SLC24A2

Chr 9

solute carrier family 24 member 2

Also known as: NCKX2

NCBI Gene: 25769ENSG00000155886UniProt: Q9UI40

This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

214
ClinVar variants
75
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— SLC24A2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
75 Pathogenic / Likely Pathogenic· 107 VUS of 214 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.006
Z-score 3.26
OE 0.33 (0.20–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.21Z-score
OE missense 1.03 (0.95–1.13)
365 obs / 353.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.20–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.95–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 9 / 27.4Missense obs/exp: 365 / 353.8Syn Z: -2.02

ClinVar Variant Classifications

214 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic5
VUS107
Likely Benign16
Benign1
70
Pathogenic
5
Likely Pathogenic
107
VUS
16
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
70
0
70
Likely Pathogenic
0
0
5
0
5
VUS
0
95
12
0
107
Likely Benign
0
6
10
0
16
Benign
0
0
1
0
1
Total0101980199

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC24A2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic susceptibility and validation of angiographic patterns in Takayasu arteritis.
Casares-Marfil D et al.·J Autoimmun
2025
Pyrolae herba alleviates cognitive impairment via hippocampal TREM2 signaling modulating neuroinflammation and neurogenesis in lipopolysaccharide-treated mice.
Sun Y et al.·J Ethnopharmacol
2024
Mutated alleles of the rod and cone Na-Ca+K-exchanger genes in patients with retinal diseases.
Sharon D et al.·Invest Ophthalmol Vis Sci
2002Cohort
A SLC24A2 Gene Variant Uncovered in Pancreatic Ductal Adenocarcinoma by Whole Exome Sequencing.
Wang L et al.·Tohoku J Exp Med
2017
Genetic Effects on the Correlation Structure of CVD Risk Factors: Exome-Wide Data From a Ghanaian Population.
Kodaman N et al.·Glob Heart
2017Review
Identification of novel variants for complicating cardiac disease in the scrub typhus infection using whole genome sequencing.
Kang KW et al.·Korean J Intern Med
2023
Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p.
Yoshioka H et al.·Int J Mol Sci
2021
Associations between sun sensitive pigmentary genes and serum prostate specific antigen levels.
Nair-Shalliker V et al.·PLoS One
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools