PTH1R (parathyroid hormone 1 receptor)

Gene

• Entrez ID: 5745
• Gene name: Parathyroid hormone 1 receptor
• Gene symbol: PTH1R
• Synonyms: EKNS, PFE, PTHR, PTHR1
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: The protein encoded by this gene is a member of the G-protein coupled receptor family 2. This protein is a receptor for parathyroid hormone (PTH) and for parathyroid hormone-like hormone (PTHLH). The activity of this receptor is mediated by G proteins whi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121434597	A>G	Pathogenic	Missense variant, coding sequence variant
rs121434598	A>C	Pathogenic	Missense variant, synonymous variant, coding sequence variant
rs121434599	C>T	Pathogenic	Missense variant, coding sequence variant
rs121434600	T>G	Pathogenic	Missense variant, coding sequence variant
rs121434602	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs121434603	C>T	Pathogenic	Stop gained, synonymous variant, coding sequence variant
rs121434604	C>T	Pathogenic	Stop gained, coding sequence variant
rs121434605	G>A,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs398122843	G>A	Pathogenic	Missense variant, coding sequence variant
rs769180471	T>A,C	Pathogenic	Coding sequence variant, missense variant
rs1575524795	C>G	Pathogenic	Intron variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	TAS	9745456
GO:0001701	Process	In utero embryonic development	IEA
GO:0002062	Process	Chondrocyte differentiation	IEA
GO:0002076	Process	Osteoblast development	IEA
GO:0004991	Function	Parathyroid hormone receptor activity	IBA	21873635
GO:0004991	Function	Parathyroid hormone receptor activity	IDA	8397094, 19674967
GO:0005515	Function	Protein binding	IPI	19674967, 23124878, 32296183
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IDA	19674967
GO:0005887	Component	Integral component of plasma membrane	IMP	8397094
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	9927325
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IBA	21873635
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IDA	19674967
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA	21873635
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	8397094, 27160269
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IC	19608645
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IEA
GO:0007568	Process	Aging	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0008285	Process	Negative regulation of cell population proliferation	IEA
GO:0008528	Function	G protein-coupled peptide receptor activity	IBA	21873635
GO:0016323	Component	Basolateral plasma membrane	ISS
GO:0016324	Component	Apical plasma membrane	ISS
GO:0017046	Function	Peptide hormone binding	IBA	21873635
GO:0017046	Function	Peptide hormone binding	IDA	19674967
GO:0030282	Process	Bone mineralization	IEA
GO:0031526	Component	Brush border membrane	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	27160269
GO:0043235	Component	Receptor complex	ISS
GO:0043621	Function	Protein self-association	IDA	19674967
GO:0045453	Process	Bone resorption	IEA
GO:0048469	Process	Cell maturation	IEA
GO:0060732	Process	Positive regulation of inositol phosphate biosynthetic process	ISS

Other IDs

• MIM: 168468
• HGNC: 9608
• e!Ensembl: ENSG00000160801

Protein

• UniProt ID: Q03431
• Protein name: Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP type I receptor) (PTH/PTHr receptor) (Parathyroid hormone 1 receptor) (PTH1 receptor)
• Protein function: G-protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH) (PubMed:10913300, PubMed:18375760, PubMed:19674967, PubMed:27160269, PubMed:30975883, PubMed:35932760, PubMed:8397094). Ligand binding c
• PDB: 1BL1, 3C4M, 3H3G, 3L2J, 4Z8J, 5EMB, 6NBF, 6NBH, 6NBI, 7UZO, 7UZP, 7VVJ, 7VVK, 7VVL, 7VVM, 7VVN, 7VVO, 7Y35, 7Y36, 8BIA, 8BJ0, 8D51, 8D52, 8FLQ, 8FLR, 8FLS, 8FLT, 8FLU, 8GW8, 8HA0, 8HAF, 8HAO, 8JR9, 9JR2, 9JR3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02793	HRM	105 → 173	Hormone receptor domain	Family
  PF00002	7tm_2	184 → 455	7 transmembrane receptor (Secretin family)	Family

• Sequence:

  MGTARIAPGLALLLCCPVLSSAYALVDADDVMTKEEQIFLLHRAQAQCEKRLKEVLQRPA
  SIMESDKGWTSASTSGKPRKDKASGKLYPESEEDKEAPTGSRYRGRPCLPEWDHILCWPL
  GAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWELVPGHNRTWANYSECVKFLTNETRE
  REVFDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVK
  DAVLYSGATLDEAERLTEEELRAIAQAPPPPATAAAGYAGCRVAVTFFLYFLATNYYWIL
  VEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTGCWDLSSGNKK
  WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVH
  YIVFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSRWTLA
  LDFKRKARSGSSSYSYGPMVSHTSVTNVGPRVGLGLPLSPRLLPTATTNGHPQLPGHAKP
  GTPALETLETTPPAMAAPKDDGFLNGSCSGLDEEASGPERPPALLQEEWETVM

• Sequence length: 593

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling
Parathyroid hormone synthesis, secretion and action
Endocrine and other factor-regulated calcium reabsorption

Reactome:

Class B/2 (Secretin family receptors)
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Brachydactyly	Brachydactyly	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142
Cataract	Cataract	rs118203965, rs118203966, rs104893685, rs121908938, rs104894175, rs121909048, rs28937573, rs121909049, rs121909050, rs74315488, rs80358200, rs80358203, rs121434643, rs56141211, rs132630322, rs121917775, rs121917735, rs121917736, rs137853199, rs137853200, rs121917867, rs121917869, rs121913555, rs104893736, rs121909595, rs121909596, rs121909597, rs28931605, rs121909598, rs104893618, rs1695062782, rs74315486, rs74315487, rs74315490, rs74315489, rs745938679, rs1566402656, rs74315439, rs74315441, rs121912973, rs121917823, rs1593332981, rs121917825, rs121917827, rs113994108, rs387906963, rs387906964, rs1240503246, rs387906965, rs387906966, rs750207077, rs387907336, rs387907337, rs387907342, rs140332366, rs397514703, rs398122937, rs398122378, rs398122392, rs398122944, rs137853924, rs398122947, rs397515623, rs397515624, rs397515625, rs397515626, rs398122948, rs587778872, rs398123066, rs587777601, rs370424081, rs786205221, rs786205222, rs864309684, rs864309688, rs864309701, rs864309689, rs864309690, rs864309681, rs864309686, rs864309696, rs864309693, rs864309687, rs864309691, rs864309692, rs864309695, rs864309678, rs864309685, rs864309700, rs864309698, rs864309683, rs864309682, rs864309679, rs111534978, rs864309680, rs864309702, rs864622780, rs756898971, rs869312732, rs775038545, rs878852983, rs1114167312, rs1114167313, rs1114167314, rs1114167315, rs1114167307, rs886041410, rs886041412, rs1057518738, rs1057517926, rs1057518878, rs1057519616, rs12799308, rs1064793935, rs1064797219, rs1085307126, rs1085307127, rs765628635, rs1114167427, rs1114167433, rs1554744860, rs1554743428, rs747093432, rs1411557416, rs1555179713, rs1481963503, rs1555549755, rs1456161420, rs1555547008, rs1555889308, rs1555888762, rs766522434, rs1264025914, rs1553585262, rs1567671947, rs1337897299, rs764945940, rs1307969607, rs949335475, rs1184095219, rs776129797, rs1569203234, rs1567668570, rs749141857, rs764098604, rs1184398243, rs1578956689, rs1568480054, rs1564745688, rs1564722302, rs1564723150, rs1571175950, rs1569602837, rs1576552712, rs1575369255, rs981126461, rs1570403798, rs200557771, rs1477743112, rs1651879427, rs1651881222, rs1651919374, rs2024441691, rs148284531, rs1246080692
Chondrodysplasia punctata	Chondrodysplasia, blomstrand type	rs80338714, rs398122843, rs121434599, rs121434604, rs2107055197, rs2089231699	8723092, 9745456, 9649554, 9832466
Chondrosarcoma	Chondrosarcoma	rs587776540, rs1586279285, rs886039356, rs1554578798, rs1817895168
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	30054458
Eiken syndrome	Eiken syndrome	rs121434603
Enchondromatosis	Enchondromatosis	rs62193615, rs121913500, rs121913499	11850620, 18559376
Epiphyseal dysplasia	Epiphyseal dysplasia	rs137852652, rs28936668, rs1600786629, rs1600786748, rs606231367, rs1569763139, rs1569763108, rs1085307973, rs1555821817
Failure of tooth eruption	Failure of Tooth Eruption, Primary, Primary failure of tooth eruption	rs121434597, rs1575524795, rs2107035467, rs121434605, rs769180471	20830195, 9745456, 23910200, 19061984
Hydrops fetalis	Hydrops Fetalis	rs28935477, rs1131691986
Hypercalcemia	Hypercalcemia	rs876657376, rs387907322, rs777676129, rs387907323, rs114368325, rs6068812, rs387907324, rs777947329, rs201304511, rs769409705, rs200095793, rs876661338, rs1554095500, rs139763321, rs774432244, rs781367354
Hyperparathyroidism	Hyperparathyroidism	rs28942098, rs121434262, rs80356649, rs121434264, rs587776558, rs587776559, rs121909259, rs104893689, rs28936684, rs104893690, rs869320729, rs104893700, rs104893705, rs104893707, rs104893709, rs863223311, rs80356650, rs193922432, rs886041637, rs201633414, rs1057519419, rs766719790, rs1281361203, rs759393722, rs1342435095, rs1200458339, rs755916513, rs1586190048, rs1558280170	11014383
Hypoparathyroidism	Hypoparathyroidism	rs104893959, rs104894271, rs2134093224, rs104894272, rs6256, rs193922430, rs886037646, rs1554103179
Metaphyseal chondrodysplasia	Metaphyseal chondrodysplasia, Jansen type metaphyseal chondrodysplasia, Metaphyseal chondrodysplasia, Jansen type	rs121909500, rs121434597, rs121434598, rs121434600, rs121434602, rs199476103, rs727502774, rs1554651507, rs727502776, rs1554651446, rs727502778, rs1554651469, rs878853178, rs796065036, rs111033544, rs111033545, rs111033546, rs1562122372, rs111033543, rs111033547, rs111033549, rs111033550, rs111033551, rs111033552, rs111033548, rs111033553, rs111033554, rs111033556, rs2114276588, rs140059558, rs369083541, rs786204684, rs1554651506, rs753874439, rs1554651455, rs1085307765, rs1131691804, rs1383432106, rs1554651508, rs1340624774, rs751921616, rs551450545, rs752934195, rs549085067, rs1156413585, rs772443941, rs1554651395, rs1554651397, rs1554651396, rs1554651403, rs1554651424, rs1554651427, rs727502777, rs1230629953, rs1554651481, rs1554651491, rs1554651503, rs1554651532, rs1554651544, rs1554651365, rs1218494857, rs1587919129, rs1554651422, rs1554651428, rs1554651486, rs1554651489, rs1554651526, rs1554651405, rs1554651400, rs1587919165, rs1554651404, rs1554651411, rs1554651461, rs1554651471, rs1554651473, rs1554651505, rs781730798, rs1554651513, rs1554651153, rs759665242, rs1554651368, rs1554651382, rs1554651418, rs1554651413, rs1554651425, rs1554651451, rs1554651453, rs1554651462, rs1554651466, rs920074067, rs1554651499, rs1554651512, rs1554651524, rs1554651543, rs936059863, rs749667892, rs769180471, rs192060920, rs948931144, rs1554651373, rs1563907881, rs1563907883, rs1563907946, rs1563908212, rs1563908167, rs1582811858, rs1554651445	9745456, 8703170, 10487664, 9178745, 7701349, 27160269, 15240651
Osteochondrodysplasia	Osteochondrodysplasias	rs386833498, rs104893919, rs104893916, rs386833492, rs121908078, rs386833497, rs386833507, rs200963884, rs121908077, rs786204675, rs763198695, rs1554095433, rs766836061
Precocious puberty	Precocious Puberty	rs879255238, rs879255239, rs879255240, rs1264639964, rs1566764505
Skeletal dysplasia	Skeletal dysplasia	rs121912632, rs121912633, rs121912634, rs121912636, rs121912637, rs267607147, rs387906324, rs267607150, rs397514473, rs398123438, rs515726153, rs515726154, rs515726162, rs515726163, rs515726172, rs757011098

Unknown
Disease name	Disease term	dbSNP ID	References
Cubitus valgus	Acquired cubitus valgus
Aortic coarctation	Aortic coarctation
Blomstrand lethal chondrodysplasia	Blomstrand lethal chondrodysplasia
Brachycephaly	Brachycephaly
Camptodactyly of fingers	Clinodactyly of the 5th finger
Choanal atresia	Choanal Atresia
Pulmonary hypoplasia	Congenital hypoplasia of lung	rs1569032634
Dwarfism	Dwarfism
Dyschondroplasias	Dyschondroplasias		18559376, 11850620
Eiken skeletal dysplasia	Eiken Skeletal Dysplasia		9745456, 15525660
Hip contracture	Hip Contracture
Hypodontia	Hypodontia
Laryngeal calcification	Laryngeal calcification
Liver carcinoma	Liver carcinoma		28284560
Lung diseases	Lung diseases		20857298
Lymphangioma	Lymphangioma
Mesomelia	Mesomelia
Micrognathism	Micrognathism
Micromelia	Micromelia
Nephrocalcinosis	Nephrocalcinosis
Ollier disease	Ollier disease
Osseous ankylosis	Osseous ankylosis
Osteopenia	Osteopenia
Osteosclerosis	Osteosclerosis
Phosphate diabetes	Phosphate Diabetes
Proptosis	Exophthalmos
Rhizomelia	Rhizomelia
Rickets	Rickets		10375030
Sacral agenesis	Sacral agenesis
Spade-like hand	Spade-like hand
Talipes transversoplanus	Talipes transversoplanus
Visceral angiomatosis	Visceral angiomatosis