Dyschromatosis universalis hereditaria

Summary

Dyschromatosis universalis hereditaria (MONDO:0000736) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 9

Clinical features

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001034	Hypermelanotic macule	Very frequent (80-99%)
HP:0001053	Hypopigmented skin patches	Very frequent (80-99%)
HP:0005590	Spotty hypopigmentation	Very frequent (80-99%)
HP:0012733	Macule	Very frequent (80-99%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000992	Cutaneous photosensitivity	Frequent (30-79%)
HP:0001480	Freckling	Frequent (30-79%)
HP:0007565	Multiple cafe-au-lait spots	Frequent (30-79%)
HP:0004322	Short stature	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dyschromatosis universalis hereditaria
Mondo ID	MONDO:0000736
MeSH	C535730
OMIM	127500
Orphanet	241
DOID	DOID:0060304
ICD-11	480710406
NCIT	C173131
SNOMED CT	239082002
UMLS	C2930995
MedGen	419691
GARD	0001996
Is cancer (heuristic)	no

Also known as: DUH · dyschromatosis universalis

Data availability: 1 GenCC gene-disease record · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (23): cafe au lait spots, multiple, dermatopathia pigmentosa reticularis, dyschromatosis symmetrica hereditaria, extrasystoles-short stature-hyperpigmentation-microcephaly syndrome, gastrocutaneous syndrome, hyperkeratosis-hyperpigmentation syndrome, familial generalized lentiginosis, Naegeli-Franceschetti-Jadassohn syndrome, schwannomatosis, Dowling-Degos disease, H syndrome, Legius syndrome, familial progressive hyperpigmentation, linear and whorled nevoid hypermelanosis, reticulate acropigmentation of Kitamura, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome, leukonychia totalis-acanthosis-nigricans-like lesions-abnormal hair syndrome, osteopathia striata-pigmentary dermopathy-white forelock syndrome, phakomatosis pigmentovascularis, acromelanosis, hyperpigmentation, progressive cribriform and zosteriform, mosaic Legius syndrome

Subtypes (3): dyschromatosis universalis hereditaria 2, dyschromatosis universalis hereditaria 3, 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

No tiered GWAS variants or ClinVar records for this disease.

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

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.