oculocutaneous albinism type 1A

Summary

oculocutaneous albinism type 1A (MONDO:0008745) is a disease caused by TYR (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: TYR (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 222
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.3	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001010	Hypopigmentation of the skin	Very frequent (80-99%)
HP:0001022	Albinism	Very frequent (80-99%)
HP:0001107	Ocular albinism	Very frequent (80-99%)
HP:0005599	Hypopigmentation of hair	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0007750	Hypoplasia of the fovea	Very frequent (80-99%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000587	Abnormal optic nerve morphology	Frequent (30-79%)
HP:0000649	Abnormality of visual evoked potentials	Frequent (30-79%)
HP:0001480	Freckling	Frequent (30-79%)
HP:0000962	Hyperkeratosis	Occasional (5-29%)
HP:0001072	Thickened skin	Occasional (5-29%)
HP:0002671	Basal cell carcinoma	Occasional (5-29%)
HP:0006739	Squamous cell carcinoma of the skin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 1A
Mondo ID	MONDO:0008745
OMIM	203100
Orphanet	79431
DOID	DOID:0070094
ICD-11	1168847652
NCIT	C168731
SNOMED CT	6483008
UMLS	C4551504
MedGen	1643910
GARD	0016721
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type IA · OCA1A · oculocutaneous albinism caused by mutation in TYR · oculocutaneous albinism caused by mutation in Tyr · oculocutaneous albinism, tyrosinase-negative · TYR oculocutaneous albinism · Tyr oculocutaneous albinism · tyrosinase-negative oculocutaneous albinism

Data availability: 222 ClinVar variants · 5 GenCC gene-disease records · 10 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: 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 › oculocutaneous albinism type 1A

Related subtypes (2): minimal pigment oculocutaneous albinism type 1, temperature-sensitive oculocutaneous albinism type 1

Subtypes (1): oculocutaneous albinism type 1B

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

222 retrieved; paginated sample, class counts are floors:

60 pathogenic/likely pathogenic, 59 likely pathogenic, 46 pathogenic, 29 conflicting classifications of pathogenicity, 23 uncertain significance, 2 likely benign, 1 not provided, 1 conflicting classifications of pathogenicity; other, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066111	NM_000372.5(TYR):c.132T>A (p.Ser44Arg)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1175803	NM_000372.5(TYR):c.1036+1G>A	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180809	NM_000372.5(TYR):c.996G>A (p.Met332Ile)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299540	NM_000372.5(TYR):c.859dup (p.Ser287fs)	TYR	Pathogenic	criteria provided, single submitter
1381832	NM_000372.5(TYR):c.1366+1G>T	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1390436	NM_000372.5(TYR):c.71G>A (p.Cys24Tyr)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1438386	NM_000372.5(TYR):c.773_774del (p.Thr258fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
144105	NM_000372.5(TYR):c.551C>G (p.Ser184Ter)	TYR	Pathogenic	criteria provided, single submitter
144106	NM_000372.5(TYR):c.739T>C (p.Cys247Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442280	NM_000372.5(TYR):c.290G>T (p.Gly97Val)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453014	NM_000372.5(TYR):c.216del (p.Val74fs)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1455534	NM_000372.5(TYR):c.626C>T (p.Pro209Leu)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458009	NM_000372.5(TYR):c.862_863del (p.Leu288fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458013	NM_000372.5(TYR):c.1036+2T>G	TYR	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
1458819	NM_000372.5(TYR):c.606T>G (p.His202Gln)	TYR	Pathogenic/Likely 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
212522	NM_000372.5(TYR):c.446A>G (p.Tyr149Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212523	NM_000372.5(TYR):c.658C>T (p.Gln220Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212524	NM_000372.5(TYR):c.661G>A (p.Glu221Lys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212705	NM_000372.5(TYR):c.580del (p.Ile194fs)	TYR	Pathogenic	criteria provided, single submitter
2137224	NM_000372.5(TYR):c.229C>G (p.Arg77Gly)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
2137228	NM_000372.5(TYR):c.593T>C (p.Ile198Thr)	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
2501774	NM_000372.5(TYR):c.1322del (p.Ser441fs)	TYR	Pathogenic	criteria provided, single submitter
2663760	NM_000372.5(TYR):c.255del (p.Phe84_Tyr85insTer)	TYR	Pathogenic	criteria provided, single submitter
2679405	NM_000372.5(TYR):c.1045_1046insAT (p.Ser349fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679408	NM_000372.5(TYR):c.241C>T (p.Pro81Ser)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2735722	NM_000372.5(TYR):c.425A>T (p.Lys142Met)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
2735734	NM_000372.5(TYR):c.1200G>T (p.Trp400Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
TYR	Definitive	Autosomal recessive	oculocutaneous albinism type 1A	10

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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	gencc,clinvar
DRD5	HGNC:3026	ENSG00000169676	P21918	D(1B) dopamine receptor	clinvar
NOX4	HGNC:7891	ENSG00000086991	Q9NPH5	NADPH oxidase 4	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.
DRD5	D(1B) dopamine receptor	Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
NOX4	NADPH oxidase 4	NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
GPCR	1	8.0×	0.345
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

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
DRD5	GPCR	yes		GPCR_Rhodpsn, Dopamine_D5_rcpt, Dopamine_rcpt
NOX4	Other/Unknown	no		Cyt_b245_heavy_chain, FAD-bd_8, Fe_red_NAD-bd_6

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
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
ileal mucosa	1
pancreatic ductal cell	1
tibialis anterior	1
calcaneal tendon	1
nephron tubule	1
renal glomerulus	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
DRD5	64	tissue_specific	yes	pancreatic ductal cell, tibialis anterior, ileal mucosa
NOX4	192	broad	marker	calcaneal tendon, nephron tubule, renal glomerulus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
NOX4	2,556
DRD5	1,086

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYR	P14679	1
DRD5	P21918	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NOX4	Q9NPH5	86.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dopamine receptors	1	761.3×	0.005	DRD5
Melanin biosynthesis	1	761.3×	0.005	TYR
STAT5 activation downstream of FLT3 ITD mutants	1	380.7×	0.006	NOX4
Signaling by FLT3 fusion proteins	1	190.3×	0.009	NOX4
Detoxification of Reactive Oxygen Species	1	100.2×	0.013	NOX4
Regulation of MITF-M-dependent genes involved in pigmentation	1	88.5×	0.013	TYR
G alpha (s) signalling events	1	24.4×	0.040	DRD5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete negative regulation of NAD(P)H oxidase activity	1	5617.3×	0.005	DRD5
regulation of female receptivity	1	5617.3×	0.005	DRD5
norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure	1	2808.7×	0.005	DRD5
eye pigment biosynthetic process	1	2808.7×	0.005	TYR
sensitization	1	1872.4×	0.005	DRD5
melanin biosynthetic process from tyrosine	1	1404.3×	0.005	TYR
regulation of systemic arterial blood pressure by vasopressin	1	1123.5×	0.005	DRD5
response to blue light	1	1123.5×	0.005	TYR
positive regulation of adenylate cyclase activity	1	1123.5×	0.005	DRD5
cellular response to catecholamine stimulus	1	802.5×	0.005	DRD5
synaptic transmission, dopaminergic	1	702.2×	0.005	DRD5
heart process	1	702.2×	0.005	NOX4
phospholipase C-activating dopamine receptor signaling pathway	1	702.2×	0.005	DRD5
G protein-coupled dopamine receptor signaling pathway	1	624.1×	0.005	DRD5
homocysteine metabolic process	1	624.1×	0.005	NOX4
reactive oxygen species biosynthetic process	1	624.1×	0.005	NOX4
adenylate cyclase-activating dopamine receptor signaling pathway	1	510.7×	0.006	DRD5
melanin biosynthetic process	1	432.1×	0.007	TYR
adenylate cyclase-activating adrenergic receptor signaling pathway	1	401.2×	0.007	DRD5
positive regulation of DNA biosynthetic process	1	374.5×	0.007	NOX4
superoxide metabolic process	1	330.4×	0.007	NOX4
long-term synaptic depression	1	295.6×	0.008	DRD5
response to vitamin D	1	267.5×	0.008	TYR
pigmentation	1	234.1×	0.009	TYR
superoxide anion generation	1	224.7×	0.009	NOX4
cardiac muscle cell differentiation	1	224.7×	0.009	NOX4
transmission of nerve impulse	1	216.1×	0.009	DRD5
negative regulation of blood pressure	1	216.1×	0.009	DRD5
response to cocaine	1	193.7×	0.009	DRD5
bone resorption	1	193.7×	0.009	NOX4

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 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
DRD5	IMIPRAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRD5	36	4
TYR	10	4
NOX4	5	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
IMIPRAMINE	4	DRD5
ARIPIPRAZOLE	4	DRD5
AMOXAPINE	4	DRD5
DIHYDROERGOTAMINE MESYLATE	4	DRD5
TEGASEROD MALEATE	4	DRD5
DOPAMINE HYDROCHLORIDE	4	DRD5
PALIPERIDONE	4	DRD5
DOXEPIN	4	DRD5
KETOTIFEN FUMARATE	4	DRD5
CARIPRAZINE	4	DRD5
BREXPIPRAZOLE	4	DRD5
MAPROTILINE	4	DRD5
LASMIDITAN	4	DRD5
CLOZAPINE	4	DRD5
APOMORPHINE	4	DRD5
HALOPERIDOL	4	DRD5
PROMAZINE	4	DRD5
ROPINIROLE	4	DRD5
DOPAMINE	4	DRD5
AMITRIPTYLINE	4	DRD5
CHLORPROMAZINE	4	DRD5
OLANZAPINE	4	DRD5
FLUPHENAZINE	4	DRD5
LOXAPINE	4	DRD5
RISPERIDONE	4	DRD5
CHLORPROTHIXENE	4	DRD5
CABERGOLINE	4	DRD5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DRD5	313	Binding:280, Functional:28, ADMET:5
TYR	211	Binding:209, ADMET:2
NOX4	29	Binding:27, Unclassified:1, Functional:1

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
DRD5	313

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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
IMIPRAMINE	4	DRD5
ARIPIPRAZOLE	4	DRD5
AMOXAPINE	4	DRD5
DIHYDROERGOTAMINE MESYLATE	4	DRD5
TEGASEROD MALEATE	4	DRD5
DOPAMINE HYDROCHLORIDE	4	DRD5
PALIPERIDONE	4	DRD5
DOXEPIN	4	DRD5
KETOTIFEN FUMARATE	4	DRD5
CARIPRAZINE	4	DRD5
BREXPIPRAZOLE	4	DRD5
MAPROTILINE	4	DRD5
LASMIDITAN	4	DRD5
CLOZAPINE	4	DRD5
APOMORPHINE	4	DRD5
HALOPERIDOL	4	DRD5
PROMAZINE	4	DRD5
ROPINIROLE	4	DRD5
DOPAMINE	4	DRD5
AMITRIPTYLINE	4	DRD5
CHLORPROMAZINE	4	DRD5
OLANZAPINE	4	DRD5
FLUPHENAZINE	4	DRD5
LOXAPINE	4	DRD5
RISPERIDONE	4	DRD5
CHLORPROTHIXENE	4	DRD5
CABERGOLINE	4	DRD5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TYR, DRD5
B	Phased (≥1) drug, not yet approved	1	NOX4
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.