Ocular albinism

Summary

Ocular albinism (MONDO:0017304) is a disease caused by GPR143 (GenCC Definitive), with 6 cohort genes and 1 clinical trial. The dominant Reactome pathway is Regulation of MITF-M-dependent genes involved in pigmentation (3 cohort genes).

At a glance

• Causal gene: GPR143 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 10
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ocular albinism
Mondo ID	MONDO:0017304
MeSH	D016117
Orphanet	284804
DOID	DOID:0050633
ICD-10-CM	E70.31
ICD-11	1147926040
SNOMED CT	26399002
UMLS	C0078917
MedGen	38147
GARD	0021124
MedDRA	10065276
NORD	1516
Is cancer (heuristic)	no

Also known as: ocular albinism · ocular albinism (disease) · XLOA

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record · 1 HPO phenotype.

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 › disorder of melanin metabolism › ocular albinism

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

Subtypes (3): ocular albinism with late-onset sensorineural deafness, X-linked recessive ocular albinism, autosomal recessive ocular 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

10 retrieved; paginated sample, class counts are floors:

3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 uncertain significance, 1 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
373941	NM_000273.3(GPR143):c.12_36del (p.Leu6fs)	GPR143	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191059	NM_014249.4(NR2E3):c.119-2A>C	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373911	NM_000372.5(TYR):c.74dup (p.Ser26fs)	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
3767241	NM_000273.3(GPR143):c.361-2A>G	GPR143	Likely pathogenic	criteria provided, single submitter
374021	NM_000550.3(TYRP1):c.670C>T (p.His224Tyr)	TYRP1	Likely pathogenic	criteria provided, single submitter
374020	NM_000550.3(TYRP1):c.1133A>G (p.Asn378Ser)	LURAP1L-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523363	NM_000372.5(TYR):c.1352A>G (p.Tyr451Cys)	TYR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1703816	NM_001261826.3(AP3D1):c.2516A>G (p.Lys839Arg)	AP3D1	Uncertain significance	criteria provided, single submitter
4279941	GRCh37/hg19 Xp22.2(chrX:9733608-9736005)x1	GPR143	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 12 · 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
GPR143	Definitive	X-linked	ocular albinism	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GPR143	Orphanet:54	X-linked recessive ocular albinism
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
TYRP1	Orphanet:79433	Oculocutaneous albinism type 3
AP3D1	Orphanet:1000	Ocular albinism with late-onset sensorineural deafness
AP3D1	Orphanet:54	X-linked recessive ocular albinism
AP3D1	Orphanet:664511	Early-onset severe Hermansky-Pudlak syndrome with hearing loss, due to AP3D1 deficiency
NR2E3	Orphanet:53540	Goldmann-Favre syndrome
NR2E3	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GPR143	HGNC:20145	ENSG00000101850	P51810	G-protein coupled receptor 143	gencc,clinvar
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar
TYRP1	HGNC:12450	ENSG00000107165	P17643	5,6-dihydroxyindole-2-carboxylic acid oxidase	clinvar
LURAP1L-AS1	HGNC:49761	ENSG00000235448		LURAP1L antisense RNA 1	clinvar
AP3D1	HGNC:568	ENSG00000065000	O14617	AP-3 complex subunit delta-1	clinvar
NR2E3	HGNC:7974	ENSG00000278570	Q9Y5X4	Photoreceptor-specific nuclear receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPR143	G-protein coupled receptor 143	Receptor for tyrosine, L-DOPA and dopamine.
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
TYRP1	5,6-dihydroxyindole-2-carboxylic acid oxidase	Plays a role in melanin biosynthesis.
AP3D1	AP-3 complex subunit delta-1	Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated.
NR2E3	Photoreceptor-specific nuclear receptor	Orphan nuclear receptor of retinal photoreceptor cells.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

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
Nuclear receptor	1	64.3×	0.046
Enzyme (other)	1	2.0×	0.458
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPR143	Other/Unknown	no		GPR143
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
TYRP1	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
LURAP1L-AS1	Other/Unknown	no
AP3D1	Other/Unknown	no		Clathrin/coatomer_adapt-like_N, AP3D_dom_metazoa, ARM-like
NR2E3	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt

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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pigmented layer of retina	3
male germ line stem cell (sensu Vertebrata) in testis	3
secondary oocyte	2
upper leg skin	2
oocyte	1
mammalian vulva	1
adrenal tissue	1
sural nerve	1
adenohypophysis	1
pituitary gland	1
tendon of biceps brachii	1
buccal mucosa cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPR143	170	broad	marker	oocyte, secondary oocyte, pigmented layer of retina
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
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
AP3D1	295	ubiquitous	marker	tendon of biceps brachii, adenohypophysis, pituitary gland
NR2E3	156	tissue_specific	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
TYRP1	2,635
AP3D1	2,108
GPR143	1,871
NR2E3	1,319
LURAP1L-AS1	0

Intra-cohort edges

A	B	Sources
GPR143	TYR	intact, string_interaction
GPR143	TYRP1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYRP1	P17643	13
AP3D1	O14617	6
TYR	P14679	1
NR2E3	Q9Y5X4	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GPR143	P51810	74.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 6 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
Regulation of MITF-M-dependent genes involved in pigmentation	3	199.2×	1e-06	GPR143, TYR, TYRP1
Melanin biosynthesis	2	1142.0×	2e-06	TYR, TYRP1
Amine ligand-binding receptors	1	86.5×	0.019	GPR143
Nuclear Receptor transcription pathway	1	50.1×	0.025	NR2E3
G alpha (q) signalling events	1	14.3×	0.068	GPR143

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
melanosome organization	3	388.9×	2e-06	GPR143, TYRP1, AP3D1
eye pigment biosynthetic process	2	3370.4×	2e-06	GPR143, TYR
melanin biosynthetic process	2	518.5×	9e-05	TYR, TYRP1
visual perception	3	47.7×	2e-04	GPR143, TYR, NR2E3
obsolete acetoacetic acid metabolic process	1	3370.4×	0.002	TYRP1
regulation of melanosome transport	1	3370.4×	0.002	GPR143
neurotransmitter receptor transport, postsynaptic endosome to lysosome	1	1685.2×	0.004	AP3D1
regulation of melanosome organization	1	1685.2×	0.004	GPR143
synaptic vesicle budding from endosome	1	1123.5×	0.004	AP3D1
melanin biosynthetic process from tyrosine	1	842.6×	0.004	TYR
positive regulation of NK T cell differentiation	1	842.6×	0.004	AP3D1
zinc ion import into lysosome	1	842.6×	0.004	AP3D1
response to blue light	1	674.1×	0.004	TYR
synaptic vesicle coating	1	674.1×	0.004	AP3D1
melanosome localization	1	674.1×	0.004	GPR143
synaptic vesicle membrane organization	1	674.1×	0.004	AP3D1
cell population proliferation	2	41.1×	0.004	TYR, NR2E3
clathrin-coated vesicle cargo loading, AP-3-mediated	1	481.5×	0.005	AP3D1
antigen processing and presentation, exogenous lipid antigen via MHC class Ib	1	481.5×	0.005	AP3D1
Golgi to vacuole transport	1	374.5×	0.007	AP3D1
endosome to melanosome transport	1	337.0×	0.007	AP3D1
positive regulation of melanin biosynthetic process	1	280.9×	0.008	TYRP1
protein targeting to vacuole	1	259.3×	0.008	AP3D1
synaptic vesicle recycling	1	240.7×	0.008	AP3D1
anterograde synaptic vesicle transport	1	198.3×	0.010	AP3D1
melanosome assembly	1	177.4×	0.011	AP3D1
eye photoreceptor cell development	1	168.5×	0.011	NR2E3
melanocyte differentiation	1	160.5×	0.011	TYRP1
response to vitamin D	1	160.5×	0.011	TYR
melanosome transport	1	153.2×	0.011	GPR143

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
GPR143	0	0
TYRP1	0	0
LURAP1L-AS1	0	0
AP3D1	0	0
NR2E3	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
NR2E3	6	Functional:5, Binding:1
GPR143	3	Binding:3
TYRP1	3	Binding:3
AP3D1	1	Binding: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

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	NR2E3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	GPR143, TYRP1, LURAP1L-AS1, AP3D1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GPR143	3	TYR
TYRP1	3	—
LURAP1L-AS1	0	—
AP3D1	1	—
NR2E3	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02200263	Not specified	COMPLETED	The Effects of Lutein and Zeaxanthin Supplementation on Vision in Patients With Albinism