TYR

Chr 11ADAR

tyrosinase

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.965 OMIM phenotypes
Clinical SummaryTYR
🧬
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
62 unique Pathogenic / Likely Pathogenic· 78 VUS of 200 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — TYR
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -3.29
OE 1.77 (1.331.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.95Z-score
OE missense 1.32 (1.221.44)
379 obs / 286.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.77 (1.331.96)
00.351.4
Missense OE1.32 (1.221.44)
00.61.4
Synonymous OE1.30
01.21.6
LoF obs/exp: 38 / 21.5Missense obs/exp: 379 / 286.1Syn Z: -2.41

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic40
VUS78
Likely Benign56
Conflicting4
22
Pathogenic
40
Likely Pathogenic
78
VUS
56
Likely Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
7
5
0
22
Likely Pathogenic
12
26
2
0
40
VUS
0
75
1
2
78
Likely Benign
0
0
16
40
56
Benign
0
0
0
0
0
Conflicting
4
Total221082442200

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Carcinoma, Renal Cell

Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination With Sunitinib in Patients With TKIs-resistant RCC

RECRUITING
NCT06222593Phase PHASE1, PHASE2State University of New York at BuffaloStarted 2024-10-01
Bicalutamide in combination with Sunitinib
Non-Small Cell Lung Cancer

A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)

ACTIVE NOT RECRUITING
NCT04035486Phase PHASE3AstraZenecaStarted 2019-07-02
OsimertinibPemetrexed/CarboplatinPemetrexed/Cisplatin
Advanced Solid TumorsHER2 Mutation

A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)

RECRUITING
NCT06760819Phase PHASE2BayerStarted 2025-02-13
BAY2927088
Squamous Cell Tumors of the Head and Neck (HNSCC)

Development of Patient Derived Xenografts (PDXs) and Analysis of Tyrosine Kinase Receptor Expression in Patients With Squamous Cell Head and Neck Cancer (HNSCC) to Study Resistance Mechanisms Induced by Standard Therapy

NOT YET RECRUITING
NCT07471009IRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2026-03-31
Non-Small Cell Carcinoma of Lung, TNM Stage 4Non-Small Cell Lung CancerEGFR Gene Mutation

Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

RECRUITING
NCT03042221University of Colorado, DenverStarted 2016-05-10
Acute Lymphoblastic LeukemiaPhiladelphia Chromosome-Positive

Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

ACTIVE NOT RECRUITING
NCT04329325Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2020-03-30
Blinatumomabdasatinibdexamethasone
Obesity, ChildhoodInsulin Resistance

Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance

RECRUITING
NCT04578652Phase PHASE3University of AlbertaStarted 2021-10-22
Metformin 850 mg oral tablet bidSupplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
Chronic Myeloid Leukemia, Chronic PhaseAdult CMLLeukemia, Myeloid

Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

RECRUITING
NCT05143840Phase PHASE2Augusta UniversityStarted 2022-04-22
Single Agent AsciminibLow TKIElective Free Treatment
Acute Myeloid LeukemiaAML, AdultAML With Gene Mutations

Revumenib in Combination With 7+3 + Midostaurin in AML

RECRUITING
NCT06313437Phase PHASE1Richard Stone, MDStarted 2024-12-06
RevumenibMidostaurinCytarabine
Neoplasms, Breast

Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease

ACTIVE NOT RECRUITING
NCT04915755Phase PHASE3GlaxoSmithKlineStarted 2021-06-28
NiraparibPlacebo
Pancreatic Cancer

Lidocaine Infusion in Pancreatic Cancer

RECRUITING
NCT04048278Phase EARLY_PHASE1University of Illinois at ChicagoStarted 2018-11-08
Lidocaine HydrochlorideSaline Solution for Injection
Cardiovascular Side Effects of ClozapineNeutropenia Due to ClozapineGeneral Side Effects of Clozapine

Nor)Clozapine Kinetics and Side Effects in Therapy Resistant Schizophrenia and the Optimal Sampling Time for Therapeutic Drug Monitoring

NOT YET RECRUITING
NCT06749041GGZ Noord-Holland-NoordStarted 2024-12-23
Clinical Literature
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