Ritscher-Schinzel syndrome 3
diseaseOn this page
Also known as RTSC3
Summary
Ritscher-Schinzel syndrome 3 (MONDO:0030864) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 8
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Ritscher-Schinzel syndrome 3 |
| Mondo ID | MONDO:0030864 |
| OMIM | 619135 |
| UMLS | C5436883 |
| MedGen | 1744611 |
| GARD | 0016426 |
| Is cancer (heuristic) | no |
Also known as: Ritscher-Schinzel syndrome 3 · RTSC3
Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Ritscher-Schinzel syndrome › Ritscher-Schinzel syndrome 3
Related subtypes (3): Ritscher-Schinzel syndrome 1, Ritscher-Schinzel syndrome 2, Ritscher-Schinzel syndrome 4
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:
4 pathogenic, 3 likely pathogenic, 1 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 3068428 | NM_020314.7(VPS35L):c.1383+2T>A | VPS35L | Pathogenic | no assertion criteria provided |
| 3068429 | NM_020314.7(VPS35L):c.2360C>T (p.Pro787Leu) | VPS35L | Pathogenic | no assertion criteria provided |
| 989441 | NM_020314.7(VPS35L):c.2488G>A (p.Ala830Thr) | VPS35L | Pathogenic | no assertion criteria provided |
| 989442 | NM_020314.7(VPS35L):c.830dup (p.Cys277fs) | VPS35L | Pathogenic | no assertion criteria provided |
| 3068040 | NM_020314.7(VPS35L):c.938C>G (p.Ser313Ter) | LOC126862307 | Likely pathogenic | criteria provided, single submitter |
| 3777736 | NM_020314.7(VPS35L):c.2017del (p.Gln673fs) | VPS35L | Likely pathogenic | criteria provided, single submitter |
| 4685472 | NM_020314.7(VPS35L):c.881T>C (p.Phe294Ser) | VPS35L | Likely pathogenic | criteria provided, single submitter |
| 3068427 | NM_020314.7(VPS35L):c.2715CAA[2] (p.Asn907del) | VPS35L | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · 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 |
|---|---|---|---|---|
| VPS35L | Limited | Autosomal recessive | Ritscher-Schinzel syndrome 3 | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| VPS35L | Orphanet:7 | 3C 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 |
|---|---|---|---|---|---|
| VPS35L | HGNC:24641 | ENSG00000103544 | Q7Z3J2 | VPS35 endosomal protein-sorting factor-like | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| VPS35L | VPS35 endosomal protein-sorting factor-like | Acts as a component of the retriever complex. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| VPS35L | Other/Unknown | no | VPS35L |
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 |
|---|---|
| buccal mucosa cell | 1 |
| colonic epithelium | 1 |
| stromal cell of endometrium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| VPS35L | 282 | ubiquitous | marker | buccal mucosa cell, stromal cell of endometrium, colonic epithelium |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| VPS35L | 685 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| VPS35L | Q7Z3J2 | 7 |
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 |
|---|---|---|---|---|
| Neutrophil degranulation | 1 | 23.1× | 0.043 | VPS35L |
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 |
|---|---|---|---|---|
| Golgi to plasma membrane transport | 1 | 561.7× | 0.005 | VPS35L |
| endocytic recycling | 1 | 267.5× | 0.006 | VPS35L |
| protein transport | 1 | 43.9× | 0.023 | VPS35L |
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 |
|---|---|---|
| VPS35L | 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 | 0 | |
| E | Difficult family or no structure, no drug | 1 | VPS35L |
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) |
|---|---|---|
| VPS35L | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: VPS35L