SLC12A7

protein-coding

solute carrier family 12 member 7, the group of Solute carrier family 12|MicroRNA protein coding host genes

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_006598.3

Inheritance

—

ClinVar variants

U:190B:28

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr5:1,050,384-1,112,063

External References & Databases

Ensembl (ENSG00000113504)

Transcript & Mutation Effects

hg38 • Region Span ~61.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

renal tubular acidosis, distal, 2, with progressive sensorineural hearing lossNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0009968

Submitter: ClinGen

No convincing evidence for a causal role for KCC4 in distal renal tubular acidosis or progressive nerve deafness has been reported. Although this gene-disease association is supported by a mouse model demonstrating renal acidosis and hearing loss in mutants (PMID: 27626380), no reports have directly implicated the gene in humans. This classification was approved by the ClinGen Tubulopathy GCEP on the meeting date 9/4/2024 (SOP Version 11).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC12A7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 188

not providedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006598.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	7 clinvar	7 clinvar	16
missense			180 clinvar	12 clinvar	2 clinvar	194
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	190	19	9	218

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006598.3	RefSeq	NP_006589.2	24	MANE Select
ENST00000264930.10	Ensembl	ENSP00000264930.5	24	MANE Select
ENST00000504576.2	Ensembl	ENSP00000489272.1	2	Standard
ENST00000513223.2	Ensembl	ENSP00000428854.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Collecting duct acid secretion - Homo sapiens (human)
Cation-coupled Chloride cotransporters
Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

ion transport
cell volume homeostasis
chemical synaptic transmission
chloride ion homeostasis
potassium ion homeostasis

Molecular Function

potassium:chloride symporter activity
protein kinase binding

Cellular Component

plasma membrane
integral component of plasma membrane
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264930
Coding exons: 24
Length: 61652
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125737
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	622	722	0.861	0.0000511	6998
Missense (PolyPhen)		204	273.74	0.74523		2514
Synonymous	-3.05	419	347	1.21	0.0000295	2221
Loss of Function	2.23	35	52.4	0.668	0.00000263	554

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00067	0.00065	rare
European (Non-Finnish)	0.00038	0.00036	rare
South Asian	0.00063	0.00059	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10913127}.;

Intolerance Scores

LoFtool: 0.0914
RVIS EVS: -2.79
RVIS percentile EVS: 0.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.224

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium