Megalencephalic leukoencephalopathy with subcortical cysts 3
disease diseaseOn this page
Summary
Megalencephalic leukoencephalopathy with subcortical cysts 3 (MONDO:0957533) is a disease caused by GPRC5B (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: GPRC5B (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 4
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | megalencephalic leukoencephalopathy with subcortical cysts 3 |
| Mondo ID | MONDO:0957533 |
| OMIM | 620447 |
| UMLS | C5830625 |
| MedGen | 1841261 |
| Is cancer (heuristic) | no |
Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › leukoencephalopathy, megalencephalic › megalencephalic leukoencephalopathy with subcortical cysts 3
Related subtypes (2): megalencephalic leukoencephalopathy with subcortical cysts, megalencephalic leukoencephalopathy with subcortical cysts 4, remitting
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
4 retrieved; paginated sample, class counts are floors:
2 pathogenic, 2 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2573133 | NM_016235.3(GPRC5B):c.523ATC[3] (p.Ile176_Ala177insIle) | GPRC5B | Pathogenic | no assertion criteria provided |
| 2573134 | NM_016235.3(GPRC5B):c.528_530dup (p.Ala177_Val178insAla) | GPRC5B | Pathogenic | no assertion criteria provided |
| 4277714 | NM_016235.3(GPRC5B):c.1037G>C (p.Arg346Pro) | GPRC5B | Uncertain significance | criteria provided, single submitter |
| 4846802 | NM_016235.3(GPRC5B):c.535G>C (p.Glu179Gln) | GPRC5B | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 0 · 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 |
|---|---|---|---|---|
| GPRC5B | Strong | Autosomal dominant | megalencephalic leukoencephalopathy with subcortical cysts 1 | 3 |
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 |
|---|---|---|---|---|---|
| GPRC5B | HGNC:13308 | ENSG00000167191 | Q9NZH0 | G-protein coupled receptor family C group 5 member B | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GPRC5B | G-protein coupled receptor family C group 5 member B | G-protein coupled receptor involved in the regulation of cell volume. |
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 |
|---|---|---|---|
| GPCR | 1 | 23.9× | 0.042 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GPRC5B | GPCR | yes | GPCR_3_C, RA-inducible_GPCR3 |
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 |
|---|---|
| globus pallidus | 1 |
| inferior olivary complex | 1 |
| medial globus pallidus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GPRC5B | 278 | ubiquitous | marker | medial globus pallidus, globus pallidus, inferior olivary complex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GPRC5B | 1,112 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GPRC5B | Q9NZH0 | 74.39 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| cell volume homeostasis | 1 | 601.9× | 0.003 | GPRC5B |
| intracellular signal transduction | 1 | 38.1× | 0.026 | GPRC5B |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 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 |
|---|---|---|
| GPRC5B | 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 |
|---|---|---|
| GPRC5B | 2 | Binding:2 |
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 | GPRC5B |
| 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) |
|---|---|---|
| GPRC5B | 2 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: GPRC5B