Band heterotopia of brain

Summary

Band heterotopia of brain (MONDO:0010873) is a disease caused by EML1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EML1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	band heterotopia of brain
Mondo ID	MONDO:0010873
MeSH	C563950
OMIM	600348
UMLS	C4284594
MedGen	924885
GARD	0002250
Is cancer (heuristic)	no

Also known as: band heterotopia of brain · BH

Data availability: 13 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › subcortical band heterotopia › band heterotopia of brain

Related subtypes (1): lissencephaly type 1 due to doublecortin gene mutation

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

13 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 uncertain significance, 3 likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031421	NM_004434.3(EML1):c.1820+1G>C	EML1	Pathogenic	criteria provided, single submitter
254258	NM_004434.3(EML1):c.412C>T (p.Arg138Ter)	EML1	Pathogenic	no assertion criteria provided
254260	NM_004434.3(EML1):c.673T>C (p.Trp225Arg)	EML1	Pathogenic	no assertion criteria provided
548146	NM_004434.3(EML1):c.1567C>T (p.Arg523Ter)	EML1	Pathogenic	criteria provided, single submitter
1028240	NM_004434.3(EML1):c.1897C>T (p.Arg633Ter)	EML1	Likely pathogenic	criteria provided, single submitter
1710368	NM_004434.3(EML1):c.136C>T (p.Gln46Ter)	EML1	Likely pathogenic	criteria provided, single submitter
254259	NM_004434.3(EML1):c.727A>G (p.Thr243Ala)	EML1	Likely pathogenic	criteria provided, single submitter
1252021	NM_004434.3(EML1):c.2233G>A (p.Val745Ile)	EML1	Uncertain significance	no assertion criteria provided
1805488	NM_004434.3(EML1):c.941A>G (p.Asn314Ser)	EML1	Uncertain significance	criteria provided, single submitter
1805489	NM_004434.3(EML1):c.2272G>A (p.Asp758Asn)	EML1	Uncertain significance	criteria provided, single submitter
3359059	NM_004434.3(EML1):c.841C>A (p.Pro281Thr)	EML1	Uncertain significance	criteria provided, single submitter
1255382	NM_004434.3(EML1):c.276T>C (p.Pro92=)	EML1	Benign	criteria provided, multiple submitters, no conflicts
1255383	NM_004434.3(EML1):c.1666T>C (p.Ser556Pro)	EML1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
EML1	Strong	Autosomal recessive	band heterotopia of brain	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EML1	Orphanet:99796	Subcortical band heterotopia

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
EML1	HGNC:3330	ENSG00000066629	O00423	Echinoderm microtubule-associated protein-like 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EML1	Echinoderm microtubule-associated protein-like 1	Modulates the assembly and organization of the microtubule cytoskeleton, and probably plays a role in regulating the orientation of the mitotic spindle and the orientation of the plane of cell division.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EML1	Scaffold/PPI	no		WD40_rpt, HELP, Quinoprotein_ADH-like_sf

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
cortical plate	1
ganglionic eminence	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EML1	285	ubiquitous	marker	cortical plate, ganglionic eminence, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EML1	1,958

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EML1	O00423	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
neuroblast proliferation	1	366.4×	0.007	EML1
mitotic spindle organization	1	271.8×	0.007	EML1
hematopoietic progenitor cell differentiation	1	237.3×	0.007	EML1
microtubule cytoskeleton organization	1	121.2×	0.010	EML1
brain development	1	79.5×	0.013	EML1

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
EML1	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	EML1

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)
EML1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.