OCA2

Chr 15AR

OCA2 melanosomal transmembrane protein

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

NCBI Gene: 4948 ENSG00000104044 UniProt: Q04671

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]

Primary Disease Associations & Inheritance

Albinism, oculocutaneous, type IIMIM #203200

Albinism, brown oculocutaneousMIM #203200

{Albinism, oculocutaneous, type II, modifier of}MIM #203200

[Skin/hair/eye pigmentation 1, blond/brown hair]MIM #227220

[Skin/hair/eye pigmentation 1, blue/nonblue eyes]MIM #227220

Albinism, brown oculocutaneousMIM #203200

Albinism, oculocutaneous, type IIMIM #203200

690

ClinVar variants

262

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— OCA2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

262 Pathogenic / Likely Pathogenic· 116 VUS of 690 total submissions

Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

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.

0.86LOEUF

pLI 0.000

Z-score 2.32

OE 0.62 (0.46–0.86)

Tolerant

Typical tolerance to LoF variation

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.

-0.83Z-score

OE missense 1.11 (1.03–1.19)

535 obs / 483.5 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.0.62 (0.46–0.86)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.03–1.19)

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.1.13

0≤1.21.6

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

ClinVar Variant Classifications

690 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic171

Likely Pathogenic91

VUS116

Likely Benign274

Benign14

Conflicting24

171

Pathogenic

Likely Pathogenic

116

VUS

274

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	9	120	0	171
Likely Pathogenic	40	29	20	2	91
VUS	1	97	16	2	116
Likely Benign	0	3	137	134	274
Benign	0	2	4	8	14
Conflicting	—				24
Total	83	140	297	146	690

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.

Gene2Phenotype Curations

OCA2-related oculocutaneous albinism

definitive

ARLoss Of FunctionAbsent Gene Product

EyeSkin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

ALBINISM, OCULOCUTANEOUS, TYPE II; OCA2

MIM #203200 · #

Albinism, oculocutaneous, type II

MIM #203200