Dowling-Degos disease 4
diseaseOn this page
Also known as DDD4Dowling-Degos disease caused by mutation in POGLUT1Dowling-Degos disease type 4POGLUT1 Dowling-Degos disease
Summary
Dowling-Degos disease 4 (MONDO:0014307) is a disease caused by POGLUT1 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: POGLUT1 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 8
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Dowling-Degos disease 4 |
| Mondo ID | MONDO:0014307 |
| OMIM | 615696 |
| UMLS | C3810313 |
| MedGen | 816643 |
| GARD | 0016002 |
| Is cancer (heuristic) | no |
Also known as: DDD4 · Dowling-Degos disease 4 · Dowling-Degos disease caused by mutation in POGLUT1 · Dowling-Degos disease type 4 · POGLUT1 Dowling-Degos disease
Data availability: 8 ClinVar variants · 4 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 4
Related subtypes (3): Dowling-Degos disease 2, dowling-degos disease 3, 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
8 retrieved; paginated sample, class counts are floors:
3 pathogenic, 2 benign, 2 uncertain significance, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 126528 | NM_152305.3(POGLUT1):c.11G>A (p.Trp4Ter) | POGLUT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 126529 | NM_152305.3(POGLUT1):c.652C>T (p.Arg218Ter) | POGLUT1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 126530 | NM_152305.3(POGLUT1):c.798-2A>C | POGLUT1 | Pathogenic | no assertion criteria provided |
| 126531 | NM_152305.3(POGLUT1):c.835dup (p.Arg279fs) | POGLUT1 | Pathogenic | no assertion criteria provided |
| 126532 | NM_152305.3(POGLUT1):c.835C>T (p.Arg279Trp) | POGLUT1 | Uncertain significance | criteria provided, single submitter |
| 664362 | NM_152305.3(POGLUT1):c.733A>G (p.Met245Val) | POGLUT1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1235843 | NM_152305.3(POGLUT1):c.456+39G>T | POGLUT1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1251162 | NM_152305.3(POGLUT1):c.457-25G>A | POGLUT1 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| POGLUT1 | Strong | Autosomal dominant | Dowling-Degos disease 4 | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| POGLUT1 | Orphanet:480682 | POGLUT1-related limb-girdle muscular dystrophy R21 |
| POGLUT1 | 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 |
|---|---|---|---|---|---|
| POGLUT1 | HGNC:22954 | ENSG00000163389 | Q8NBL1 | Protein O-glucosyltransferase 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| POGLUT1 | Protein O-glucosyltransferase 1 | Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C. |
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) |
|---|---|---|---|---|
| POGLUT1 | Enzyme (other) | yes | 2.4.1.376 | CAP10, O-Glucosyltr/Glycosyltrsf_90 |
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 |
|---|---|
| monocyte | 1 |
| seminal vesicle | 1 |
| stromal cell of endometrium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| POGLUT1 | 254 | ubiquitous | marker | seminal vesicle, stromal cell of endometrium, monocyte |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| POGLUT1 | 800 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| POGLUT1 | Q8NBL1 | 6 |
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 | POGLUT1 |
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 xylose | 1 | 16852.0× | 7e-04 | POGLUT1 |
| axial mesoderm development | 1 | 3370.4× | 8e-04 | POGLUT1 |
| muscle tissue development | 1 | 3370.4× | 8e-04 | POGLUT1 |
| regulation of gastrulation | 1 | 2808.7× | 8e-04 | POGLUT1 |
| protein O-linked glycosylation via glucose | 1 | 2808.7× | 8e-04 | POGLUT1 |
| paraxial mesoderm development | 1 | 1685.2× | 0.001 | POGLUT1 |
| circulatory system development | 1 | 1404.3× | 0.001 | POGLUT1 |
| gastrulation | 1 | 702.2× | 0.002 | POGLUT1 |
| somitogenesis | 1 | 374.5× | 0.003 | POGLUT1 |
| positive regulation of Notch signaling pathway | 1 | 351.1× | 0.003 | POGLUT1 |
| protein O-linked glycosylation | 1 | 224.7× | 0.004 | POGLUT1 |
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 |
|---|---|---|
| POGLUT1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| POGLUT1 | 2.4.1.376, 2.4.2.63 | EGF-domain serine glucosyltransferase, EGF-domain serine xylosyltransferase |
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 | POGLUT1 |
| 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) |
|---|---|---|
| POGLUT1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: POGLUT1