Dowling-Degos disease 2

Summary

Dowling-Degos disease 2 (MONDO:0014130) is a disease caused by POFUT1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: POFUT1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 87

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Dowling-Degos disease 2
Mondo ID	MONDO:0014130
OMIM	615327
UMLS	C3809147
MedGen	815477
GARD	0015944
Is cancer (heuristic)	no

Also known as: DDD2 · Dowling-Degos disease 2 · Dowling-Degos disease caused by mutation in POFUT1 · Dowling-Degos disease type 2 · POFUT1 Dowling-Degos disease

Data availability: 87 ClinVar variants · 5 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 › reticulate pigment disorder › Dowling-Degos disease › Dowling-Degos disease 2

Related subtypes (3): dowling-degos disease 3, Dowling-Degos disease 4, Dowling-Degos disease 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

87 retrieved; paginated sample, class counts are floors:

31 uncertain significance, 28 likely benign, 18 benign, 5 pathogenic, 4 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344696	NM_015352.2(POFUT1):c.889_890del (p.Trp297fs)	POFUT1	Pathogenic	no assertion criteria provided
3252104	NM_015352.2(POFUT1):c.246+5del	POFUT1	Pathogenic	no assertion criteria provided
56808	NM_015352.2(POFUT1):c.430G>T (p.Glu144Ter)	POFUT1	Pathogenic	no assertion criteria provided
56809	NM_015352.2(POFUT1):c.482del (p.Lys161fs)	POFUT1	Pathogenic	no assertion criteria provided
574378	NM_015352.2(POFUT1):c.289C>T (p.Gln97Ter)	POFUT1	Pathogenic	criteria provided, single submitter
1533470	NM_015352.2(POFUT1):c.836C>T (p.Thr279Met)	POFUT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1046967	NM_015352.2(POFUT1):c.784A>G (p.Met262Val)	POFUT1	Uncertain significance	criteria provided, single submitter
1058589	NM_015352.2(POFUT1):c.416C>T (p.Thr139Met)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370881	NM_015352.2(POFUT1):c.814C>T (p.Arg272Cys)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1461585	NM_015352.2(POFUT1):c.671C>A (p.Ala224Asp)	POFUT1	Uncertain significance	criteria provided, single submitter
1492767	NM_015352.2(POFUT1):c.1036C>G (p.Gln346Glu)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1716975	NM_015352.2(POFUT1):c.394C>G (p.Gln132Glu)	POFUT1	Uncertain significance	criteria provided, single submitter
1984968	NM_015352.2(POFUT1):c.245A>C (p.Asn82Thr)	POFUT1	Uncertain significance	criteria provided, single submitter
2142663	NM_015352.2(POFUT1):c.698C>T (p.Pro233Leu)	POFUT1	Uncertain significance	criteria provided, single submitter
2188087	NM_015352.2(POFUT1):c.694C>T (p.Arg232Trp)	POFUT1	Uncertain significance	criteria provided, single submitter
2409829	NM_015352.2(POFUT1):c.227A>G (p.His76Arg)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2716879	NM_015352.2(POFUT1):c.188G>A (p.Arg63His)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2722718	NM_015352.2(POFUT1):c.1091G>A (p.Arg364Gln)	POFUT1	Uncertain significance	criteria provided, single submitter
2795389	NM_015352.2(POFUT1):c.1019A>G (p.Asp340Gly)	POFUT1	Uncertain significance	criteria provided, single submitter
2870892	NM_015352.2(POFUT1):c.971A>G (p.Lys324Arg)	POFUT1	Uncertain significance	criteria provided, single submitter
2971519	NM_015352.2(POFUT1):c.429+13G>A	POFUT1	Uncertain significance	criteria provided, single submitter
2976526	NM_015352.2(POFUT1):c.719G>A (p.Arg240His)	POFUT1	Uncertain significance	criteria provided, single submitter
3015660	NM_015352.2(POFUT1):c.480C>A (p.Asn160Lys)	POFUT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3623250	NM_015352.2(POFUT1):c.770C>G (p.Ala257Gly)	POFUT1	Uncertain significance	criteria provided, single submitter
3626689	NM_015352.2(POFUT1):c.1108G>A (p.Gly370Arg)	POFUT1	Uncertain significance	criteria provided, single submitter
3633993	NM_015352.2(POFUT1):c.307A>G (p.Ile103Val)	POFUT1	Uncertain significance	criteria provided, single submitter
3668841	NM_015352.2(POFUT1):c.246C>T (p.Asn82=)	POFUT1	Uncertain significance	criteria provided, single submitter
3702767	NM_015352.2(POFUT1):c.398G>A (p.Arg133Gln)	POFUT1	Uncertain significance	criteria provided, single submitter
4694346	NM_015352.2(POFUT1):c.502A>G (p.Ile168Val)	POFUT1	Uncertain significance	criteria provided, single submitter
4705789	NM_015352.2(POFUT1):c.424A>G (p.Met142Val)	POFUT1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
POFUT1	Definitive	Autosomal dominant	Dowling-Degos disease 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POFUT1	Orphanet:79145	Dowling-Degos disease

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
POFUT1	HGNC:14988	ENSG00000101346	Q9H488	GDP-fucose protein O-fucosyltransferase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POFUT1	GDP-fucose protein O-fucosyltransferase 1	Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cy…

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POFUT1	Enzyme (other)	yes	2.4.1.221	GDP-Fuc_O-FucTrfase, POFUT1

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
adrenal tissue	1
stromal cell of endometrium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POFUT1	160	ubiquitous	marker	stromal cell of endometrium, ventricular zone, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POFUT1	1,227

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POFUT1	Q9H488	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	1903.3×	5e-04	POFUT1

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
protein O-linked glycosylation via fucose	1	3370.4×	0.002	POFUT1
fucose metabolic process	1	2407.4×	0.002	POFUT1
regulation of Notch signaling pathway	1	842.6×	0.003	POFUT1
somitogenesis	1	374.5×	0.005	POFUT1
Notch signaling pathway	1	141.6×	0.011	POFUT1
heart development	1	78.8×	0.017	POFUT1
angiogenesis	1	62.4×	0.018	POFUT1
nervous system development	1	45.9×	0.022	POFUT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 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
POFUT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POFUT1	2.4.1.221	peptide-O-fucosyltransferase

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	POFUT1
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)
POFUT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.