Oculocutaneous albinism type 8

Summary

Oculocutaneous albinism type 8 (MONDO:0030899) is a disease caused by DCT (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DCT (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 8
Mondo ID	MONDO:0030899
OMIM	619165
Orphanet	597733
UMLS	C5436929
MedGen	1754121
GARD	0018017
Is cancer (heuristic)	no

Also known as: OCA8 · oculocutaneous albinism, type 8 · oculocutaneous albinism, type VIII

Data availability: 13 ClinVar variants · 2 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 8

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 6, 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

13 retrieved; paginated sample, class counts are floors:

5 pathogenic, 4 pathogenic/likely pathogenic, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1268230	NM_001922.5(DCT):c.176G>T (p.Gly59Val)	DCT	Pathogenic	no assertion criteria provided
1268231	NM_001922.5(DCT):c.876C>A (p.Tyr292Ter)	DCT	Pathogenic	no assertion criteria provided
1268232	NM_001922.5(DCT):c.1407G>A (p.Trp469Ter)	DCT	Pathogenic	no assertion criteria provided
3233659	NM_001922.5(DCT):c.212G>A (p.Trp71Ter)	DCT	Pathogenic	criteria provided, single submitter
3779220	NM_001922.5(DCT):c.697C>T (p.Arg233Ter)	DCT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4819284	NM_001922.5(DCT):c.976C>T (p.Arg326Ter)	DCT	Pathogenic	criteria provided, single submitter
929863	NM_001922.5(DCT):c.118T>A (p.Cys40Ser)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
929864	NM_001922.5(DCT):c.183C>G (p.Cys61Trp)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
930182	NM_001922.5(DCT):c.1307_1320del (p.Phe435_Phe436insTer)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
3893090	NM_001922.5(DCT):c.555dup (p.Val186fs)	DCT	Likely pathogenic	criteria provided, single submitter
3779221	NC_000004.12:g.94200007_94200023dup	SMARCAD1-DT	Likely pathogenic	criteria provided, single submitter
2688920	NM_001922.5(DCT):c.100A>C (p.Ser34Arg)	DCT	Uncertain significance	criteria provided, single submitter
3779219	NM_001922.5(DCT):c.638G>A (p.Gly213Glu)	DCT	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
DCT	Strong	Autosomal recessive	oculocutaneous albinism type 8	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCT	Orphanet:597733	Oculocutaneous albinism type 8

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCT	HGNC:2709	ENSG00000080166	P40126	L-dopachrome tautomerase	gencc,clinvar
SMARCAD1-DT	HGNC:53364	ENSG00000246541		SMARCAD1 divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCT	L-dopachrome tautomerase	Plays a role in melanin biosynthesis.

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)
DCT	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
SMARCAD1-DT	Other/Unknown	no

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)	1
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	1
upper arm skin	1
upper leg skin	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCT	184	broad	marker	upper leg skin, upper arm skin, secondary oocyte
SMARCAD1-DT	17		marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCT	1,692
SMARCAD1-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCT	P40126	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Melanin biosynthesis	1	2284.0×	9e-04	DCT
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.004	DCT

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
melanin biosynthetic process from tyrosine	1	4213.0×	7e-04	DCT
ventricular zone neuroblast division	1	4213.0×	7e-04	DCT
response to blue light	1	3370.4×	7e-04	DCT
developmental pigmentation	1	2106.5×	8e-04	DCT
cell development	1	887.0×	0.002	DCT
positive regulation of neuroblast proliferation	1	581.1×	0.002	DCT
epidermis development	1	210.7×	0.005	DCT

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
DCT	0	0
SMARCAD1-DT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	2	DCT, SMARCAD1-DT

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)
DCT	0	—
SMARCAD1-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.