SLC9A1

Chr 1AR

solute carrier family 9 member A1

Also known as: APNH, LIKNS, NHE-1, NHE1, PPP1R143

NCBI Gene: 6548 ENSG00000090020 UniProt: P19634 OMIM: 107310

The protein is a plasma membrane sodium/hydrogen antiporter that maintains intracellular pH homeostasis and cell volume by exchanging intracellular protons for extracellular sodium ions. Mutations cause Lichtenstein-Knorr syndrome, which follows autosomal recessive inheritance. The gene shows high constraint against loss-of-function variants (LOEUF 0.375), indicating that heterozygous loss-of-function mutations are likely tolerated while biallelic variants cause disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lichtenstein-Knorr syndromeMIM #616291

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Lichtenstein-Knorr syndrome · AR · ClinGen 2025

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

0.38

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.38LOEUF

pLI 0.790

Z-score 4.22

OE 0.19 (0.10–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.55Z-score

OE missense 0.56 (0.51–0.62)

292 obs / 519.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.19 (0.10–0.38)

0≤0.351.4

Missense OE?0.56 (0.51–0.62)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 31.6Missense obs/exp: 292 / 519.8Syn Z: 1.66

Background carrier burden — how many people carry a rare variant somewhere in SLC9A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

808 rare PASS variants

Rare truncating (LoF)

1 in 2,100

74 rare PASS variants

Rare synonymous (reference)

1 in 73

472 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC9A1. 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 87	1 in 1,800
South Asian	~43k	1 in 97	1 in 3,500
Remaining (unassigned)	~30k	1 in 88	1 in 4,100
European (Finnish)	~27k	1 in 130	≈ 1 in 27,000
Admixed American	~22k	1 in 94	1 in 1,200
African / African American	~21k	1 in 78	≈ 1 in 15,000
East Asian	~20k	1 in 93	≈ 1 in 5,800
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 80	≈ 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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓