X-linked recessive ocular albinism

Summary

X-linked recessive ocular albinism (MONDO:0021019) is a disease caused by GPR143 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: GPR143 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 44
• Phenotypes (HPO): 14

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.58	Europe	Validated
Point prevalence	1-9 / 1 000 000		Denmark	Validated
Prevalence at birth	1-9 / 1 000 000	0.84	Denmark	Validated
Prevalence at birth	1-9 / 100 000	1	United States	Validated
Point prevalence	1-9 / 100 000		United States	Not yet validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0000483	Astigmatism	Very frequent (80-99%)
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0000615	Abnormal pupil morphology	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001107	Ocular albinism	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001103	Abnormal macular morphology	Frequent (30-79%)
HP:0001480	Freckling	Frequent (30-79%)
HP:0007750	Hypoplasia of the fovea	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0005592	Giant melanosomes in melanocytes	Occasional (5-29%)
HP:0008069	Neoplasm of the skin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked recessive ocular albinism
Mondo ID	MONDO:0021019
MeSH	C537863
OMIM	300500
Orphanet	54
ICD-11	846740259
NCIT	C118785
SNOMED CT	78642008
UMLS	C0342684
MedGen	90991
GARD	0008471
Is cancer (heuristic)	no

Also known as: albinism, ocular, type I · Nettleship-Falls syndrome · OA1 · ocular albinism type 1 · ocular albinism, Nettleship-Falls type · ocular albinism, type I, Nettleship-Falls type · X-linked ocular albinism · XLOA

Data availability: 44 ClinVar variants · 2 GenCC gene-disease records · 3 cell lines.

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 › ocular albinism › X-linked recessive ocular albinism

Related subtypes (2): ocular albinism with late-onset sensorineural deafness, 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

44 retrieved; paginated sample, class counts are floors:

23 pathogenic, 8 likely pathogenic, 4 uncertain significance, 4 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
10514	NM_000273.3(GPR143):c.933_934dup (p.Gly312fs)	GPR143	Pathogenic	no assertion criteria provided
10518	NM_000273.3(GPR143):c.695C>A (p.Thr232Lys)	GPR143	Pathogenic	no assertion criteria provided
10519	NM_000273.3(GPR143):c.397T>A (p.Trp133Arg)	GPR143	Pathogenic	no assertion criteria provided
10521	NM_000273.3(GPR143):c.104G>A (p.Gly35Asp)	GPR143	Pathogenic	no assertion criteria provided
1184536	NM_000273.3(GPR143):c.346T>G (p.Cys116Gly)	GPR143	Pathogenic	criteria provided, single submitter
1213999	NM_000273.3(GPR143):c.361-2A>C	GPR143	Pathogenic	criteria provided, single submitter
1308636	NM_000273.3(GPR143):c.360+2T>C	GPR143	Pathogenic	criteria provided, multiple submitters, no conflicts
1323033	NM_000273.3(GPR143):c.73C>T (p.Gln25Ter)	GPR143	Pathogenic	criteria provided, multiple submitters, no conflicts
1408135	NM_000273.3(GPR143):c.885+748G>A	GPR143	Pathogenic	criteria provided, multiple submitters, no conflicts
1527939	NM_000273.3(GPR143):c.548+2T>C	GPR143	Pathogenic	criteria provided, single submitter
1805629	NM_000273.3(GPR143):c.36del (p.Thr13fs)	GPR143	Pathogenic	criteria provided, single submitter
2138471	NM_000273.3(GPR143):c.703G>A (p.Glu235Lys)	GPR143	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2580351	GRCh37/hg19 Xp22.2(chrX:9702717-9709328)x0	GPR143	Pathogenic	criteria provided, single submitter
29984	NC_000023.9:g.9688757-?_9693917+?del	GPR143	Pathogenic	no assertion criteria provided
3602102	NM_000273.3(GPR143):c.370C>T (p.Gln124Ter)	GPR143	Pathogenic	criteria provided, single submitter
373941	NM_000273.3(GPR143):c.12_36del (p.Leu6fs)	GPR143	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4077132	NM_000273.3(GPR143):c.333G>A (p.Trp111Ter)	GPR143	Pathogenic	criteria provided, single submitter
4077133	NM_000273.3(GPR143):c.360+1G>A	GPR143	Pathogenic	criteria provided, single submitter
4077134	NM_000273.3(GPR143):c.707GGA[1] (p.Arg237del)	GPR143	Pathogenic	criteria provided, single submitter
4077135	NM_000273.3(GPR143):c.768_769del (p.Cys256fs)	GPR143	Pathogenic	criteria provided, single submitter
4077137	NM_000273.3(GPR143):c.904del (p.Gln302fs)	GPR143	Pathogenic	criteria provided, single submitter
4819418	NM_000273.3(GPR143):c.121_148del (p.Leu41fs)	GPR143	Pathogenic	criteria provided, single submitter
4819425	NM_000273.3(GPR143):c.659_767del	GPR143	Pathogenic	criteria provided, single submitter
915839	NM_000273.3(GPR143):c.548+2T>A	GPR143	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98619	NM_000273.3(GPR143):c.216_232del (p.Ala73fs)	GPR143	Pathogenic	no assertion criteria provided
98643	NM_000273.3(GPR143):c.756_767+2del	GPR143	Pathogenic	no assertion criteria provided
98650	NM_000273.3(GPR143):c.885+1G>A	GPR143	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1012853	NM_000273.3(GPR143):c.935G>T (p.Gly312Val)	GPR143	Likely pathogenic	criteria provided, multiple submitters, no conflicts
10516	NM_000273.3(GPR143):c.397T>C (p.Trp133Arg)	GPR143	Likely pathogenic	criteria provided, single submitter
1184535	NM_000273.3(GPR143):c.767+1G>A	GPR143	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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

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
GPR143	HGNC:20145	ENSG00000101850	P51810	G-protein coupled receptor 143	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPR143	Other/Unknown	no		GPR143

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
oocyte	1
pigmented layer of retina	1
secondary oocyte	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPR143	1,871

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GPR143	P51810	74.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Amine ligand-binding receptors	1	346.1×	0.006	GPR143
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.006	GPR143
G alpha (q) signalling events	1	57.4×	0.017	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of melanosome transport	1	16852.0×	4e-04	GPR143
eye pigment biosynthetic process	1	8426.0×	4e-04	GPR143
regulation of melanosome organization	1	8426.0×	4e-04	GPR143
melanosome localization	1	3370.4×	7e-04	GPR143
melanosome transport	1	766.0×	0.003	GPR143
melanosome organization	1	648.1×	0.003	GPR143
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.011	GPR143
visual perception	1	79.5×	0.016	GPR143
G protein-coupled receptor signaling pathway	1	36.2×	0.031	GPR143
signal transduction	1	16.1×	0.062	GPR143

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GPR143	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GPR143	3	Binding:3

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	GPR143

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)
GPR143	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.