SLC12A3 (solute carrier family 12 member 3)

Gene

• Entrez ID: 6559
• Gene name: Solute carrier family 12 member 3
• Gene symbol: SLC12A3
• Synonyms (NCBI Gene): NCC, NCCT, TSC
• Chromosome: 16
• Chromosome location: 16q13
• Summary: This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman s

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs13306668	G>A,C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs28936387	T>C	Pathogenic	Missense variant, coding sequence variant
rs28936388	C>T	Pathogenic	Missense variant, coding sequence variant
rs34803727	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121909379	T>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121909380	G>A,T	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs121909382	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs121909383	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121909384	G>T	Pathogenic	Coding sequence variant, missense variant
rs121909385	T>C	Pathogenic	Coding sequence variant, missense variant
rs138977195	G>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs139743444	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs140012781	C>T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs140551719	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs142679083	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs145337602	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs146158333	C>A,G,T	Pathogenic	Coding sequence variant, missense variant
rs146632606	G>C	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs147200024	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs147901432	G>A	Pathogenic	Coding sequence variant, missense variant
rs148038173	C>T	Pathogenic	Coding sequence variant, missense variant
rs185927948	T>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs199849117	G>A	Pathogenic	Missense variant, coding sequence variant
rs200697179	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs200817545	A>C,G,T	Pathogenic	Missense variant, coding sequence variant
rs201255508	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs201555148	G>A	Pathogenic	Splice acceptor variant
rs201945662	G>A,C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs267607050	C>T	Pathogenic	Missense variant, coding sequence variant
rs267607051	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs369360334	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs370175770	G>A	Pathogenic	Missense variant, coding sequence variant
rs371443644	C>T	Pathogenic	Missense variant, coding sequence variant
rs373899077	C>T	Pathogenic	Missense variant, coding sequence variant
rs373901523	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs374055486	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs374163823	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs374182921	C>G,T	Pathogenic	Intron variant
rs374324018	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs377456965	A>C	Likely-pathogenic	Splice acceptor variant, intron variant
rs568513106	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs747139582	C>A,T	Likely-benign, pathogenic	Synonymous variant, stop gained, coding sequence variant
rs748547209	A>T	Likely-pathogenic	Missense variant, coding sequence variant
rs749098014	G>T	Pathogenic	Splice donor variant
rs750710315	CA>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs751409326	C>A	Pathogenic	Stop gained, coding sequence variant
rs752101663	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs753523115	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs754220610	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs754378340	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs755560627	G>T	Pathogenic	Splice acceptor variant
rs758035631	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs759377924	G>A	Pathogenic	Missense variant, coding sequence variant
rs759426055	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs759801838	GTACTG>-	Likely-pathogenic	Coding sequence variant, splice donor variant, intron variant
rs764220175	T>C	Likely-pathogenic	Splice donor variant
rs768527231	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs770513014	->TC	Likely-pathogenic	Coding sequence variant, frameshift variant
rs771701344	ACCAAGT>-	Pathogenic	Coding sequence variant, frameshift variant
rs775931992	C>T	Pathogenic	Coding sequence variant, missense variant
rs779160677	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs780299444	->CC	Pathogenic	Coding sequence variant, frameshift variant
rs886039753	C>T	Pathogenic	Stop gained, coding sequence variant
rs886039754	A>G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs886041108	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1064793879	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1215667472	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1274973729	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1347239469	G>C,T	Pathogenic	Splice donor variant
rs1366655422	G>A	Pathogenic	Stop gained, coding sequence variant
rs1441228030	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1555499123	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555499151	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1555499234	C>-	Pathogenic	Frameshift variant, intron variant, coding sequence variant
rs1555501437	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1555501632	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1596883431	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1596890176	T>A,C	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017508	hsa-miR-335-5p	Microarray	18185580
MIRT708972	hsa-miR-4780	HITS-CLIP	19536157
MIRT708971	hsa-miR-6780b-3p	HITS-CLIP	19536157
MIRT708970	hsa-miR-136-5p	HITS-CLIP	19536157
MIRT708969	hsa-miR-4469	HITS-CLIP	19536157
MIRT708968	hsa-miR-7113-3p	HITS-CLIP	19536157
MIRT708967	hsa-miR-4287	HITS-CLIP	19536157
MIRT708966	hsa-miR-4685-3p	HITS-CLIP	19536157
MIRT708965	hsa-miR-623	HITS-CLIP	19536157
MIRT708964	hsa-miR-515-5p	HITS-CLIP	19536157
MIRT708963	hsa-miR-519e-5p	HITS-CLIP	19536157
MIRT708962	hsa-miR-6867-3p	HITS-CLIP	19536157
MIRT708961	hsa-miR-676-3p	HITS-CLIP	19536157
MIRT708960	hsa-miR-629-3p	HITS-CLIP	19536157
MIRT708959	hsa-miR-2355-3p	HITS-CLIP	19536157
MIRT444616	hsa-miR-5680	PAR-CLIP	22100165
MIRT444615	hsa-miR-4329	PAR-CLIP	22100165
MIRT444614	hsa-miR-4524a-3p	PAR-CLIP	22100165
MIRT444613	hsa-miR-1273e	PAR-CLIP	22100165
MIRT444616	hsa-miR-5680	PAR-CLIP	22100165
MIRT444615	hsa-miR-4329	PAR-CLIP	22100165
MIRT444614	hsa-miR-4524a-3p	PAR-CLIP	22100165
MIRT444613	hsa-miR-1273e	PAR-CLIP	22100165
MIRT708972	hsa-miR-4780	HITS-CLIP	19536157
MIRT708971	hsa-miR-6780b-3p	HITS-CLIP	19536157
MIRT708970	hsa-miR-136-5p	HITS-CLIP	19536157
MIRT708969	hsa-miR-4469	HITS-CLIP	19536157
MIRT708968	hsa-miR-7113-3p	HITS-CLIP	19536157
MIRT708967	hsa-miR-4287	HITS-CLIP	19536157
MIRT708966	hsa-miR-4685-3p	HITS-CLIP	19536157
MIRT708965	hsa-miR-623	HITS-CLIP	19536157
MIRT708964	hsa-miR-515-5p	HITS-CLIP	19536157
MIRT708963	hsa-miR-519e-5p	HITS-CLIP	19536157
MIRT708962	hsa-miR-6867-3p	HITS-CLIP	19536157
MIRT708961	hsa-miR-676-3p	HITS-CLIP	19536157
MIRT708960	hsa-miR-629-3p	HITS-CLIP	19536157
MIRT708959	hsa-miR-2355-3p	HITS-CLIP	19536157
MIRT444616	hsa-miR-5680	PAR-CLIP	22100165
MIRT444615	hsa-miR-4329	PAR-CLIP	22100165
MIRT444614	hsa-miR-4524a-3p	PAR-CLIP	22100165
MIRT444613	hsa-miR-1273e	PAR-CLIP	22100165
MIRT444616	hsa-miR-5680	PAR-CLIP	22100165
MIRT444615	hsa-miR-4329	PAR-CLIP	22100165
MIRT444614	hsa-miR-4524a-3p	PAR-CLIP	22100165
MIRT444613	hsa-miR-1273e	PAR-CLIP	22100165
MIRT1351987	hsa-miR-1285	CLIP-seq
MIRT1351988	hsa-miR-1301	CLIP-seq
MIRT1351989	hsa-miR-1303	CLIP-seq
MIRT1351990	hsa-miR-3187-5p	CLIP-seq
MIRT1351991	hsa-miR-3614-5p	CLIP-seq
MIRT1351992	hsa-miR-3914	CLIP-seq
MIRT1351993	hsa-miR-4293	CLIP-seq
MIRT1351994	hsa-miR-4660	CLIP-seq
MIRT1351995	hsa-miR-4680-5p	CLIP-seq
MIRT1351996	hsa-miR-4698	CLIP-seq
MIRT1351997	hsa-miR-502-5p	CLIP-seq
MIRT1351998	hsa-miR-5047	CLIP-seq
MIRT1351999	hsa-miR-5096	CLIP-seq
MIRT1352000	hsa-miR-558	CLIP-seq
MIRT1352001	hsa-miR-596	CLIP-seq
MIRT1352002	hsa-miR-612	CLIP-seq
MIRT1352003	hsa-miR-651	CLIP-seq
MIRT1352004	hsa-miR-661	CLIP-seq
MIRT1351988	hsa-miR-1301	CLIP-seq
MIRT1351989	hsa-miR-1303	CLIP-seq
MIRT1351997	hsa-miR-502-5p	CLIP-seq
MIRT1351998	hsa-miR-5047	CLIP-seq
MIRT1553708	hsa-miR-3665	CLIP-seq
MIRT1553709	hsa-miR-4268	CLIP-seq
MIRT1553710	hsa-miR-657	CLIP-seq
MIRT2104308	hsa-miR-205	CLIP-seq
MIRT2104309	hsa-miR-3122	CLIP-seq
MIRT2104310	hsa-miR-3689a-3p	CLIP-seq
MIRT2104311	hsa-miR-3689c	CLIP-seq
MIRT2104312	hsa-miR-3913-5p	CLIP-seq
MIRT2104313	hsa-miR-4428	CLIP-seq
MIRT2104314	hsa-miR-508-5p	CLIP-seq
MIRT2328623	hsa-miR-24	CLIP-seq
MIRT2104309	hsa-miR-3122	CLIP-seq
MIRT2328624	hsa-miR-3124-3p	CLIP-seq
MIRT2104312	hsa-miR-3913-5p	CLIP-seq
MIRT2328625	hsa-miR-4284	CLIP-seq
MIRT2328626	hsa-miR-587	CLIP-seq
MIRT2394610	hsa-miR-1293	CLIP-seq
MIRT2104309	hsa-miR-3122	CLIP-seq
MIRT2104310	hsa-miR-3689a-3p	CLIP-seq
MIRT2104311	hsa-miR-3689c	CLIP-seq
MIRT2104312	hsa-miR-3913-5p	CLIP-seq
MIRT2394611	hsa-miR-4483	CLIP-seq
MIRT2623125	hsa-miR-1226	CLIP-seq
MIRT2623126	hsa-miR-3591-3p	CLIP-seq
MIRT2623127	hsa-miR-3675-3p	CLIP-seq
MIRT2623128	hsa-miR-4684-5p	CLIP-seq
MIRT2623129	hsa-miR-505	CLIP-seq
MIRT2623125	hsa-miR-1226	CLIP-seq
MIRT2623126	hsa-miR-3591-3p	CLIP-seq
MIRT2623127	hsa-miR-3675-3p	CLIP-seq
MIRT2623128	hsa-miR-4684-5p	CLIP-seq
MIRT2623129	hsa-miR-505	CLIP-seq
MIRT2690828	hsa-miR-548c-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	22406640
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	8670281
GO:0006811	Process	Ion transport	TAS
GO:0006814	Process	Sodium ion transport	ISS
GO:0006884	Process	Cell volume homeostasis	IBA	21873635
GO:0008511	Function	Sodium:potassium:chloride symporter activity	IBA	21873635
GO:0015081	Function	Sodium ion transmembrane transporter activity	ISS
GO:0015378	Function	Sodium:chloride symporter activity	TAS
GO:0015379	Function	Potassium:chloride symporter activity	IBA	21873635
GO:0016020	Component	Membrane	TAS	8670281
GO:0016324	Component	Apical plasma membrane	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IDA	21397062
GO:0016324	Component	Apical plasma membrane	ISS
GO:0035725	Process	Sodium ion transmembrane transport	IBA	21873635
GO:0035725	Process	Sodium ion transmembrane transport	ISS
GO:0055064	Process	Chloride ion homeostasis	IBA	21873635
GO:0055075	Process	Potassium ion homeostasis	IBA	21873635
GO:0055078	Process	Sodium ion homeostasis	IBA	21873635
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070062	Component	Extracellular exosome	IDA	21082674
GO:1902476	Process	Chloride transmembrane transport	IBA	21873635
GO:1990573	Process	Potassium ion import across plasma membrane	IBA	21873635

Other IDs

• MIM: 600968
• HGNC: 10912
• e!Ensembl: ENSG00000070915

Protein

• UniProt ID: P55017
• Protein name: Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter)
• Protein function: Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Als
• PDB: 7Y6I, 7YG0, 7YG1, 8FHN, 8FHO, 8FHP, 8FHQ, 8FHR, 8FHT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08403	AA_permease_N	45 → 116	Amino acid permease N-terminal	Family
  PF00324	AA_permease	141 → 647	Amino acid permease	Family
  PF03522	SLC12	655 → 810	Solute carrier family 12	Family
  PF03522	SLC12	795 → 1020	Solute carrier family 12	Family

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in the kidney (at protein level) (PubMed:29993276, PubMed:8812482). Localizes to the distal convoluted tubules (at protein level) (PubMed:29993276). Not detected in normal aorta, but abundantly expressed in fatt
• Sequence:

  MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNT
  IDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEG
  EAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVT
  VTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAE
  TVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANY
  LVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANI
  SGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLA
  CSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVF
  QCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSY
  ALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLL
  LYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVD
  FVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRG
  VQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGL
  NVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDG
  GLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDIN
  QNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLN
  EIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYC
  Q

• Sequence length: 1021

Pathways

KEGG:

Parathyroid hormone synthesis, secretion and action

Reactome:

Cation-coupled Chloride cotransporters
Defective SLC12A3 causes Gitelman syndrome (GS)

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Bartter syndrome	Bartter Disease	rs74315284, rs74315285, rs1389952796, rs74315286, rs74315287, rs74315288, rs74315289, rs121908144, rs121908145, rs121909137, rs121909138, rs121909131, rs121909132, rs121909133, rs121909134, rs121909135, rs779908241, rs121909136, rs104893706, rs137853158, rs137853159, rs774515747, rs1057519608, rs104894244, rs2135941091, rs104894245, rs104894253, rs104894254, rs104894250, rs104894251, rs397514729, rs863224858, rs765347751, rs878854404, rs878854405, rs878854406, rs878854407, rs875989852, rs886039870, rs779588655, rs201707868, rs1057516207, rs185212943, rs1057520300, rs1057520301, rs1057520302, rs1057520303, rs1057520304, rs370221310, rs779593707, rs377205432, rs1555466999, rs953686324, rs768286324, rs746509804, rs771232166, rs1566857461, rs373367600, rs1159737562, rs769554073, rs1570334344, rs201781905, rs377215024, rs755714542, rs1570340095, rs1570341086, rs1180658535, rs764247288, rs865973286, rs1007109925, rs1411280373, rs1380025163, rs758961147
Chondrocalcinosis	Calcium pyrophosphate deposition disease	rs121908405, rs28939080, rs121908407, rs2126640512, rs121908408, rs121908409, rs121908410
Diabetes mellitus	Diabetes Mellitus, Insulin-Dependent, Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs1362648752, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, 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, 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, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, 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, rs80356663, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, 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, rs371977235, 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, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261
Fanconi syndrome	Adult Fanconi syndrome	rs398124646
Hypertension	Hypertensive disease	rs13306026	18480177
Hypomagnesemia	Hypomagnesemia 2, renal	rs118203979, rs118203980, rs118203981, rs104893720, rs104893721, rs104893722, rs104893723, rs104893724, rs104893725, rs104893727, rs104893728, rs104893729, rs104893730, rs104893731, rs104893732, rs121908543, rs121909379, rs28936387, rs28936388, rs755560627, rs121909380, rs1347239469, rs121909382, rs121909383, rs2144723103, rs121909384, rs121909385, rs267607050, rs121918067, rs387906880, rs371443644, rs786205909, rs786205910, rs794726858, rs138977195, rs568513106, rs185927948, rs886041108, rs201255508, rs374163823, rs147901432, rs199974259, rs13306668, rs200697179, rs200817545, rs140012781, rs202114767, rs749098014, rs373899077, rs1553809654, rs201555148, rs140551719, rs775931992, rs771701344, rs199849117, rs1555499234, rs759801838, rs1555499151, rs1555501632, rs765256758, rs1253995767, rs138308105, rs1557551678, rs779160677, rs752101663, rs759426055, rs1563974797, rs759377924, rs1366655422, rs754378340, rs34803727, rs370175770, rs1557785499, rs1557785503, rs781629728, rs1570980551, rs768527231, rs201945662, rs145337602, rs1596890176, rs139743444, rs780299444, rs1596883431, rs751409326, rs1274973729, rs146158333, rs747139582, rs753523115, rs148038173, rs374182921, rs761242621, rs751959432, rs1577430815, rs758035631, rs369360334, rs374055486, rs750710315, rs770513014, rs758683818, rs746818109, rs747249619, rs771326058, rs746623621, rs781209989, rs772241737
Kidney disease	Kidney Diseases	rs74315342, rs749740335, rs757649673, rs112417755, rs35138315	21865292
Mitochondrial encephalopathy	Mitochondrial encephalopathy	rs199474671, rs199474672, rs776019250, rs35135520
Parathyroid adenoma	Parathyroid Adenoma	rs587776557
Ventricular fibrillation	Ventricular Fibrillation	rs137854604, rs587782933, rs190140598

Unknown
Disease term	Disease name	Evidence	References	Source
Breast Cancer	Breast Cancer	Importantly, breast cancer patients bearing PRC2 LOF mutations displayed significantly worse prognosis compared with PRC2 wild-type patients		GWAS, CBGDA
Metabolic Syndrome	Metabolic Syndrome			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
Acidosis Renal Tubular	Associate	39210578
Albuminuria	Associate	32634861
Alkalosis	Associate	12911530, 18520105, 26770037, 32758178, 34046503, 37327293
Antiphospholipid Syndrome	Associate	27803420
Arachnoiditis	Associate	22568564
Bartter Syndrome	Associate	21631963, 32758178
Bartter syndrome type 3	Associate	33807568
Bartter Syndrome Type 3 with Hypocalciuria	Associate	18520105, 26770037, 27783806, 29378538, 32758178
Brain Ischemia	Associate	22568564
Breast Neoplasms	Associate	35113855
Calcinosis	Associate	30340552
Carcinoma Renal Cell	Associate	32144299, 34449964, 37657024, 38290445, 39348357
Cerebrovascular Disorders	Associate	29661184
Chondrocalcinosis	Associate	32292023, 33807568
Coronary Artery Disease	Associate	31480784
Diabetes Mellitus	Associate	28446151, 34348722
Diabetes Mellitus Type 2	Associate	17653210, 32600448, 32634861, 32702863, 34348722, 34617250, 37327293
Diabetic Nephropathies	Associate	17653210, 32634861
Disease	Associate	18391953
Dwarfism Pituitary	Associate	31577716
Dyslipidemias	Associate	31480784
Essential Hypertension	Associate	18362449, 21644207, 28274929, 29808706
Fractures Bone	Associate	33542107
Genetic Diseases Inborn	Associate	33542107
Gitelman Syndrome	Associate	11168953, 12008755, 12172059, 12472765, 12911530, 14675033, 15198479, 15206555, 16543691, 18520105, 21051746, 21415153, 21628937, 21631963, 21757836, 21970949, 22214629, 22728489, 23328711, 23345488, 23756661, 24162365, 24965226, 25060058, 25273610, 26306968, 26770037, 27173320, 27582097, 27783806, 27803420, 28003083, 28125972, 28446151, 28700713, 29378538, 29808706, 30305584, 30340552, 30945685, 30999883, 31105122, 31285285, 31305454, 31398183, 31577716, 31916727, 32292023, 32702863, 32758178, 32758191, 33328404, 33370877, 33462018, 33542107, 33735743, 33807568, 34046503, 34348722, 34607911, 34617250, 35131782, 35148746, 35327948, 35509038, 35545335, 35883046, 36302598, 36597580, 37327293, 37537162, 37657006, 38630244, 39183425, 39210578, 8900229, 9260778, 9734597
Gitelman Syndrome	Inhibit	31586298
Glomerulonephritis Membranous	Associate	35883046
Growth Disorders	Associate	14675033
Hashimoto Disease	Associate	34046503
Hereditary Breast and Ovarian Cancer Syndrome	Associate	35113855
Hypercalciuria	Associate	32758178
Hypercholesterolemia	Associate	31480784
Hyperglycemia	Associate	32702863
Hyperparathyroidism Primary	Associate	39183425
Hyperphosphatemia	Associate	31305454
Hypertension	Associate	18391953, 20555294, 21644207, 23328711, 24266877, 26336164, 26751802, 29661184, 30248150, 37065732, 38634133
Hypertriglyceridemia	Associate	31480784
Hypokalemia	Associate	18520105, 25273610, 27783806, 30340552, 32758178, 34046503, 34617250, 37657006, 39183425
Hypoparathyroidism	Associate	31305454
Hypotension	Associate	18391953
Hypovolemia	Associate	34046503
Islet cell tumor syndrome	Associate	35627249
Kidney Calculi	Associate	32758178
Kidney Diseases	Associate	34046503, 37248651
Kidney Failure Chronic	Associate	35327948
Long QT Syndrome	Associate	30305584
Lung Diseases	Associate	35113855
Lung Neoplasms	Associate	35113855
Mitochondrial Diseases	Associate	34607911
Myocardial Infarction	Associate	20031564
Neoplasms	Associate	32144299, 38290445
Nephrolithiasis	Associate	12472765
Nephrotic Syndrome	Associate	35883046
Nervous System Diseases	Associate	32292023
Obesity	Associate	25768006
Pheochromocytoma	Associate	35627249
Pre Eclampsia	Associate	30248150
Prostatic Neoplasms	Associate	35113855
Prostatitis	Associate	35113855
Proteinuria	Associate	30340552, 34046503
Pseudotumor Cerebri	Associate	21757836
Renal Insufficiency	Associate	24162365
Renal Insufficiency Chronic	Associate	34617250, 40262004
SeSAME syndrome	Associate	32292023
Syndrome	Associate	35627249, 37058043, 37657006
Taste Disorders	Associate	31305454, 35327948
Tetany	Associate	37058043
Uveal melanoma	Associate	36925204
Vasospasm Intracranial	Associate	22568564
Wilms Tumor	Associate	37904849