megalencephalic leukoencephalopathy with subcortical cysts 2A
disease diseaseOn this page
Also known as megalencephalic leukoencephalopathy with subcortical cysts type 2AMLC2A
Summary
megalencephalic leukoencephalopathy with subcortical cysts 2A (MONDO:0013490) is a disease caused by HEPACAM (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: HEPACAM (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 27
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | megalencephalic leukoencephalopathy with subcortical cysts 2A |
| Mondo ID | MONDO:0013490 |
| OMIM | 613925 |
| DOID | DOID:0080318 |
| UMLS | C3151355 |
| MedGen | 462705 |
| GARD | 0015728 |
| Is cancer (heuristic) | no |
Also known as: megalencephalic leukoencephalopathy with subcortical cysts 2A · megalencephalic leukoencephalopathy with subcortical cysts type 2A · MLC2A
Data availability: 27 ClinVar variants · 3 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 › megalencephalic leukoencephalopathy with subcortical cysts 2A
Related subtypes (2): megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability, megalencephalic leukoencephalopathy with subcortical cysts 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
27 retrieved; paginated sample, class counts are floors:
9 uncertain significance, 5 conflicting classifications of pathogenicity, 4 pathogenic, 3 likely pathogenic, 2 benign, 2 pathogenic/likely pathogenic, 1 likely benign, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 30914 | NM_152722.5(HEPACAM):c.587C>A (p.Ser196Tyr) | HEPACAM | Pathogenic | criteria provided, single submitter |
| 30915 | NM_152722.5(HEPACAM):c.789G>A (p.Trp263Ter) | HEPACAM | Pathogenic | no assertion criteria provided |
| 30916 | NM_152722.5(HEPACAM):c.275G>A (p.Arg92Gln) | HEPACAM | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 30917 | NM_152722.5(HEPACAM):c.631G>A (p.Asp211Asn) | HEPACAM | Pathogenic | no assertion criteria provided |
| 30919 | NM_152722.5(HEPACAM):c.265G>A (p.Gly89Ser) | HEPACAM | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 30921 | NM_152722.5(HEPACAM):c.274C>T (p.Arg92Trp) | HEPACAM | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 30918 | NM_152722.5(HEPACAM):c.292C>T (p.Arg98Cys) | HEPACAM | Likely pathogenic | criteria provided, single submitter |
| 3233388 | NM_152722.5(HEPACAM):c.949-2A>G | HEPACAM | Likely pathogenic | criteria provided, single submitter |
| 433199 | NM_152722.5(HEPACAM):c.442C>T (p.Pro148Ser) | HEPACAM | Likely pathogenic | no assertion criteria provided |
| 1031210 | NM_152722.5(HEPACAM):c.259G>A (p.Val87Ile) | HEPACAM | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1218905 | NM_152722.5(HEPACAM):c.382G>A (p.Asp128Asn) | HEPACAM | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1367723 | NM_152722.5(HEPACAM):c.96G>C (p.Glu32Asp) | HEPACAM | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 393149 | NM_152722.5(HEPACAM):c.1198G>A (p.Val400Met) | HEPACAM | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 931058 | NM_152722.5(HEPACAM):c.139G>A (p.Val47Met) | HEPACAM | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1031211 | NM_152722.5(HEPACAM):c.665C>T (p.Pro222Leu) | HEPACAM | Uncertain significance | criteria provided, single submitter |
| 1031682 | NM_152722.5(HEPACAM):c.922A>G (p.Met308Val) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1187211 | NM_152722.5(HEPACAM):c.217C>T (p.Arg73Trp) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1203684 | NM_152722.5(HEPACAM):c.1169_1180del (p.Ser390_Arg393del) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1339869 | NM_152722.5(HEPACAM):c.616C>T (p.Arg206Cys) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1510664 | NM_152722.5(HEPACAM):c.484G>A (p.Glu162Lys) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3362692 | NM_152722.5(HEPACAM):c.1238A>T (p.Glu413Val) | HEPACAM | Uncertain significance | criteria provided, single submitter |
| 435410 | NM_152722.5(HEPACAM):c.614C>T (p.Thr205Ile) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 638399 | NM_152722.5(HEPACAM):c.128T>A (p.Ile43Asn) | HEPACAM | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1582595 | NM_152722.5(HEPACAM):c.1062C>T (p.Pro354=) | HEPACAM | Likely benign | criteria provided, multiple submitters, no conflicts |
| 262680 | NM_152722.5(HEPACAM):c.618C>T (p.Arg206=) | HEPACAM | Benign | criteria provided, multiple submitters, no conflicts |
| 262681 | NM_152722.5(HEPACAM):c.652A>G (p.Met218Val) | HEPACAM | Benign | criteria provided, multiple submitters, no conflicts |
| 303335 | NM_152722.5(HEPACAM):c.258G>A (p.Glu86=) | HEPACAM | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · 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 |
|---|---|---|---|---|
| HEPACAM | Strong | Autosomal recessive | megalencephalic leukoencephalopathy with subcortical cysts 2A | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| HEPACAM | Orphanet:210548 | Macrocephaly-intellectual disability-autism syndrome |
| HEPACAM | Orphanet:2478 | Megalencephalic leukoencephalopathy with subcortical cysts |
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 |
|---|---|---|---|---|---|
| HEPACAM | HGNC:26361 | ENSG00000165478 | Q14CZ8 | Hepatic and glial cell adhesion molecule | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| HEPACAM | Hepatic and glial cell adhesion molecule | Involved in regulating cell motility and cell-matrix interactions. |
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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 1 | 29.2× | 0.034 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| HEPACAM | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, Ig-like_dom |
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 |
|---|---|
| lateral globus pallidus | 1 |
| medial globus pallidus | 1 |
| substantia nigra pars reticulata | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| HEPACAM | 167 | broad | marker | lateral globus pallidus, substantia nigra pars reticulata, medial globus pallidus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HEPACAM | 661 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| HEPACAM | Q14CZ8 | 1 |
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 |
|---|---|---|---|---|
| protein localization to cell-cell junction | 1 | 1872.4× | 0.002 | HEPACAM |
| regulation of cell cycle | 1 | 74.6× | 0.027 | HEPACAM |
| immune response | 1 | 47.1× | 0.027 | HEPACAM |
| cell adhesion | 1 | 37.5× | 0.027 | HEPACAM |
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 |
|---|---|---|
| HEPACAM | 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 | 1 | HEPACAM |
| 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) |
|---|---|---|
| HEPACAM | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: HEPACAM