PTH1R (Q03431) variants and mutations
PTH1R (also known as Q03431) is a human protein-coding gene encoding a parathyroid hormone/parathyroid hormone-related peptide receptor protein. It responds to parathyroid hormone and PTH-related peptide to coordinate calcium homeostasis and growth-plate development through cyclic-AMP and other pathways. Gain- and loss-of-function variants cause distinct skeletal disorders including Jansen metaphyseal chondrodysplasia and Blomstrand chondrodysplasia. This analysis covers 964 PTH1R variants and mutations. Of these, 84% have computational variant effect predictions. Disease context includes metaphyseal chondrodysplasia, Jansen type, chondrodysplasia Blomstrand type, and primary failure of tooth eruption. Example PTH1R variants include G2A, G2W, and G2V.
Variant analysis overview
- Gene: PTH1R
- Protein: Q03431
- UniProt accession: Q03431
- Organism: Homo sapiens
- Variants analyzed: 964
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 765 unspecified-consequence records; 108 missense variants; 72 synonymous variants; 10 frameshift variants; 3 in-frame deletions; 2 stop-gained variants; 3 splice-region variants; 1 substitution
- Prediction scores: 810 variants have prediction scores (84% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: metaphyseal chondrodysplasia, Jansen type, chondrodysplasia Blomstrand type, primary failure of tooth eruption, Eiken syndrome, Blomstrand lethal chondrodysplasia, osteoporosis, hypoparathyroidism, postmenopausal osteoporosis, bone fracture, Abnormality of the skeletal system, osteogenesis imperfecta, Hypocalcemia.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 5 post-translational modification sites.
- Structural context: 183 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, ClinGen, MaveDB, LitVar.
Notable PTH1R variants
Examples include G2A, G2W, G2V, G2E, G2G, T3A, T3S, T3I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2A (p.Gly2Ala), gnomAD rs1312508427, REVEL 0.15, CADD 24.30, Uncertain significance, Inborn genetic diseases
- G2W (p.Gly2Trp), gnomAD 3-46883563-G-T, REVEL 0.19, CADD 31.00
- G2V (p.Gly2Val), gnomAD 3-46883564-G-T, REVEL 0.20, CADD 26.80
- G2E (p.Gly2Glu), gnomAD 3-46883564-G-A, REVEL 0.17, CADD 27.10
- G2G (p.Gly2Gly), rs756013791, gnomAD 3-46883565-G-T, CADD 15.00
- T3A (p.Thr3Ala), Ensembl rs2106957445
- T3S (p.Thr3Ser), gnomAD 3-46883566-A-T, REVEL 0.05, CADD 14.60
- T3I (p.Thr3Ile), gnomAD 3-46883567-C-T, REVEL 0.03, CADD 23.50
- T3N (p.Thr3Asn), gnomAD 3-46883567-C-A, REVEL 0.04, CADD 23.20
- T3T (p.Thr3Thr), rs1228518305, gnomAD 3-46883568-C-A, CADD 14.50
- A4T (p.Ala4Thr), NCI-TCGA TCGA novel, REVEL 0.05, CADD 22.70, Variant assessed as somatic; moderate impact.
- A4V (p.Ala4Val), cosmic curated COSV57318, REVEL 0.05, CADD 18.00
- A4P (p.Ala4Pro), gnomAD 3-46883568-CG-C, CADD 29.50
- A4S (p.Ala4Ser), gnomAD 3-46883569-G-T, REVEL 0.04, CADD 21.70
- A4D (p.Ala4Asp), gnomAD 3-46883570-C-A, REVEL 0.08, CADD 20.90
- A4A (p.Ala4Ala), gnomAD 3-46883571-C-T, CADD 15.80
- R5G (p.Arg5Gly), rs1250201262, ClinGen CA352502871, ClinVar RCV001914905, gnomAD rs1250201262, REVEL 0.07, CADD 22.70, Uncertain significance, not provided
- R5P (p.Arg5Pro), gnomAD rs1479370698, REVEL 0.13, CADD 24.30
- R5Q (p.Arg5Gln), gnomAD rs1479370698, REVEL 0.05, CADD 23.70
- R5W (p.Arg5Trp), gnomAD rs1250201262, REVEL 0.19, CADD 25.30, Uncertain significance
- R5R (p.Arg5Arg), rs1250201262, gnomAD 3-46883572-C-A, CADD 15.20
- R5L (p.Arg5Leu), gnomAD 3-46883573-G-T, REVEL 0.13, CADD 23.40
- I6V (p.Ile6Val), Ensembl rs2106957564
- I6L (p.Ile6Leu), gnomAD 3-46883575-A-C, REVEL 0.10, CADD 22.60
- I6T (p.Ile6Thr), gnomAD 3-46883576-T-C, REVEL 0.13, CADD 22.70
- I6N (p.Ile6Asn), gnomAD 3-46883576-T-A, REVEL 0.13, CADD 24.10
- I6I (p.Ile6Ile), gnomAD 3-46883577-C-T, CADD 15.20
- A7T (p.Ala7Thr), rs959937327, Ensembl rs959937327, REVEL 0.05, CADD 22.40, Variant assessed as somatic; moderate impact.
- A7S (p.Ala7Ser), gnomAD 3-46883578-G-T, REVEL 0.06, CADD 20.00
- A7E (p.Ala7Glu), gnomAD 3-46883579-C-A, REVEL 0.06, CADD 22.70
- A7A (p.Ala7Ala), rs1202762678, gnomAD 3-46883580-A-G, CADD 16.20
- P8R (p.Pro8Arg), rs1257452316, ClinGen CA352502917, ClinVar RCV003882217, TOPMed rs1257452316, REVEL 0.08, CADD 22.50, Uncertain significance, Inborn genetic diseases; not provided
- P8T (p.Pro8Thr), gnomAD 3-46883581-C-A, REVEL 0.03, CADD 21.90
- P8S (p.Pro8Ser), gnomAD 3-46883581-C-T, REVEL 0.03, CADD 21.90
- P8L (p.Pro8Leu), gnomAD 3-46883582-C-T, REVEL 0.08, CADD 22.60
- P8H (p.Pro8His), gnomAD 3-46883582-C-A, REVEL 0.07, CADD 22.30
- P8P (p.Pro8Pro), gnomAD 3-46883583-C-T, CADD 15.80
- G9D (p.Gly9Asp), cosmic curated COSV57314, REVEL 0.03, CADD 23.40
- G9S (p.Gly9Ser), rs2545000601, ClinGen CA352502923, ClinVar RCV002294825, ClinVar RCV003269164, REVEL 0.07, CADD 22.60, Uncertain significance, Inborn genetic diseases; not provided
- G9V (p.Gly9Val), TOPMed rs975589924, gnomAD rs975589924, REVEL 0.04, CADD 23.10, Uncertain significance, Primary failure of tooth eruption; Metaphyseal chondrodysplasia, Jansen type; Ei
- G9C (p.Gly9Cys), gnomAD 3-46883584-G-T, REVEL 0.07, CADD 23.40
- G9G (p.Gly9Gly), gnomAD 3-46883586-C-A, CADD 15.00
- L10W (p.Leu10Trp), gnomAD 3-46883585-GC-G, CADD 25.50
- L10M (p.Leu10Met), gnomAD 3-46883587-C-A, REVEL 0.05, CADD 22.40
- L10L (p.Leu10Leu), rs1457911130, gnomAD 3-46883587-C-T, CADD 15.00
- L10Q (p.Leu10Gln), gnomAD 3-46883588-T-A, REVEL 0.15, CADD 24.80
- L10P (p.Leu10Pro), gnomAD 3-46883588-T-C, REVEL 0.22, CADD 25.30
- A11E (p.Ala11Glu), cosmic curated COSV57314, REVEL 0.15, CADD 22.60
- A11T (p.Ala11Thr), NCI-TCGA TCGA novel, REVEL 0.04, CADD 23.10, Variant assessed as somatic; moderate impact.
- A11V (p.Ala11Val), gnomAD rs1182088526, REVEL 0.11, CADD 22.90
- A11P (p.Ala11Pro), gnomAD 3-46883590-G-C, REVEL 0.14, CADD 23.20
- A11S (p.Ala11Ser), gnomAD 3-46883590-G-T, REVEL 0.04, CADD 22.70
- A11A (p.Ala11Ala), rs1392275686, gnomAD 3-46883592-G-T, CADD 15.80
- L12F (p.Leu12Phe), rs567440911, ClinGen CA73796169, ClinVar RCV002832642, 1000Genomes rs567440911, REVEL 0.04, CADD 22.50, Uncertain significance, Inborn genetic diseases
- L12G (p.Leu12Gly), rs2030809154, gnomAD 3-46883586-C-CCTG, CADD 26.70
- L12I (p.Leu12Ile), gnomAD 3-46883593-C-A, REVEL 0.04, CADD 22.50
- L12P (p.Leu12Pro), gnomAD 3-46883594-T-C, REVEL 0.26, CADD 24.00
- L12L (p.Leu12Leu), gnomAD 3-46883595-C-A, CADD 13.40
- L13L (p.Leu13Leu), gnomAD 3-46883596-C-T, CADD 15.40
- L13M (p.Leu13Met), gnomAD 3-46883596-C-A, REVEL 0.04, CADD 23.40
- L13P (p.Leu13Pro), gnomAD 3-46883597-T-C, REVEL 0.33, CADD 24.90
- L13Q (p.Leu13Gln), gnomAD 3-46883597-T-A, REVEL 0.20, CADD 24.70
- L14I (p.Leu14Ile), gnomAD 3-46883599-C-A, REVEL 0.03, CADD 23.10
- L14P (p.Leu14Pro), gnomAD 3-46883600-T-C, REVEL 0.28, CADD 24.90
- L14H (p.Leu14His), gnomAD 3-46883600-T-A, REVEL 0.17, CADD 27.20
- L14L (p.Leu14Leu), gnomAD 3-46883601-C-G, CADD 11.70
- C15Y (p.Cys15Tyr), cosmic curated COSV99067, REVEL 0.27, CADD 22.90
- C15F (p.Cys15Phe), gnomAD 3-46883603-G-T, REVEL 0.24, CADD 23.00
- C15C (p.Cys15Cys), gnomAD 3-46883604-C-T, CADD 15.70
- C15* (p.Cys15Ter), gnomAD 3-46883604-C-A, CADD 36.00
- C16del (p.Cys16del), gnomAD 3-46883600-TCTG-T, CADD 21.40
- C16R (p.Cys16Arg), gnomAD 3-46883605-T-C, REVEL 0.34, CADD 23.50
- C16S (p.Cys16Ser), gnomAD 3-46883605-T-A, REVEL 0.21, CADD 22.90
- C16F (p.Cys16Phe), gnomAD 3-46883606-G-T, REVEL 0.20, CADD 23.30
- C16Y (p.Cys16Tyr), gnomAD 3-46883606-G-A, REVEL 0.24, CADD 23.40
- C16C (p.Cys16Cys), rs2030809966, gnomAD 3-46883607-C-T, CADD 14.70
- C16* (p.Cys16Ter), gnomAD 3-46883607-C-A, CADD 35.00
- P17L (p.Pro17Leu), rs1169828626, ClinGen CA352503028, cosmic curated COSV10461, ClinVar RCV003842002, REVEL 0.10, CADD 21.10, Uncertain significance, not provided; Inborn genetic diseases
- P17R (p.Pro17Arg), TOPMed rs1169828626, gnomAD rs1169828626, REVEL 0.12, CADD 22.00, Uncertain significance
- P17S (p.Pro17Ser), cosmic curated COSV57316, TOPMed rs2030810164, REVEL 0.06, CADD 20.70
- P17T (p.Pro17Thr), TOPMed rs2030810164
- P17H (p.Pro17His), gnomAD 3-46883609-C-A, REVEL 0.10, CADD 21.50
- P17P (p.Pro17Pro), rs749062175, gnomAD 3-46883610-C-T, CADD 9.24
- V18L (p.Val18Leu), ExAC rs772304416, TOPMed rs772304416, gnomAD rs772304416, REVEL 0.06, CADD 20.90
- V18M (p.Val18Met), rs772304416, ExAC rs772304416, TOPMed rs772304416, gnomAD rs772304416, REVEL 0.08, CADD 22.60, Variant assessed as somatic; moderate impact.
- V18C (p.Val18Cys), gnomAD 3-46883606-GC-G, CADD 25.60
- V18E (p.Val18Glu), gnomAD 3-46883612-T-A, REVEL 0.15, CADD 24.30
- V18A (p.Val18Ala), gnomAD 3-46883612-T-C, REVEL 0.11, CADD 22.90
- V18V (p.Val18Val), gnomAD 3-46883613-G-T, CADD 12.90
- L19F (p.Leu19Phe), gnomAD rs1406684330, REVEL 0.08, CADD 23.20
- L19I (p.Leu19Ile), gnomAD 3-46883614-C-A, REVEL 0.03, CADD 19.70
- L19P (p.Leu19Pro), gnomAD 3-46883615-T-C, REVEL 0.32, CADD 29.80
- L19L (p.Leu19Leu), rs780469309, gnomAD 3-46883616-C-G, CADD 12.90
- S20R (p.Ser20Arg), TOPMed rs2030811984, REVEL 0.10, CADD 22.30, Uncertain significance, Inborn genetic diseases
- S20A (p.Ser20Ala), gnomAD 3-46883616-CA-C, CADD 28.00
- S20G (p.Ser20Gly), gnomAD 3-46883617-A-G, REVEL 0.04, CADD 21.70
- S20N (p.Ser20Asn), gnomAD 3-46883618-G-A, REVEL 0.04, CADD 22.00
- S20I (p.Ser20Ile), gnomAD 3-46883618-G-T, REVEL 0.08, CADD 22.70
- S20S (p.Ser20Ser), gnomAD 3-46883619-C-T, CADD 15.30
- S21Y (p.Ser21Tyr), gnomAD rs1334383998, REVEL 0.13, CADD 22.20
- S21F (p.Ser21Phe), rs1358477136, gnomAD 3-46883619-C-CT, CADD 32.00
- S21P (p.Ser21Pro), gnomAD 3-46883620-T-C, REVEL 0.17, CADD 23.10
- S21C (p.Ser21Cys), gnomAD 3-46883621-C-G, REVEL 0.12, CADD 22.60
- S21S (p.Ser21Ser), gnomAD 3-46883622-C-G, CADD 14.40
- A22T (p.Ala22Thr), TOPMed rs1420036600, gnomAD rs1420036600, REVEL 0.06, CADD 23.40
- A22V (p.Ala22Val), rs2106957940, ClinGen CA352503096, ClinVar RCV001872359, Ensembl rs2106957940, REVEL 0.05, CADD 22.70, Uncertain significance, not provided
- A22S (p.Ala22Ser), gnomAD 3-46883623-G-T, REVEL 0.06, CADD 22.90
- A22E (p.Ala22Glu), gnomAD 3-46883624-C-A, REVEL 0.14, CADD 23.70
- A22A (p.Ala22Ala), gnomAD 3-46883625-G-A, CADD 10.10
- Y23* (p.Tyr23Ter), cosmic curated COSV10942, CADD 34.00
- Y23F (p.Tyr23Phe), gnomAD 3-46883627-A-T, REVEL 0.07, CADD 21.90
- Y23Y (p.Tyr23Tyr), rs1294394312, gnomAD 3-46883628-C-T, CADD 9.54
- A24E (p.Ala24Glu), cosmic curated COSV10963, REVEL 0.21, CADD 21.70
- A24V (p.Ala24Val), gnomAD rs1305304363, REVEL 0.05, CADD 22.40
- A24T (p.Ala24Thr), gnomAD 3-46883629-G-A, REVEL 0.06, CADD 23.00
- A24S (p.Ala24Ser), gnomAD 3-46883629-G-T, REVEL 0.06, CADD 22.60
- A24A (p.Ala24Ala), rs1234738292, gnomAD 3-46883631-G-T, CADD 14.50
- L25L (p.Leu25Leu), gnomAD 3-46883632-C-T, CADD 22.20
- L25M (p.Leu25Met), gnomAD 3-46883632-C-A, REVEL 0.06, CADD 24.30
- L25P (p.Leu25Pro), gnomAD 3-46883633-T-C, REVEL 0.26, CADD 27.60
- V26G (p.Val26Gly), cosmic curated COSV10642, ExAC rs201200407, gnomAD rs201200407, REVEL 0.38, CADD 33.00
- V26M (p.Val26Met), TOPMed rs200498439, gnomAD rs200498439, REVEL 0.16, CADD 33.00
- D27G (p.Asp27Gly), ExAC rs79218323, gnomAD rs79218323, REVEL 0.28, CADD 32.00
- D27V (p.Asp27Val), ExAC rs79218323, gnomAD rs79218323, REVEL 0.40, CADD 29.80
- D27N (p.Asp27Asn), gnomAD 3-46893910-G-A, REVEL 0.25, CADD 28.80
- D27E (p.Asp27Glu), gnomAD 3-46893912-T-G, REVEL 0.12, CADD 18.00
- D27D (p.Asp27Asp), rs1176120255, gnomAD 3-46893912-T-C, CADD 7.89
- A28S (p.Ala28Ser), ExAC rs757054789
- A28V (p.Ala28Val), ExAC rs780415938
- A28T (p.Ala28Thr), gnomAD 3-46893913-G-A, REVEL 0.05, CADD 22.10
- A28A (p.Ala28Ala), rs1291292658, gnomAD 3-46893915-A-G, CADD 5.62
- D29A (p.Asp29Ala), TOPMed rs2031578640
- D29Y (p.Asp29Tyr), ExAC rs747161757
- D29V (p.Asp29Val), gnomAD 3-46893917-A-T, REVEL 0.69, CADD 32.00
- D29D (p.Asp29Asp), gnomAD 3-46893918-T-C, CADD 11.80
- D30Y (p.Asp30Tyr), ExAC rs755263801, gnomAD rs755263801, REVEL 0.63, CADD 32.00
- D30N (p.Asp30Asn), gnomAD 3-46893919-G-A, REVEL 0.27, CADD 32.00
- D30D (p.Asp30Asp), rs781370785, gnomAD 3-46893921-C-T, CADD 13.80
- V31I (p.Val31Ile), cosmic curated COSV10517, ExAC rs748205910, TOPMed rs748205910, gnomAD rs748205910, REVEL 0.18, CADD 23.50
- V31F (p.Val31Phe), gnomAD 3-46893922-G-T, REVEL 0.32, CADD 31.00
- V31V (p.Val31Val), rs1016653806, gnomAD 3-46893924-C-T, CADD 14.40
- M32T (p.Met32Thr), NCI-TCGA Cosmic COSV5731, cosmic curated COSV57314, gnomAD rs2031579553, REVEL 0.08, CADD 24.10, Variant assessed as somatic; moderate impact.
- T33T (p.Thr33Thr), gnomAD 3-46893930-T-A, CADD 12.80
- K34N (p.Lys34Asn), cosmic curated COSV57316
- K34E (p.Lys34Glu), gnomAD 3-46893931-A-G, REVEL 0.07, CADD 24.20
- E35K (p.Glu35Lys), rs1559532562, ClinGen CA352490852, ClinVar RCV000714279, Ensembl rs1559532562, AlphaMissense 0.79, MetaLR 0.26, Uncertain significance, Eiken syndrome
- E36K (p.Glu36Lys), cosmic curated COSV57318
- E36Q (p.Glu36Gln), gnomAD 3-46893937-G-C, REVEL 0.47, CADD 29.10
- Q37K (p.Gln37Lys), rs794727622, ClinGen CA245094, ClinVar RCV000178075, Ensembl rs794727622, AlphaMissense 0.80, MetaLR 0.42, Uncertain significance, not provided
- Q37L (p.Gln37Leu), cosmic curated COSV10736
- Q37R (p.Gln37Arg), rs1369706285, gnomAD 3-46893936-G-GGAA, CADD 32.00
- I38S (p.Ile38Ser), gnomAD 3-46893942-GA-G, CADD 32.00
- I38V (p.Ile38Val), gnomAD 3-46893943-A-G, REVEL 0.22, CADD 26.20
- I38N (p.Ile38Asn), gnomAD 3-46893944-T-A, REVEL 0.57, CADD 28.70
- F39C (p.Phe39Cys), TOPMed rs1470435775, gnomAD rs1470435775, REVEL 0.03, CADD 23.20
- F39S (p.Phe39Ser), TOPMed rs1470435775, gnomAD rs1470435775
- F39Y (p.Phe39Tyr), gnomAD 3-46893947-T-A, REVEL 0.01, CADD 14.90
- F39F (p.Phe39Phe), rs552828104, gnomAD 3-46893948-C-T, CADD 13.80
- L40L (p.Leu40Leu), gnomAD 3-46893949-C-T, CADD 11.90
- L40R (p.Leu40Arg), gnomAD 3-46893950-T-G, REVEL 0.53, CADD 28.40
- L41P (p.Leu41Pro), gnomAD 3-46893953-T-C, REVEL 0.73, CADD 29.50
- L41L (p.Leu41Leu), rs1378624313, gnomAD 3-46893954-G-A, CADD 11.70
- H42Y (p.His42Tyr), rs387907458, ClinGen CA216056, cosmic curated COSV57315, ClinVar RCV000054584, AlphaMissense 0.10, MetaLR 0.07, Uncertain significance, not provided
- H42R (p.His42Arg), gnomAD 3-46893956-A-G, REVEL 0.13, CADD 19.10
- R43C (p.Arg43Cys), 1000Genomes rs571011973, ExAC rs571011973, gnomAD rs571011973, REVEL 0.30, CADD 26.00
- R43G (p.Arg43Gly), 1000Genomes rs571011973, ExAC rs571011973, gnomAD rs571011973, REVEL 0.10, CADD 20.50
- R43H (p.Arg43His), rs141466964, ClinGen CA2359084, ClinVar RCV000336084, ClinVar RCV000394373, REVEL 0.11, CADD 26.60, Conflicting interpretations, Inborn genetic diseases; Primary failure of tooth eruption; Chondrodysplasia Blo
- R43S (p.Arg43Ser), cosmic curated COSV10048
- R43L (p.Arg43Leu), gnomAD 3-46893959-G-T, REVEL 0.16, CADD 24.70
- R43R (p.Arg43Arg), rs771352880, gnomAD 3-46893960-T-C, CADD 3.31
- A44G (p.Ala44Gly), gnomAD rs2031582004, REVEL 0.50, CADD 26.20
- A44S (p.Ala44Ser), gnomAD rs1658380264, REVEL 0.42, CADD 26.80
- A44V (p.Ala44Val), gnomAD 3-46893962-C-T, REVEL 0.46, CADD 26.30
- Q45* (p.Gln45Ter), Ensembl rs200169682, CADD 37.00
- Q45R (p.Gln45Arg), rs201908157, ClinGen CA2359086, ClinVar RCV002976384, 1000Genomes rs201908157, REVEL 0.07, CADD 22.50, Uncertain significance, not provided
- Q45K (p.Gln45Lys), gnomAD 3-46893964-C-A, REVEL 0.05, CADD 16.60
- A46D (p.Ala46Asp), rs199670451, ClinGen CA2359088, ClinVar RCV001145804, ClinVar RCV001145805, REVEL 0.08, CADD 21.20, Conflicting interpretations, Chondrodysplasia Blomstrand type; Metaphyseal chondrodysplasia, Jansen type; Pri
- A46T (p.Ala46Thr), rs201320537, ClinGen CA2359087, cosmic curated COSV57316, ClinVar RCV003087114, REVEL 0.05, CADD 22.50, Uncertain significance, not provided; Inborn genetic diseases; Chondrodysplasia Blomstrand type
- Q47E (p.Gln47Glu), ESP rs138009937, ExAC rs138009937, TOPMed rs138009937, gnomAD rs138009937, REVEL 0.04, CADD 19.90
- Q47H (p.Gln47His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public PTH1R analysis runs
- PTH1R analysis run — PTH1R (964 variants) — completed 2026-08-19