SLC24A1

Chr 15

solute carrier family 24 member 1

Also known as: CSNB1D, HsT17412, NCKX, NCKX1, RODX

NCBI Gene: 9187 ENSG00000074621 UniProt: O60721

This gene encodes a calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) and is critical for controlling calcium concentration in retinal rod and cone photoreceptor outer segments during light adaptation. Mutations cause autosomal recessive congenital stationary night blindness (complete), type 1D, affecting visual function from birth. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the potassium-dependent sodium/calcium exchanger protein family. The encoded protein plays an important role in sodium/calcium exchange in retinal rod and cone photoreceptors by mediating the extrusion of one calcium ion and one potassium ion in exchange for four sodium ions. Mutations in this gene may play a role in congenital stationary night blindness. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNight blindness, congenital stationary, 1D

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · inherited retinal dystrophy · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.000

Z-score 3.65

OE 0.36 (0.24–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.80Z-score

OE missense 0.79 (0.73–0.85)

471 obs / 594.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.24–0.57)

0≤0.351.4

Missense OE?0.79 (0.73–0.85)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 14 / 38.4Missense obs/exp: 471 / 594.7Syn Z: 0.78

Background carrier burden — how many people carry a rare variant somewhere in SLC24A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,312 rare PASS variants

Rare truncating (LoF)

1 in 740

183 rare PASS variants

Rare synonymous (reference)

1 in 85

502 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC24A1. 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 61	1 in 720
South Asian	~43k	1 in 40	1 in 570
Remaining (unassigned)	~30k	1 in 39	1 in 880
European (Finnish)	~27k	1 in 180	1 in 1,700
Admixed American	~22k	1 in 44	1 in 700
African / African American	~21k	1 in 36	1 in 470
East Asian	~20k	1 in 50	1 in 900
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 52	≈ 1 in 810

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 9.? see exons ↓