SLC24A3

Chr 20

solute carrier family 24 member 3

Also known as: NCKX3

NCBI Gene: 57419ENSG00000185052UniProt: Q9HC58

The SLC24A3 protein is a plasma membrane calcium, potassium:sodium antiporter that transports 1 calcium and 1 potassium ion in exchange for 4 sodium ions, maintaining intracellular calcium homeostasis and supporting electrical conduction. Mutations cause autosomal recessive congenital stationary night blindness, a retinal disorder affecting vision in low-light conditions. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
24
P/LP submissions
0%
P/LP missense
0.35
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SLC24A3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 85 VUS of 124 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
0.35LOEUF
pLI 0.879
Z-score 4.39
OE 0.18 (0.10–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.09Z-score
OE missense 0.70 (0.63–0.77)
264 obs / 378.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.18 (0.10–0.35)
0≤0.351.4
Missense OE0.70 (0.63–0.77)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 6 / 33.3Missense obs/exp: 264 / 378.3Syn Z: 0.08
DN
0.6647th %ile
GOF
0.73top 25%
LOF
0.4332th %ile

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.

GOFprediction above median
DNprediction 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

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS85
Likely Benign2
Benign1
22
Pathogenic
2
Likely Pathogenic
85
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
82
3
0
85
Likely Benign
0
1
0
1
2
Benign
0
0
0
1
1
Total083272112

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC24A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients