TYRP1

Chr 9AR

tyrosinase related protein 1

Also known as: CAS2, CATB, GP75, OCA3, TRP, TRP1, TYRP, b-PROTEIN

NCBI Gene: 7306 ENSG00000107165 UniProt: P17643 OMIM: 115501

The protein is a melanosomal enzyme that catalyzes the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in melanin biosynthesis and may regulate the type of melanin synthesized. Mutations cause oculocutaneous albinism type III and contribute to variation in skin, hair, and eye pigmentation including Melanesian blond hair. Inheritance is autosomal recessive.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)]MIM #612271

Albinism, oculocutaneous, type IIIMIM #203290

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Albinism, oculocutaneous, type III; 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

115

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.000

Z-score -2.04

OE 1.48 (1.11–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.15Z-score

OE missense 1.35 (1.24–1.47)

404 obs / 299.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.48 (1.11–1.89)

0≤0.351.4

Missense OE?1.35 (1.24–1.47)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 31 / 20.9Missense obs/exp: 404 / 299.5Syn Z: -2.17

Background carrier burden — how many people carry a rare variant somewhere in TYRP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

909 rare PASS variants

Rare truncating (LoF)

1 in 600

156 rare PASS variants

Rare synonymous (reference)

1 in 190

298 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TYRP1. 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 64	1 in 770
South Asian	~43k	1 in 57	1 in 500
Remaining (unassigned)	~30k	1 in 43	1 in 350
European (Finnish)	~27k	1 in 130	1 in 2,400
Admixed American	~22k	1 in 59	1 in 240
African / African American	~21k	1 in 45	1 in 170
East Asian	~20k	1 in 71	1 in 910
Ashkenazi Jewish	~13k	1 in 210	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 56	1 in 480

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.