Oculocutaneous albinism type 4

Summary

Oculocutaneous albinism type 4 (MONDO:0011683) is a disease caused by SLC45A2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC45A2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 131
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0007703	Abnormality of retinal pigmentation	Very frequent (80-99%)
HP:0007750	Hypoplasia of the fovea	Very frequent (80-99%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0001010	Hypopigmentation of the skin	Frequent (30-79%)
HP:0001022	Albinism	Frequent (30-79%)
HP:0001072	Thickened skin	Frequent (30-79%)
HP:0001107	Ocular albinism	Frequent (30-79%)
HP:0005599	Hypopigmentation of hair	Frequent (30-79%)
HP:0007730	Iris hypopigmentation	Frequent (30-79%)
HP:0011364	White hair	Frequent (30-79%)
HP:0025551	Optic nerve misrouting	Frequent (30-79%)
HP:0003764	Nevus	Very rare (<1-4%)
HP:0008069	Neoplasm of the skin	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 4
Mondo ID	MONDO:0011683
MeSH	C564696
OMIM	606574
Orphanet	79435
DOID	DOID:0070098
ICD-11	1286886811
SNOMED CT	715632003
UMLS	C1847836
MedGen	338324
GARD	0016722
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type IV · OCA4 · oculocutaneous albinism caused by mutation in SLC45A2 · SLC45A2 oculocutaneous albinism

Data availability: 131 ClinVar variants · 5 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 4

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

131 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 29 conflicting classifications of pathogenicity, 21 likely pathogenic, 18 pathogenic, 17 pathogenic/likely pathogenic, 2 benign, 2 benign/likely benign, 1 not provided, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184503	NM_016180.5(SLC45A2):c.533_534dup (p.Gly179fs)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1325093	NM_016180.5(SLC45A2):c.478G>C (p.Asp160His)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334440	NM_016180.5(SLC45A2):c.563G>T (p.Gly188Val)	SLC45A2	Pathogenic	criteria provided, single submitter
1338319	NM_016180.5(SLC45A2):c.1166_1167del (p.Lys389fs)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443630	NM_016180.5(SLC45A2):c.305G>A (p.Arg102Gln)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451393	NM_016180.5(SLC45A2):c.1280T>C (p.Leu427Pro)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1451395	NM_016180.5(SLC45A2):c.1256C>T (p.Pro419Leu)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451401	NM_016180.5(SLC45A2):c.277G>A (p.Asp93Asn)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1458150	NM_016180.5(SLC45A2):c.1156+1G>C	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458648	NM_016180.5(SLC45A2):c.802dup (p.Tyr268fs)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1512077	NM_016180.5(SLC45A2):c.365A>G (p.Asn122Ser)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2075883	NM_016180.5(SLC45A2):c.2T>C (p.Met1Thr)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209971	NM_016180.5(SLC45A2):c.1273del (p.Leu425fs)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
242518	NM_016180.5(SLC45A2):c.264del (p.Gly89fs)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734711	NM_016180.5(SLC45A2):c.113A>G (p.His38Arg)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2790804	NM_016180.5(SLC45A2):c.1014del (p.Phe338fs)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2820302	NM_016180.5(SLC45A2):c.798C>A (p.Tyr266Ter)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2838909	NM_016180.5(SLC45A2):c.1435del (p.Leu479fs)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
286788	NM_016180.5(SLC45A2):c.834C>G (p.Tyr278Ter)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2982245	NM_016180.5(SLC45A2):c.581del (p.Gly194fs)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3062089	NM_016180.5(SLC45A2):c.1266C>G (p.Tyr422Ter)	SLC45A2	Pathogenic	criteria provided, single submitter
3238625	NM_016180.5(SLC45A2):c.1157-765C>G	SLC45A2	Pathogenic	criteria provided, single submitter
3336588	NM_016180.5(SLC45A2):c.1456G>A (p.Ala486Thr)	SLC45A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
353216	NM_016180.5(SLC45A2):c.1076_1077del (p.Glu359fs)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
374397	NM_016180.5(SLC45A2):c.163dup (p.Tyr55fs)	SLC45A2	Pathogenic	no assertion criteria provided
436759	NM_016180.5(SLC45A2):c.1368+1G>T	SLC45A2	Pathogenic	criteria provided, single submitter
436760	NM_016180.5(SLC45A2):c.210C>A (p.Tyr70Ter)	SLC45A2	Pathogenic	criteria provided, single submitter
4498	NM_016180.5(SLC45A2):c.563-1G>A	SLC45A2	Pathogenic	no assertion criteria provided
4500	NM_016180.5(SLC45A2):c.986del (p.Thr329fs)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts
4503	NM_016180.5(SLC45A2):c.469G>A (p.Asp157Asn)	SLC45A2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 8 · 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
SLC45A2	Definitive	Autosomal recessive	oculocutaneous albinism type 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC45A2	Orphanet:79435	Oculocutaneous albinism type 4
MITF	Orphanet:293822	MITF-related melanoma and renal cell carcinoma predisposition syndrome
MITF	Orphanet:319298	Papillary renal cell carcinoma
MITF	Orphanet:404511	Clear cell papillary renal cell carcinoma
MITF	Orphanet:42665	Tietz syndrome
MITF	Orphanet:618	Familial melanoma
MITF	Orphanet:895	Waardenburg syndrome type 2
MITF	Orphanet:897	Waardenburg-Shah 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
SLC45A2	HGNC:16472	ENSG00000164175	Q9UMX9	Membrane-associated transporter protein	gencc,clinvar
MITF	HGNC:7105	ENSG00000187098	O75030	Microphthalmia-associated transcription factor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC45A2	Membrane-associated transporter protein	Proton-associated glucose and sucrose transporter.
MITF	Microphthalmia-associated transcription factor	Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC45A2	Transporter	yes		MFS, MFS_trans_sf
MITF	Transcription factor	no		bHLH_dom, MiT/TFE_C, MiT/TFE_N

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
pigmented layer of retina	2
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
retina	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC45A2	100	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, primordial germ cell in gonad
MITF	293	ubiquitous	marker	pigmented layer of retina, retina, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MITF	2,908
SLC45A2	1,295

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MITF	O75030	12

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC45A2	Q9UMX9	77.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 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 metabolism	1	1903.3×	0.006	MITF
Regulation of MITF-M dependent genes involved in invasion	1	1427.5×	0.006	MITF
Melanin biosynthesis	1	1142.0×	0.006	SLC45A2
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	815.7×	0.006	MITF
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	439.2×	0.007	MITF
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	335.9×	0.007	MITF
Regulation of MITF-M-dependent genes involved in apoptosis	1	317.2×	0.007	MITF
SUMOylation of transcription factors	1	285.5×	0.007	MITF
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	285.5×	0.007	MITF
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.014	MITF
SUMO E3 ligases SUMOylate target proteins	1	89.2×	0.018	MITF
Transcriptional and post-translational regulation of MITF-M expression and activity	1	89.2×	0.018	MITF
SUMOylation	1	81.6×	0.018	MITF
MITF-M-regulated melanocyte development	1	57.1×	0.024	MITF
Metabolism of amino acids and derivatives	1	33.8×	0.037	SLC45A2
Post-translational protein modification	1	9.6×	0.121	MITF
Developmental Biology	1	7.2×	0.149	MITF
Metabolism of proteins	1	6.2×	0.164	MITF
Metabolism	1	5.8×	0.165	SLC45A2

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
melanocyte apoptotic process	1	4213.0×	0.003	MITF
regulation of RNA biosynthetic process	1	4213.0×	0.003	MITF
sucrose transport	1	2808.7×	0.003	SLC45A2
melanin biosynthetic process from tyrosine	1	2106.5×	0.003	SLC45A2
lysosomal lumen pH elevation	1	1685.2×	0.003	SLC45A2
developmental pigmentation	1	1053.2×	0.004	SLC45A2
positive regulation of DNA-templated transcription initiation	1	936.2×	0.004	MITF
regulation of osteoclast differentiation	1	766.0×	0.004	MITF
bone remodeling	1	468.1×	0.006	MITF
melanocyte differentiation	1	401.2×	0.006	MITF
camera-type eye development	1	179.3×	0.012	MITF
osteoclast differentiation	1	172.0×	0.012	MITF
cell fate commitment	1	147.8×	0.013	MITF
regulation of cell population proliferation	1	57.7×	0.028	MITF
protein-containing complex assembly	1	56.9×	0.028	MITF
negative regulation of cell migration	1	55.8×	0.028	MITF
Wnt signaling pathway	1	49.9×	0.029	MITF
visual perception	1	39.8×	0.035	SLC45A2
positive regulation of gene expression	1	19.4×	0.067	MITF
negative regulation of apoptotic process	1	17.4×	0.071	MITF
regulation of DNA-templated transcription	1	15.8×	0.074	MITF
positive regulation of DNA-templated transcription	1	14.0×	0.080	MITF
negative regulation of transcription by RNA polymerase II	1	8.9×	0.119	MITF
positive regulation of transcription by RNA polymerase II	1	7.4×	0.135	MITF
regulation of transcription by RNA polymerase II	1	5.8×	0.164	MITF

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
MITF	PERHEXILINE MALEATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MITF	3	4
SLC45A2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PERHEXILINE MALEATE	4	MITF
NIFUROXAZIDE	3	MITF
HOMIDIUM BROMIDE	2	MITF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MITF	10	Functional:10

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

3 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)
PERHEXILINE MALEATE	4	MITF
NIFUROXAZIDE	3	MITF
HOMIDIUM BROMIDE	2	MITF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MITF
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SLC45A2
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)
SLC45A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.