Oculocutaneous albinism

Summary

Oculocutaneous albinism (MONDO:0018910) is a disease (an umbrella term covering 9 Mondo subtypes) with 5 cohort genes and 9 clinical trials. Top therapeutic interventions include carbidopa anhydrous, erythromycin, and levodopa.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 133
• Clinical trials: 9

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	5.9	Worldwide	Validated
Point prevalence	1-5 / 10 000	45	South Africa	Validated
Prevalence at birth	1-9 / 100 000	3.9	Denmark	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism
Mondo ID	MONDO:0018910
MeSH	D016115
OMIM	203100
Orphanet	55
DOID	DOID:0050632
ICD-10-CM	E70.32
ICD-11	1189424097
NCIT	C84941
SNOMED CT	63844009
UMLS	C0078918
MedGen	36250
GARD	0010958
NORD	1522
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous · non-syndromic oculocutaneous albinism · nonsyndromic oculocutaneous albinism · OCA

Data availability: 133 ClinVar variants · 2 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 9 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 › disorder of melanin metabolism › oculocutaneous albinism

Related subtypes (2): ocular albinism, syndromic oculocutaneous albinism

Subtypes (9): oculocutaneous albinism type 2, oculocutaneous albinism type 3, 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

133 retrieved; paginated sample, class counts are floors:

38 conflicting classifications of pathogenicity, 35 pathogenic/likely pathogenic, 29 pathogenic, 15 likely pathogenic, 13 uncertain significance, 2 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
667388	NM_205850.3(SLC24A5):c.1078+1G>A	MYEF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460031	NM_000275.3(OCA2):c.2323G>C (p.Gly775Arg)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
211767	NM_000275.3(OCA2):c.1427A>G (p.Asn476Ser)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137638	NM_000275.3(OCA2):c.287A>C (p.Glu96Ala)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2445913	NM_000275.3(OCA2):c.1911_1914del (p.Phe638fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
255717	NM_000275.3(OCA2):c.1080C>T (p.Ser360=)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581176	NM_000275.3(OCA2):c.2279A>T (p.Glu760Val)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677399	NM_000275.3(OCA2):c.406C>T (p.Arg136Ter)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
2677403	NM_000275.3(OCA2):c.1426A>G (p.Asn476Asp)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
2677404	NM_000275.3(OCA2):c.1832T>C (p.Leu611Pro)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
2736158	NM_000275.3(OCA2):c.2491G>C (p.Ala831Pro)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2907462	NM_000275.3(OCA2):c.1079C>T (p.Ser360Phe)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
373071	NM_000275.3(OCA2):c.440dup (p.Ser148fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430966	NM_000275.3(OCA2):c.2055del (p.Phe685fs)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
436090	NM_000275.3(OCA2):c.2339G>A (p.Gly780Asp)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627604	NM_000275.3(OCA2):c.2363C>T (p.Ser788Leu)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817597	NM_000275.3(OCA2):c.2051_2052delinsG (p.Phe684fs)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
817980	NM_000275.3(OCA2):c.565_566del (p.Leu189fs)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
953	NM_000275.3(OCA2):c.1842+1G>T	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
956	NM_000275.3(OCA2):c.2228C>T (p.Pro743Leu)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
960	NM_000275.3(OCA2):c.2037G>C (p.Trp679Cys)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
961	NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369307	NM_000372.5(TYR):c.706T>C (p.Trp236Arg)	TYR	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
1455534	NM_000372.5(TYR):c.626C>T (p.Pro209Leu)	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
1477155	NM_000372.5(TYR):c.1036G>A (p.Gly346Arg)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
2137222	NM_000372.5(TYR):c.124G>A (p.Asp42Asn)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
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

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 11 · 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
OCA2	Definitive	Autosomal recessive	oculocutaneous albinism type 2	7
PMEL	Limited	Autosomal recessive	oculocutaneous albinism

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OCA2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
OCA2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
OCA2	Orphanet:79432	Oculocutaneous albinism type 2
OCA2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
OCA2	Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion
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
HPS4	Orphanet:231500	Hermansky-Pudlak syndrome due to BLOC-3 deficiency

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	gencc,clinvar
PMEL	HGNC:10880	ENSG00000185664	P40967	Melanocyte protein PMEL	gencc
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar
HPS4	HGNC:15844	ENSG00000100099	Q9NQG7	BLOC-3 complex member HPS4	clinvar
MYEF2	HGNC:17940	ENSG00000104177	Q9P2K5	Myelin expression factor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OCA2	P protein	Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation.
PMEL	Melanocyte protein PMEL	Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation.
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
HPS4	BLOC-3 complex member HPS4	Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form.
MYEF2	Myelin expression factor 2	Transcriptional repressor of the myelin basic protein gene (MBP).

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.6

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
Ion channel	1	22.3×	0.176
Antibody/Immunoglobulin	1	5.8×	0.320
Enzyme (other)	1	2.4×	0.471
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter
PMEL	Antibody/Immunoglobulin	yes		PKD_dom, Ig-like_fold, PKD/Chitinase_dom
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
HPS4	Other/Unknown	no		HPS4, CCZ1/INTU/HSP4_longin_1, CCZ1/INTU/HSP4_longin_3
MYEF2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, MYEF2_RRM1

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pigmented layer of retina	3
upper leg skin	2
choroid plexus epithelium	1
secondary oocyte	1
mammalian vulva	1
male germ line stem cell (sensu Vertebrata) in testis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
ganglionic eminence	1
mucosa of stomach	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte
PMEL	175	broad	marker	pigmented layer of retina, upper leg skin, mammalian vulva
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
HPS4	261	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
MYEF2	249	ubiquitous	marker	ventricular zone, ganglionic eminence, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
OCA2	2,132
MYEF2	2,086
PMEL	1,901
HPS4	623

Intra-cohort edges

A	B	Sources
OCA2	TYR	string_interaction
PMEL	TYR	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PMEL	P40967	20
TYR	P14679	1
HPS4	Q9NQG7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OCA2	Q04671	73.79
MYEF2	Q9P2K5	62.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	2	1142.0×	3e-06	OCA2, TYR
Regulation of MITF-M-dependent genes involved in pigmentation	2	132.8×	1e-04	PMEL, TYR
RAB GEFs exchange GTP for GDP on RABs	1	31.0×	0.032	HPS4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanin biosynthetic process	3	777.8×	1e-07	OCA2, PMEL, TYR
melanin biosynthetic process from tyrosine	2	1685.2×	6e-06	OCA2, TYR
melanocyte differentiation	2	321.0×	1e-04	OCA2, HPS4
positive regulation of eye pigmentation	1	3370.4×	0.002	HPS4
eye pigment biosynthetic process	1	1685.2×	0.003	TYR
cell population proliferation	2	41.1×	0.004	OCA2, TYR
response to blue light	1	674.1×	0.005	TYR
lysosomal lumen pH elevation	1	674.1×	0.005	OCA2
myotube differentiation	1	421.3×	0.007	MYEF2
hemostasis	1	337.0×	0.008	HPS4
positive regulation of melanin biosynthetic process	1	280.9×	0.009	PMEL
melanosome assembly	1	177.4×	0.013	HPS4
response to vitamin D	1	160.5×	0.013	TYR
pigmentation	1	140.4×	0.013	TYR
platelet dense granule organization	1	134.8×	0.013	HPS4
melanosome organization	1	129.6×	0.013	PMEL
response to cAMP	1	102.1×	0.016	TYR
obsolete positive regulation of protein targeting to mitochondrion	1	99.1×	0.016	HPS4
protein targeting	1	73.3×	0.019	HPS4
response to UV	1	73.3×	0.019	TYR
thymus development	1	67.4×	0.020	TYR
lysosome organization	1	61.3×	0.021	HPS4
blood coagulation	1	34.8×	0.035	HPS4
spermatid development	1	29.1×	0.040	OCA2
neuron differentiation	1	20.1×	0.055	MYEF2
vesicle-mediated transport	1	19.3×	0.055	HPS4
visual perception	1	15.9×	0.064	TYR
protein stabilization	1	13.4×	0.073	HPS4

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Levodopa	Phase 2

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
OCA2	0	0
PMEL	0	0
HPS4	0	0
MYEF2	0	0

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: 5; 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	1	PMEL
D	Druggable family + AlphaFold only, no drug	1	OCA2
E	Difficult family or no structure, no drug	2	HPS4, MYEF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
OCA2	0	TYR
PMEL	0	TYR
HPS4	0	—
MYEF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT01663935	PHASE2	TERMINATED	Vision Response to Dopamine Replacement
NCT07313618	EARLY_PHASE1	RECRUITING	Safety and Efficacy of a Single Suprachoroidal Injection of JWK010 Gene Therapy in Subjects With Oculocutaneous Albinism Type 1 (OCA1)
NCT06138509	Not specified	RECRUITING	Peripheral Serotonin and Albinism
NCT00001153	Not specified	COMPLETED	Visual Function and Ocular Pigmentation in Albinism
NCT00808106	Not specified	COMPLETED	Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism
NCT02200263	Not specified	COMPLETED	The Effects of Lutein and Zeaxanthin Supplementation on Vision in Patients With Albinism
NCT04068961	Not specified	COMPLETED	New Strategies of Genetic Study of Patients With Oculocutaneous Albinism

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBIDOPA ANHYDROUS	4	3
ERYTHROMYCIN	4	1
LEVODOPA	4	1
PIRFENIDONE	4	1
PRAVASTATIN	4	1
ZILEUTON	4	1
CHEMBL5435500	0	1
CHEMBL351042	0	1