autosomal dominant Robinow syndrome 3
diseaseOn this page
Also known as autosomal dominant Robinow syndrome type 3DRS3DVL3 Robinow syndromeRobinow syndrome caused by mutation in DVL3Robinow syndrome, autosomal dominant 3Robinow syndrome, autosomal dominant type 3
Summary
autosomal dominant Robinow syndrome 3 (MONDO:0014819) is a disease caused by DVL3 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: DVL3 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 29
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | autosomal dominant Robinow syndrome 3 |
| Mondo ID | MONDO:0014819 |
| OMIM | 616894 |
| DOID | DOID:0060767 |
| UMLS | C4225164 |
| MedGen | 907878 |
| GARD | 0018549 |
| Is cancer (heuristic) | no |
Also known as: autosomal dominant Robinow syndrome type 3 · DRS3 · DVL3 Robinow syndrome · Robinow syndrome caused by mutation in DVL3 · Robinow syndrome, autosomal dominant 3 · Robinow syndrome, autosomal dominant type 3
Data availability: 29 ClinVar variants · 3 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 › autosomal dominant disease › autosomal dominant Robinow syndrome › autosomal dominant Robinow syndrome 3
Related subtypes (2): autosomal dominant Robinow syndrome 2, autosomal dominant Robinow syndrome 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
29 retrieved; paginated sample, class counts are floors:
13 uncertain significance, 7 pathogenic, 5 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 219218 | NM_004423.4(DVL3):c.1585del (p.Ala529fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 219219 | NM_004423.4(DVL3):c.1715-2A>G | DVL3 | Pathogenic | criteria provided, single submitter |
| 219220 | NM_004423.4(DVL3):c.1715-1G>A | DVL3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 219221 | NM_004423.4(DVL3):c.1716del (p.Ser573fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 219222 | NM_004423.4(DVL3):c.1749del (p.Ser583fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 3764613 | NM_004423.4(DVL3):c.1672_1705del (p.Tyr558fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 689755 | NM_004423.4(DVL3):c.1592del (p.Pro531fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 817264 | NM_004423.4(DVL3):c.1751_1754del (p.Asp584fs) | DVL3 | Pathogenic | criteria provided, single submitter |
| 488050 | NM_001466.4(FZD2):c.1301G>T (p.Gly434Val) | FZD2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1333918 | NM_004423.4(DVL3):c.1473C>G (p.Tyr491Ter) | DVL3 | Likely pathogenic | criteria provided, single submitter |
| 2664033 | NM_004423.4(DVL3):c.292del (p.Glu98fs) | DVL3 | Likely pathogenic | no assertion criteria provided |
| 3775469 | NM_004423.4(DVL3):c.1688dup (p.Ser564fs) | DVL3 | Likely pathogenic | criteria provided, single submitter |
| 800837 | NM_004423.4(DVL3):c.1715-1G>C | DVL3 | Likely pathogenic | no assertion criteria provided |
| 981469 | NM_004423.4(DVL3):c.1715-2del | DVL3 | Likely pathogenic | no assertion criteria provided |
| 1445049 | NM_004423.4(DVL3):c.683G>A (p.Arg228Gln) | DVL3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2482080 | NM_004423.4(DVL3):c.466A>T (p.Thr156Ser) | DVL3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2095173 | NM_004423.4(DVL3):c.950G>A (p.Arg317Gln) | DVL3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2441051 | NM_004423.4(DVL3):c.1949_1950del (p.His650fs) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 2441052 | NM_004423.4(DVL3):c.1738C>T (p.Arg580Cys) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 2985708 | NM_004423.4(DVL3):c.808G>A (p.Glu270Lys) | DVL3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3233373 | NM_004423.4(DVL3):c.903G>C (p.Gln301His) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 3338369 | NM_004423.4(DVL3):c.1947_1950del (p.His650fs) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 3376190 | NM_004423.4(DVL3):c.899T>C (p.Leu300Ser) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 3377076 | NM_004423.4(DVL3):c.883C>G (p.Pro295Ala) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 3588983 | NM_004423.4(DVL3):c.190A>T (p.Asn64Tyr) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 3764584 | NM_004423.4(DVL3):c.1552C>T (p.Gln518Ter) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 4078535 | NM_004423.4(DVL3):c.1510C>G (p.Leu504Val) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 930245 | NM_004423.4(DVL3):c.1120G>A (p.Ala374Thr) | DVL3 | Uncertain significance | criteria provided, single submitter |
| 931200 | NM_004423.4(DVL3):c.706A>G (p.Ser236Gly) | DVL3 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| DVL3 | Definitive | Autosomal dominant | autosomal dominant Robinow syndrome 3 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DVL3 | Orphanet:3107 | Autosomal dominant Robinow syndrome |
| FZD2 | Orphanet:3107 | Autosomal dominant Robinow syndrome |
| FZD2 | Orphanet:93328 | Autosomal dominant omodysplasia |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DVL3 | HGNC:3087 | ENSG00000161202 | Q92997 | Segment polarity protein dishevelled homolog DVL-3 | gencc,clinvar |
| FZD2 | HGNC:4040 | ENSG00000180340 | Q14332 | Frizzled-2 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DVL3 | Segment polarity protein dishevelled homolog DVL-3 | Involved in the signal transduction pathway mediated by multiple Wnt genes. |
| FZD2 | Frizzled-2 | Receptor for Wnt proteins. |
Protein-family classification
Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| GPCR | 1 | 12.0× | 0.112 |
| Scaffold/PPI | 1 | 8.6× | 0.112 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DVL3 | Scaffold/PPI | no | DEP_dom, DIX, PDZ | |
| FZD2 | GPCR | yes | Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ganglionic eminence | 1 |
| mucosa of stomach | 1 |
| stromal cell of endometrium | 1 |
| dorsal root ganglion | 1 |
| embryo | 1 |
| ventricular zone | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DVL3 | 287 | ubiquitous | marker | stromal cell of endometrium, ganglionic eminence, mucosa of stomach |
| FZD2 | 197 | ubiquitous | marker | ventricular zone, embryo, dorsal root ganglion |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DVL3 | 3,185 |
| FZD2 | 1,764 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| DVL3 | Q92997 | 9 |
| FZD2 | Q14332 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Disassembly of the destruction complex and recruitment of AXIN to the membrane | 2 | 356.9× | 9e-05 | DVL3, FZD2 |
| TCF dependent signaling in response to WNT | 2 | 117.7× | 4e-04 | DVL3, FZD2 |
| Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 1 | 1142.0× | 0.004 | DVL3 |
| WNT mediated activation of DVL | 1 | 713.8× | 0.004 | DVL3 |
| WNT5:FZD7-mediated leishmania damping | 1 | 475.8× | 0.005 | DVL3 |
| WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 1 | 439.2× | 0.005 | FZD2 |
| PCP/CE pathway | 1 | 150.3× | 0.011 | DVL3 |
| Degradation of DVL | 1 | 119.0× | 0.012 | DVL3 |
| Asymmetric localization of PCP proteins | 1 | 102.0× | 0.012 | FZD2 |
| Class B/2 (Secretin family receptors) | 1 | 95.2× | 0.012 | FZD2 |
| Ca2+ pathway | 1 | 89.2× | 0.012 | FZD2 |
| RHO GTPases Activate Formins | 1 | 38.8× | 0.026 | DVL3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| non-canonical Wnt signaling pathway | 2 | 581.1× | 5e-05 | DVL3, FZD2 |
| Wnt signaling pathway, planar cell polarity pathway | 2 | 455.5× | 5e-05 | DVL3, FZD2 |
| canonical Wnt signaling pathway | 2 | 153.2× | 3e-04 | DVL3, FZD2 |
| muscular septum morphogenesis | 1 | 1685.2× | 0.003 | FZD2 |
| inner ear receptor cell development | 1 | 1203.7× | 0.003 | FZD2 |
| positive regulation of neuron projection arborization | 1 | 1053.2× | 0.003 | DVL3 |
| membranous septum morphogenesis | 1 | 842.6× | 0.003 | FZD2 |
| hard palate development | 1 | 842.6× | 0.003 | FZD2 |
| positive regulation of DNA-templated transcription | 2 | 27.9× | 0.003 | DVL3, FZD2 |
| endothelial cell differentiation | 1 | 561.7× | 0.004 | FZD2 |
| cochlea morphogenesis | 1 | 290.6× | 0.007 | FZD2 |
| outflow tract morphogenesis | 1 | 153.2× | 0.012 | FZD2 |
| regulation of protein localization | 1 | 102.8× | 0.017 | DVL3 |
| small GTPase-mediated signal transduction | 1 | 91.6× | 0.017 | DVL3 |
| positive regulation of JNK cascade | 1 | 81.8× | 0.017 | DVL3 |
| regulation of actin cytoskeleton organization | 1 | 78.8× | 0.017 | DVL3 |
| sensory perception of smell | 1 | 78.0× | 0.017 | FZD2 |
| neuron differentiation | 1 | 50.1× | 0.024 | FZD2 |
| Wnt signaling pathway | 1 | 49.9× | 0.024 | FZD2 |
| cell-cell signaling | 1 | 34.8× | 0.031 | FZD2 |
| response to xenobiotic stimulus | 1 | 34.5× | 0.031 | DVL3 |
| protein stabilization | 1 | 33.4× | 0.031 | DVL3 |
| positive regulation of transcription by RNA polymerase II | 1 | 7.4× | 0.130 | DVL3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 2 of 2 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 |
|---|---|---|
| DVL3 | 0 | 0 |
| FZD2 | 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 |
|---|---|---|
| FZD2 | 18 | Functional:18 |
| DVL3 | 3 | Binding:2, Functional:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | FZD2 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | DVL3 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| DVL3 | 3 | — |
| FZD2 | 18 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.