TYR

Chr 11

tyrosinase

Also known as: ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3

NCBI Gene: 7299 ENSG00000077498 UniProt: P14679

The protein is a copper-containing oxidase that catalyzes the rate-limiting conversion of tyrosine to DOPA and subsequent oxidation steps in melanin biosynthesis. Mutations cause oculocutaneous albinism types IA and IB through autosomal recessive inheritance, with complete loss of enzyme function in type IA and reduced function in type IB. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern where heterozygous carriers have normal pigmentation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAlbinism, oculocutaneous, 1A

UniProtAlbinism, oculocutaneous, 1B

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · oculocutaneous albinism type 1 · AR · ClinGen 2020

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

1392

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.96

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TYR

Authoritative clinical overview · Recommended first read

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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?

1.96LOEUF

pLI 0.000

Z-score -3.29

OE 1.77 (1.33–1.96)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.95Z-score

OE missense 1.32 (1.22–1.44)

379 obs / 286.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.77 (1.33–1.96)

0≤0.351.4

Missense OE?1.32 (1.22–1.44)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 38 / 21.5Missense obs/exp: 379 / 286.1Syn Z: -2.41

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

799 rare PASS variants

Rare truncating (LoF)

1 in 390

139 rare PASS variants

Rare synonymous (reference)

1 in 160

289 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TYR. 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 77	1 in 530
South Asian	~43k	1 in 62	1 in 540
Remaining (unassigned)	~30k	1 in 58	1 in 970
European (Finnish)	~27k	1 in 210	1 in 1,500
Admixed American	~22k	1 in 65	1 in 730
African / African American	~21k	1 in 78	1 in 450
East Asian	~20k	1 in 58	1 in 1,500
Ashkenazi Jewish	~13k	1 in 340	1 in 1,500
Middle Eastern	~2,884	1 in 67	≈ 1 in 710

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓