Weill-Marchesani 4 syndrome, recessive
diseaseOn this page
Also known as 15q26.3 microdeletion syndromeichthyosis-short stature-brachydactyly-microspherophakia syndromeWeill-Marchesani syndrome 4Weill-Marchesani-like syndromeWMS4
Summary
Weill-Marchesani 4 syndrome, recessive (MONDO:0013176) is a disease caused by ADAMTS17 (GenCC Definitive), with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: ADAMTS17 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 361
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 7 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Weill-Marchesani 4 syndrome, recessive |
| Mondo ID | MONDO:0013176 |
| MeSH | C567710 |
| OMIM | 613195 |
| Orphanet | 363992 |
| DOID | DOID:0061276 |
| UMLS | C2750787 |
| MedGen | 416383 |
| GARD | 0017579 |
| Is cancer (heuristic) | no |
Also known as: 15q26.3 microdeletion syndrome · ichthyosis-short stature-brachydactyly-microspherophakia syndrome · Weill-Marchesani syndrome 4 · Weill-Marchesani-like syndrome · WMS4
Data availability: 361 ClinVar variants · 6 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › Weill-Marchesani syndrome › Weill-Marchesani 4 syndrome, recessive
Related subtypes (3): Weill-Marchesani syndrome 1, Weill-Marchesani syndrome 2, dominant, Weill-Marchesani syndrome 3
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
361 retrieved; paginated sample, class counts are floors:
165 uncertain significance, 91 benign, 65 conflicting classifications of pathogenicity, 20 likely benign, 6 benign/likely benign, 5 likely pathogenic, 5 pathogenic, 4 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1687282 | NM_139057.4(ADAMTS17):c.662_665del (p.Glu221fs) | ADAMTS17 | Pathogenic | criteria provided, single submitter |
| 2570579 | NM_139057.4(ADAMTS17):c.2560C>T (p.Arg854Ter) | ADAMTS17 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3065118 | NM_139057.4(ADAMTS17):c.197_206del (p.Arg66fs) | ADAMTS17 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3153 | NM_139057.4(ADAMTS17):c.2456-1dup | ADAMTS17 | Pathogenic | no assertion criteria provided |
| 3154 | NM_139057.4(ADAMTS17):c.760C>T (p.Gln254Ter) | ADAMTS17 | Pathogenic | no assertion criteria provided |
| 4761867 | NM_139057.4(ADAMTS17):c.1297C>T (p.Arg433Ter) | ADAMTS17 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 492940 | NM_139057.4(ADAMTS17):c.652del (p.Asp218fs) | ADAMTS17 | Pathogenic | criteria provided, single submitter |
| 492941 | NM_139057.4(ADAMTS17):c.873+1G>T | ADAMTS17 | Pathogenic | no assertion criteria provided |
| 3155 | NM_139057.4(ADAMTS17):c.1721+1G>A | LOC130058037 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1210284 | NM_139057.4(ADAMTS17):c.2254A>G (p.Ile752Val) | ADAMTS17 | Likely pathogenic | no assertion criteria provided |
| 1210285 | NM_139057.4(ADAMTS17):c.2984G>A (p.Arg995Gln) | ADAMTS17 | Likely pathogenic | no assertion criteria provided |
| 2570576 | NM_139057.4(ADAMTS17):c.1239G>C (p.Met413Ile) | ADAMTS17 | Likely pathogenic | criteria provided, single submitter |
| 2570577 | NM_139057.4(ADAMTS17):c.1630G>T (p.Gly544Ter) | ADAMTS17 | Likely pathogenic | criteria provided, single submitter |
| 2570578 | NC_000015.10:g.(99976222_99993049)_(99997590_100048857)del | LOC113939942 | Likely pathogenic | criteria provided, single submitter |
| 1442566 | NM_139057.4(ADAMTS17):c.1873G>T (p.Ala625Ser) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1528321 | NM_139057.4(ADAMTS17):c.1924_1929dup (p.Lys642_Glu643dup) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315247 | NM_139057.4(ADAMTS17):c.3285G>A (p.Ser1095=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315250 | NM_139057.4(ADAMTS17):c.3165G>C (p.Thr1055=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315254 | NM_139057.4(ADAMTS17):c.3127+12C>T | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315256 | NM_139057.4(ADAMTS17):c.3068G>A (p.Cys1023Tyr) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315259 | NM_139057.4(ADAMTS17):c.2883G>A (p.Pro961=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315263 | NM_139057.4(ADAMTS17):c.2592-9G>A | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315264 | NM_139057.4(ADAMTS17):c.2592-10C>T | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315268 | NM_139057.4(ADAMTS17):c.2364G>A (p.Ala788=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315271 | NM_139057.4(ADAMTS17):c.2109G>A (p.Lys703=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315272 | NM_139057.4(ADAMTS17):c.2067C>T (p.Cys689=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315273 | NM_139057.4(ADAMTS17):c.2040C>T (p.Ile680=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315274 | NM_139057.4(ADAMTS17):c.2004C>T (p.His668=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315275 | NM_139057.4(ADAMTS17):c.1981T>C (p.Tyr661His) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 315276 | NM_139057.4(ADAMTS17):c.1971C>G (p.Pro657=) | ADAMTS17 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · 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 |
|---|---|---|---|---|
| ADAMTS17 | Definitive | Autosomal recessive | Weill-Marchesani 4 syndrome, recessive | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ADAMTS17 | Orphanet:3449 | Weill-Marchesani syndrome |
| ADAMTS17 | Orphanet:363992 | Ichthyosis-short stature-brachydactyly-microspherophakia syndrome |
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 |
|---|---|---|---|---|---|
| ADAMTS17 | HGNC:17109 | ENSG00000140470 | Q8TE56 | A disintegrin and metalloproteinase with thrombospondin motifs 17 | gencc,clinvar |
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 |
|---|---|---|---|
| Protease | 1 | 36.6× | 0.027 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ADAMTS17 | Protease | yes | TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N |
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 |
|---|---|
| primordial germ cell in gonad | 1 |
| right lobe of liver | 1 |
| thymus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ADAMTS17 | 177 | broad | marker | thymus, primordial germ cell in gonad, right lobe of liver |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ADAMTS17 | 817 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ADAMTS17 | Q8TE56 | 70.06 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. 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 B3GALTL causes PpS | 1 | 308.6× | 0.014 | ADAMTS17 |
| O-glycosylation of TSR domain-containing proteins | 1 | 300.5× | 0.014 | ADAMTS17 |
| Diseases associated with O-glycosylation of proteins | 1 | 215.5× | 0.014 | ADAMTS17 |
| O-linked glycosylation | 1 | 144.6× | 0.014 | ADAMTS17 |
| Diseases of glycosylation | 1 | 131.3× | 0.014 | ADAMTS17 |
| Diseases of metabolism | 1 | 80.4× | 0.019 | ADAMTS17 |
| Post-translational protein modification | 1 | 19.2× | 0.067 | ADAMTS17 |
| Disease | 1 | 13.1× | 0.081 | ADAMTS17 |
| Metabolism of proteins | 1 | 12.4× | 0.081 | ADAMTS17 |
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 |
|---|---|---|---|---|
| extracellular matrix organization | 1 | 122.1× | 0.016 | ADAMTS17 |
| proteolysis | 1 | 34.2× | 0.029 | ADAMTS17 |
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 |
|---|---|---|
| ADAMTS17 | 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 | 1 | ADAMTS17 |
| 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) |
|---|---|---|
| ADAMTS17 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: ADAMTS17