SLC12A7

Summary

SLC12A7 (solute carrier family 12 member 7, HGNC:10915) is a protein-coding gene on chromosome 5p15.33, encoding Solute carrier family 12 member 7 (Q9Y666). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling.

Enables protein kinase binding activity. Predicted to be involved in several processes, including chloride ion homeostasis; monoatomic ion transmembrane transport; and potassium ion homeostasis. Part of protein-containing complex.

Source: NCBI Gene 10723 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (No Known Disease Relationship, ClinGen)
• GWAS associations: 62
• Clinical variants (ClinVar): 305 total
• MANE Select transcript: NM_006598

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10915
Approved symbol	SLC12A7
Name	solute carrier family 12 member 7
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	KCC4, DKFZP434F076
Ensembl gene	ENSG00000113504
Ensembl biotype	protein_coding
OMIM	604879
Entrez	10723

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000264930, ENST00000504576, ENST00000510943, ENST00000513223, ENST00000514994, ENST00000634447, ENST00000851006, ENST00000902220, ENST00000922388, ENST00000945163

RefSeq mRNA: 1 — MANE Select: NM_006598 NM_006598

CCDS: CCDS34129

Canonical transcript exons

ENST00000264930 — 24 exons

Exon	Start	End
ENSE00001134885	1065283	1065478
ENSE00001134894	1073633	1073801
ENSE00001134958	1081577	1081744
ENSE00001134965	1083745	1083956
ENSE00001134974	1085232	1085473
ENSE00001135012	1093533	1093655
ENSE00001135020	1094154	1094248
ENSE00001229352	1064083	1064252
ENSE00001505480	1078701	1078758
ENSE00001606424	1063844	1063975
ENSE00001631677	1053349	1053482
ENSE00001632022	1074567	1074671
ENSE00001710218	1057471	1057649
ENSE00001719438	1088982	1089128
ENSE00001743994	1077833	1078007
ENSE00001751144	1076694	1076812
ENSE00001760248	1086903	1087033
ENSE00001780047	1088306	1088360
ENSE00001795588	1076138	1076236
ENSE00002042397	1050384	1052451
ENSE00002055502	1111868	1112063
ENSE00003575187	1075371	1075490
ENSE00003601396	1060344	1060451
ENSE00003659989	1079398	1079496

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7123 / max 566.9519, expressed in 1615 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60755	6.0763	1508
60754	5.8144	1344
60749	0.9451	67
60753	0.5588	287
60748	0.1896	34
60746	0.0646	10
60747	0.0636	12

Top tissues by expression

140 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.80	gold quality
heart left ventricle	UBERON:0002084	95.87	gold quality
metanephros cortex	UBERON:0010533	95.78	gold quality
right lobe of liver	UBERON:0001114	95.07	gold quality
gall bladder	UBERON:0002110	94.88	gold quality
duodenum	UBERON:0002114	94.42	gold quality
cortex of kidney	UBERON:0001225	93.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.05	gold quality
heart	UBERON:0000948	93.04	gold quality
right atrium auricular region	UBERON:0006631	92.89	gold quality
adult mammalian kidney	UBERON:0000082	92.88	gold quality
small intestine	UBERON:0002108	92.75	gold quality
liver	UBERON:0002107	92.68	gold quality
body of stomach	UBERON:0001161	92.46	gold quality
spleen	UBERON:0002106	92.01	gold quality
granulocyte	CL:0000094	91.85	gold quality
right testis	UBERON:0004534	91.59	gold quality
right lobe of thyroid gland	UBERON:0001119	91.58	gold quality
left testis	UBERON:0004533	91.47	gold quality
transverse colon	UBERON:0001157	91.37	gold quality
upper lobe of left lung	UBERON:0008952	91.14	gold quality
left lobe of thyroid gland	UBERON:0001120	91.12	gold quality
kidney	UBERON:0002113	90.79	gold quality
thyroid gland	UBERON:0002046	90.75	gold quality
testis	UBERON:0000473	90.61	gold quality
stomach	UBERON:0000945	90.57	gold quality
mucosa of transverse colon	UBERON:0004991	90.52	gold quality
body of pancreas	UBERON:0001150	90.50	gold quality
fundus of stomach	UBERON:0001160	90.48	gold quality
monocyte	CL:0000576	90.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.73
E-GEOD-137537	yes	5.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting SLC12A7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1283	99.69	72.42	3009

Literature-anchored findings (GeneRIF, showing 14)

• Mice lacking SLC12A7 function suffer from deafness and renal metabolic acidosis. The phenotype suggests a function in inner ear potassium recycling. A function in the proton secreting alpha-intercalating cells of the kidney is shown. (PMID:11976689)
• human osteoblasts express functional K-Cl cotransporters in their cell membrane that seem to be able to induce the indirect activation of volume-sensitive Cl- channels by KCl through an increase in the intracellular ions, water influx and cell swelling. (PMID:12637262)
• KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers. (PMID:15262997)
• Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression. (PMID:17133354)
• KCC4 and H+,K+-ATPase are the main machineries for basal HCl secretion in the apical canalicular membrane of the resting parietal cell. They also may contribute in part to massive acid secretion in the stimulated state. (PMID:18984587)
• In the metastatic cancer tissues, KCC4 colocalizes with IGF-I or EGF. (PMID:19887603)
• analysis of differences in large extracellular loop between the K(+)-Cl(-) cotransporters KCC2 and KCC4 (PMID:20516068)
• The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. (PMID:21613606)
• KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity (PMID:21733850)
• Negative stain transmission electron microscopy and single particle analysis of KCC4 and the aquaporin-1 AQP1 water channel, revealed the expected quaternary structures within homogeneous preparations, and thus correct protein folding and assembly. (PMID:21760919)
• SLC12A7 gene amplification and overexpression occurs frequently in adrenocortical carcinoma and may play a role in adrenocortical carcinoma tumorigenesis. (PMID:26454676)
• SLC12A7 alters adrenocortical carcinoma cell adhesion properties to promote an aggressive invasive behavior (PMID:29884238)
• The IGF1 gene was amplified in 9 of 19 ACC samples, similar to findings in The Cancer Genome Atlas database. The IGF1 overexpression was observed in 5 samples and was associated with SLC12A7 overexpression and non-functional, early-stage tumors (p < 0.05). endogenous overexpression and silencing of SLC12A7 significantly altered IGF1 and IGF1R expression without impacting other IGFs. (PMID:31034883)
• SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus. (PMID:31393094)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc12a7b	ENSDARG00000062058
danio_rerio	slc12a7a	ENSDARG00000073756
mus_musculus	Slc12a7	ENSMUSG00000017756
rattus_norvegicus	Slc12a7	ENSRNOG00000016372
drosophila_melanogaster	CG10413	FBGN0032689
drosophila_melanogaster	Ncc69	FBGN0036279
drosophila_melanogaster	kcc	FBGN0261794
caenorhabditis_elegans		WBGENE00012543
caenorhabditis_elegans		WBGENE00019205
caenorhabditis_elegans		WBGENE00020207

Paralogs (8): SLC12A2 (ENSG00000064651), SLC12A3 (ENSG00000070915), SLC12A1 (ENSG00000074803), SLC12A4 (ENSG00000124067), SLC12A5 (ENSG00000124140), SLC12A6 (ENSG00000140199), SLC12A9 (ENSG00000146828), SLC12A8 (ENSG00000221955)

Protein

Protein identifiers

Solute carrier family 12 member 7 — Q9Y666 (reviewed: Q9Y666)

Alternative names: Electroneutral potassium-chloride cotransporter 4, K-Cl cotransporter 4

All UniProt accessions (4): A0A0U1RR10, A0A0U1RR18, Q9Y666, H0YB78

UniProt curated annotations — full annotation on UniProt →

Function. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May mediate K(+) uptake into Deiters’ cells in the cochlea and contribute to K(+) recycling in the inner ear. Important for the survival of cochlear outer and inner hair cells and the maintenance of the organ of Corti. May be required for basolateral Cl(-) extrusion in the kidney and contribute to renal acidification.

Subunit / interactions. Homodimer; adopts a domain-swap conformation at the scissor helices connecting the transmembrane domain and C-terminal domain. Heterodimer with K-Cl cotransporter SLC12A5.

Subcellular location. Cell membrane.

Tissue specificity. Detected in muscle, brain, lung, heart and kidney.

Activity regulation. Activated by N-ethylmaleimide (NEM). Inhibited by furosemide, DIDS and bumetanide. The inhibition is much stronger in the presence of 50 mM K(+) in the uptake medium. Inhibited by DIOA. Inhibited by WNK3.

Similarity. Belongs to the SLC12A transporter family. K/Cl co-transporter subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y666-1	1	yes
Q9Y666-2	2

RefSeq proteins (1): NP_006589* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000076	KCL_cotranspt	Family
IPR004841	AA-permease/SLC12A_dom	Domain
IPR004842	SLC12A_fam	Family
IPR018491	SLC12_C	Domain

Pfam: PF00324, PF03522

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) + chloride(in) = K(+)(out) + chloride(out) (RHEA:72427)

UniProt features (116 total): helix 40, strand 23, transmembrane region 12, topological domain 10, binding site 9, modified residue 5, turn 5, region of interest 2, glycosylation site 2, disulfide bond 2, splice variant 2, chain 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7D99	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y666-F1	80.86	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 131; 132; 135; 429; 429; 432; 433; 434; 589

Post-translational modifications (5): 30, 50, 62, 973, 980

Disulfide bonds (2): 308–323, 343–352

Glycosylation sites (2): 312, 360

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-426117	Cation-coupled Chloride cotransporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 265 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, IRF7_01, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_CHLORIDE_TRANSPORT, ROZANOV_MMP14_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (11): monoatomic ion transport (GO:0006811), cell volume homeostasis (GO:0006884), chemical synaptic transmission (GO:0007268), chloride ion homeostasis (GO:0055064), potassium ion homeostasis (GO:0055075), cellular response to glucose stimulus (GO:0071333), potassium ion transmembrane transport (GO:0071805), chloride transmembrane transport (GO:1902476), potassium ion import across plasma membrane (GO:1990573), potassium ion transport (GO:0006813), transmembrane transport (GO:0055085)

GO Molecular Function (5): potassium:chloride symporter activity (GO:0015379), protein kinase binding (GO:0019901), symporter activity (GO:0015293), chloride:monoatomic cation symporter activity (GO:0015377), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): plasma membrane (GO:0005886), protein-containing complex (GO:0032991), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
inorganic ion homeostasis	2
regulation of cell size	1
cellular homeostasis	1
anterograde trans-synaptic signaling	1
monoatomic anion homeostasis	1
monoatomic cation homeostasis	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
metal ion transport	1
cellular process	1
potassium ion transmembrane transporter activity	1
chloride:monoatomic cation symporter activity	1
kinase binding	1
secondary active transmembrane transporter activity	1
chloride transmembrane transporter activity	1
monoatomic anion:monoatomic cation symporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
cellular_component	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC12A7	STK39	Q9UEW8	655
SLC12A7	WNK3	Q9BYP7	636
SLC12A7	WNK4	Q96J92	556
SLC12A7	EZR	P15311	555
SLC12A7	WNK1	P54963	555
SLC12A7	OXSR1	O95747	519
SLC12A7	SLC4A5	Q9BY07	479
SLC12A7	CCT5	P48643	452
SLC12A7	MPDZ	O75970	450
SLC12A7	TAS2R1	Q9NYW7	432
SLC12A7	GLDC	P23378	431
SLC12A7	MED10	Q9BTT4	422
SLC12A7	LNX1	Q8TBB1	420
SLC12A7	KCNJ1	P48048	420
SLC12A7	TYRP1	P17643	412

IntAct

111 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FSHR	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
SLC12A4	CLGN	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
NRN1	SLC1A1	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
SLC12A4	JAGN1	psi-mi:“MI:0914”(association)	0.530
SLC12A4	LGALS3	psi-mi:“MI:0914”(association)	0.530
MGA	SLC12A7	psi-mi:“MI:0915”(physical association)	0.400
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
C5AR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
LGALS9	PODXL	psi-mi:“MI:0914”(association)	0.350
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.350
LGALS9C	LGALS9	psi-mi:“MI:0914”(association)	0.350
SLC17A2	PSMD11	psi-mi:“MI:0914”(association)	0.350
PTGIR	GPAA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (193): SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Proximity Label-MS), SLC12A7 (Proximity Label-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS)

ESM2 similar proteins: A0A078H868, A0AAS4, A0JP80, A6X919, D4AD75, O70536, O77760, O77761, P23913, P35610, P53439, P56079, Q14739, Q20696, Q20735, Q28677, Q2PZI1, Q4JM44, Q4R763, Q5R7H4, Q5RK27, Q60457, Q61263, Q63632, Q63633, Q657W3, Q6AX73, Q6Z0E2, Q7T3T4, Q7TSX5, Q86VZ5, Q8IWX5, Q8NHU3, Q8VCQ6, Q91V14, Q924N4, Q965Q4, Q9D4B1, Q9FJB4, Q9H2X9

Diamond homologs: Q09573, Q28677, Q2UVJ5, Q5RK27, Q63632, Q63633, Q6Z0E2, Q7YRU6, Q91V14, Q924N4, Q9H2X9, Q9JIS8, Q9UHW9, Q9UP95, Q9WVL3, Q9Y666, Q0VGW6, Q657W3, A0AV02, Q8VI23, Q9BXP2, Q66HR0, P38329

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
WNK3	“down-regulates activity”	SLC12A7	phosphorylation
SLC12A7	“down-regulates quantity”	chloride	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

305 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	20
Benign	73

Top pathogenic / likely-pathogenic (0)

SpliceAI

6489 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1063841:CA:C	donor_loss	1.0000
5:1063842:A:AC	donor_gain	1.0000
5:1063842:AC:A	donor_gain	1.0000
5:1063843:C:CC	donor_gain	1.0000
5:1063843:C:CT	donor_loss	1.0000
5:1063843:CC:C	donor_gain	1.0000
5:1063843:CCAT:C	donor_gain	1.0000
5:1063852:C:CT	donor_gain	1.0000
5:1063853:C:CT	donor_gain	1.0000
5:1063857:TCC:T	donor_gain	1.0000
5:1063971:CACAC:C	acceptor_gain	1.0000
5:1063973:CAC:C	acceptor_gain	1.0000
5:1063973:CACCT:C	acceptor_loss	1.0000
5:1063976:C:CA	acceptor_loss	1.0000
5:1063976:C:CC	acceptor_gain	1.0000
5:1063977:T:A	acceptor_loss	1.0000
5:1064079:CCA:C	donor_loss	1.0000
5:1064080:CA:C	donor_loss	1.0000
5:1064081:A:AT	donor_loss	1.0000
5:1064082:C:CG	donor_loss	1.0000
5:1065278:CCTA:C	donor_loss	1.0000
5:1065279:CTACC:C	donor_loss	1.0000
5:1065281:A:AC	donor_gain	1.0000
5:1065281:AC:A	donor_gain	1.0000
5:1065281:ACCC:A	donor_loss	1.0000
5:1065282:C:CA	donor_loss	1.0000
5:1065282:C:CC	donor_gain	1.0000
5:1065282:CC:C	donor_gain	1.0000
5:1065282:CCCA:C	donor_gain	1.0000
5:1065295:T:TA	donor_gain	1.0000

AlphaMissense

7086 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1076164:C:A	W607C	1.000
5:1076164:C:G	W607C	1.000
5:1079433:C:T	G454E	1.000
5:1079434:C:A	G454W	1.000
5:1079463:A:G	L444P	1.000
5:1079463:A:T	L444H	1.000
5:1079475:C:G	R440P	1.000
5:1079484:C:T	G437D	1.000
5:1079485:C:G	G437R	1.000
5:1088326:G:T	A175D	1.000
5:1089087:G:C	C128W	1.000
5:1052441:A:C	F1057L	0.999
5:1052441:A:T	F1057L	0.999
5:1052443:A:G	F1057L	0.999
5:1063972:A:G	W871R	0.999
5:1063972:A:T	W871R	0.999
5:1064145:A:G	W849R	0.999
5:1064145:A:T	W849R	0.999
5:1074656:C:A	W661C	0.999
5:1074656:C:G	W661C	0.999
5:1075474:C:G	G622R	0.999
5:1076166:A:G	W607R	0.999
5:1076166:A:T	W607R	0.999
5:1076206:G:C	N593K	0.999
5:1076206:G:T	N593K	0.999
5:1077876:A:G	L529P	0.999
5:1077894:A:G	L523P	0.999
5:1077896:G:C	S522R	0.999
5:1077896:G:T	S522R	0.999
5:1077898:T:G	S522R	0.999

dbSNP variants (sampled 300 via entrez): RS1000015587 (5:1109526 C>A,G,T), RS1000041260 (5:1054436 C>A,G,T), RS1000057494 (5:1083303 C>T), RS1000065022 (5:1139443 C>T), RS1000072327 (5:1054578 C>T), RS1000137971 (5:1066104 C>T), RS1000227874 (5:1069308 A>G), RS1000247102 (5:1126892 A>G,T), RS1000252990 (5:1104891 C>T), RS1000320048 (5:1097347 G>A,C), RS1000372619 (5:1050968 C>T), RS1000423081 (5:1079822 C>T), RS1000452308 (5:1131157 G>A), RS1000493961 (5:1109495 G>A,C), RS1000500070 (5:1073961 A>G)

Disease associations

OMIM: gene MIM:604879 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss	No Known Disease Relationship	UD

Mondo (1): renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (MONDO:0009968)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST000582_5	Mean corpuscular hemoglobin concentration	5.000000e-10
GCST002553_8	Pancreatic cancer	1.000000e-13
GCST004599_96	Mean platelet volume	3.000000e-26
GCST004601_60	Red blood cell count	5.000000e-13
GCST004602_32	Mean corpuscular volume	2.000000e-30
GCST004605_71	Mean corpuscular hemoglobin concentration	2.000000e-12
GCST004605_72	Mean corpuscular hemoglobin concentration	2.000000e-22
GCST004613_134	Sum neutrophil eosinophil counts	1.000000e-09
GCST004614_153	Granulocyte count	1.000000e-09
GCST004616_5	Platelet distribution width	1.000000e-18
GCST004620_147	Sum basophil neutrophil counts	3.000000e-09
GCST004621_151	Red cell distribution width	4.000000e-32
GCST004621_152	Red cell distribution width	5.000000e-43
GCST004621_153	Red cell distribution width	2.000000e-53
GCST004621_154	Red cell distribution width	1.000000e-21
GCST004621_155	Red cell distribution width	3.000000e-25
GCST004621_156	Red cell distribution width	1.000000e-44
GCST004621_157	Red cell distribution width	7.000000e-121
GCST004626_43	Myeloid white cell count	5.000000e-10
GCST004629_64	Neutrophil count	3.000000e-09
GCST004744_73	Lung adenocarcinoma	1.000000e-07
GCST004748_45	Lung cancer	8.000000e-06
GCST005992_6	Mean corpuscular hemoglobin concentration	2.000000e-41
GCST006804_114	Red cell distribution width	2.000000e-17
GCST006804_158	Red cell distribution width	1.000000e-09
GCST006804_18	Red cell distribution width	1.000000e-78
GCST006804_98	Red cell distribution width	1.000000e-21
GCST008152_159	Weight	7.000000e-06
GCST010083_323	Hemoglobin levels	2.000000e-08
GCST010320_105	PR interval	4.000000e-19

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004305	erythrocyte count
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0007984	platelet component distribution width
EFO:0005090	basophil count
EFO:0009188	Red cell distribution width
EFO:0004338	body weight
EFO:0004462	PR interval
EFO:0007885	JT interval
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562897	Renal Tubular Acidosis, Distal, with Progressive Nerve Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC12 family of cation-coupled chloride transporters

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	5
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Cyclosporine	decreases methylation, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
nickel sulfate	increases expression	1
1-hydroxypyrene	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
candoxin	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Arsenicals	increases methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Diazinon	increases methylation	1
Methotrexate	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4HQ	HCT116-SLC12A7-KO-c13	Cancer cell line	Male
CVCL_D4HR	HCT116-SLC12A7-KO-c22	Cancer cell line	Male
CVCL_TL55	HAP1 SLC12A7 (-) 1	Cancer cell line	Male
CVCL_TL56	HAP1 SLC12A7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.