OCA2

Chr 15AR

OCA2 melanosomal transmembrane protein

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.867 OMIM phenotypes
Clinical SummaryOCA2
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Gene-Disease Validity (ClinGen)
oculocutaneous albinism type 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
79 unique Pathogenic / Likely Pathogenic· 57 VUS of 200 total submissions
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GeneReview available — OCA2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.32
OE 0.62 (0.460.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.83Z-score
OE missense 1.11 (1.031.19)
535 obs / 483.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.460.86)
00.351.4
Missense OE1.11 (1.031.19)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 27 / 43.5Missense obs/exp: 535 / 483.5Syn Z: -1.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveOCA2-related oculocutaneous albinismLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.73top 25%
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic33
VUS57
Likely Benign62
Conflicting2
46
Pathogenic
33
Likely Pathogenic
57
VUS
62
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
2
29
0
46
Likely Pathogenic
18
8
6
1
33
VUS
1
46
9
1
57
Likely Benign
0
1
31
30
62
Benign
0
0
0
0
0
Conflicting
2
Total34577532200

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

View in ClinVar →

Protein Context — Lollipop Plot

OCA2 · 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

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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC