GHR (Growth hormone receptor) variants and mutations
GHR (also known as Growth hormone receptor) is a human protein-coding gene encoding a growth hormone receptor protein. Its activation by growth hormone triggers JAK2-STAT signaling that promotes IGF-1 production, linear growth, and metabolic effects. Biallelic or dominant-negative loss-of-function variants can cause growth-hormone insensitivity, while activating alterations are rare. This analysis covers 1,097 GHR variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes Laron syndrome, short stature due to partial GHR deficiency, and Turner syndrome. Example GHR variants include M1?, M1V, and D2H.
Variant analysis overview
- Gene: GHR
- Protein: Growth hormone receptor
- UniProt accession: P10912
- Organism: Homo sapiens
- Variants analyzed: 1097
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 985 unspecified-consequence records; 64 missense variants; 7 frameshift variants; 33 synonymous variants; 1 in-frame insertions; 3 stop-gained variants; 2 splice-region variants; 2 substitution
- Prediction scores: 697 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Laron syndrome, short stature due to partial GHR deficiency, Turner syndrome, acromegaly, pituitary dwarfism, Growth delay, Prader-Willi syndrome, chronic kidney disease, gonadal dysgenesis, growth hormone insensitivity syndrome, endocrine system disorder, Short stature.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 8 post-translational modification sites.
- Structural context: 201 variants have structural context.
- PTM context: 8 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 GHR variants
Examples include M1?, M1V, D2H, D2V, D2Y, D2G, D2D, L3F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV50122, cosmic curated COSV10005
- M1V (p.Met1Val), rs752025877, ClinGen CA3254276, ClinVar RCV003555187, Pathogenic, not provided
- D2H (p.Asp2His), ExAC rs756257972, gnomAD rs756257972, REVEL 0.42, CADD 24.40
- D2V (p.Asp2Val), gnomAD rs1336478651, REVEL 0.53, CADD 25.90, Uncertain significance, Inborn genetic diseases
- D2Y (p.Asp2Tyr), cosmic curated COSV10940
- D2G (p.Asp2Gly), gnomAD 5-42565879-A-G, REVEL 0.35, CADD 27.10
- D2D (p.Asp2Asp), rs1185116615, gnomAD 5-42565880-T-C, CADD 12.00
- L3F (p.Leu3Phe), cosmic curated COSV50119, TOPMed rs1241437411, gnomAD rs1241437411, REVEL 0.48, CADD 25.70
- L3L (p.Leu3Leu), rs1247837271, gnomAD 5-42565883-C-T, CADD 9.02
- W4* (p.Trp4Ter), rs2478311889, ClinGen CA359694396, ClinVar RCV003555188, CADD 37.00, Pathogenic
- W4C (p.Trp4Cys), rs1554020272, ClinGen CA359694400, ClinVar RCV000582223, Ensembl rs1554020272, Uncertain significance, Laron-type isolated somatotropin defect
- W4R (p.Trp4Arg), ExAC rs34838342, TOPMed rs34838342, gnomAD rs34838342, REVEL 0.42, CADD 24.10, Uncertain significance, not provided
- Q5K (p.Gln5Lys), gnomAD 5-42565887-C-A, REVEL 0.18, CADD 16.20
- Q5H (p.Gln5His), gnomAD 5-42565889-G-C, REVEL 0.24, CADD 23.10
- L6Q (p.Leu6Gln), TOPMed rs1473609561
- L6V (p.Leu6Val), ExAC rs750933471, gnomAD rs750933471, REVEL 0.18, CADD 18.80
- L6L (p.Leu6Leu), gnomAD 5-42565890-C-T, CADD 10.60
- L7M (p.Leu7Met), gnomAD 5-42565893-C-A, REVEL 0.39, CADD 23.20
- L7L (p.Leu7Leu), rs756572945, gnomAD 5-42565895-G-A, CADD 8.70
- L8F (p.Leu8Phe), gnomAD 5-42565898-G-T, REVEL 0.15, CADD 22.10
- L8L (p.Leu8Leu), gnomAD 5-42565898-G-A, CADD 9.26
- T9A (p.Thr9Ala), rs528933970, ClinGen CA3254281, ClinVar RCV003855895, 1000Genomes rs528933970, REVEL 0.28, CADD 23.10, Uncertain significance, not provided
- T9S (p.Thr9Ser), 1000Genomes rs528933970, ExAC rs528933970, TOPMed rs528933970, gnomAD rs528933970, REVEL 0.32, CADD 24.10, Uncertain significance
- T9Y (p.Thr9Tyr), rs747188385, gnomAD 5-42565867-C-CT, CADD 25.10
- T9T (p.Thr9Thr), gnomAD 5-42565871-A-C, CADD 12.10
- L10V (p.Leu10Val), gnomAD 5-42565902-T-G, REVEL 0.15, CADD 22.40
- L10L (p.Leu10Leu), gnomAD 5-42565904-G-A, CADD 10.80
- A11P (p.Ala11Pro), cosmic curated COSV10956
- A11S (p.Ala11Ser), ESP rs369651256, ExAC rs369651256, TOPMed rs369651256, gnomAD rs369651256, REVEL 0.52, CADD 24.80, Uncertain significance, not specified
- A11T (p.Ala11Thr), NCI-TCGA Cosmic COSV5012, cosmic curated COSV50128, Variant assessed as somatic; moderate impact.
- A11A (p.Ala11Ala), rs1749901140, gnomAD 5-42565907-A-G, CADD 12.80
- L12L (p.Leu12Leu), rs1437977068, gnomAD 5-42565908-C-T, CADD 9.10
- A13T (p.Ala13Thr), cosmic curated COSV50130, TOPMed rs1488219538, gnomAD rs1488219538, REVEL 0.23, CADD 24.00
- A13S (p.Ala13Ser), gnomAD 5-42565911-G-T, REVEL 0.34, CADD 25.30
- G14* (p.Gly14Ter), cosmic curated COSV50109
- G14E (p.Gly14Glu), NCI-TCGA Cosmic COSV5012, cosmic curated COSV50126, Variant assessed as somatic; moderate impact.
- G14R (p.Gly14Arg), rs372245866, ClinGen CA3254285, cosmic curated COSV50108, ClinVar RCV002948992, REVEL 0.30, CADD 23.20, Uncertain significance, not provided
- G14D (p.Gly14Asp), rs1362754836, gnomAD 5-42565864-G-A, CADD 31.00
- G14S (p.Gly14Ser), gnomAD 5-42565872-G-A, CADD 26.10
- G14G (p.Gly14Gly), rs1250687306, gnomAD 5-42565916-A-G, CADD 12.50
- p.Ser15 Ser16insArgSer, gnomAD 5-42565914-G-GGAT, CADD 17.40
- S15P (p.Ser15Pro), gnomAD 5-42565917-T-C, REVEL 0.51, CADD 22.80
- S16G (p.Ser16Gly), 1000Genomes rs547124461, ExAC rs547124461, gnomAD rs547124461, REVEL 0.12, CADD 16.30, Uncertain significance
- S16R (p.Ser16Arg), TOPMed rs1174610023, gnomAD rs1174610023, REVEL 0.36, CADD 22.70, Uncertain significance, Inborn genetic diseases; not provided
- D17G (p.Asp17Gly), ExAC rs745825846, gnomAD rs745825846, REVEL 0.39, CADD 22.70
- D17D (p.Asp17Asp), rs1460897433, gnomAD 5-42565925-T-C, CADD 10.30
- A18S (p.Ala18Ser), cosmic curated COSV50135, Uncertain significance, not specified
- A18T (p.Ala18Thr), rs1749903679, ClinGen CA359694477, ClinVar RCV002806466, TOPMed rs1749903679, REVEL 0.19, CADD 21.50, Uncertain significance, not provided
- A18V (p.Ala18Val), NCI-TCGA TCGA novel, REVEL 0.37, CADD 23.20, Variant assessed as somatic; moderate impact.
- A18D (p.Ala18Asp), gnomAD 5-42565927-C-A, REVEL 0.48, CADD 24.60
- F19L (p.Phe19Leu), TOPMed rs1167904304, gnomAD rs1167904304, REVEL 0.15, CADD 21.80, Uncertain significance, not provided
- F19S (p.Phe19Ser), rs1397295577, ClinGen CA359694487, ClinVar RCV003677667, TOPMed rs1397295577, REVEL 0.47, CADD 27.20, Uncertain significance, not provided
- F19F (p.Phe19Phe), rs1393290129, gnomAD 5-42565931-T-C, CADD 9.37
- S20P (p.Ser20Pro), cosmic curated COSV50107
- S20S (p.Ser20Ser), rs1449015244, gnomAD 5-42565934-T-G, CADD 10.60
- G21E (p.Gly21Glu), NCI-TCGA Cosmic COSV5010, cosmic curated COSV50109, NCI-TCGA Cosmic COSV5013, Variant assessed as somatic; moderate impact.
- G21R (p.Gly21Arg), rs769835036, ClinGen CA3254289, cosmic curated COSV50117, ClinVar RCV003828869, REVEL 0.22, CADD 24.30, Likely benign, not provided
- G21V (p.Gly21Val), cosmic curated COSV50136
- G21G (p.Gly21Gly), gnomAD 5-42565937-A-G, CADD 7.81
- S22N (p.Ser22Asn), Ensembl rs1749905207, REVEL 0.10, CADD 16.20
- S22S (p.Ser22Ser), rs1749905390, gnomAD 5-42565940-T-C, CADD 7.97
- E23G (p.Glu23Gly), rs775749224, ClinGen CA3254290, ClinVar RCV001152148, ExAC rs775749224, REVEL 0.17, CADD 19.40, Uncertain significance, Laron-type isolated somatotropin defect
- E23K (p.Glu23Lys), TOPMed rs1749905585, REVEL 0.14, CADD 20.00
- E23* (p.Glu23Ter), gnomAD 5-42565941-G-T, CADD 35.00
- A24T (p.Ala24Thr), gnomAD 5-42565944-G-A, REVEL 0.23, CADD 22.20
- A24V (p.Ala24Val), gnomAD 5-42629038-C-T, REVEL 0.10, CADD 7.44
- A24D (p.Ala24Asp), gnomAD 5-42629038-C-A, REVEL 0.26, CADD 6.99
- A24A (p.Ala24Ala), rs763594388, gnomAD 5-42629039-C-T, CADD 9.50
- T25A (p.Thr25Ala), ESP rs373055838, ExAC rs373055838, gnomAD rs373055838, REVEL 0.18, CADD 9.83
- T25R (p.Thr25Arg), cosmic curated COSV99039
- T25Q (p.Thr25Gln), gnomAD 5-42629037-GC-G, CADD 25.30
- T25S (p.Thr25Ser), gnomAD 5-42629040-A-T, REVEL 0.14, CADD 11.10
- T25K (p.Thr25Lys), gnomAD 5-42629041-C-A, REVEL 0.45, CADD 8.81
- T25I (p.Thr25Ile), gnomAD 5-42629041-C-T, REVEL 0.14, CADD 7.11
- T25T (p.Thr25Thr), gnomAD 5-42629042-A-G, CADD 5.30
- A26E (p.Ala26Glu), gnomAD rs1305179629, REVEL 0.31, CADD 15.50
- A26S (p.Ala26Ser), ExAC rs756925109, gnomAD rs756925109, REVEL 0.17, CADD 5.73
- A26T (p.Ala26Thr), gnomAD 5-42629043-G-A, REVEL 0.19, CADD 7.18
- A26V (p.Ala26Val), gnomAD 5-42629044-C-T, REVEL 0.23, CADD 17.60
- A26A (p.Ala26Ala), rs904748525, gnomAD 5-42629045-A-G, CADD 9.01
- A27T (p.Ala27Thr), gnomAD rs1294606823, REVEL 0.11, CADD 13.90
- A27D (p.Ala27Asp), gnomAD 5-42629047-C-A, REVEL 0.49, CADD 17.60
- A27V (p.Ala27Val), gnomAD 5-42629047-C-T, REVEL 0.14, CADD 13.40
- A27A (p.Ala27Ala), rs781185088, gnomAD 5-42629048-T-C, CADD 7.00
- I28N (p.Ile28Asn), NCI-TCGA Cosmic COSV5010, cosmic curated COSV50109, Variant assessed as somatic; moderate impact.
- I28S (p.Ile28Ser), ExAC rs756184879, gnomAD rs756184879, REVEL 0.26, CADD 9.27
- I28V (p.Ile28Val), rs143287692, ClinGen CA3254307, cosmic curated COSV50135, ClinVar RCV000913004, REVEL 0.14, CADD 0.00, Conflicting interpretations, Laron-type isolated somatotropin defect; not provided; Inborn genetic diseases
- I28G (p.Ile28Gly), gnomAD 5-42629046-GCTATC, CADD 23.30
- I28F (p.Ile28Phe), gnomAD 5-42629049-A-T, REVEL 0.21, CADD 0.01
- I28T (p.Ile28Thr), gnomAD 5-42629050-T-C, REVEL 0.17, CADD 6.06
- I28I (p.Ile28Ile), rs776748737, gnomAD 5-42629051-C-A, CADD 2.74
- L29V (p.Leu29Val), Ensembl rs1324187200, REVEL 0.09, CADD 16.70
- L29I (p.Leu29Ile), gnomAD 5-42629052-C-A, REVEL 0.11, CADD 13.90
- L29P (p.Leu29Pro), gnomAD 5-42629053-T-C, REVEL 0.52, CADD 17.20
- L29L (p.Leu29Leu), gnomAD 5-42629054-T-C, CADD 4.34
- S30A (p.Ser30Ala), gnomAD 5-42629052-CT-C, CADD 21.80
- S30N (p.Ser30Asn), gnomAD 5-42629056-G-A, REVEL 0.08, CADD 4.59
- S30S (p.Ser30Ser), gnomAD 5-42629057-C-T, CADD 7.82
- S30R (p.Ser30Arg), gnomAD 5-42629057-C-A, REVEL 0.26, CADD 11.00
- R31K (p.Arg31Lys), ExAC rs779840197, gnomAD rs779840197, REVEL 0.15, CADD 8.46
- R31T (p.Arg31Thr), NCI-TCGA Cosmic COSV5012, cosmic curated COSV50122, Variant assessed as somatic; moderate impact.
- R31* (p.Arg31Ter), gnomAD 5-42629058-A-T, CADD 32.00
- R31G (p.Arg31Gly), gnomAD 5-42629058-A-G, REVEL 0.30, CADD 13.60
- R31I (p.Arg31Ile), gnomAD 5-42629059-G-T, REVEL 0.35, CADD 17.90
- R31R (p.Arg31Arg), gnomAD 5-42629060-A-G, CADD 8.07
- R31S (p.Arg31Ser), gnomAD 5-42629060-A-T, REVEL 0.13, CADD 13.80
- A32V (p.Ala32Val), TOPMed rs759746207, gnomAD rs759746207, REVEL 0.21, CADD 4.14
- A32T (p.Ala32Thr), gnomAD 5-42629061-G-A, REVEL 0.12, CADD 16.80
- A32E (p.Ala32Glu), gnomAD 5-42629062-C-A, REVEL 0.25, CADD 2.04
- A32A (p.Ala32Ala), gnomAD 5-42629063-A-G, CADD 4.65
- P33H (p.Pro33His), ESP rs377297987, ExAC rs377297987, gnomAD rs377297987, REVEL 0.18, CADD 14.90, Uncertain significance
- P33R (p.Pro33Arg), rs377297987, ClinGen CA359694693, ClinVar RCV001931643, ESP rs377297987, Uncertain significance, not provided
- P33S (p.Pro33Ser), NCI-TCGA TCGA novel, REVEL 0.16, CADD 0.01, Variant assessed as somatic; moderate impact.
- P33P (p.Pro33Pro), rs185241673, gnomAD 5-42565868-T-C, CADD 7.39
- P33T (p.Pro33Thr), gnomAD 5-42629064-C-A, REVEL 0.13, CADD 0.05
- P33L (p.Pro33Leu), gnomAD 5-42629065-C-T, REVEL 0.19, CADD 10.10
- W34* (p.Trp34Ter), rs121909370, ClinGen CA119813, ClinVar RCV000009189, ClinVar RCV003398476, CADD 15.50, Pathogenic
- W34C (p.Trp34Cys), cosmic curated COSV10608, TOPMed rs121909370, gnomAD rs121909370, REVEL 0.17, CADD 17.30, Pathogenic
- W34R (p.Trp34Arg), NCI-TCGA TCGA novel, REVEL 0.27, CADD 6.96, Variant assessed as somatic; moderate impact.
- W34L (p.Trp34Leu), gnomAD 5-42629068-G-T, REVEL 0.26, CADD 3.71
- S35I (p.Ser35Ile), Ensembl rs1014385043, REVEL 0.44, CADD 15.90
- S35G (p.Ser35Gly), gnomAD 5-42629070-A-G, REVEL 0.21, CADD 16.40
- S35N (p.Ser35Asn), gnomAD 5-42629071-G-A, REVEL 0.23, CADD 14.90
- S35S (p.Ser35Ser), gnomAD 5-42629072-T-C, CADD 10.10
- L36M (p.Leu36Met), gnomAD 5-42629073-C-A, REVEL 0.33, CADD 22.80
- L36L (p.Leu36Leu), gnomAD 5-42629073-C-T, CADD 9.34
- L36P (p.Leu36Pro), gnomAD 5-42629074-T-C, REVEL 0.48, CADD 23.40
- L36Q (p.Leu36Gln), gnomAD 5-42629074-T-A, REVEL 0.43, CADD 24.30
- Q37K (p.Gln37Lys), NCI-TCGA TCGA novel, REVEL 0.43, CADD 22.50, Variant assessed as somatic; moderate impact.
- Q37* (p.Gln37Ter), gnomAD 5-42629076-C-T, CADD 35.00
- Q37H (p.Gln37His), gnomAD 5-42629078-A-T, REVEL 0.45, CADD 23.70
- Q37Q (p.Gln37Gln), gnomAD 5-42629078-A-G, CADD 7.95
- S38V (p.Ser38Val), gnomAD 5-42629076-CA-C, CADD 23.20
- S38G (p.Ser38Gly), gnomAD 5-42629079-A-G, REVEL 0.11, CADD 17.70
- S38C (p.Ser38Cys), gnomAD 5-42629079-A-T, REVEL 0.24, CADD 22.60
- S38N (p.Ser38Asn), gnomAD 5-42629080-G-A, REVEL 0.13, CADD 13.60
- V39F (p.Val39Phe), gnomAD 5-42629082-G-T, REVEL 0.41, CADD 19.30
- V39I (p.Val39Ile), gnomAD 5-42629082-G-A, REVEL 0.31, CADD 10.40
- V39A (p.Val39Ala), gnomAD 5-42629083-T-C, REVEL 0.26, CADD 22.30
- V39V (p.Val39Val), gnomAD 5-42629084-T-A, CADD 8.81
- N40I (p.Asn40Ile), 1000Genomes rs181298988, ExAC rs181298988, gnomAD rs181298988, REVEL 0.27, CADD 18.30
- N40Y (p.Asn40Tyr), ExAC rs774448311, gnomAD rs774448311, REVEL 0.25, CADD 10.30
- N40T (p.Asn40Thr), rs1447810758, gnomAD 5-42424593-A-C, CADD 3.19
- N40K (p.Asn40Lys), rs1023566603, gnomAD 5-42424594-C-G, CADD 1.23
- N40H (p.Asn40His), gnomAD 5-42629085-A-C, REVEL 0.23, CADD 11.40
- N40D (p.Asn40Asp), gnomAD 5-42629085-A-G, REVEL 0.15, CADD 15.10
- N40S (p.Asn40Ser), gnomAD 5-42629086-A-G, REVEL 0.13, CADD 16.60
- N40N (p.Asn40Asn), gnomAD 5-42629087-T-C, CADD 8.02
- P41S (p.Pro41Ser), Ensembl rs1753835556, REVEL 0.19, CADD 17.70
- P41Q (p.Pro41Gln), gnomAD 5-42629087-TC-T, CADD 26.20
- P41T (p.Pro41Thr), gnomAD 5-42629088-C-A, REVEL 0.32, CADD 21.80
- P41L (p.Pro41Leu), gnomAD 5-42629089-C-T, REVEL 0.29, CADD 24.20
- P41P (p.Pro41Pro), gnomAD 5-42629090-A-T, CADD 11.10
- G42S (p.Gly42Ser), ExAC rs772258414, gnomAD rs772258414, REVEL 0.22, CADD 15.10
- G42V (p.Gly42Val), NCI-TCGA Cosmic COSV5012, cosmic curated COSV50120, Variant assessed as somatic; moderate impact.
- G42D (p.Gly42Asp), gnomAD 5-42629092-G-A, REVEL 0.23, CADD 6.96
- G42G (p.Gly42Gly), rs773634630, gnomAD 5-42629093-C-A, CADD 7.75
- L43V (p.Leu43Val), ExAC rs761015692, gnomAD rs761015692, REVEL 0.16, CADD 16.80
- L43L (p.Leu43Leu), gnomAD 5-42629094-C-T, CADD 9.22
- L43I (p.Leu43Ile), gnomAD 5-42629094-C-A, REVEL 0.16, CADD 16.60
- L43P (p.Leu43Pro), gnomAD 5-42629095-T-C, REVEL 0.14, CADD 15.60
- L43Q (p.Leu43Gln), gnomAD 5-42629095-T-A, REVEL 0.54, CADD 20.50
- K44N (p.Lys44Asn), rs1167022629, ClinGen CA359694836, ClinVar RCV004390556, gnomAD rs1167022629, REVEL 0.13, CADD 15.30, Uncertain significance, Inborn genetic diseases
- K44R (p.Lys44Arg), gnomAD 5-42629095-TA-T, CADD 22.80
- K44E (p.Lys44Glu), gnomAD 5-42629097-A-G, REVEL 0.17, CADD 6.51
- K44M (p.Lys44Met), gnomAD 5-42629098-A-T, REVEL 0.42, CADD 7.31
- K44K (p.Lys44Lys), gnomAD 5-42629099-G-A, CADD 7.99
- T45R (p.Thr45Arg), Ensembl rs1753836482
- T45A (p.Thr45Ala), gnomAD 5-42629100-A-G, REVEL 0.27, CADD 23.50
- T45I (p.Thr45Ile), gnomAD 5-42629101-C-T, REVEL 0.33, CADD 29.50
- T45K (p.Thr45Lys), gnomAD 5-42629101-C-A, REVEL 0.41, CADD 23.20
- T45T (p.Thr45Thr), gnomAD 5-42629102-A-C, CADD 21.50
- N46I (p.Asn46Ile), rs1401911314, ClinGen CA359694541, ClinVar RCV002860688, gnomAD rs1401911314, REVEL 0.24, CADD 24.80, Uncertain significance, Inborn genetic diseases
- N46K (p.Asn46Lys), Ensembl rs1388750022
- N46S (p.Asn46Ser), gnomAD rs1401911314, Uncertain significance
- N46D (p.Asn46Asp), gnomAD 5-42629103-A-G, REVEL 0.15, CADD 20.50
- S47C (p.Ser47Cys), rs777008477, ClinGen CA3254340, ClinVar RCV003703358, ExAC rs777008477, REVEL 0.41, CADD 25.90, Likely benign, not provided
- S47Y (p.Ser47Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S48C (p.Ser48Cys), ExAC rs770307280, TOPMed rs770307280, gnomAD rs770307280
- S48F (p.Ser48Phe), cosmic curated COSV10005
Public GHR analysis runs
- GHR analysis run — GHR (1,097 variants) — completed 2026-08-19