GeneBe

TYR

tyrosinase

Basic information

Region (hg38): 11:89177875-89295759

Links

ENSG00000077498 ∙ NCBI:7299 ∙ OMIM:606933 ∙ HGNC:12442 ∙ Uniprot:P14679 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • oculocutaneous albinism type 1 (Definitive), mode of inheritance: AR
  • oculocutaneous albinism type 1A (Strong), mode of inheritance: AR
  • oculocutaneous albinism type 1A (Supportive), mode of inheritance: AR
  • oculocutaneous albinism type 1B (Supportive), mode of inheritance: AR
  • minimal pigment oculocutaneous albinism type 1 (Supportive), mode of inheritance: AR
  • temperature-sensitive oculocutaneous albinism type 1 (Supportive), mode of inheritance: AR
  • Waardenburg syndrome type 2 (Supportive), mode of inheritance: AD
  • oculocutaneous albinism type 1A (Definitive), mode of inheritance: AR
  • oculocutaneous albinism type 1A (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Albinism, oculocutaneous, type IA; Albinism, oculocutaneous, type IBARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic; Ophthalmologic666627; 1970634; 8477259; 8190479; 9158138; 17999355; 17952075; 18488028; 19533789; 18488027; 19578364; 20806075; 20861488; 21458243; 21541274; 22294196
Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TYR gene.

  • not_provided (628 variants)
  • Oculocutaneous_albinism_type_1A (213 variants)
  • SKIN/HAIR/EYE_PIGMENTATION_3,_LIGHT/DARK_SKIN (163 variants)
  • Oculocutaneous_albinism_type_1B (158 variants)
  • Oculocutaneous_albinism (77 variants)
  • not_specified (63 variants)
  • TYR-related_disorder (56 variants)
  • Inborn_genetic_diseases (55 variants)
  • Oculocutaneous_albinism_type_1 (30 variants)
  • Nonsyndromic_Oculocutaneous_Albinism (14 variants)
  • Albinism_or_congenital_nystagmus (11 variants)
  • Ocular_albinism_with_congenital_sensorineural_hearing_loss (11 variants)
  • Albinism (8 variants)
  • Abnormality_of_the_skin (7 variants)
  • Ocular_albinism (3 variants)
  • Horizontal_nystagmus (3 variants)
  • See_cases (3 variants)
  • Hypopigmentation_of_the_skin (3 variants)
  • Myopia (2 variants)
  • Abnormal_optic_nerve_morphology (2 variants)
  • Slow_decrease_in_visual_acuity (2 variants)
  • Abnormality_of_metabolism/homeostasis (2 variants)
  • Fair_hair (2 variants)
  • Foveal_hypoplasia (2 variants)
  • Abnormal_retinal_morphology (2 variants)
  • Elevated_circulating_hepatic_transaminase_concentration (2 variants)
  • Strabismus (2 variants)
  • Nystagmus (2 variants)
  • Choroidal_neovascularization (2 variants)
  • Hypopigmentation_of_hair (1 variants)
  • Congenital_nystagmus (1 variants)
  • Iris_transillumination_defect (1 variants)
  • Pigmentary_skin_disorders (1 variants)
  • Autosomal_recessive_TYR-related_disorders (1 variants)
  • Hearing_impairment (1 variants)
  • Temperature-sensitive_oculocutaneous_albinism_type_1 (1 variants)
  • Abnormality_of_the_eye (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000372.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
6
clinvar
158
clinvar
1
clinvar
 166
missense
43
clinvar
159
clinvar
220
clinvar
6
clinvar
1
clinvar
 429
nonsense
34
clinvar
16
clinvar
3
clinvar
 53
start loss
1
1
2
frameshift
42
clinvar
21
clinvar
7
clinvar
 70
splice donor/acceptor (+/-2bp)
7
clinvar
8
clinvar
 15
Total 128 205 236 164 2

Highest pathogenic variant AF is 0.004543678

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TYRprotein_codingprotein_codingENST00000263321 5118308
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
12557401741257480.000692
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.953792861.320.00001553499
Missense in Polyphen156113.591.37341442
Synonymous-2.411391071.300.00000601990
Loss of Function-3.293821.51.770.00000120244

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001200.00119
Ashkenazi Jewish0.00009930.0000992
East Asian0.0009790.000979
Finnish0.0001390.000139
European (Non-Finnish)0.0006790.000598
Middle Eastern0.0009790.000979
South Asian0.001670.00167
Other0.0004910.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4- dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6- dihydroxyindole) to indole-5,6 quinone. {ECO:0000250|UniProtKB:P11344}.;
Disease
DISEASE: Albinism, oculocutaneous, 1A (OCA1A) [MIM:203100]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is absent in skin, hair, and eyes. It is characterized by complete lack of tyrosinase activity due to production of an inactive enzyme. Patients present with a life-long absence of melanin pigment after birth, and manifest increased sensitivity to ultraviolet radiation with predisposition to skin cancer. Visual anomalies include decreased acuity, nystagmus, strabismus and photophobia. {ECO:0000269|PubMed:10571953, ECO:0000269|PubMed:10671066, ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:11858948, ECO:0000269|PubMed:1487241, ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278, ECO:0000269|PubMed:1899321, ECO:0000269|PubMed:1943686, ECO:0000269|PubMed:1970634, ECO:0000269|PubMed:22981120, ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:24934919, ECO:0000269|PubMed:7902671, ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955, ECO:0000269|PubMed:8644824, ECO:0000269|PubMed:9259202}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Albinism, oculocutaneous, 1B (OCA1B) [MIM:606952]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. It is characterized by partial lack of tyrosinase activity. Patients have white hair at birth that rapidly turns yellow or blond. They manifest the development of minimal-to-moderate amounts of cutaneous and ocular pigment. Some patients may have with white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities). This variant phenotype is due to a loss of tyrosinase activity above 35-37 degrees C. {ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:1900309, ECO:0000269|PubMed:1903591, ECO:0000269|PubMed:8128955}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Tyrosine metabolism - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Riboflavin Metabolism;Dopamine metabolism;Metabolism of amino acids and derivatives;Tyrosine metabolism;Metabolism;Melanin biosynthesis;L-dopachrome biosynthesis;eumelanin biosynthesis;(S)-reticuline biosynthesis;Tyrosine metabolism (Consensus)

Recessive Scores

pRec
0.893

Intolerance Scores

loftool
0.0937
rvis_EVS
-0.95
rvis_percentile_EVS
9.27

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.781

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Zebrafish Information Network

Gene name
tyr
Affected structure
melanoblast
Phenotype tag
abnormal
Phenotype quality
unpigmented

Gene ontology

Biological process
melanin biosynthetic process from tyrosine;eye pigment biosynthetic process;visual perception;cell population proliferation;response to UV;response to vitamin D;melanin biosynthetic process;pigmentation;thymus development;response to cAMP;oxidation-reduction process
Cellular component
nucleus;cytoplasm;lysosome;Golgi-associated vesicle;cytosol;integral component of membrane;melanosome membrane;melanosome;intracellular membrane-bounded organelle;perinuclear region of cytoplasm
Molecular function
monooxygenase activity;monophenol monooxygenase activity;copper ion binding;protein binding;protein homodimerization activity;protein heterodimerization activity
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