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.

GeneReviews 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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.892 OMIM phenotypes

Clinical Summary— TYRP1

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Population Constraint (gnomAD)

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

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ClinVar Variants

97 unique Pathogenic / Likely Pathogenic· 298 VUS of 716 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

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GeneReview available — TYRP1

Authoritative clinical overview · Recommended first read

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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

ClinVar Variant Classifications

716 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62

Likely Pathogenic35

VUS298

Likely Benign267

Benign15

Conflicting35

Pathogenic

Likely Pathogenic

298

VUS

267

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	54	3	5	0	62
Likely Pathogenic	28	7	0	0	35
VUS	7	251	39	1	298
Likely Benign	5	3	93	166	267
Benign	0	2	10	3	15
Conflicting	—				35
Total	94	266	147	170	712

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 136) ClinVar copy-number / structural variants overlap TYRP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →