Oculocutaneous albinism type 7

Summary

Oculocutaneous albinism type 7 (MONDO:0014070) is a disease caused by LRMDA (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LRMDA (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 7
Mondo ID	MONDO:0014070
OMIM	615179
Orphanet	352745
DOID	DOID:0070100
SNOMED CT	722059002
UMLS	C3808786
MedGen	815116
GARD	0017531
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type VII · LRMDA oculocutaneous albinism · OCA7 · oculocutaneous albinism caused by mutation in LRMDA

Data availability: 12 ClinVar variants · 4 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 7

Related subtypes (8): oculocutaneous albinism type 2, oculocutaneous albinism type 3, oculocutaneous albinism type 4, 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

12 retrieved; paginated sample, class counts are floors:

3 benign, 3 uncertain significance, 2 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
280098	NM_001029896.2(WDR45):c.19C>T (p.Arg7Ter)	LOC126863256	Pathogenic	criteria provided, multiple submitters, no conflicts
41917	NM_001305581.2(LRMDA):c.150dup (p.Ala51fs)	LRMDA	Pathogenic	criteria provided, multiple submitters, no conflicts
209972	NM_001305581.2(LRMDA):c.351C>A (p.Asn117Lys)	LRMDA	Likely pathogenic	criteria provided, single submitter
41916	NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter)	LRMDA	Likely pathogenic	criteria provided, single submitter
261986	NM_001305581.2(LRMDA):c.193C>T (p.Leu65=)	LOC110121427	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891588	NM_001305581.2(LRMDA):c.2T>C (p.Met1Thr)	LRMDA	Uncertain significance	criteria provided, single submitter
3892887	NM_001029896.2(WDR45):c.577A>C (p.Ser193Arg)	WDR45	Uncertain significance	criteria provided, single submitter
540347	NM_001029896.2(WDR45):c.254C>T (p.Ala85Val)	WDR45	Uncertain significance	criteria provided, multiple submitters, no conflicts
1192588	NM_001305581.2(LRMDA):c.398+31A>C	LRMDA	Benign	criteria provided, multiple submitters, no conflicts
1192589	NM_001305581.2(LRMDA):c.516+53C>T	LRMDA	Benign	criteria provided, multiple submitters, no conflicts
261990	NM_001305581.2(LRMDA):c.364T>C (p.Leu122=)	LRMDA	Benign	criteria provided, multiple submitters, no conflicts
282969	NM_001029896.2(WDR45):c.838G>A (p.Val280Met)	WDR45	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
LRMDA	Strong	Autosomal recessive	oculocutaneous albinism type 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRMDA	Orphanet:352745	Oculocutaneous albinism type 7
WDR45	Orphanet:329284	Beta-propeller protein-associated neurodegeneration
WDR45	Orphanet:697160	Infantile epileptic spasms syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRMDA	HGNC:23405	ENSG00000148655	Q9H2I8	Leucine-rich melanocyte differentiation-associated protein	gencc,clinvar
WDR45	HGNC:28912	ENSG00000196998	Q9Y484	WD repeat domain phosphoinositide-interacting protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRMDA	Leucine-rich melanocyte differentiation-associated protein	Required for melanocyte differentiation.
WDR45	WD repeat domain phosphoinositide-interacting protein 4	Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRMDA	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, LRMDA
WDR45	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
left adrenal gland cortex	1
right adrenal gland cortex	1
apex of heart	1
granulocyte	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRMDA	208	ubiquitous	marker	calcaneal tendon, right adrenal gland cortex, left adrenal gland cortex
WDR45	293	ubiquitous	marker	apex of heart, mucosa of stomach, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR45	1,233
LRMDA	1,165

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR45	Q9Y484	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRMDA	Q9H2I8	78.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Macroautophagy	1	115.3×	0.009	WDR45

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nucleophagy	1	1685.2×	0.004	WDR45
glycophagy	1	702.2×	0.004	WDR45
pexophagy	1	526.6×	0.004	WDR45
protein localization to phagophore assembly site	1	495.6×	0.004	WDR45
melanocyte differentiation	1	401.2×	0.004	LRMDA
positive regulation of autophagosome assembly	1	401.2×	0.004	WDR45
autophagy of mitochondrion	1	366.4×	0.004	WDR45
autophagosome assembly	1	112.3×	0.011	WDR45
cellular response to starvation	1	96.8×	0.011	WDR45
autophagy	1	55.1×	0.018	WDR45

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRMDA	0	0
WDR45	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	LRMDA, WDR45

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRMDA	0	—
WDR45	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.