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. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.46

Clinical Summary— SLC9C2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

97 VUS of 126 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.79top 25%

GOF

0.76top 25%

LOF

0.1598th %ile

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

DNprediction above median

GOFprediction 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

126 submitted variants in ClinVar

ClinVar

Classification Summary

VUS97

Likely Benign15

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	97	97
Likely Benign	15	15
Benign	1	1
Total	113	113

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap SLC9C2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →