SLC24A5

Chr 15AR

solute carrier family 24 member 5

Also known as: JSX, NCKX5, OCA6, SHEP4

NCBI Gene: 283652 ENSG00000188467 UniProt: Q71RS6 OMIM: 609802

The protein functions as a calcium, potassium:sodium antiporter that transports calcium and potassium into melanosomes in exchange for cytoplasmic sodium, serving as the predominant sodium-calcium exchanger in melanocytes. Mutations cause oculocutaneous albinism type VI and variations in skin/hair/eye pigmentation, inherited in an autosomal recessive pattern. The gene shows high tolerance to loss-of-function variants (low constraint), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Skin/hair/eye pigmentation 4, fair/dark skin]MIM #113750

Albinism, oculocutaneous, type VIMIM #113750

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Albinism, oculocutaneous, type VI; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 0.97

OE 0.78 (0.53–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.95 (0.85–1.05)

256 obs / 270.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.53–1.16)

0≤0.351.4

Missense OE?0.95 (0.85–1.05)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 17 / 21.9Missense obs/exp: 256 / 270.7Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in SLC24A5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

657 rare PASS variants

Rare truncating (LoF)

1 in 690

108 rare PASS variants

Rare synonymous (reference)

1 in 290

256 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SLC24A5; this gene does not show strong loss-of-function constraint by this measure. 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 180	1 in 630
South Asian	~43k	1 in 160	1 in 1,000
Remaining (unassigned)	~30k	1 in 120	1 in 1,000
European (Finnish)	~27k	1 in 540	1 in 510
Admixed American	~22k	1 in 120	1 in 1,100
African / African American	~21k	1 in 72	1 in 2,300
East Asian	~20k	1 in 100	1 in 1,300
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 120	≈ 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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓