Dyschromatosis universalis hereditaria 3

Summary

Dyschromatosis universalis hereditaria 3 (MONDO:0014169) is a disease caused by ABCB6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ABCB6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyschromatosis universalis hereditaria 3
Mondo ID	MONDO:0014169
OMIM	615402
UMLS	C3809394
MedGen	815724
GARD	0015959
Is cancer (heuristic)	no

Also known as: ABCB6 dyschromatosis universalis hereditaria · DUH3 · dyschromatosis universalis hereditaria 3 · dyschromatosis universalis hereditaria caused by mutation in ABCB6 · dyschromatosis universalis hereditaria type 3

Data availability: 16 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › skin pigmentation disorder › hyperpigmentation of the skin › dyschromatosis universalis hereditaria › dyschromatosis universalis hereditaria 3

Related subtypes (2): dyschromatosis universalis hereditaria 2, dyschromatosis universalis hereditaria 1

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

16 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
208249	NM_005689.4(ABCB6):c.1663C>A (p.Gln555Lys)	ABCB6	Pathogenic	no assertion criteria provided
64646	NM_005689.4(ABCB6):c.1067T>C (p.Leu356Pro)	ABCB6	Pathogenic	no assertion criteria provided
64647	NM_005689.4(ABCB6):c.508A>G (p.Ser170Gly)	ABCB6	Pathogenic	no assertion criteria provided
64648	NM_005689.4(ABCB6):c.1736G>A (p.Gly579Glu)	ABCB6	Pathogenic	no assertion criteria provided
218180	NM_005689.4(ABCB6):c.1123C>T (p.Arg375Trp)	ABCB6	Likely pathogenic	criteria provided, single submitter
3066330	NM_005689.4(ABCB6):c.1452+2T>A	ABCB6	Likely pathogenic	criteria provided, single submitter
1283915	NM_005689.4(ABCB6):c.1511T>C (p.Val504Ala)	ABCB6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
771341	NM_005689.4(ABCB6):c.1361T>C (p.Val454Ala)	ABCB6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1686417	NM_005689.4(ABCB6):c.459del (p.Trp154fs)	ABCB6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2054878	NM_005689.4(ABCB6):c.1694T>C (p.Phe565Ser)	ABCB6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2438736	NM_005689.4(ABCB6):c.659A>T (p.Glu220Val)	ABCB6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065232	NM_005689.4(ABCB6):c.2029A>T (p.Asn677Tyr)	ABCB6	Uncertain significance	criteria provided, single submitter
3377363	NM_005689.4(ABCB6):c.192G>C (p.Trp64Cys)	ABCB6	Uncertain significance	criteria provided, single submitter
3585678	NM_005689.4(ABCB6):c.2359A>G (p.Thr787Ala)	ABCB6	Uncertain significance	criteria provided, single submitter
3585679	NM_005689.4(ABCB6):c.1864-4A>G	ABCB6	Uncertain significance	criteria provided, single submitter
783355	NM_005689.4(ABCB6):c.688-9C>T	ABCB6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 9 · 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
ABCB6	Strong	Autosomal dominant	dyschromatosis universalis hereditaria 3	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCB6	Orphanet:241	Dyschromatosis universalis hereditaria
ABCB6	Orphanet:90044	Familial pseudohyperkalemia
ABCB6	Orphanet:98938	Colobomatous microphthalmia
ABCB6	Orphanet:98942	Coloboma of choroid and retina
ABCB6	Orphanet:98943	Coloboma of eye lens
ABCB6	Orphanet:98944	Coloboma of iris
ABCB6	Orphanet:98945	Coloboma of macula
ABCB6	Orphanet:98946	Coloboma of eyelid
ABCB6	Orphanet:98947	Coloboma of optic disc

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
ABCB6	HGNC:47	ENSG00000115657	Q9NP58	ATP-binding cassette sub-family B member 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCB6	ATP-binding cassette sub-family B member 6	ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCB6	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom

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
left ovary	1
right hemisphere of cerebellum	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCB6	140	ubiquitous	marker	right ovary, right hemisphere of cerebellum, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB6	1,480

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB6	Q9NP58	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Defective ABCB6 causes MCOPCB7	1	11420.0×	6e-04	ABCB6
Mitochondrial ABC transporters	1	2855.0×	0.001	ABCB6
ABC transporter disorders	1	439.2×	0.005	ABCB6
Disorders of transmembrane transporters	1	139.3×	0.012	ABCB6
ABC-family protein mediated transport	1	121.5×	0.012	ABCB6
Transport of small molecules	1	25.1×	0.046	ABCB6
Disease	1	13.1×	0.076	ABCB6

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
tetrapyrrole metabolic process	1	16852.0×	5e-04	ABCB6
heme transmembrane transport	1	8426.0×	5e-04	ABCB6
cellular detoxification of cadmium ion	1	5617.3×	5e-04	ABCB6
porphyrin-containing compound metabolic process	1	4213.0×	5e-04	ABCB6
porphyrin-containing compound biosynthetic process	1	4213.0×	5e-04	ABCB6
heme transport	1	4213.0×	5e-04	ABCB6
heme metabolic process	1	3370.4×	6e-04	ABCB6
intracellular copper ion homeostasis	1	936.2×	0.002	ABCB6
melanosome assembly	1	887.0×	0.002	ABCB6
skin development	1	443.5×	0.003	ABCB6
intracellular iron ion homeostasis	1	244.2×	0.005	ABCB6
transmembrane transport	1	168.5×	0.006	ABCB6
brain development	1	79.5×	0.013	ABCB6

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
ABCB6	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
ABCB6	3	Functional: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	1	ABCB6
D	Druggable family + AlphaFold only, no drug	0
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)
ABCB6	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.