TYR

Chr 11ADAR

tyrosinase

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

NCBI Gene: 7299 ENSG00000077498 UniProt: P14679

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]

Primary Disease Associations & Inheritance

[Skin/hair/eye pigmentation 3, blue/green eyes]MIM #601800

[Skin/hair/eye pigmentation 3, light/dark/freckling skin]MIM #601800

{Melanoma, cutaneous malignant, susceptibility to, 8}MIM #601800

Albinism, oculocutaneous, type IAMIM #203100

Albinism, oculocutaneous, type IBMIM #606952

584

ClinVar variants

210

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— TYR

🧬

Gene-Disease Validity (ClinGen)

oculocutaneous albinism type 1 · 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.

📋

ClinVar Variants

210 Pathogenic / Likely Pathogenic· 140 VUS of 584 total submissions

💊

Clinical Trials

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

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.

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?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.

-1.95Z-score

OE missense 1.32 (1.22–1.44)

379 obs / 286.1 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.1.77 (1.33–1.96)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.32 (1.22–1.44)

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.1.30

0≤1.21.6

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

ClinVar Variant Classifications

584 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic98

Likely Pathogenic112

VUS140

Likely Benign184

Benign12

Conflicting38

Pathogenic

112

Likely Pathogenic

140

VUS

184

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	35	23	40	0	98
Likely Pathogenic	21	68	23	0	112
VUS	1	119	16	4	140
Likely Benign	0	2	46	136	184
Benign	0	1	10	1	12
Conflicting	—				38
Total	57	213	135	141	584

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

View in ClinVar →

Protein Context — Lollipop Plot

TYR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TYR-related oculocutaneous albinism

definitive

ARLoss Of FunctionAbsent Gene Product

Dev. DisordersEyeSkin

G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

TYROSINASE; TYR

MIM #606933 · *

[Skin/hair/eye pigmentation 3, blue/green eyes]

MIM #601800