GeneBe

TYRP1

protein-coding

tyrosinase related protein 1

Gene summary

This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]

Previous symbols:
  • TYRP
  • CAS2

MANE transcript

NM_000550.3

Inheritance

AR

ClinVar variants

P:109U:267B:199

Top phenotype

Albinism, oculocutaneous, type III

gnomAD constraint

pLI —, LoF o/e 1.48

Max pathogenic AF

—

Genomic locus

chr9:12,685,439-12,710,285

External References & Databases

Ensembl (ENSG00000107165)NCBI Gene (7306)OMIM (115501)HGNC:12450GenCCUniProt (P17643)AlphaFoldClinVar (TYRP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~24.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oculocutaneous albinism type 3DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008747

Submitter: G2P

oculocutaneous albinism type 3SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008747

Submitter: Orphanet

oculocutaneous albinism type 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008747

Submitter: PanelApp Australia

oculocutaneous albinism type 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008747

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Albinism, oculocutaneous, type IIIAR

Manifestation: Dermatologic; Ophthalmologic

Intervention: General

Rationale: 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

Comments: Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer

Refs: 3935994; 8651291; 9345097; 16704458; 18680187; 19533799; 20861488; 21471978; 21996312; 22556244Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TYRP1 variants in ClinVar

12 Conditions Cataloged
not providedTotal: 603
Oculocutaneous albinism type 3Total: 83
not specifiedTotal: 74
Inborn genetic diseasesTotal: 74
TYRP1-related disorderTotal: 42
MELANESIAN BLOND HAIRTotal: 31
Nonsyndromic Oculocutaneous AlbinismTotal: 3
Ocular albinismTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000550.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
177
clinvar
 177
missense
20
clinvar
257
clinvar
17
clinvar
 294
nonsense
19
clinvar
12
clinvar
2
clinvar
1
clinvar
 34
start loss
2
clinvar
 2
frameshift
31
clinvar
10
clinvar
6
clinvar
4
clinvar
 51
splice donor/acceptor (+/-2bp)
2
clinvar
13
clinvar
2
clinvar
 17
Total54552671990575

Highest pathogenic variant AF is 0.00023193425

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000550.3RefSeqNP_000541.17MANE Select
ENST00000388918.10EnsemblENSP00000373570.47MANE Select
ENST00000381136.2EnsemblENSP00000370528.25Standard
ENST00000381136.3EnsemblENSP00000370528.25Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
tyrp1aDanio rerio

Structure: melanocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Tyrosine metabolism - Homo sapiens (human)
  • Melanogenesis - Homo sapiens (human)
  • Degradation of Superoxides
  • Metabolism of amino acids and derivatives
  • Metabolism

Biological Process

  • melanin metabolic process
  • melanocyte differentiation
  • melanosome organization
  • melanin biosynthetic process
  • acetoacetic acid metabolic process

Molecular Function

  • monooxygenase activity
  • protein binding
  • oxidoreductase activity
  • protein homodimerization activity
  • metal ion binding

Cellular Component

  • endosome membrane
  • integral component of membrane
  • clathrin-coated endocytic vesicle membrane
  • melanosome membrane
  • melanosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000388918
Coding exons
7
Length
24852
Individuals with no LoFs
125476
Homozygous LoFs
0
Heterozygous LoFs
270
Defined
125746
p
0.00107
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-2.154042991.350.00001573529
Missense (PolyPhen)172124.421.38241588
Synonymous-2.171361071.270.000005381057
Loss of Function-2.043120.91.480.00000109243

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00750.0075notable
Latino/Admixed American0.00140.0014notable
Ashkenazi Jewish0.000200.00020rare
East Asian0.000440.00044rare
Finnish0.000320.00032rare
European (Non-Finnish)0.000600.00060rare
South Asian0.000460.00046rare
Other0.000490.00049rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.101

Intolerance Scores

LoFtool
0.191
RVIS EVS
-0.26
RVIS percentile EVS
34.93

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.986

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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