Oculocutaneous albinism type 1

Summary

Oculocutaneous albinism type 1 (MONDO:0018135) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide)
• Cohort genes: 1
• ClinVar variants: 32
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.5	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0000635	Blue irides	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000649	Abnormality of visual evoked potentials	Very frequent (80-99%)
HP:0000992	Cutaneous photosensitivity	Very frequent (80-99%)
HP:0007513	Generalized hypopigmentation	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0007680	Depigmented fundus	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0007750	Hypoplasia of the fovea	Very frequent (80-99%)
HP:0011358	Generalized hypopigmentation of hair	Very frequent (80-99%)
HP:0012805	Iris transillumination defect	Very frequent (80-99%)
HP:0025551	Optic nerve misrouting	Very frequent (80-99%)
HP:0025568	Abnormal morphology of the choroidal vasculature	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000646	Amblyopia	Frequent (30-79%)
HP:0002226	White eyebrow	Frequent (30-79%)
HP:0002227	White eyelashes	Frequent (30-79%)
HP:0001072	Thickened skin	Occasional (5-29%)
HP:0008069	Neoplasm of the skin	Very rare (<1-4%)
HP:0025127	Actinic keratosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 1
Mondo ID	MONDO:0018135
MeSH	C537728
Orphanet	352731
SNOMED CT	765146000
UMLS	C0268494
MedGen	82809
GARD	0004037
Is cancer (heuristic)	no

Also known as: ATN · OCA1 · oculocutaneous albinism type 1 · oculocutaneous albinism, tyrosinase negative

Data availability: 32 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

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 › inborn disorder of amino acid metabolism › inborn disorder of phenylalanine and tyrosine metabolism › disorder of tyrosine metabolism › oculocutaneous albinism type 1

Related subtypes (4): tyrosinemia, hawkinsinuria, alkaptonuria, TH-deficient dopa-responsive dystonia

Subtypes (3): oculocutaneous albinism type 1A, minimal pigment oculocutaneous albinism type 1, temperature-sensitive oculocutaneous albinism type 1

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

32 retrieved; paginated sample, class counts are floors:

17 pathogenic/likely pathogenic, 10 pathogenic, 3 likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323729	NM_000372.5(TYR):c.715C>T (p.Arg239Trp)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1406975	NM_000372.5(TYR):c.1366+3A>T	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458014	NM_000372.5(TYR):c.1106A>G (p.Tyr369Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1699463	NM_000372.5(TYR):c.1237del (p.Glu413fs)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
190217	NM_000372.5(TYR):c.902C>T (p.Pro301Leu)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137234	NM_000372.5(TYR):c.1037-3C>G	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679405	NM_000372.5(TYR):c.1045_1046insAT (p.Ser349fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3366828	NM_000372.5(TYR):c.272G>C (p.Cys91Ser)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3772	NM_000372.5(TYR):c.242C>T (p.Pro81Leu)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
3781	NM_000372.5(TYR):c.265T>C (p.Cys89Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3791	NM_000372.5(TYR):c.616G>A (p.Ala206Thr)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3792	NM_000372.5(TYR):c.1255G>A (p.Gly419Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3796	NM_000372.5(TYR):c.896G>A (p.Arg299His)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
3800	NM_000372.5(TYR):c.1209G>T (p.Arg403Ser)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4073695	NM_000372.5(TYR):c.264dup (p.Cys89fs)	TYR	Pathogenic	criteria provided, single submitter
4073697	NM_000372.5:c.(1184+1_1185-1)_(1366+1_1367-1)del	TYR	Pathogenic	criteria provided, single submitter
4073707	NM_000372.5(TYR):c.38del (p.Phe13fs)	TYR	Pathogenic	criteria provided, single submitter
4081816	NM_000372.5(TYR):c.1169A>G (p.His390Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081817	NM_000372.5(TYR):c.265del (p.Cys89fs)	TYR	Pathogenic	criteria provided, single submitter
437179	NM_000372.5(TYR):c.1036G>T (p.Gly346Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449541	NM_000372.5(TYR):c.116G>A (p.Trp39Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
497973	NM_000372.5(TYR):c.1392dup (p.Lys465Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585280	NM_000372.5(TYR):c.980A>G (p.Tyr327Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
617799	NM_000372.5(TYR):c.1037G>A (p.Gly346Glu)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99539	NM_000372.5(TYR):c.1168C>G (p.His390Asp)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99558	NM_000372.5(TYR):c.25del (p.Leu9fs)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
99583	NM_000372.5(TYR):c.832C>T (p.Arg278Ter)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
3907545	NM_000372.5(TYR):c.1469C>A (p.Ala490Asp)	TYR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4073696	NM_000372.5(TYR):c.1453G>C (p.Gly485Arg)	TYR	Likely pathogenic	criteria provided, single submitter
4073698	NM_000372.5(TYR):c.1366+4629A>G	TYR	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TYR	Orphanet:352734	Minimal pigment oculocutaneous albinism type 1
TYR	Orphanet:352737	Temperature-sensitive oculocutaneous albinism type 1
TYR	Orphanet:79431	Oculocutaneous albinism type 1A
TYR	Orphanet:79434	Oculocutaneous albinism type 1B
TYR	Orphanet:895	Waardenburg syndrome type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYR	P14679	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 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	TYR
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.004	TYR

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
eye pigment biosynthetic process	1	8426.0×	0.001	TYR
melanin biosynthetic process from tyrosine	1	4213.0×	0.001	TYR
response to blue light	1	3370.4×	0.001	TYR
melanin biosynthetic process	1	1296.3×	0.002	TYR
response to vitamin D	1	802.5×	0.003	TYR
pigmentation	1	702.2×	0.003	TYR
response to cAMP	1	510.7×	0.003	TYR
response to UV	1	366.4×	0.004	TYR
thymus development	1	337.0×	0.004	TYR
cell population proliferation	1	102.8×	0.011	TYR
visual perception	1	79.5×	0.013	TYR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TYR	ASCORBIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYR	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TYR	211	Binding:209, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYR	1.14.18.1	tyrosinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TYR	211

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

10 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.

Compound	Max phase	Cohort target (bioactivity)
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYR
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.