Periventricular nodular heterotopia 7

Summary

Periventricular nodular heterotopia 7 (MONDO:0014966) is a disease caused by NEDD4L (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: NEDD4L (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 111

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	periventricular nodular heterotopia 7
Mondo ID	MONDO:0014966
OMIM	617201
DOID	DOID:0061270
UMLS	C4310669
MedGen	934636
GARD	0016210
Is cancer (heuristic)	no

Also known as: NEDD4L periventricular nodular heterotopia · periventricular nodular heterotopia 7 · periventricular nodular heterotopia 7; PVNH7 · periventricular nodular heterotopia caused by mutation in NEDD4L · periventricular nodular heterotopia type 7 · PVNH7

Data availability: 111 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 7

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 6, 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

111 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 24 likely benign, 19 conflicting classifications of pathogenicity, 15 benign/likely benign, 5 benign, 5 likely pathogenic, 2 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
225191	NM_001144967.3(NEDD4L):c.2677G>A (p.Glu893Lys)	NEDD4L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225192	NM_001144967.3(NEDD4L):c.2082G>T (p.Gln694His)	NEDD4L	Pathogenic	no assertion criteria provided
225193	NM_001144967.3(NEDD4L):c.2036A>G (p.Tyr679Cys)	NEDD4L	Pathogenic	no assertion criteria provided
864862	NM_001144967.3(NEDD4L):c.623G>A (p.Arg208Gln)	NEDD4L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1684293	NM_001144967.3(NEDD4L):c.814-6T>A	NEDD4L	Likely pathogenic	criteria provided, single submitter
3065173	NM_001144967.3(NEDD4L):c.1126-1G>A	NEDD4L	Likely pathogenic	criteria provided, single submitter
3370506	NM_001144967.3(NEDD4L):c.1855G>C (p.Glu619Gln)	NEDD4L	Likely pathogenic	criteria provided, single submitter
592171	t(X;18)(p21.1;q21.31)	NEDD4L	Likely pathogenic	no assertion criteria provided
812181	NM_001144967.3(NEDD4L):c.2245A>G (p.Met749Val)	NEDD4L	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098657	NM_001144967.3(NEDD4L):c.1888G>C (p.Glu630Gln)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1530834	NM_001144967.3(NEDD4L):c.349-9del	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1620360	NM_001144967.3(NEDD4L):c.449T>C (p.Met150Thr)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679631	NM_001144967.3(NEDD4L):c.1576-4G>T	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225190	NM_001144967.3(NEDD4L):c.2690G>A (p.Arg897Gln)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2672208	NM_001144967.3(NEDD4L):c.1258-6A>G	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392668	NM_001144967.3(NEDD4L):c.2093A>G (p.Asn698Ser)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4079422	NM_001144967.3(NEDD4L):c.361A>G (p.Thr121Ala)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451267	NM_001144967.3(NEDD4L):c.1316C>T (p.Pro439Leu)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548597	NM_001144967.3(NEDD4L):c.1088C>T (p.Ala363Val)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598222	NM_001144967.3(NEDD4L):c.965A>G (p.Asn322Ser)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
649335	NM_001144967.3(NEDD4L):c.740G>A (p.Arg247Gln)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
661947	NM_001144967.3(NEDD4L):c.871C>G (p.Leu291Val)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
839125	NM_001144967.3(NEDD4L):c.1882T>A (p.Phe628Ile)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
847387	NM_001144967.3(NEDD4L):c.1033G>A (p.Asp345Asn)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
848101	NM_001144967.3(NEDD4L):c.1279G>A (p.Gly427Arg)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
849775	NM_001144967.3(NEDD4L):c.2273A>G (p.Asn758Ser)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
858486	NM_001144967.3(NEDD4L):c.812A>C (p.Glu271Ala)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
958778	NM_001144967.3(NEDD4L):c.1691C>A (p.Thr564Lys)	NEDD4L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1359734	NM_001144967.3(NEDD4L):c.328G>A (p.Val110Met)	LOC126862763	Uncertain significance	criteria provided, multiple submitters, no conflicts
1301721	NM_001144967.3(NEDD4L):c.23C>T (p.Pro8Leu)	LOC130062568	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
NEDD4L	Definitive	Autosomal dominant	periventricular nodular heterotopia 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEDD4L	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
NEDD4L	HGNC:7728	ENSG00000049759	Q96PU5	E3 ubiquitin-protein ligase NEDD4-like	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEDD4L	E3 ubiquitin-protein ligase NEDD4-like	E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repai…

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)
NEDD4L	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_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
ganglionic eminence	1
olfactory segment of nasal mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEDD4L	281	ubiquitous	marker	ventricular zone, ganglionic eminence, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEDD4L	3,458

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NEDD4L	Q96PU5	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Budding and maturation of HIV virion	1	407.9×	0.015	NEDD4L
Downregulation of TGF-beta receptor signaling	1	407.9×	0.015	NEDD4L
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	368.4×	0.015	NEDD4L
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	368.4×	0.015	NEDD4L
TGF-beta receptor signaling activates SMADs	1	326.3×	0.015	NEDD4L
Signaling by TGF-beta Receptor Complex	1	200.3×	0.019	NEDD4L
Late Phase of HIV Life Cycle	1	167.9×	0.019	NEDD4L
HIV Life Cycle	1	160.8×	0.019	NEDD4L
Stimuli-sensing channels	1	135.9×	0.019	NEDD4L
HIV Infection	1	119.0×	0.019	NEDD4L
Signaling by TGFB family members	1	115.3×	0.019	NEDD4L
Ion channel transport	1	96.0×	0.021	NEDD4L
Class I MHC mediated antigen processing & presentation	1	70.1×	0.026	NEDD4L
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.046	NEDD4L
Viral Infection Pathways	1	30.8×	0.050	NEDD4L
Adaptive Immune System	1	29.8×	0.050	NEDD4L
Transport of small molecules	1	25.1×	0.054	NEDD4L
Infectious disease	1	24.8×	0.054	NEDD4L
RNA Polymerase II Transcription	1	22.5×	0.056	NEDD4L
Gene expression (Transcription)	1	17.8×	0.067	NEDD4L
Generic Transcription Pathway	1	15.1×	0.076	NEDD4L
Disease	1	13.1×	0.080	NEDD4L
Immune System	1	13.0×	0.080	NEDD4L
Signal Transduction	1	10.2×	0.098	NEDD4L

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
negative regulation of sodium ion import across plasma membrane	1	8426.0×	0.002	NEDD4L
positive regulation of caveolin-mediated endocytosis	1	4213.0×	0.002	NEDD4L
negative regulation of sodium ion transmembrane transport	1	2808.7×	0.002	NEDD4L
negative regulation of potassium ion export across plasma membrane	1	2407.4×	0.002	NEDD4L
regulation of membrane depolarization	1	1872.4×	0.002	NEDD4L
negative regulation of potassium ion transmembrane transport	1	1404.3×	0.002	NEDD4L
regulation of membrane repolarization	1	1296.3×	0.002	NEDD4L
negative regulation of protein localization to cell surface	1	1296.3×	0.002	NEDD4L
receptor catabolic process	1	1123.5×	0.002	NEDD4L
regulation of sodium ion transmembrane transport	1	1053.2×	0.002	NEDD4L
ventricular cardiac muscle cell action potential	1	991.3×	0.002	NEDD4L
regulation of dendrite morphogenesis	1	732.7×	0.003	NEDD4L
positive regulation of dendrite extension	1	732.7×	0.003	NEDD4L
regulation of synapse organization	1	648.1×	0.003	NEDD4L
neuromuscular junction development	1	526.6×	0.003	NEDD4L
protein monoubiquitination	1	343.9×	0.005	NEDD4L
receptor internalization	1	324.1×	0.005	NEDD4L
regulation of membrane potential	1	230.8×	0.006	NEDD4L
monoatomic ion transmembrane transport	1	208.1×	0.006	NEDD4L
positive regulation of protein catabolic process	1	203.0×	0.006	NEDD4L
protein K48-linked ubiquitination	1	168.5×	0.007	NEDD4L
regulation of protein stability	1	125.8×	0.009	NEDD4L
neuron projection development	1	122.1×	0.009	NEDD4L
ubiquitin-dependent protein catabolic process	1	74.2×	0.015	NEDD4L
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.020	NEDD4L
protein ubiquitination	1	41.4×	0.024	NEDD4L

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
NEDD4L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NEDD4L	2.3.2.26, 2.3.2.B8	HECT-type E3 ubiquitin transferase,

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	NEDD4L

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)
NEDD4L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.