GNA11 (P29992) variants and mutations
GNA11 (also known as P29992) is a human protein-coding gene encoding a guanine nucleotide-binding protein subunit alpha-11 protein. It transmits signals from Gq-coupled receptors to phospholipase C and downstream calcium and protein-kinase-C pathways. Germline activating variants can cause autosomal dominant hypocalcemia, while somatic activating variants drive uveal melanoma and some vascular lesions. This analysis covers 1,168 GNA11 variants and mutations. Of these, 40% have computational variant effect predictions. Disease context includes Familial isolated hypoparathyroidism, familial hypocalciuric hypercalcemia 2, and Familial hypocalciuric hypercalcemia type 2. Example GNA11 variants include T2A, T2I, and T2S.
Variant analysis overview
- Gene: GNA11
- Protein: P29992
- UniProt accession: P29992
- Organism: Homo sapiens
- Variants analyzed: 1168
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 980 unspecified-consequence records; 100 missense variants; 75 synonymous variants; 4 stop-gained variants; 2 frameshift variants; 2 in-frame deletions; 2 splice-region variants; 1 in-frame insertions; 1 substitution
- Prediction scores: 471 variants have prediction scores (40% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Familial isolated hypoparathyroidism, familial hypocalciuric hypercalcemia 2, Familial hypocalciuric hypercalcemia type 2, autosomal dominant hypocalcemia, congenital hemangioma, uveal melanoma, phakomatosis pigmentovascularis, lung carcinoma, superficial spreading melanoma, nodular malignant melanoma, Transitional Meningioma, capillary hemangioma.
Protein structure and variant hotspots
- Protein features: 1 domains; 6 binding sites; 1 post-translational modification sites.
- Structural context: 1,011 variants have structural context.
- PTM context: 7 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 GNA11 variants
Examples include T2A, T2I, T2S, T2N, T2T, L3P, L3L, L3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- T2A (p.Thr2Ala), Ensembl rs2145300227, REVEL 0.28, CADD 19.00
- T2I (p.Thr2Ile), gnomAD rs1417344175, REVEL 0.38, CADD 22.30
- T2S (p.Thr2Ser), gnomAD 19-3094655-A-T, REVEL 0.30, CADD 18.50
- T2N (p.Thr2Asn), gnomAD 19-3094656-C-A, REVEL 0.35, AlphaMissense 0.09
- T2T (p.Thr2Thr), rs758302558, gnomAD 19-3094657-T-C, AlphaMissense 0.17, MetaLR 0.52
- L3P (p.Leu3Pro), Ensembl rs1913317207, REVEL 0.56, CADD 26.80
- L3L (p.Leu3Leu), gnomAD 19-3094658-C-T, CADD 14.50
- L3V (p.Leu3Val), gnomAD 19-3094658-C-G, REVEL 0.23, CADD 22.90
- L3M (p.Leu3Met), gnomAD 19-3094658-C-A, REVEL 0.26, CADD 20.90
- L3Q (p.Leu3Gln), gnomAD 19-3094659-T-A, REVEL 0.45, CADD 26.30
- E4G (p.Glu4Gly), Ensembl rs2145300247, REVEL 0.27, CADD 23.50
- E4Q (p.Glu4Gln), Ensembl rs2145300242, REVEL 0.30, AlphaMissense 0.07
- E4V (p.Glu4Val), Ensembl rs2145300247
- E4E (p.Glu4Glu), gnomAD 19-3094663-G-A, CADD 14.00
- E4D (p.Glu4Asp), gnomAD 19-3094663-G-T, REVEL 0.25, CADD 20.70
- S5A (p.Ser5Ala), Ensembl rs2145300250, REVEL 0.17, CADD 21.50
- S5P (p.Ser5Pro), gnomAD 19-3094664-T-C, REVEL 0.45, CADD 24.00
- S5C (p.Ser5Cys), gnomAD 19-3094665-C-G, REVEL 0.49, CADD 24.60
- S5Y (p.Ser5Tyr), gnomAD 19-3094665-C-A, REVEL 0.47, CADD 22.60
- S5S (p.Ser5Ser), rs1913317282, gnomAD 19-3094666-C-T, CADD 15.70
- M6I (p.Met6Ile), Ensembl rs1913317498, REVEL 0.27, CADD 21.70, Uncertain significance, not provided
- M6L (p.Met6Leu), TOPMed rs1387105467, gnomAD rs1387105467, REVEL 0.29, CADD 22.60, Uncertain significance
- M6T (p.Met6Thr), Ensembl rs1599293107, REVEL 0.27, CADD 22.60
- M6V (p.Met6Val), rs1387105467, ClinGen CA403299045, ClinVar RCV003055757, TOPMed rs1387105467, REVEL 0.29, CADD 21.80, Uncertain significance, not provided
- M7R (p.Met7Arg), gnomAD rs1401199158
- M7T (p.Met7Thr), gnomAD rs1401199158, REVEL 0.70, CADD 23.90
- M7V (p.Met7Val), Ensembl rs1913317570, REVEL 0.57, CADD 23.40
- M7L (p.Met7Leu), gnomAD 19-3094670-A-T, REVEL 0.48, CADD 22.80
- M7I (p.Met7Ile), gnomAD 19-3094672-G-A, REVEL 0.66, CADD 24.50
- A8P (p.Ala8Pro), TOPMed rs1913317685
- A8V (p.Ala8Val), rs141078172, ClinGen CA9074691, ClinVar RCV001934609, ESP rs141078172, REVEL 0.33, CADD 22.90, Uncertain significance, not provided
- A8S (p.Ala8Ser), gnomAD 19-3094673-G-T, REVEL 0.41, CADD 22.80
- A8E (p.Ala8Glu), gnomAD 19-3094674-C-A, REVEL 0.41, CADD 22.50
- A8A (p.Ala8Ala), gnomAD 19-3094675-G-T, AlphaMissense 0.51, MetaLR 0.81
- C9G (p.Cys9Gly), Ensembl rs2145300277
- C9W (p.Cys9Trp), Ensembl rs2145300285
- C9Y (p.Cys9Tyr), Ensembl rs2145300284, REVEL 0.80, CADD 29.70
- C9R (p.Cys9Arg), gnomAD 19-3094676-T-C, REVEL 0.65, CADD 25.50
- C9F (p.Cys9Phe), gnomAD 19-3094677-G-T, REVEL 0.81, CADD 31.00
- C10* (p.Cys10Ter), Ensembl rs2145300289
- C10W (p.Cys10Trp), Ensembl rs2145300289
- C10R (p.Cys10Arg), gnomAD 19-3094679-T-C, REVEL 0.73, CADD 29.30
- C10Y (p.Cys10Tyr), gnomAD 19-3094680-G-A, REVEL 0.77, CADD 27.20
- C10F (p.Cys10Phe), gnomAD 19-3094680-G-T, REVEL 0.59, CADD 24.50
- C10C (p.Cys10Cys), gnomAD 19-3094681-C-T, CADD 15.40
- L11V (p.Leu11Val), TOPMed rs1913317841
- L11M (p.Leu11Met), gnomAD 19-3094682-C-A, REVEL 0.33, CADD 22.70
- L11L (p.Leu11Leu), rs1913317841, gnomAD 19-3094682-C-T, CADD 15.40
- L11R (p.Leu11Arg), gnomAD 19-3094683-T-G, REVEL 0.48, CADD 25.10
- L11P (p.Leu11Pro), gnomAD 19-3094683-T-C, REVEL 0.64, CADD 31.00
- S12G (p.Ser12Gly), Ensembl rs2145300305, REVEL 0.44, CADD 24.60
- S12I (p.Ser12Ile), gnomAD 19-3094686-G-T, REVEL 0.51, AlphaMissense 0.48
- S12N (p.Ser12Asn), gnomAD 19-3094686-G-A, REVEL 0.38, AlphaMissense 0.16
- S12R (p.Ser12Arg), gnomAD 19-3094687-C-A, REVEL 0.70, CADD 25.80
- S12S (p.Ser12Ser), rs2145300307, gnomAD 19-3094687-C-T, CADD 15.90
- D13G (p.Asp13Gly), TOPMed rs1913317982, gnomAD rs1913317982, REVEL 0.27, CADD 23.10
- D13N (p.Asp13Asn), gnomAD 19-3094688-G-A, REVEL 0.30, CADD 23.50
- D13D (p.Asp13Asp), gnomAD 19-3094690-T-C, CADD 12.90
- D13E (p.Asp13Glu), gnomAD 19-3094690-T-G, REVEL 0.17, CADD 9.88
- E14G (p.Glu14Gly), gnomAD rs1338184866, REVEL 0.73, CADD 32.00
- E14K (p.Glu14Lys), rs1913318065, ClinGen CA403299383, ClinVar RCV003729586, REVEL 0.59, CADD 32.00, Uncertain significance, not provided
- E14Q (p.Glu14Gln), TOPMed rs1913318065
- E14* (p.Glu14Ter), gnomAD 19-3094691-G-T, AlphaMissense 0.13, MetaLR 0.52
- E14D (p.Glu14Asp), gnomAD 19-3094693-G-T, REVEL 0.30, CADD 22.80
- V15E (p.Val15Glu), Ensembl rs2145300320, REVEL 0.19, CADD 19.60
- V15G (p.Val15Gly), Ensembl rs2145300320, REVEL 0.23, CADD 22.90
- V15M (p.Val15Met), NCI-TCGA TCGA novel, REVEL 0.36, CADD 24.20, Variant assessed as somatic; moderate impact.
- V15L (p.Val15Leu), gnomAD 19-3094694-G-T, REVEL 0.31, CADD 22.70
- V15A (p.Val15Ala), gnomAD 19-3094695-T-C, REVEL 0.15, CADD 20.60
- V15V (p.Val15Val), rs1416324400, gnomAD 19-3094696-G-C, CADD 14.50
- K16R (p.Lys16Arg), gnomAD 19-3094696-GA-G, CADD 32.00
- K16N (p.Lys16Asn), gnomAD 19-3094699-G-T, REVEL 0.50, CADD 28.20
- K16K (p.Lys16Lys), rs776560028, gnomAD 19-3094699-G-A, CADD 15.50
- E17* (p.Glu17Ter), rs2512078200, ClinGen CA403299488, ClinVar RCV003011047, AlphaMissense 0.35, MetaLR 0.70, Uncertain significance
- E17G (p.Glu17Gly), gnomAD 19-3094701-A-G, REVEL 0.75, CADD 31.00
- E17D (p.Glu17Asp), gnomAD 19-3094702-G-C, REVEL 0.47, CADD 23.20
- E17E (p.Glu17Glu), gnomAD 19-3094702-G-A, CADD 13.90
- S18C (p.Ser18Cys), Ensembl rs1913318349
- S18F (p.Ser18Phe), NCI-TCGA Cosmic COSV5001, NCI-TCGA Cosmic COSV9931, Variant assessed as somatic; moderate impact.
- S18A (p.Ser18Ala), gnomAD 19-3094703-T-G, REVEL 0.23, CADD 20.70
- S18Y (p.Ser18Tyr), gnomAD 19-3094704-C-A, REVEL 0.51, CADD 24.60
- S18S (p.Ser18Ser), rs748439096, gnomAD 19-3094705-C-T, CADD 14.70
- K19R (p.Lys19Arg), gnomAD 19-3094707-A-G, REVEL 0.26, CADD 20.30
- K19K (p.Lys19Lys), gnomAD 19-3094708-G-A, AlphaMissense 0.36, MetaLR 0.55
- R20W (p.Arg20Trp), gnomAD rs1242029660, REVEL 0.59, CADD 25.90
- R20R (p.Arg20Arg), gnomAD 19-3094709-C-A, CADD 14.40
- R20Q (p.Arg20Gln), gnomAD 19-3094710-G-A, REVEL 0.45, CADD 23.60
- R20L (p.Arg20Leu), gnomAD 19-3094710-G-T, REVEL 0.71, CADD 25.30
- I21S (p.Ile21Ser), Ensembl rs2145300340
- I21V (p.Ile21Val), gnomAD 19-3094712-A-G, REVEL 0.39, CADD 22.40
- I21I (p.Ile21Ile), rs2145300342, gnomAD 19-3094714-C-T, CADD 15.70
- N22D (p.Asn22Asp), gnomAD 19-3094715-A-G, REVEL 0.65, CADD 24.30
- N22N (p.Asn22Asn), gnomAD 19-3094717-C-T, AlphaMissense 0.15, MetaLR 0.56
- A23T (p.Ala23Thr), Ensembl rs2145300347, REVEL 0.33, CADD 24.70
- A23S (p.Ala23Ser), gnomAD 19-3094718-G-T, REVEL 0.29, CADD 23.10
- A23V (p.Ala23Val), gnomAD 19-3094719-C-T, REVEL 0.31, CADD 23.20
- A23D (p.Ala23Asp), gnomAD 19-3094719-C-A, REVEL 0.25, CADD 21.40
- A23A (p.Ala23Ala), rs375505077, gnomAD 19-3094720-C-T, CADD 14.00
- E24V (p.Glu24Val), rs1913318572, ClinGen CA403299691, ClinVar RCV003328751, TOPMed rs1913318572, REVEL 0.74, AlphaMissense 0.99, Uncertain significance, not provided
- E24* (p.Glu24Ter), gnomAD 19-3094721-G-T, AlphaMissense 0.33, MetaLR 0.58
- E24K (p.Glu24Lys), gnomAD 19-3094721-G-A, REVEL 0.63, CADD 26.00
- E24D (p.Glu24Asp), gnomAD 19-3094723-G-T, REVEL 0.36, CADD 24.50
- E24E (p.Glu24Glu), gnomAD 19-3094723-G-A, CADD 14.70
- I25V (p.Ile25Val), gnomAD 19-3094724-A-G, REVEL 0.66, CADD 26.40
- I25T (p.Ile25Thr), gnomAD 19-3094725-T-C, REVEL 0.85, CADD 26.80
- I25I (p.Ile25Ile), gnomAD 19-3094726-C-A, CADD 15.00
- E26K (p.Glu26Lys), rs2512078232, ClinGen CA403299731, ClinVar RCV003677674, REVEL 0.80, CADD 26.20, Uncertain significance, not provided
- E26G (p.Glu26Gly), gnomAD 19-3094728-A-G, REVEL 0.81, AlphaMissense 0.56
- K27K (p.Lys27Lys), gnomAD 19-3094732-G-A, CADD 14.50
- Q28* (p.Gln28Ter), TOPMed rs1479867877, CADD 38.00
- Q28K (p.Gln28Lys), TOPMed rs1479867877
- Q28R (p.Gln28Arg), gnomAD 19-3094734-A-G, REVEL 0.49, CADD 22.90
- Q28L (p.Gln28Leu), gnomAD 19-3094734-A-T, REVEL 0.68, CADD 24.90
- Q28Q (p.Gln28Gln), gnomAD 19-3094735-G-A, CADD 13.80
- L29M (p.Leu29Met), gnomAD 19-3094736-C-A, REVEL 0.75, CADD 25.20
- L29L (p.Leu29Leu), rs1280763414, gnomAD 19-3094736-C-T, CADD 14.80
- L29P (p.Leu29Pro), gnomAD 19-3094737-T-C, REVEL 0.89, CADD 29.30
- R30L (p.Arg30Leu), NCI-TCGA TCGA novel, TOPMed rs1913318778, REVEL 0.66, CADD 25.10, Variant assessed as somatic; moderate impact.
- R30W (p.Arg30Trp), rs2145300360, ClinGen CA403299840, ClinVar RCV002851853, Ensembl rs2145300360, REVEL 0.66, CADD 32.00, Uncertain significance, not provided
- R30Q (p.Arg30Gln), gnomAD 19-3094740-G-A, REVEL 0.28, CADD 23.30
- R30R (p.Arg30Arg), gnomAD 19-3094741-G-C, AlphaMissense 1.00, MetaLR 0.76
- R31W (p.Arg31Trp), TOPMed rs1599293133, REVEL 0.75, CADD 27.60
- R31R (p.Arg31Arg), gnomAD 19-3094742-C-A, CADD 15.20
- R31L (p.Arg31Leu), gnomAD 19-3094743-G-T, REVEL 0.37, AlphaMissense 0.84
- R31Q (p.Arg31Gln), gnomAD 19-3094743-G-A, REVEL 0.31, AlphaMissense 0.85
- D32G (p.Asp32Gly), rs200234790, ClinGen CA304298984, ClinVar RCV000857316, Ensembl rs200234790, REVEL 0.63, AlphaMissense 0.75, Uncertain significance, Familial hypocalciuric hypercalcemia 2
- D32Y (p.Asp32Tyr), TOPMed rs1913318982, gnomAD rs1913318982, REVEL 0.86, CADD 31.00
- D32N (p.Asp32Asn), gnomAD 19-3094745-G-A, REVEL 0.70, CADD 29.70
- D32H (p.Asp32His), gnomAD 19-3094745-G-C, REVEL 0.67, CADD 25.00
- D32E (p.Asp32Glu), gnomAD 19-3094747-C-A, REVEL 0.33, CADD 22.00
- D32D (p.Asp32Asp), rs2145300379, gnomAD 19-3094747-C-T, CADD 15.30
- K33E (p.Lys33Glu), gnomAD 19-3094748-A-G, REVEL 0.64, CADD 25.50
- K33R (p.Lys33Arg), gnomAD 19-3094749-A-G, REVEL 0.34, CADD 22.90
- K33M (p.Lys33Met), gnomAD 19-3094749-A-T, REVEL 0.83, CADD 28.30
- K33K (p.Lys33Lys), rs1205089245, gnomAD 19-3094750-G-A, AlphaMissense 0.37, MetaLR 0.55
- R34C (p.Arg34Cys), Ensembl rs1913319191, REVEL 0.67, CADD 31.00
- R34G (p.Arg34Gly), Ensembl rs1913319191
- R34S (p.Arg34Ser), gnomAD 19-3094751-C-A, REVEL 0.38, CADD 23.20
- R34H (p.Arg34His), gnomAD 19-3094752-G-A, REVEL 0.32, AlphaMissense 0.19
- R34R (p.Arg34Arg), gnomAD 19-3094753-C-T, CADD 15.10
- D35G (p.Asp35Gly), Ensembl rs2145300391, REVEL 0.49, CADD 23.90, Uncertain significance, not provided
- D35N (p.Asp35Asn), Ensembl rs2145300387, REVEL 0.23, CADD 23.20
- D35V (p.Asp35Val), gnomAD 19-3094755-A-T, REVEL 0.67, CADD 25.30
- D35D (p.Asp35Asp), rs2145300393, gnomAD 19-3094756-C-T, AlphaMissense 0.49, MetaLR 0.54
- A36S (p.Ala36Ser), ExAC rs773203722, gnomAD rs773203722, REVEL 0.30, CADD 22.40, Uncertain significance, not provided
- A36T (p.Ala36Thr), ExAC rs773203722, gnomAD rs773203722, REVEL 0.52, CADD 23.30
- A36V (p.Ala36Val), Ensembl rs2145300399, REVEL 0.45, AlphaMissense 0.89
- A36A (p.Ala36Ala), rs2145300403, gnomAD 19-3094759-C-T, CADD 15.90
- R37L (p.Arg37Leu), TOPMed rs1486864119, gnomAD rs1486864119, REVEL 0.65, CADD 27.50
- R37Q (p.Arg37Gln), TOPMed rs1486864119, gnomAD rs1486864119, REVEL 0.46, CADD 24.70
- R37W (p.Arg37Trp), gnomAD 19-3094760-C-T, REVEL 0.76, CADD 28.40
- R37R (p.Arg37Arg), gnomAD 19-3094760-C-A, CADD 15.40
- R38C (p.Arg38Cys), gnomAD 19-3094763-C-T, REVEL 0.73, CADD 32.00
- R38S (p.Arg38Ser), gnomAD 19-3094763-C-A, REVEL 0.55, CADD 24.80
- R38H (p.Arg38His), gnomAD 19-3094764-G-A, REVEL 0.55, AlphaMissense 0.98
- R38R (p.Arg38Arg), rs1212022673, gnomAD 19-3094765-C-G, CADD 14.70
- E39Q (p.Glu39Gln), Ensembl rs2145300421, REVEL 0.64, AlphaMissense 0.93
- E39K (p.Glu39Lys), gnomAD 19-3094766-G-A, REVEL 0.74, CADD 32.00
- E39G (p.Glu39Gly), gnomAD 19-3094767-A-G, REVEL 0.81, CADD 32.00
- E39E (p.Glu39Glu), rs1257166339, gnomAD 19-3094768-G-A, CADD 14.60
- L40I (p.Leu40Ile), gnomAD 19-3094769-C-A, REVEL 0.48, CADD 23.80
- L40P (p.Leu40Pro), gnomAD 19-3094770-T-C, REVEL 0.89, CADD 32.00
- L40L (p.Leu40Leu), rs1422256430, gnomAD 19-3094771-C-G, CADD 13.10
- K41Q (p.Lys41Gln), gnomAD 19-3094772-A-C, REVEL 0.86, CADD 29.30
- K41E (p.Lys41Glu), gnomAD 19-3094772-A-G, REVEL 0.85, CADD 31.00
- K41M (p.Lys41Met), gnomAD 19-3094773-A-T, REVEL 0.89, CADD 32.00
- K41R (p.Lys41Arg), gnomAD 19-3094773-A-G, REVEL 0.77, CADD 29.90
- K41N (p.Lys41Asn), gnomAD 19-3094774-G-T, REVEL 0.69, CADD 26.10
- K41K (p.Lys41Lys), rs1913319650, gnomAD 19-3094774-G-A, CADD 14.20
- L42V (p.Leu42Val), TOPMed rs1342252945, REVEL 0.49, CADD 24.10
- L42M (p.Leu42Met), gnomAD 19-3094775-C-A, REVEL 0.62, CADD 24.20
- L42L (p.Leu42Leu), rs1342252945, gnomAD 19-3094775-C-T, CADD 15.00
- L42P (p.Leu42Pro), gnomAD 19-3094776-T-C, REVEL 0.89, CADD 29.20
- L43L (p.Leu43Leu), gnomAD 19-3094778-C-T, CADD 15.00
- L43M (p.Leu43Met), gnomAD 19-3094778-C-A, REVEL 0.71, CADD 25.60
- L43P (p.Leu43Pro), gnomAD 19-3094779-T-C, REVEL 0.90, CADD 32.00
- L44M (p.Leu44Met), gnomAD 19-3094781-C-A, REVEL 0.61, CADD 26.70
- L44L (p.Leu44Leu), gnomAD 19-3094781-C-T, CADD 15.40
- L44P (p.Leu44Pro), gnomAD 19-3094782-T-C, REVEL 0.87, CADD 31.00
- L45I (p.Leu45Ile), Ensembl rs1007210976, REVEL 0.47, CADD 22.90
Public GNA11 analysis runs
- GNA11 analysis run — GNA11 (1,168 variants) — completed 2026-08-19