Oculocutaneous albinism type 3

Summary

Oculocutaneous albinism type 3 (MONDO:0008747) is a disease caused by TYRP1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: TYRP1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 116
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	11.7647	Africa	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000635	Blue irides	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001010	Hypopigmentation of the skin	Frequent (30-79%)
HP:0001480	Freckling	Frequent (30-79%)
HP:0002297	Red hair	Frequent (30-79%)
HP:0007730	Iris hypopigmentation	Frequent (30-79%)
HP:0011358	Generalized hypopigmentation of hair	Frequent (30-79%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0002226	White eyebrow	Occasional (5-29%)
HP:0002227	White eyelashes	Occasional (5-29%)
HP:0025551	Optic nerve misrouting	Occasional (5-29%)
HP:0100814	Blue nevus	Occasional (5-29%)
HP:0200098	Absent skin pigmentation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 3
Mondo ID	MONDO:0008747
MeSH	C537731
OMIM	203290, 278400
Orphanet	79433
DOID	DOID:0070097
ICD-11	1565320806
SNOMED CT	63450009
UMLS	C0342683
MedGen	87450
GARD	0004039
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type 3 · albinism, oculocutaneous, type III · OCA3 · oculocutaneous albinism caused by mutation in TYRP1 · oculocutaneous albinism type 3 · Red oculocutaneous albinism · ROCA · rufous OCA · rufous oculocutaneous albinism · TYRP1 oculocutaneous albinism · Xanthism · xanthous oculocutaneous albinism

Data availability: 116 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › disorder of melanin metabolism › oculocutaneous albinism › oculocutaneous albinism type 3

Related subtypes (8): oculocutaneous albinism type 2, oculocutaneous albinism type 4, oculocutaneous albinism type 7, oculocutaneous albinism type 5, oculocutaneous albinism type 1, oculocutaneous albinism type 6, oculocutaneous albinism type 8, autosomal dominant oculocutaneous albinism

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

116 retrieved; paginated sample, class counts are floors:

52 uncertain significance, 24 conflicting classifications of pathogenicity, 10 benign, 9 pathogenic/likely pathogenic, 8 likely pathogenic, 6 pathogenic, 4 benign/likely benign, 3 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17593	NM_000550.3(TYRP1):c.1103del (p.Lys368fs)	LURAP1L-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17595	NM_000550.3(TYRP1):c.1120C>T (p.Arg374Ter)	LURAP1L-AS1	Pathogenic	criteria provided, multiple submitters, no conflicts
4077125	NM_000550.3(TYRP1):c.1262-1G>C	LURAP1L-AS1	Pathogenic	criteria provided, single submitter
4077126	NM_000550.3(TYRP1):c.1525G>T (p.Glu509Ter)	LURAP1L-AS1	Pathogenic	criteria provided, single submitter
437186	NM_000550.3(TYRP1):c.1261+1G>A	LURAP1L-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325324	NM_000550.3(TYRP1):c.351G>A (p.Trp117Ter)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334531	NM_000550.3(TYRP1):c.859C>T (p.Arg287Ter)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458626	NM_000550.3(TYRP1):c.418G>T (p.Glu140Ter)	TYRP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1481935	NM_000550.3(TYRP1):c.913+2T>G	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17594	NM_000550.3(TYRP1):c.497C>G (p.Ser166Ter)	TYRP1	Pathogenic	criteria provided, multiple submitters, no conflicts
17597	NM_000550.3(TYRP1):c.107del (p.Ala35_Leu36insTer)	TYRP1	Pathogenic	no assertion criteria provided
17598	NM_000550.3(TYRP1):c.1057_1060del (p.Asn353fs)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2633925	NM_000550.3(TYRP1):c.176C>G (p.Ser59Ter)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2735262	NM_000550.3(TYRP1):c.782_793del (p.Cys261_Asp264del)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2767322	NM_000550.3(TYRP1):c.570G>A (p.Trp190Ter)	TYRP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382144	NM_000550.3(TYRP1):c.985G>T (p.Glu329Ter)	LURAP1L-AS1	Likely pathogenic	criteria provided, single submitter
3596430	NM_000550.3(TYRP1):c.1372_1375dup (p.Asn459fs)	LURAP1L-AS1	Likely pathogenic	criteria provided, single submitter
3336274	NM_000550.3(TYRP1):c.88T>C (p.Cys30Arg)	TYRP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3393457	NM_000550.3(TYRP1):c.554A>G (p.Tyr185Cys)	TYRP1	Likely pathogenic	criteria provided, single submitter
3596428	NM_000550.3(TYRP1):c.1082-1G>C	TYRP1	Likely pathogenic	criteria provided, single submitter
3596429	NM_000550.3(TYRP1):c.1167del (p.Gln390fs)	TYRP1	Likely pathogenic	criteria provided, single submitter
3596431	NM_000550.3(TYRP1):c.1377_1380dup (p.Gly461fs)	TYRP1	Likely pathogenic	criteria provided, single submitter
4849328	NM_000550.3(TYRP1):c.566_569del (p.Val189fs)	TYRP1	Likely pathogenic	criteria provided, single submitter
1422257	NM_000550.3(TYRP1):c.1262-1_1264dup	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212527	NM_000550.3(TYRP1):c.1145T>C (p.Leu382Pro)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
256641	NM_000550.3(TYRP1):c.1082-9T>C	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374020	NM_000550.3(TYRP1):c.1133A>G (p.Asn378Ser)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
384337	NM_000550.3(TYRP1):c.1263T>C (p.Asp421=)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
423157	NM_000550.3(TYRP1):c.1226C>T (p.Ala409Val)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912542	NM_000550.3(TYRP1):c.933T>C (p.Ile311=)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TYRP1	Definitive	Autosomal recessive	oculocutaneous albinism type 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TYRP1	Orphanet:79433	Oculocutaneous albinism type 3

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TYRP1	HGNC:12450	ENSG00000107165	P17643	5,6-dihydroxyindole-2-carboxylic acid oxidase	gencc,clinvar
LURAP1L-AS1	HGNC:49761	ENSG00000235448		LURAP1L antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TYRP1	5,6-dihydroxyindole-2-carboxylic acid oxidase	Plays a role in melanin biosynthesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TYRP1	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
LURAP1L-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mammalian vulva	1
pigmented layer of retina	1
upper leg skin	1
adrenal tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TYRP1	206	broad	marker	pigmented layer of retina, upper leg skin, mammalian vulva
LURAP1L-AS1	151	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, sural nerve, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYRP1	2,635
LURAP1L-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYRP1	P17643	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	1	2284.0×	9e-04	TYRP1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.004	TYRP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete acetoacetic acid metabolic process	1	16852.0×	3e-04	TYRP1
positive regulation of melanin biosynthetic process	1	1404.3×	0.001	TYRP1
melanin biosynthetic process	1	1296.3×	0.001	TYRP1
melanocyte differentiation	1	802.5×	0.002	TYRP1
melanosome organization	1	648.1×	0.002	TYRP1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYRP1	0	0
LURAP1L-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TYRP1	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	TYRP1, LURAP1L-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TYRP1	3	—
LURAP1L-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.