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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.52

OE 0.90 (0.68–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.04 (0.96–1.13)

429 obs / 411.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.90 (0.68–1.23)

0≤0.351.4

Missense OE?1.04 (0.96–1.13)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 30 / 33.2Missense obs/exp: 429 / 411.5Syn Z: -0.24

Background carrier burden — how many people carry a rare variant somewhere in SLC12A8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 44

1,036 rare PASS variants

Rare truncating (LoF)

1 in 480

164 rare PASS variants

Rare synonymous (reference)

1 in 150

375 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC12A8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 54	1 in 590
South Asian	~43k	1 in 37	1 in 670
Remaining (unassigned)	~30k	1 in 41	1 in 290
European (Finnish)	~27k	1 in 220	1 in 1,000
Admixed American	~22k	1 in 43	1 in 370
African / African American	~21k	1 in 43	1 in 820
East Asian	~20k	1 in 48	1 in 680
Ashkenazi Jewish	~13k	1 in 99	1 in 1,000
Middle Eastern	~2,884	1 in 41	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 13.? see exons ↓