PTH (Parathyroid hormone) variants and mutations
PTH (also known as Parathyroid hormone) is a human protein-coding gene encoding a parathyroid hormone protein. After secretion from the parathyroid glands, it raises extracellular calcium by acting on bone and kidney and indirectly increasing intestinal calcium absorption. Deficiency causes hypoparathyroidism, whereas excessive secretion produces hyperparathyroidism and characteristic skeletal and renal complications. This analysis covers 282 PTH variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes hypoparathyroidism, familial isolated 1, Familial isolated hypoparathyroidism, and neurodegenerative disease. Example PTH variants include M1?, I2L, and I2T.
Variant analysis overview
- Gene: PTH
- Protein: Parathyroid hormone
- UniProt accession: P01270
- Organism: Homo sapiens
- Variants analyzed: 282
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 158 unspecified-consequence records; 1 stop lost; 1 stop retained variant; 55 synonymous variants; 55 missense variants; 2 stop-gained variants; 8 frameshift variants; 4 in-frame deletions; 1 splice-region variants
- Prediction scores: 220 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypoparathyroidism, familial isolated 1, Familial isolated hypoparathyroidism, neurodegenerative disease, familial isolated hypoparathyroidism due to impaired PTH secretion, primary hyperparathyroidism, Alzheimer disease, Parkinson disease, multiple sclerosis, lysosomal storage disease, familial hypoparathyroidism, arthropathy, enteritis.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PTH variants
Examples include M1?, I2L, I2T, I2V, P3L, P3P, P3S, A4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV56378, ExAC rs761419105
- I2L (p.Ile2Leu), Ensembl rs1016031508, REVEL 0.10, MetaLR 0.25
- I2T (p.Ile2Thr), gnomAD 11-13492851-A-G, REVEL 0.22, MetaLR 0.20
- I2V (p.Ile2Val), gnomAD 11-13492852-T-C, REVEL 0.14, MetaLR 0.17
- P3L (p.Pro3Leu), TOPMed rs1225809627
- P3P (p.Pro3Pro), rs1006011428, gnomAD 11-13492847-A-G, CADD 11.80
- P3S (p.Pro3Ser), gnomAD 11-13492849-G-A, REVEL 0.11, MetaLR 0.08
- A4A (p.Ala4Ala), rs886189291, gnomAD 11-13492844-T-C, CADD 9.11
- K5K (p.Lys5Lys), gnomAD 11-13492841-T-C, CADD 8.56
- D6H (p.Asp6His), gnomAD rs1847493015, REVEL 0.19, MetaLR 0.41
- D6Y (p.Asp6Tyr), cosmic curated COSV56379
- D6V (p.Asp6Val), gnomAD 11-13492839-T-A, REVEL 0.15, MetaLR 0.38
- M7I (p.Met7Ile), Ensembl rs1847492905
- M7T (p.Met7Thr), gnomAD 11-13492836-A-G, REVEL 0.27, MetaLR 0.32
- K9T (p.Lys9Thr), TOPMed rs1847492843
- V10V (p.Val10Val), rs1847492788, gnomAD 11-13492826-A-G, CADD 2.87
- V10A (p.Val10Ala), gnomAD 11-13492827-A-G, REVEL 0.21, MetaLR 0.34
- V10I (p.Val10Ile), gnomAD 11-13492828-C-T, REVEL 0.17, MetaLR 0.35
- M11T (p.Met11Thr), gnomAD rs1847492713, REVEL 0.30, MetaLR 0.39
- M11R (p.Met11Arg), gnomAD 11-13492824-A-C, REVEL 0.56, MetaLR 0.38
- I12T (p.Ile12Thr), ExAC rs779984006, gnomAD rs779984006, REVEL 0.48, MetaLR 0.51
- I12F (p.Ile12Phe), gnomAD 11-13492822-T-A, REVEL 0.29, MetaLR 0.35
- V13A (p.Val13Ala), Ensembl rs2134093288, REVEL 0.48, MetaLR 0.52
- V13V (p.Val13Val), gnomAD 11-13492817-G-T, CADD 9.86
- M14T (p.Met14Thr), Ensembl rs2134093287
- M14V (p.Met14Val), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
- M14I (p.Met14Ile), gnomAD 11-13492814-C-T, REVEL 0.28, MetaLR 0.43
- L15L (p.Leu15Leu), rs758268920, gnomAD 11-13492811-C-T, CADD 8.28
- L15F (p.Leu15Phe), gnomAD 11-13492811-C-A, REVEL 0.13, MetaLR 0.22
- A16E (p.Ala16Glu), rs2499940358, ClinGen CA379724970, ClinVar RCV003050424, Uncertain significance, not provided
- A16K (p.Ala16Lys), rs2134093283, ClinGen CA2573053455, ClinVar RCV001817693, Ensembl rs2134093283, Likely pathogenic, not provided
- A16V (p.Ala16Val), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
- C18G (p.Cys18Gly), TOPMed rs104894271, gnomAD rs104894271, REVEL 0.32, AlphaMissense 0.72, Pathogenic, in FIH1
- C18R (p.Cys18Arg), rs104894271, ClinGen CA123436, ClinVar RCV000014764, UniProt VAR 006047, AlphaMissense 0.72, MetaLR 0.53, Pathogenic, Hypoparathyroidism, familial isolated 1
- C18Y (p.Cys18Tyr), TOPMed rs1847492368
- C18C (p.Cys18Cys), gnomAD 11-13492802-A-G, CADD 7.74
- F19S (p.Phe19Ser), TOPMed rs979065769, REVEL 0.54, MetaLR 0.46
- L20F (p.Leu20Phe), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
- L20I (p.Leu20Ile), NCI-TCGA Cosmic COSV5637, Variant assessed as somatic; moderate impact.
- L20P (p.Leu20Pro), Ensembl rs2134093265
- p.Leu20 Thr21delinsPro, rs1565290530, gnomAD 11-13492794-GTAA-, CADD 17.10
- T21I (p.Thr21Ile), Ensembl rs1565290527, REVEL 0.38, MetaLR 0.59
- T21R (p.Thr21Arg), Ensembl rs1565290527, REVEL 0.51, MetaLR 0.62
- T21Q (p.Thr21Gln), gnomAD 11-13492794-GT-G, CADD 22.80
- K22Q (p.Lys22Gln), TOPMed rs1847491962
- K22T (p.Lys22Thr), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
- K22R (p.Lys22Arg), rs1382095004, gnomAD 11-13492789-ATTTT, CADD 23.10
- S23* (p.Ser23Ter), ExAC rs750295789, gnomAD rs750295789, CADD 35.00
- S23L (p.Ser23Leu), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact., in FIH1
- S23P (p.Ser23Pro), rs104894272, ClinGen CA123437, ClinVar RCV000014766, UniProt VAR 018464, AlphaMissense 0.20, MetaLR 0.34, Pathogenic, Hypoparathyroidism, familial isolated 1
- S23S (p.Ser23Ser), rs377308600, gnomAD 11-13492787-C-T, CADD 0.86
- D24N (p.Asp24Asn), cosmic curated COSV56378
- D24Y (p.Asp24Tyr), ExAC rs756406117, gnomAD rs756406117, REVEL 0.40, MetaLR 0.54
- D24D (p.Asp24Asp), rs1847491689, gnomAD 11-13492784-A-G, CADD 6.39
- D24G (p.Asp24Gly), gnomAD 11-13492785-T-C, REVEL 0.44, MetaLR 0.60
- D24H (p.Asp24His), gnomAD 11-13492786-C-G, REVEL 0.43, MetaLR 0.62
- G25E (p.Gly25Glu), cosmic curated COSV56379
- G25V (p.Gly25Val), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
- G25G (p.Gly25Gly), rs752828673, gnomAD 11-13492781-C-T, CADD 7.99
- K26N (p.Lys26Asn), gnomAD rs1311289285, REVEL 0.28, MetaLR 0.41
- K26K (p.Lys26Lys), gnomAD 11-13492778-T-C, CADD 7.30
- S27F (p.Ser27Phe), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, REVEL 0.23, MetaLR 0.33, Variant assessed as somatic; moderate impact.
- S27P (p.Ser27Pro), TOPMed rs1431925612, gnomAD rs1431925612
- S27Y (p.Ser27Tyr), ExAC rs767807443, gnomAD rs767807443, REVEL 0.26, MetaLR 0.33
- V28A (p.Val28Ala), ExAC rs759709735, gnomAD rs759709735, REVEL 0.32, MetaLR 0.44
- V28F (p.Val28Phe), gnomAD rs1170883858, REVEL 0.37, MetaLR 0.37, Uncertain significance, not specified
- V28L (p.Val28Leu), gnomAD 11-13492774-C-G, REVEL 0.16, MetaLR 0.30
- K29N (p.Lys29Asn), gnomAD rs1214802214, REVEL 0.35, MetaLR 0.47
- K29R (p.Lys29Arg), ExAC rs774514236, gnomAD rs774514236, REVEL 0.08, MetaLR 0.22
- K29K (p.Lys29Lys), rs1214802214, gnomAD 11-13492666-C-T, CADD 16.30
- K30N (p.Lys30Asn), TOPMed rs1847490033, REVEL 0.65, MetaLR 0.71
- K30Q (p.Lys30Gln), Ensembl rs1847490110
- R31T (p.Arg31Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S32C (p.Ser32Cys), Ensembl rs2134093140
- V33E (p.Val33Glu), rs2499939905, ClinGen CA379724852, ClinVar RCV003388783, Uncertain significance, Hypoparathyroidism, familial isolated 1
- V33L (p.Val33Leu), ESP rs370564990, ExAC rs370564990, TOPMed rs370564990, gnomAD rs370564990, REVEL 0.62, MetaLR 0.83
- S34G (p.Ser34Gly), ExAC rs767865413, TOPMed rs767865413, gnomAD rs767865413, REVEL 0.58, MetaLR 0.72
- S34I (p.Ser34Ile), TOPMed rs1230332004, gnomAD rs1230332004
- S34N (p.Ser34Asn), TOPMed rs1230332004, gnomAD rs1230332004, REVEL 0.50, MetaLR 0.69, Uncertain significance, not provided
- S34R (p.Ser34Arg), ExAC rs767865413, TOPMed rs767865413, gnomAD rs767865413
- S34V (p.Ser34Val), gnomAD 11-13492653-TC-T, CADD 26.70
- E35E (p.Glu35Glu), gnomAD 11-13492648-T-C, CADD 9.22
- Q37* (p.Gln37Ter), cosmic curated COSV56378, CADD 38.00
- Q37H (p.Gln37His), gnomAD rs1336480236, REVEL 0.71, MetaLR 0.80
- Q37K (p.Gln37Lys), NCI-TCGA Cosmic COSV5637, NCI-TCGA Cosmic COSV9996, cosmic curated COSV99961, Variant assessed as somatic; moderate impact.
- Q37R (p.Gln37Arg), gnomAD 11-13492643-T-C, REVEL 0.88, MetaLR 0.83
- M39T (p.Met39Thr), gnomAD rs769151895, REVEL 0.90, MetaLR 0.77, Uncertain significance, not specified
- H40H (p.His40His), rs977965204, gnomAD 11-13492633-A-G, CADD 7.77
- H40Y (p.His40Tyr), gnomAD 11-13492635-G-A, REVEL 0.91, MetaLR 0.87
- N41K (p.Asn41Lys), rs755183877, ClinGen CA379724792, ClinVar RCV001108379, ExAC rs755183877, AlphaMissense 0.87, MetaLR 0.63, Uncertain significance, Familial hypoparathyroidism
- N41S (p.Asn41Ser), rs387907454, ClinGen CA216050, ClinVar RCV000054581, Ensembl rs387907454, AlphaMissense 0.15, MetaLR 0.53, Uncertain significance, not provided
- N41N (p.Asn41Asn), rs755183877, gnomAD 11-13492630-G-A, AlphaMissense 0.87, MetaLR 0.63
- N41D (p.Asn41Asp), gnomAD 11-13492632-T-C, REVEL 0.31, MetaLR 0.39
- L42P (p.Leu42Pro), gnomAD 11-13492628-A-G, REVEL 0.79, MetaLR 0.64
- L42L (p.Leu42Leu), rs751747610, gnomAD 11-13492629-G-A, CADD 8.95
- G43E (p.Gly43Glu), cosmic curated COSV10516, REVEL 0.60, MetaLR 0.73, Uncertain significance, Hypoparathyroidism, familial isolated 1
- G43R (p.Gly43Arg), ESP rs142613980, ExAC rs142613980, TOPMed rs142613980, gnomAD rs142613980, REVEL 0.31, MetaLR 0.53
- G43G (p.Gly43Gly), rs773625324, gnomAD 11-13492624-T-C, CADD 8.61
- K44Q (p.Lys44Gln), gnomAD rs1162770261, REVEL 0.22, MetaLR 0.41
- H45Q (p.His45Gln), cosmic curated COSV56378
- H45H (p.His45His), rs149916515, gnomAD 11-13492618-A-G, CADD 7.45
- H45L (p.His45Leu), gnomAD 11-13492619-T-A, REVEL 0.72, MetaLR 0.68
- H45N (p.His45Asn), gnomAD 11-13492620-G-T, REVEL 0.38, MetaLR 0.46
- H45Y (p.His45Tyr), gnomAD 11-13492620-G-A, REVEL 0.54, MetaLR 0.51
- L46M (p.Leu46Met), TOPMed rs923216818, gnomAD rs923216818, REVEL 0.33, MetaLR 0.62
- L46V (p.Leu46Val), TOPMed rs923216818, gnomAD rs923216818, Uncertain significance, not specified
- L46L (p.Leu46Leu), rs923216818, gnomAD 11-13492617-G-A, CADD 9.40
- N47N (p.Asn47Asn), gnomAD 11-13492612-G-A, CADD 5.63
- S48L (p.Ser48Leu), rs762100011, NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, ExAC rs762100011, REVEL 0.12, MetaLR 0.37, Variant assessed as somatic; moderate impact.
- S48S (p.Ser48Ser), rs376145884, gnomAD 11-13492609-C-T, CADD 0.77
- M49V (p.Met49Val), ESP rs147730858, TOPMed rs147730858, gnomAD rs147730858, REVEL 0.14, MetaLR 0.19
- M49I (p.Met49Ile), gnomAD 11-13492606-C-T, REVEL 0.16, MetaLR 0.34
- M49T (p.Met49Thr), gnomAD 11-13492607-A-G, REVEL 0.17, MetaLR 0.31
- E50D (p.Glu50Asp), gnomAD 11-13492603-C-G, REVEL 0.24, MetaLR 0.35
- E50E (p.Glu50Glu), rs1269833882, gnomAD 11-13492603-C-T, CADD 5.00
- E50Q (p.Glu50Gln), gnomAD 11-13492605-C-G, REVEL 0.34, MetaLR 0.53
- R51T (p.Arg51Thr), ExAC rs768367860, gnomAD rs768367860, REVEL 0.77, MetaLR 0.87
- R51K (p.Arg51Lys), gnomAD 11-13492601-C-T, REVEL 0.74, MetaLR 0.87
- V52E (p.Val52Glu), ExAC rs746647774, gnomAD rs746647774, REVEL 0.44, MetaLR 0.39
- V52del (p.Val52del), gnomAD 11-13492595-TCTA-, CADD 16.60
- V52G (p.Val52Gly), gnomAD 11-13492598-A-C, REVEL 0.42, MetaLR 0.43
- V52A (p.Val52Ala), gnomAD 11-13492598-A-G, REVEL 0.15, MetaLR 0.40
- V52I (p.Val52Ile), gnomAD 11-13492599-C-T, REVEL 0.12, MetaLR 0.34
- E53Q (p.Glu53Gln), ExAC rs775025715, TOPMed rs775025715, gnomAD rs775025715, REVEL 0.16, MetaLR 0.34
- E53E (p.Glu53Glu), rs1847488979, gnomAD 11-13492594-T-C, CADD 9.03
- E53A (p.Glu53Ala), gnomAD 11-13492595-T-G, REVEL 0.30, MetaLR 0.44
- W54* (p.Trp54Ter), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Ensembl rs2134093056, CADD 38.00, Variant assessed as somatic; high impact.
- W54R (p.Trp54Arg), cosmic curated COSV10958, ExAC rs771537090, gnomAD rs771537090, REVEL 0.88, MetaLR 0.81, Uncertain significance, not provided
- L55L (p.Leu55Leu), rs1351486691, gnomAD 11-13492588-C-T, CADD 2.17
- R56C (p.Arg56Cys), rs199955107, ClinGen CA5893182, NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, REVEL 0.36, MetaLR 0.57, Likely pathogenic, not provided
- R56H (p.Arg56His), cosmic curated COSV56378, ExAC rs778737005, gnomAD rs778737005, REVEL 0.36, MetaLR 0.55, Uncertain significance, Hypoparathyroidism, familial isolated 1
- R56P (p.Arg56Pro), NCI-TCGA Cosmic COSV5637, ExAC rs778737005, gnomAD rs778737005, Variant assessed as somatic; moderate impact.
- R56R (p.Arg56Arg), gnomAD 11-13492585-A-T, CADD 4.35
- K57E (p.Lys57Glu), Ensembl rs1847488757, REVEL 0.22, MetaLR 0.32
- K57K (p.Lys57Lys), gnomAD 11-13492582-C-T, CADD 7.80
- K57* (p.Lys57Ter), rs2134093042, gnomAD 11-13492584-T-TA, CADD 23.50
- K58K (p.Lys58Lys), rs1314166014, gnomAD 11-13492579-C-T, CADD 7.05
- L59L (p.Leu59Leu), rs374608791, gnomAD 11-13492576-C-T, CADD 6.78
- Q60Q (p.Gln60Gln), gnomAD 11-13492573-C-T, CADD 7.39
- D61D (p.Asp61Asp), rs370961197, gnomAD 11-13492570-A-G, CADD 8.22
- D61E (p.Asp61Glu), gnomAD 11-13492570-A-C, REVEL 0.29, MetaLR 0.36
- V62M (p.Val62Met), cosmic curated COSV56378, REVEL 0.49, MetaLR 0.52, Uncertain significance, not specified
- V62V (p.Val62Val), rs2134093020, gnomAD 11-13492567-C-T, CADD 7.03
- V62L (p.Val62Leu), gnomAD 11-13492569-C-G, REVEL 0.67, MetaLR 0.64
- H63Q (p.His63Gln), gnomAD 11-13492564-G-T, REVEL 0.63, MetaLR 0.60
- H63P (p.His63Pro), gnomAD 11-13492565-T-G, REVEL 0.67, MetaLR 0.63
- H63T (p.His63Thr), gnomAD 11-13492566-GC-G, CADD 23.70
- N64I (p.Asn64Ile), cosmic curated COSV56378
- N64S (p.Asn64Ser), rs1370035454, ClinGen CA379724641, ClinVar RCV001108378, TOPMed rs1370035454, AlphaMissense 0.08, MetaLR 0.48, Uncertain significance, Familial hypoparathyroidism
- N64T (p.Asn64Thr), cosmic curated COSV56378
- N64H (p.Asn64His), gnomAD 11-13492563-T-G, REVEL 0.50, MetaLR 0.59
- F65V (p.Phe65Val), gnomAD 11-13492560-A-C, REVEL 0.53, MetaLR 0.49
- F65L (p.Phe65Leu), gnomAD 11-13492560-A-G, REVEL 0.51, MetaLR 0.46
- V66I (p.Val66Ile), rs200119869, ClinGen CA5893178, ClinVar RCV004218546, ESP rs200119869, REVEL 0.20, MetaLR 0.37, Likely benign, not specified
- V66V (p.Val66Val), gnomAD 11-13492555-A-C, CADD 5.80
- A67G (p.Ala67Gly), TOPMed rs1452502191, gnomAD rs1452502191, REVEL 0.26, MetaLR 0.43
- A67T (p.Ala67Thr), gnomAD rs1383913477, REVEL 0.28, MetaLR 0.44, Uncertain significance, not provided
- A67A (p.Ala67Ala), rs540157071, gnomAD 11-13492552-G-A, CADD 7.38
- A67S (p.Ala67Ser), gnomAD 11-13492554-C-A, REVEL 0.10, MetaLR 0.27
- L68F (p.Leu68Phe), ExAC rs369252497, gnomAD rs369252497, REVEL 0.20, MetaLR 0.44
- L68P (p.Leu68Pro), ESP rs150454177, TOPMed rs150454177, gnomAD rs150454177, REVEL 0.17, MetaLR 0.40
- L68R (p.Leu68Arg), ESP rs150454177, TOPMed rs150454177, gnomAD rs150454177, REVEL 0.17, MetaLR 0.37
- L68L (p.Leu68Leu), rs1847488185, gnomAD 11-13492549-A-C, CADD 1.07
- L68I (p.Leu68Ile), gnomAD 11-13492551-G-T, REVEL 0.28, MetaLR 0.50
- G69R (p.Gly69Arg), ExAC rs780385257, TOPMed rs780385257, gnomAD rs780385257, REVEL 0.15, MetaLR 0.40
- G69E (p.Gly69Glu), rs749037995, gnomAD 11-13492550-AG-A, CADD 24.20
- A70T (p.Ala70Thr), TOPMed rs964652258
- A70A (p.Ala70Ala), gnomAD 11-13492543-A-G, CADD 5.11
- P71L (p.Pro71Leu), cosmic curated COSV10586
- P71S (p.Pro71Ser), rs2499939587, ClinGen CA379724603, ClinVar RCV004162699, REVEL 0.08, MetaLR 0.17, Likely benign, not specified
- P71A (p.Pro71Ala), gnomAD 11-13492542-G-C, REVEL 0.09, MetaLR 0.25
- L72I (p.Leu72Ile), cosmic curated COSV56379
- L72P (p.Leu72Pro), NCI-TCGA TCGA novel, REVEL 0.24, MetaLR 0.28, Variant assessed as somatic; moderate impact.
- L72R (p.Leu72Arg), gnomAD rs1396530954, REVEL 0.15, MetaLR 0.26
- L72V (p.Leu72Val), cosmic curated COSV10875, Ensembl rs1847488057
- L72L (p.Leu72Leu), gnomAD 11-13492539-G-A, CADD 0.72
- P74L (p.Pro74Leu), TOPMed rs1396832925
- P74R (p.Pro74Arg), gnomAD 11-13492532-G-C, REVEL 0.18, MetaLR 0.32
- R75I (p.Arg75Ile), cosmic curated COSV56378
- D76N (p.Asp76Asn), NCI-TCGA Cosmic COSV5637, cosmic curated COSV56378, Variant assessed as somatic; moderate impact.
Public PTH analysis runs
- PTH analysis run — PTH (282 variants) — completed 2026-08-22