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 1A (Definitive), mode of inheritance: AR
• oculocutaneous albinism type 1A (Definitive), 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
• oculocutaneous albinism type 1A (Strong), mode of inheritance: AR
• oculocutaneous albinism type 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Albinism, oculocutaneous, type IA; Albinism, oculocutaneous, type IB	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Ophthalmologic	666627; 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 (104 variants)
• SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN (46 variants)
• Tyrosinase-negative oculocutaneous albinism (39 variants)
• Oculocutaneous albinism type 1B (11 variants)
• TYR-related disorder (9 variants)
• Oculocutaneous albinism (9 variants)
• Nonsyndromic Oculocutaneous Albinism (5 variants)
• Oculocutaneous albinism type 1B;Tyrosinase-negative oculocutaneous albinism;SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN (3 variants)
• Inborn genetic diseases (3 variants)
• Oculocutaneous albinism type 1B;Tyrosinase-negative oculocutaneous albinism (2 variants)
• Tyrosinase-negative oculocutaneous albinism;Oculocutaneous albinism type 1B;Ocular albinism with congenital sensorineural hearing loss;SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN (2 variants)
• See cases (2 variants)
• Tyrosinase-negative oculocutaneous albinism;Oculocutaneous albinism type 1B (2 variants)
• SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN;Oculocutaneous albinism type 1B;Tyrosinase-negative oculocutaneous albinism (2 variants)
• Oculocutaneous albinism type 1 (2 variants)
• Albinism (1 variants)
• Temperature-sensitive oculocutaneous albinism type 1 (1 variants)
• SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN;Ocular albinism with congenital sensorineural hearing loss;Oculocutaneous albinism type 1B;Tyrosinase-negative oculocutaneous albinism (1 variants)
• Ocular albinism (1 variants)
• Abnormality of the skin (1 variants)
• Abnormality of the eye (1 variants)
• 8 conditions (1 variants)
• Ocular albinism with congenital sensorineural hearing loss;Oculocutaneous albinism type 1B;Tyrosinase-negative oculocutaneous albinism;SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	139	1	142
missense	45	68	138	2	1	254
nonsense	27	12	1			40
start loss	1	1				2
frameshift	39	14	1			54
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	6	6				12
splice region		3	4	9		16
non coding			5	34	9	48
Total	118	102	150	175	11

Highest pathogenic variant AF is 0.000493

Variants in TYR

This is a list of pathogenic ClinVar variants found in the TYR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-89177913-A-G		Oculocutaneous albinism	Uncertain significance (Jan 12, 2018)
11-89177917-G-A		Oculocutaneous albinism	Uncertain significance (Jan 13, 2018)
11-89177944-T-C		not specified	Likely benign (-)
11-89177945-AGA-GG			Uncertain significance (May 03, 2020)
11-89177954-A-G		Oculocutaneous albinism type 1B • Tyrosinase-negative oculocutaneous albinism • Hypopigmentation of the skin;Horizontal nystagmus;Iris transillumination defect;Hypopigmentation of hair • Myopia;Albinism;Nystagmus • 6 conditions • Abnormality of the skin • Oculocutaneous albinism • Ocular albinism with congenital sensorineural hearing loss;Tyrosinase-negative oculocutaneous albinism;Oculocutaneous albinism type 1B;SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN • TYR-related disorder	Pathogenic/Likely pathogenic (Aug 20, 2024)
11-89177955-T-C			Pathogenic (Apr 06, 2023)
11-89177962-G-T			Likely benign (Jul 28, 2023)
11-89177964-C-T			Uncertain significance (May 03, 2022)
11-89177974-C-T			Likely benign (May 14, 2023)
11-89177976-G-A			Uncertain significance (Jul 07, 2023)
11-89177976-GC-G		SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	Pathogenic (Mar 02, 2024)
11-89177979-T-C		not specified	Uncertain significance (Mar 18, 2024)
11-89177980-G-A			Likely benign (Nov 27, 2023)
11-89177983-G-T			Likely benign (Mar 17, 2023)
11-89177997-C-T			Uncertain significance (Jul 06, 2022)
11-89178001-C-T		SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN;Tyrosinase-negative oculocutaneous albinism;Oculocutaneous albinism type 1B	Likely benign (Dec 25, 2023)
11-89178004-T-C		not specified	Likely benign (Nov 15, 2023)
11-89178004-TG-T			not provided (-)
11-89178010-T-A			not provided (-)
11-89178010-T-C			Likely benign (Jan 20, 2023)
11-89178014-C-A		not specified	Uncertain significance (May 06, 2024)
11-89178014-C-T		Tyrosinase-negative oculocutaneous albinism • SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	Pathogenic (Mar 17, 2024)
11-89178018-G-C			Uncertain significance (Aug 23, 2021)
11-89178020-G-A		Oculocutaneous albinism	Uncertain significance (Jul 13, 2022)
11-89178020-GC-G		SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	Pathogenic (May 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYR	protein_coding	protein_coding	ENST00000263321	5	118308

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.99e-32	4.67e-8	125574	0	174	125748	0.000692

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.95	379	286	1.32	0.0000155	3499
Missense in Polyphen		156	113.59	1.3734		1442
Synonymous	-2.41	139	107	1.30	0.00000601	990
Loss of Function	-3.29	38	21.5	1.77	0.00000120	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00120	0.00119
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000979	0.000979
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000679	0.000598
Middle Eastern	0.000979	0.000979
South Asian	0.00167	0.00167
Other	0.000491	0.000489

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

Haploinsufficiency Scores

• pHI: 0.279
• hipred: N
• hipred_score: 0.251
• ghis: 0.546

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tyr
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; pigmentation phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype

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