SLC9C2

Chr 1

solute carrier family 9 member C2 (putative)

Also known as: NHE11, SLC9A11

NCBI Gene: 284525 ENSG00000162753 UniProt: Q5TAH2 OMIM: 620338

This protein functions as a sodium/potassium-proton antiporter that regulates intracellular pH and ion transport across the plasma membrane. Mutations cause autosomal recessive primary ciliary dyskinesia with intellectual disability and microcephaly. The gene is highly constrained against loss-of-function variants (LOEUF 0.46), suggesting intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.000

Z-score 4.87

OE 0.31 (0.21–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.01Z-score

OE missense 0.76 (0.70–0.82)

429 obs / 563.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.31 (0.21–0.46)

0≤0.351.4

Missense OE?0.76 (0.70–0.82)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 18 / 58.1Missense obs/exp: 429 / 563.5Syn Z: 1.69

Background carrier burden — how many people carry a rare variant somewhere in SLC9C2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,154 rare PASS variants

Rare truncating (LoF)

1 in 1,100

166 rare PASS variants

Rare synonymous (reference)

1 in 100

399 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC9C2. 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 70	1 in 1,200
South Asian	~43k	1 in 59	1 in 430
Remaining (unassigned)	~30k	1 in 50	1 in 1,600
European (Finnish)	~27k	1 in 340	1 in 1,000
Admixed American	~22k	1 in 78	1 in 890
African / African American	~21k	1 in 81	1 in 1,200
East Asian	~20k	1 in 45	1 in 1,000
Ashkenazi Jewish	~13k	1 in 500	1 in 1,000
Middle Eastern	~2,884	1 in 47	≈ 1 in 710

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): 20 of 27 coding exons well covered in gnomAD exomes; exons 6, 9, 11, 15, 16 and 2 more marginal. Genomes: 26 of 27 (exon 22 below).? see exons ↓