TYRP1

tyrosinase related protein 1

Basic information

Region (hg38): 9:12685438-12710285

Previous symbols: [ "TYRP", "CAS2" ]

Links

ENSG00000107165 ∙ NCBI:7306 ∙ OMIM:115501 ∙ HGNC:12450 ∙ Uniprot:P17643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculocutaneous albinism type 3 (Definitive), mode of inheritance: AR
• oculocutaneous albinism type 3 (Supportive), mode of inheritance: AR
• oculocutaneous albinism type 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Albinism, oculocutaneous, type III	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	3935994; 8651291; 9345097; 16704458; 18680187; 19533799; 20861488; 21471978; 21996312; 22556244
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 TYRP1 gene.

• not provided (417 variants)
• Oculocutaneous albinism type 3 (88 variants)
• not specified (28 variants)
• Inborn genetic diseases (13 variants)
• Oculocutaneous albinism type 3;Skin/hair/eye pigmentation, variation in, 11 (8 variants)
• TYRP1-related condition (5 variants)
• Oculocutaneous albinism (4 variants)
• Albinism (2 variants)
• Ocular albinism (2 variants)
• Skin/hair/eye pigmentation, variation in, 11;Oculocutaneous albinism type 3 (2 variants)
• Nonsyndromic Oculocutaneous Albinism (2 variants)
• OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF (1 variants)
• Skin/hair/eye pigmentation, variation in, 11 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYRP1 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	77	5	84
missense		6	210	4	2	222
nonsense	15	3		1		19
start loss	1					1
frameshift	12	1	7	2		22
inframe indel	1					1
splice donor/acceptor (+/-2bp)		9	2			11
splice region			7	10		17
non coding			27	36	11	74
Total	29	19	248	120	18

Highest pathogenic variant AF is 0.000197

Variants in TYRP1

This is a list of pathogenic ClinVar variants found in the TYRP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-12693397-G-A		Oculocutaneous albinism type 3	Uncertain significance (Jan 12, 2018)
9-12693403-G-T		Oculocutaneous albinism type 3	Benign (Jan 12, 2018)
9-12693445-G-T		Oculocutaneous albinism type 3	Uncertain significance (Jan 12, 2018)
9-12693453-T-C		Oculocutaneous albinism type 3	Uncertain significance (Jan 13, 2018)
9-12693927-C-T		Oculocutaneous albinism type 3 • Oculocutaneous albinism type 3;Skin/hair/eye pigmentation, variation in, 11	Uncertain significance (Aug 13, 2021)
9-12693928-G-A		Oculocutaneous albinism type 3	Uncertain significance (Jan 13, 2018)
9-12693928-G-T		Oculocutaneous albinism type 3	Uncertain significance (Jan 13, 2018)
9-12693982-C-G		Oculocutaneous albinism type 3	Uncertain significance (Jan 12, 2018)
9-12693991-A-G		Oculocutaneous albinism type 3	Uncertain significance (Jan 13, 2018)
9-12693999-G-T			Pathogenic (Jan 29, 2024)
9-12694002-T-C			Likely benign (Jun 07, 2023)
9-12694004-C-T			Uncertain significance (Feb 11, 2022)
9-12694005-T-C			Likely benign (Oct 07, 2023)
9-12694007-C-T			Uncertain significance (Nov 01, 2022)
9-12694017-C-A			Likely benign (Aug 19, 2023)
9-12694017-C-G			Benign (Jan 22, 2024)
9-12694018-T-A			Uncertain significance (Jun 08, 2022)
9-12694019-C-T			Uncertain significance (Apr 24, 2021)
9-12694024-G-C			Uncertain significance (Dec 02, 2021)
9-12694031-T-G			Uncertain significance (Jul 30, 2022)
9-12694039-C-A			Uncertain significance (Jul 30, 2022)
9-12694042-T-A			Uncertain significance (Aug 19, 2022)
9-12694043-TG-T			Pathogenic (Oct 26, 2023)
9-12694044-G-T			Uncertain significance (Mar 20, 2021)
9-12694063-C-T		Oculocutaneous albinism type 3	Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYRP1	protein_coding	protein_coding	ENST00000388918	7	24852

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.56e-25	0.00000744	125476	0	270	125746	0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.15	404	299	1.35	0.0000157	3529
Missense in Polyphen		172	124.42	1.3824		1588
Synonymous	-2.17	136	107	1.27	0.00000538	1057
Loss of Function	-2.04	31	20.9	1.48	0.00000109	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00882	0.00883
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000436	0.000435
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000601	0.000598
Middle Eastern	0.000436	0.000435
South Asian	0.000458	0.000457
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the oxidation of 5,6-dihydroxyindole-2- carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu(2+) ions (PubMed:28661582). May regulate or influence the type of melanin synthesized (PubMed:22556244, PubMed:16704458). Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (By similarity). {ECO:0000250|UniProtKB:P07147, ECO:0000269|PubMed:28661582, ECO:0000305|PubMed:16704458, ECO:0000305|PubMed:22556244, ECO:0000305|PubMed:23504663}.
• Disease: DISEASE: Albinism, oculocutaneous, 3 (OCA3) [MIM:203290]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Tyrosinase activity is normal and patients have only moderate reduction of pigment. The eyes present red reflex on transillumination of the iris, dilution of color of iris, nystagmus and strabismus. Darker-skinned individuals have bright copper-red coloration of the skin and hair. {ECO:0000269|PubMed:16704458, ECO:0000269|PubMed:23504663}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tyrosine metabolism - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Degradation of Superoxides;Metabolism of amino acids and derivatives;Metabolism;Melanin biosynthesis;eumelanin biosynthesis;Direct p53 effectors (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.93

Haploinsufficiency Scores

• pHI: 0.412
• hipred: N
• hipred_score: 0.251
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tyrp1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; pigmentation phenotype; 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); reproductive system phenotype; hematopoietic system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; 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); skeleton phenotype; cellular phenotype; homeostasis/metabolism 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); growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: tyrp1a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: melanin metabolic process;melanocyte differentiation;melanosome organization;melanin biosynthetic process;acetoacetic acid metabolic process;positive regulation of melanin biosynthetic process;oxidation-reduction process;response to thyroid hormone
• Cellular component: endosome membrane;integral component of membrane;clathrin-coated endocytic vesicle membrane;melanosome membrane;melanosome
• Molecular function: monooxygenase activity;protein binding;oxidoreductase activity;protein homodimerization activity;metal ion binding;protein heterodimerization activity