Oculocutaneous albinism type 6

Summary

Oculocutaneous albinism type 6 (MONDO:0018264) is a disease caused by SLC24A5 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC24A5 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 11
• Phenotypes (HPO): 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001098	Abnormal fundus morphology	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0008034	Abnormal iris pigmentation	Very frequent (80-99%)
HP:0008059	Aplasia/Hypoplasia of the macula	Very frequent (80-99%)
HP:0030613	Abnormal foveal morphology on macular OCT	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 6
Mondo ID	MONDO:0018264
OMIM	113750
Orphanet	370097
DOID	DOID:0080614
SNOMED CT	722058005
UMLS	C3805375
MedGen	811705
GARD	0017599
Is cancer (heuristic)	no

Also known as: OCA6

Data availability: 11 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 6

Related subtypes (8): oculocutaneous albinism type 2, oculocutaneous albinism type 3, oculocutaneous albinism type 4, oculocutaneous albinism type 7, oculocutaneous albinism type 5, oculocutaneous albinism type 1, 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

11 retrieved; paginated sample, class counts are floors:

5 pathogenic, 3 uncertain significance, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2431038	NM_205850.3(SLC24A5):c.494C>G (p.Ser165Ter)	MYEF2	Pathogenic	criteria provided, single submitter
436742	NM_205850.3(SLC24A5):c.528T>A (p.Cys176Ter)	MYEF2	Pathogenic	criteria provided, single submitter
440483	NM_205850.3(SLC24A5):c.641del (p.Leu214fs)	MYEF2	Pathogenic	criteria provided, single submitter
440484	NM_205850.3(SLC24A5):c.521G>A (p.Arg174Lys)	MYEF2	Pathogenic	no assertion criteria provided
60559	NM_205850.3(SLC24A5):c.591G>A (p.Trp197Ter)	MYEF2	Pathogenic	no assertion criteria provided
60560	NM_205850.3(SLC24A5):c.1361dup (p.Leu454fs)	MYEF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3027497	NM_205850.3(SLC24A5):c.301+1G>T	SLC24A5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4073705	NM_205850.3(SLC24A5):c.328G>C (p.Gly110Arg)	SLC24A5	Likely pathogenic	criteria provided, single submitter
2188917	NM_205850.3(SLC24A5):c.1325C>A (p.Thr442Asn)	MYEF2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4073706	NM_205850.3(SLC24A5):c.598G>A (p.Gly200Arg)	MYEF2	Uncertain significance	criteria provided, single submitter
4683114	NM_205850.3(SLC24A5):c.451C>A (p.Leu151Ile)	SLC24A5	Uncertain significance	criteria provided, single submitter

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
SLC24A5	Definitive	Autosomal recessive	oculocutaneous albinism type 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC24A5	Orphanet:370097	Oculocutaneous albinism type 6

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
SLC24A5	HGNC:20611	ENSG00000188467	Q71RS6	Sodium/potassium/calcium exchanger 5	gencc,clinvar
MYEF2	HGNC:17940	ENSG00000104177	Q9P2K5	Myelin expression factor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC24A5	Sodium/potassium/calcium exchanger 5	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+).
MYEF2	Myelin expression factor 2	Transcriptional repressor of the myelin basic protein gene (MBP).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC24A5	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
MYEF2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, MYEF2_RRM1

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
male germ line stem cell (sensu Vertebrata) in testis	1
quadriceps femoris	1
skin of abdomen	1
ganglionic eminence	1
mucosa of stomach	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC24A5	59	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, quadriceps femoris, skin of abdomen
MYEF2	249	ubiquitous	marker	ventricular zone, ganglionic eminence, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYEF2	2,086
SLC24A5	1,093

Intra-cohort edges

A	B	Sources
MYEF2	SLC24A5	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC24A5	Q71RS6	76.63
MYEF2	Q9P2K5	62.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Defective SLC24A5 causes oculocutaneous albinism 6 (OCA6)	1	11420.0×	7e-04	SLC24A5
Sodium/Calcium exchangers	1	1038.2×	0.004	SLC24A5
SLC transporter disorders	1	203.9×	0.012	SLC24A5
Disorders of transmembrane transporters	1	139.3×	0.012	SLC24A5
R-HSA-425393	1	129.8×	0.012	SLC24A5
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC24A5
Transport of small molecules	1	25.1×	0.045	SLC24A5
Disease	1	13.1×	0.076	SLC24A5

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
negative regulation of melanin biosynthetic process	1	1203.7×	0.004	SLC24A5
myotube differentiation	1	1053.2×	0.004	MYEF2
melanin biosynthetic process	1	648.1×	0.005	SLC24A5
calcium ion import	1	401.2×	0.006	SLC24A5
calcium ion transmembrane transport	1	105.3×	0.014	SLC24A5
monoatomic ion transmembrane transport	1	104.0×	0.014	SLC24A5
monoatomic ion transport	1	78.0×	0.015	SLC24A5
intracellular calcium ion homeostasis	1	72.6×	0.015	SLC24A5
neuron differentiation	1	50.1×	0.020	MYEF2

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
SLC24A5	0	0
MYEF2	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	SLC24A5, MYEF2

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)
SLC24A5	0	—
MYEF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.