Periventricular nodular heterotopia 6

Summary

Periventricular nodular heterotopia 6 (MONDO:0014240) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	periventricular nodular heterotopia 6
Mondo ID	MONDO:0014240
OMIM	615544
DOID	DOID:0061269
UMLS	C3809872
MedGen	816202
GARD	0015983
Is cancer (heuristic)	no

Also known as: ERMARD periventricular nodular heterotopia · periventricular nodular heterotopia 6 · periventricular nodular heterotopia caused by mutation in ERMARD · periventricular nodular heterotopia type 6 · PVNH6

Data availability: 28 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › periventricular nodular heterotopia › periventricular nodular heterotopia 6

Related subtypes (7): heterotopia, periventricular, X-linked dominant, periventricular heterotopia with microcephaly, autosomal recessive, heterotopia, periventricular, associated with chromosome 5P anomalies, chromosome 5Q14.3 deletion syndrome, distal, periventricular nodular heterotopia 7, periventricular nodular heterotopia 9, periventricular nodular heterotopia 8

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

28 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 3 likely pathogenic, 2 benign/likely benign, 2 likely benign, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
88869	NM_018341.3(ERMARD):c.1130T>A (p.Ile377Asn)	ERMARD	Pathogenic	no assertion criteria provided
1696356	NM_018341.3(ERMARD):c.605+1G>A	ERMARD	Likely pathogenic	criteria provided, single submitter
2429374	NM_018341.3(ERMARD):c.277C>T (p.Arg93Ter)	ERMARD	Likely pathogenic	criteria provided, single submitter
3068306	NM_018341.3(ERMARD):c.1395-1G>T	ERMARD	Likely pathogenic	criteria provided, single submitter
1030652	NM_018341.3(ERMARD):c.1394+1G>T	ERMARD	Uncertain significance	criteria provided, single submitter
1299254	NM_018341.3(ERMARD):c.1511del (p.Pro504fs)	ERMARD	Uncertain significance	criteria provided, single submitter
1320115	NM_018341.3(ERMARD):c.1426del (p.His476fs)	ERMARD	Uncertain significance	criteria provided, single submitter
1325618	NM_018341.3(ERMARD):c.1629_1636del (p.Arg544fs)	ERMARD	Uncertain significance	criteria provided, single submitter
1334008	NM_018341.3(ERMARD):c.1781T>C (p.Leu594Pro)	ERMARD	Uncertain significance	criteria provided, single submitter
1341867	NM_018341.3(ERMARD):c.632C>T (p.Thr211Met)	ERMARD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1343259	NM_018341.3(ERMARD):c.1521-82del	ERMARD	Uncertain significance	criteria provided, single submitter
2166561	NM_018341.3(ERMARD):c.314A>G (p.Glu105Gly)	ERMARD	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391167	NM_018341.3(ERMARD):c.902G>T (p.Gly301Val)	ERMARD	Uncertain significance	criteria provided, single submitter
3593394	NM_018341.3(ERMARD):c.1907del (p.Tyr636fs)	ERMARD	Uncertain significance	criteria provided, single submitter
3891398	NM_018341.3(ERMARD):c.1483_1485del (p.Cys495del)	ERMARD	Uncertain significance	criteria provided, single submitter
3901995	NM_018341.3(ERMARD):c.2005G>T (p.Ala669Ser)	ERMARD	Uncertain significance	criteria provided, single submitter
3901997	NM_018341.3(ERMARD):c.451_454del (p.Phe150_Leu151insTer)	ERMARD	Uncertain significance	criteria provided, single submitter
4279528	NM_018341.3(ERMARD):c.1853+1G>A	ERMARD	Uncertain significance	criteria provided, single submitter
4291903	NM_018341.3(ERMARD):c.165C>G (p.Tyr55Ter)	ERMARD	Uncertain significance	criteria provided, single submitter
4846789	NM_018341.3(ERMARD):c.1846T>C (p.Tyr616His)	ERMARD	Uncertain significance	criteria provided, single submitter
915337	NM_018341.3(ERMARD):c.1072del (p.Asp358fs)	ERMARD	Uncertain significance	criteria provided, single submitter
977406	NM_018341.3(ERMARD):c.1286G>T (p.Arg429Leu)	ERMARD	Uncertain significance	criteria provided, single submitter
977896	NM_018341.3(ERMARD):c.313G>C (p.Glu105Gln)	ERMARD	Uncertain significance	criteria provided, single submitter
380785	NM_018341.3(ERMARD):c.1505G>A (p.Arg502His)	ERMARD	Benign	criteria provided, multiple submitters, no conflicts
384622	NM_018341.3(ERMARD):c.1014T>C (p.Asp338=)	ERMARD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
384623	NM_018341.3(ERMARD):c.1060-12A>G	ERMARD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
4686720	NM_018341.3(ERMARD):c.76T>C (p.Phe26Leu)	ERMARD	Likely benign	criteria provided, single submitter
4814243	NM_018341.3(ERMARD):c.1469T>A (p.Met490Lys)	ERMARD	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
ERMARD	Supportive	Autosomal dominant	periventricular nodular heterotopia	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERMARD	Orphanet:75857	6q terminal deletion syndrome
ERMARD	Orphanet:98892	Periventricular nodular 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
ERMARD	HGNC:21056	ENSG00000130023	Q5T6L9	Endoplasmic reticulum membrane-associated RNA degradation protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERMARD	Endoplasmic reticulum membrane-associated RNA degradation protein	May play a role in neuronal migration during embryonic development.

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)
ERMARD	Other/Unknown	no		EMARD_N, ERMARD

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
left testis	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERMARD	134	ubiquitous	marker	right uterine tube, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERMARD	2,316

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ERMARD	Q5T6L9	90.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
ERMARD	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	ERMARD

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)
ERMARD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.