Periventricular nodular heterotopia 9

Summary

Periventricular nodular heterotopia 9 (MONDO:0030061) is a disease caused by MAP1B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MAP1B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 72

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	periventricular nodular heterotopia 9
Mondo ID	MONDO:0030061
OMIM	618918
DOID	DOID:0061246
UMLS	C5394503
MedGen	1718470
GARD	0016394
Is cancer (heuristic)	no

Also known as: PERIVENTRICULAR NODULAR HETEROTOPIA 9 · periventricular nodular heterotopia 9 · PVNH9

Data availability: 72 ClinVar variants · 2 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 9

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 7, 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

72 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 9 likely pathogenic, 9 pathogenic, 6 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign, 2 pathogenic; risk factor, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1708214	NM_005909.5(MAP1B):c.2995C>T (p.Arg999Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2574245	NM_005909.5(MAP1B):c.895C>T (p.Arg299Ter)	MAP1B	Pathogenic	criteria provided, multiple submitters, no conflicts
2771492	NM_005909.5(MAP1B):c.2340del (p.Lys781_Ile782insTer)	MAP1B	Pathogenic	criteria provided, multiple submitters, no conflicts
3024282	NM_005909.5(MAP1B):c.881del (p.Phe294fs)	MAP1B	Pathogenic	criteria provided, single submitter
3068466	NM_005909.5(MAP1B):c.3794C>A (p.Ser1265Ter)	MAP1B	Pathogenic	criteria provided, single submitter
3254681	NM_005909.5(MAP1B):c.3740C>A (p.Ser1247Ter)	MAP1B	Pathogenic	criteria provided, single submitter
3544372	NM_005909.5(MAP1B):c.2253dup (p.Pro752fs)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775685	NM_005909.5(MAP1B):c.253C>T (p.Arg85Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4526403	NM_005909.5(MAP1B):c.6126C>A (p.Tyr2042Ter)	MAP1B	Pathogenic	criteria provided, single submitter
4531999	NM_005909.5(MAP1B):c.4778_4779insAG (p.Val1595fs)	MAP1B	Pathogenic	criteria provided, single submitter
548632	NM_005909.5(MAP1B):c.907C>T (p.Arg303Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548633	NM_005909.5(MAP1B):c.1594C>T (p.Gln532Ter)	MAP1B	Pathogenic/Likely pathogenic	no assertion criteria provided
638688	NM_005909.5(MAP1B):c.5368C>T (p.Arg1790Ter)	MAP1B	Pathogenic	criteria provided, single submitter
800720	NM_005909.5(MAP1B):c.2134del (p.Glu712fs)	MAP1B	Pathogenic; risk factor	no assertion criteria provided
800721	NM_005909.5(MAP1B):c.3094G>T (p.Glu1032Ter)	MAP1B	Pathogenic; risk factor	no assertion criteria provided
800722	NM_005909.5(MAP1B):c.4990C>T (p.Arg1664Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
930211	NM_005909.5(MAP1B):c.2035G>T (p.Glu679Ter)	MAP1B	Pathogenic	criteria provided, single submitter
1320111	NM_005909.5(MAP1B):c.6715del (p.Asp2238_Leu2239insTer)	MAP1B	Likely pathogenic	criteria provided, single submitter
1320233	NM_005909.5(MAP1B):c.6733del (p.Thr2245fs)	MAP1B	Likely pathogenic	criteria provided, single submitter
1341820	NM_005909.5(MAP1B):c.6421C>T (p.Gln2141Ter)	MAP1B	Likely pathogenic	criteria provided, single submitter
1677307	NM_005909.5(MAP1B):c.1002del (p.Glu334fs)	MAP1B	Likely pathogenic	criteria provided, single submitter
1878324	NM_005909.5(MAP1B):c.3362dup (p.Ser1122fs)	MAP1B	Likely pathogenic	criteria provided, single submitter
2664025	NM_005909.5(MAP1B):c.260_261del (p.Ser87fs)	MAP1B	Likely pathogenic	no assertion criteria provided
3235069	NM_005909.5(MAP1B):c.3538_3539del (p.Val1180fs)	MAP1B	Likely pathogenic	criteria provided, single submitter
3338097	NM_005909.5(MAP1B):c.7191del (p.Ser2398fs)	MAP1B	Likely pathogenic	no assertion criteria provided
4292067	NM_005909.5(MAP1B):c.6960del (p.Lys2321fs)	MAP1B	Likely pathogenic	criteria provided, single submitter
2536708	NM_005909.5(MAP1B):c.3001G>A (p.Glu1001Lys)	MAP1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548634	NM_005909.5(MAP1B):c.3316C>T (p.Arg1106Ter)	MAP1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027647	NM_005909.5(MAP1B):c.742C>A (p.Pro248Thr)	MAP1B	Uncertain significance	criteria provided, single submitter
1184989	NM_005909.5(MAP1B):c.976C>T (p.Arg326Trp)	MAP1B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MAP1B	Strong	Autosomal dominant	periventricular nodular heterotopia 9	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAP1B	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1B	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
MAP1B	HGNC:6836	ENSG00000131711	P46821	Microtubule-associated protein 1B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAP1B	Microtubule-associated protein 1B	Facilitates tyrosination of alpha-tubulin in neuronal microtubules.

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)
MAP1B	Other/Unknown	no		MAP1B_neuraxin, MAP1, MAP1B/S_N

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 nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAP1B	299	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP1B	3,724

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAP1B	P46821	46.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Respiratory Syncytial Virus Infection Pathway	1	196.9×	0.016	MAP1B
RSV-host interactions	1	156.4×	0.016	MAP1B
Viral Infection Pathways	1	30.8×	0.050	MAP1B
Infectious disease	1	24.8×	0.050	MAP1B
Disease	1	13.1×	0.076	MAP1B

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
developmental maturation	1	16852.0×	9e-04	MAP1B
induction of synaptic plasticity by chemical substance	1	16852.0×	9e-04	MAP1B
establishment of monopolar cell polarity	1	8426.0×	0.001	MAP1B
negative regulation of intracellular transport	1	5617.3×	0.001	MAP1B
regulation of microtubule depolymerization	1	4213.0×	0.001	MAP1B
response to insecticide	1	2808.7×	0.002	MAP1B
peripheral nervous system axon regeneration	1	2106.5×	0.002	MAP1B
odontoblast differentiation	1	2106.5×	0.002	MAP1B
response to carbohydrate	1	1685.2×	0.002	MAP1B
mitochondrion transport along microtubule	1	1404.3×	0.002	MAP1B
response to vitamin A	1	1053.2×	0.003	MAP1B
cellular response to peptide hormone stimulus	1	842.6×	0.003	MAP1B
positive regulation of microtubule polymerization	1	674.1×	0.003	MAP1B
microtubule bundle formation	1	510.7×	0.003	MAP1B
positive regulation of axon extension	1	510.7×	0.003	MAP1B
negative regulation of microtubule depolymerization	1	495.6×	0.003	MAP1B
axon extension	1	495.6×	0.003	MAP1B
dendrite development	1	391.9×	0.004	MAP1B
regulation of postsynapse assembly	1	343.9×	0.004	MAP1B
cellular response to growth factor stimulus	1	318.0×	0.005	MAP1B
response to mechanical stimulus	1	300.9×	0.005	MAP1B
synapse assembly	1	230.8×	0.006	MAP1B
response to estradiol	1	198.3×	0.006	MAP1B
positive regulation of neuron differentiation	1	198.3×	0.006	MAP1B
axonogenesis	1	160.5×	0.007	MAP1B
neuron migration	1	133.8×	0.008	MAP1B
neuron projection development	1	122.1×	0.009	MAP1B
microtubule cytoskeleton organization	1	121.2×	0.009	MAP1B
response to xenobiotic stimulus	1	69.1×	0.014	MAP1B

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
MAP1B	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
MAP1B	10	Binding:6, Functional:4

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	MAP1B

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)
MAP1B	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.