84Tyr), cosmic curated COSV58137
- I85L (p.Ile85Leu), TOPMed rs1401376854, gnomAD rs1401376854, REVEL 0.48, CADD 23.60
- I85M (p.Ile85Met), gnomAD rs1458667131, REVEL 0.67, CADD 23.30
- I85T (p.Ile85Thr), cosmic curated COSV58142
- I85V (p.Ile85Val), TOPMed rs1401376854, gnomAD rs1401376854, REVEL 0.45, CADD 23.20
- E86* (p.Glu86Ter), cosmic curated COSV10044
- E86D (p.Glu86Asp), cosmic curated COSV58131
- W88C (p.Trp88Cys), Ensembl rs2151621140
- R89C (p.Arg89Cys), cosmic curated COSV58109, 1000Genomes rs770278704, ExAC rs770278704, gnomAD rs770278704, REVEL 0.60, CADD 27.60
- R89H (p.Arg89His), cosmic curated COSV58112, ESP rs374069724, ExAC rs374069724, TOPMed rs374069724, REVEL 0.39, CADD 21.80
- R89L (p.Arg89Leu), ESP rs374069724, ExAC rs374069724, TOPMed rs374069724, gnomAD rs374069724, REVEL 0.48, CADD 21.60, Uncertain significance, not specified
- S90G (p.Ser90Gly), ExAC rs756950618, TOPMed rs756950618, gnomAD rs756950618, REVEL 0.18, CADD 9.89
- S90R (p.Ser90Arg), ExAC rs756950618, TOPMed rs756950618, gnomAD rs756950618, REVEL 0.28, CADD 12.40
- H92R (p.His92Arg), gnomAD rs1166039282, REVEL 0.28, CADD 19.10
- H92Y (p.His92Tyr), Ensembl rs2046770421, REVEL 0.35, CADD 22.70
- T93K (p.Thr93Lys), cosmic curated COSV58133, Uncertain significance
- T93M (p.Thr93Met), rs147992979, ClinGen CA7717363, cosmic curated COSV58125, ClinVar RCV002250159, REVEL 0.81, CADD 23.20, Conflicting interpretations, not specified; Neonatal cardiomyopathy
- L94I (p.Leu94Ile), cosmic curated COSV58113
- L94R (p.Leu94Arg), gnomAD rs1441141555, REVEL 0.83, CADD 26.10
- A96S (p.Ala96Ser), ExAC rs765088970, TOPMed rs765088970, gnomAD rs765088970
- A96T (p.Ala96Thr), cosmic curated COSV10044, ExAC rs765088970, TOPMed rs765088970, gnomAD rs765088970, REVEL 0.40, CADD 20.60
- V97L (p.Val97Leu), TOPMed rs1222179640, gnomAD rs1222179640, cosmic curated COSV58150, REVEL 0.29, CADD 19.60
- V97M (p.Val97Met), cosmic curated COSV58113, TOPMed rs1222179640, gnomAD rs1222179640, REVEL 0.44, CADD 21.30
- D98N (p.Asp98Asn), cosmic curated COSV58124
- D98Y (p.Asp98Tyr), cosmic curated COSV58148, gnomAD rs1352987249, REVEL 0.76, CADD 26.00
- M99I (p.Met99Ile), ESP rs368510978, ExAC rs368510978, TOPMed rs368510978, gnomAD rs368510978
- M99T (p.Met99Thr), gnomAD rs1242339080
- M99V (p.Met99Val), cosmic curated COSV58108, gnomAD rs1283958846
Public NTRK3 analysis runs
- NTRK3 analysis run — NTRK3 (2,992 variants) — completed 2026-08-18