OCA2

Chr 15

OCA2 melanosomal transmembrane protein

Also known as: BEY, BEY1, BEY2, BOCA, D15S12, EYCL, EYCL2, EYCL3

NCBI Gene: 4948 ENSG00000104044 UniProt: Q04671

The protein functions as an integral membrane transporter that regulates melanosomal pH through chloride transport, enabling optimal tyrosinase activity required for melanin synthesis and pigmentation. Mutations cause oculocutaneous albinism type II and brown oculocutaneous albinism, conditions characterized by reduced melanin production affecting skin, hair, and eye pigmentation from birth. This gene follows autosomal recessive inheritance and is not highly constrained against loss-of-function variation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAlbinism, oculocutaneous, 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · oculocutaneous albinism type 2 · AR · ClinGen 2021

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

0.86

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — OCA2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.32

OE 0.62 (0.46–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.83Z-score

OE missense 1.11 (1.03–1.19)

535 obs / 483.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.62 (0.46–0.86)

0≤0.351.4

Missense OE?1.11 (1.03–1.19)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 27 / 43.5Missense obs/exp: 535 / 483.5Syn Z: -1.42

Background carrier burden — how many people carry a rare variant somewhere in OCA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 31

1,157 rare PASS variants

Rare truncating (LoF)

1 in 820

184 rare PASS variants

Rare synonymous (reference)

1 in 63

451 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OCA2. 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 46	1 in 1,200
South Asian	~43k	1 in 35	1 in 1,500
Remaining (unassigned)	~30k	1 in 27	1 in 1,300
European (Finnish)	~27k	1 in 130	≈ 1 in 13,000
Admixed American	~22k	1 in 37	1 in 550
African / African American	~21k	1 in 24	1 in 200
East Asian	~20k	1 in 35	1 in 840
Ashkenazi Jewish	~13k	1 in 200	none seen
Middle Eastern	~2,884	1 in 36	1 in 570

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): 21 of 23 coding exons well covered in gnomAD exomes; exons 12, 20 marginal. Genomes: all 23.? see exons ↓