Oculocutaneous albinism type 2

Summary

Oculocutaneous albinism type 2 (MONDO:0008746) is a disease caused by OCA2 (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: OCA2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 337
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.55	Worldwide	Validated
Point prevalence	6-9 / 10 000	58.34	Specific population	Validated
Point prevalence	6-9 / 10 000	71.43	Tanzania, United Republic of	Validated
Point prevalence	1-9 / 100 000	2.78	United States	Validated
Point prevalence	1-5 / 10 000	48.52	Africa	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000539	Abnormality of refraction	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0000635	Blue irides	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001010	Hypopigmentation of the skin	Frequent (30-79%)
HP:0001100	Heterochromia iridis	Frequent (30-79%)
HP:0001480	Freckling	Frequent (30-79%)
HP:0002226	White eyebrow	Frequent (30-79%)
HP:0005599	Hypopigmentation of hair	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0007703	Abnormality of retinal pigmentation	Frequent (30-79%)
HP:0007730	Iris hypopigmentation	Frequent (30-79%)
HP:0007750	Hypoplasia of the fovea	Frequent (30-79%)
HP:0007988	Macular hypopigmentation	Frequent (30-79%)
HP:0011364	White hair	Frequent (30-79%)
HP:0012805	Iris transillumination defect	Frequent (30-79%)
HP:0025551	Optic nerve misrouting	Frequent (30-79%)
HP:0002227	White eyelashes	Occasional (5-29%)
HP:0002671	Basal cell carcinoma	Occasional (5-29%)
HP:0006739	Squamous cell carcinoma of the skin	Occasional (5-29%)
HP:0012056	Cutaneous melanoma	Occasional (5-29%)
HP:0030856	Posterior staphyloma	Occasional (5-29%)
HP:0200098	Absent skin pigmentation	Occasional (5-29%)
HP:0007481	Hyperpigmented nevi	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 2
Mondo ID	MONDO:0008746
MeSH	C537730
OMIM	203200
Orphanet	79432
DOID	DOID:0070096
ICD-11	2019316252
UMLS	C0268495
MedGen	82810
GARD	0004038
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type 2 · albinism, oculocutaneous, type II · albinism, oculocutaneous, type II, modifier of · Albinoidism · OCA2 · oculocutaneous albinism type 2 · oculocutaneous albinism tyrosinase positive · oculocutaneous albinism, tyrosinase-positive · tyrosinase-positive oculocutaneous albinism

Data availability: 337 ClinVar variants · 7 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 2

Related subtypes (8): 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

337 retrieved; paginated sample, class counts are floors:

86 conflicting classifications of pathogenicity, 65 uncertain significance, 51 likely pathogenic, 50 pathogenic/likely pathogenic, 50 pathogenic, 18 benign, 14 benign/likely benign, 1 conflicting classifications of pathogenicity; risk factor, 1 not provided, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30906	nsv1197574	LOC132090298	Pathogenic	no assertion criteria provided
4077123	Single allele	LOC132090298	Pathogenic	criteria provided, single submitter
959	NG_009846.1:g.103171_225796del	LOC132090298	Pathogenic	no assertion criteria provided
217806	Single allele	LOC132090299	Pathogenic	no assertion criteria provided
1057881	NM_000275.3(OCA2):c.1580T>G (p.Leu527Arg)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070405	NM_000275.3(OCA2):c.157del (p.Arg53fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098719	Single allele	OCA2	Pathogenic	criteria provided, single submitter
1098720	Single allele	OCA2	Pathogenic	criteria provided, single submitter
1187746	NM_000275.3(OCA2):c.941T>G (p.Val314Gly)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1211398	NM_000275.3(OCA2):c.1349C>T (p.Thr450Met)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1216648	NM_000275.3(OCA2):c.868A>G (p.Arg290Gly)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1217688	NM_000275.3(OCA2):c.2086_2095del (p.Ala696fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324826	NM_000275.3(OCA2):c.1808del (p.Asn603fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332871	NM_000275.3(OCA2):c.1951+1G>C	OCA2	Pathogenic	criteria provided, single submitter
1388008	NM_000275.3(OCA2):c.1178G>T (p.Gly393Val)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1388929	NM_000275.3(OCA2):c.1504-2A>G	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1411558	NM_000275.3(OCA2):c.2244+1G>A	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1417098	NM_000275.3(OCA2):c.950del (p.Leu316_Leu317insTer)	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1420611	NM_000275.3(OCA2):c.403G>T (p.Glu135Ter)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1439928	NM_000275.3(OCA2):c.2338+1G>T	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1450195	NM_000275.3(OCA2):c.493C>T (p.Arg165Ter)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451123	NM_000275.3(OCA2):c.1076G>A (p.Gly359Asp)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454228	NM_000275.3(OCA2):c.74_78del (p.Pro25fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455886	NM_000275.3(OCA2):c.1056_1062del (p.Thr353fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458235	NM_000275.3(OCA2):c.1842+2T>C	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1700024	NM_000275.3(OCA2):c.646+1G>T	OCA2	Pathogenic	criteria provided, single submitter
1700025	NM_000275.3(OCA2):c.1365-1G>A	OCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1700026	NM_000275.3(OCA2):c.2225dup (p.Phe744fs)	OCA2	Pathogenic	criteria provided, single submitter
1704408	NM_000275.3(OCA2):c.374_375del (p.Glu125fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705444	NM_000275.3(OCA2):c.163dup (p.Ala55fs)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 9 · 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
MC1R	Moderate	Autosomal recessive	oculocutaneous albinism type 2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MC1R	Orphanet:618	Familial melanoma
MC1R	Orphanet:79432	Oculocutaneous albinism type 2
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
PDE6B	Orphanet:714096	Congenital stationary night blindness, Riggs type
PDE6B	Orphanet:791	Retinitis pigmentosa

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
MC1R	HGNC:6929	ENSG00000258839	Q01726	Melanocyte-stimulating hormone receptor	gencc,clinvar
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	gencc,clinvar
PDE6B	HGNC:8786	ENSG00000133256	P35913	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MC1R	Melanocyte-stimulating hormone receptor	G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein.
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.
PDE6B	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · 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
Ion channel	1	37.2×	0.080
GPCR	1	8.0×	0.180
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MC1R	GPCR	yes		GPCR_Rhodpsn, MSH_rcpt, Melcrt_ACTH_rcpt
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter
PDE6B	Transcription factor	no		PDEase_catalytic_dom, GAF, HD/PDEase_dom

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
right uterine tube	2
granulocyte	1
left testis	1
choroid plexus epithelium	1
pigmented layer of retina	1
secondary oocyte	1
C1 segment of cervical spinal cord	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MC1R	180	broad	yes	granulocyte, right uterine tube, left testis
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte
PDE6B	183	broad	marker	C1 segment of cervical spinal cord, right uterine tube, spinal cord

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OCA2	2,132
PDE6B	1,375
MC1R	1,169

Intra-cohort edges

A	B	Sources
MC1R	OCA2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MC1R	Q01726	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDE6B	P35913	89.72
OCA2	Q04671	73.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Melanin biosynthesis	1	761.3×	0.018	OCA2
Activation of the phototransduction cascade	1	317.2×	0.022	PDE6B
Inactivation, recovery and regulation of the phototransduction cascade	1	105.7×	0.044	PDE6B
Ca2+ pathway	1	59.5×	0.047	PDE6B
Transcriptional and post-translational regulation of MITF-M expression and activity	1	59.5×	0.047	MC1R
MITF-M-regulated melanocyte development	1	38.1×	0.061	MC1R
Class A/1 (Rhodopsin-like receptors)	1	24.7×	0.063	MC1R
Peptide ligand-binding receptors	1	24.7×	0.063	MC1R
G alpha (s) signalling events	1	24.4×	0.063	MC1R
GPCR ligand binding	1	21.4×	0.064	MC1R
GPCR downstream signalling	1	14.5×	0.085	MC1R
Signaling by GPCR	1	13.4×	0.085	MC1R
Developmental Biology	1	4.8×	0.208	MC1R
Signal Transduction	1	3.4×	0.267	MC1R

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
melanin biosynthetic process	2	864.2×	4e-05	MC1R, OCA2
retinal cell apoptotic process	1	2808.7×	0.004	PDE6B
melanin biosynthetic process from tyrosine	1	1404.3×	0.006	OCA2
lysosomal lumen pH elevation	1	1123.5×	0.006	OCA2
positive regulation of feeding behavior	1	802.5×	0.006	MC1R
positive regulation of melanin biosynthetic process	1	468.1×	0.007	MC1R
phototransduction, visible light	1	432.1×	0.007	PDE6B
UV-damage excision repair	1	432.1×	0.007	MC1R
UV protection	1	401.2×	0.007	MC1R
positive regulation of cAMP/PKA signal transduction	1	351.1×	0.007	MC1R
melanocyte differentiation	1	267.5×	0.008	OCA2
entrainment of circadian clock by photoperiod	1	244.2×	0.008	PDE6B
pigmentation	1	234.1×	0.008	MC1R
negative regulation of cAMP/PKA signal transduction	1	200.6×	0.009	PDE6B
sensory perception of pain	1	124.8×	0.013	MC1R
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1	104.0×	0.015	MC1R
retina development in camera-type eye	1	85.1×	0.017	PDE6B
negative regulation of tumor necrosis factor production	1	83.8×	0.017	MC1R
spermatid development	1	48.4×	0.027	OCA2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	43.9×	0.028	MC1R
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	37.7×	0.031	MC1R
cell population proliferation	1	34.2×	0.033	OCA2
visual perception	1	26.5×	0.041	PDE6B
intracellular signal transduction	1	12.7×	0.080	MC1R
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	MC1R

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
MC1R	BREMELANOTIDE
PDE6B	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MC1R	6	4
PDE6B	6	4
OCA2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BREMELANOTIDE	4	MC1R
SETMELANOTIDE	4	MC1R
AFAMELANOTIDE	4	MC1R
VARDENAFIL	4	PDE6B
SILDENAFIL	4	PDE6B
TADALAFIL	4	PDE6B
DIPYRIDAMOLE	4	PDE6B
INTERMEDINE	2	MC1R
PL-8177	2	MC1R
ZAPRINAST	2	PDE6B
TBA-7371	2	PDE6B
DERSIMELAGON PHOSPHATE	1	MC1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MC1R	319	Functional:164, Binding:155
PDE6B	57	Binding:54, ADMET:3

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MC1R	319

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

12 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)
BREMELANOTIDE	4	MC1R
SETMELANOTIDE	4	MC1R
AFAMELANOTIDE	4	MC1R
VARDENAFIL	4	PDE6B
SILDENAFIL	4	PDE6B
TADALAFIL	4	PDE6B
DIPYRIDAMOLE	4	PDE6B
INTERMEDINE	2	MC1R
PL-8177	2	MC1R
ZAPRINAST	2	PDE6B
TBA-7371	2	PDE6B
DERSIMELAGON PHOSPHATE	1	MC1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	MC1R, PDE6B
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	OCA2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
OCA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.