SLC9A1
Chr 1ARsolute carrier family 9 member A1
Also known as: APNH, LIKNS, NHE-1, NHE1, PPP1R143
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.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
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.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SLC9A1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools