SLC12A8

Chr 3

solute carrier family 12 member 8

Also known as: CCC9

NCBI Gene: 84561 ENSG00000221955 UniProt: A0AV02 OMIM: 611316

This cation/chloride cotransporter controls keratinocyte proliferation and has been implicated as a candidate gene for psoriasis susceptibility. The gene is not loss-of-function intolerant (pLI near zero, LOEUF >1), suggesting that complete loss of function may be tolerated. Based on the available data, this gene appears to primarily affect skin rather than the nervous system.

OMIM ResearchSummary from RefSeq, UniProt

This gene is thought to be a candidate for psoriasis susceptibility. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Sep 2010]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— SLC12A8

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ClinVar Variants

121 VUS of 160 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.74top 25%

GOF

0.84top 5%

LOF

0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

VUS121

Likely Benign8

121

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	121	121
Likely Benign	8	8
Benign	0	0
Total	129	129

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap SLC12A8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →