Periventricular nodular heterotopia 8

Summary

Periventricular nodular heterotopia 8 (MONDO:0032588) is a disease caused by ARF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ARF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	periventricular nodular heterotopia 8
Mondo ID	MONDO:0032588
OMIM	618185
DOID	DOID:0061245
UMLS	C4748602
MedGen	1648287
GARD	0016303
Is cancer (heuristic)	no

Also known as: PVNH8

Data availability: 17 ClinVar variants · 4 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 8

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 9

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

17 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 uncertain significance, 4 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1343798	NM_001658.4(ARF1):c.153C>A (p.Phe51Leu)	ARF1	Pathogenic	criteria provided, single submitter
1343799	NM_001658.4(ARF1):c.392C>G (p.Pro131Arg)	ARF1	Pathogenic	criteria provided, single submitter
1343803	NM_001658.4(ARF1):c.151T>C (p.Phe51Leu)	ARF1	Pathogenic	criteria provided, single submitter
590332	NM_001658.4(ARF1):c.103T>C (p.Tyr35His)	ARF1	Pathogenic	no assertion criteria provided
590333	NM_001658.4(ARF1):c.379A>G (p.Lys127Glu)	ARF1	Pathogenic	criteria provided, single submitter
590334	NM_001658.4(ARF1):c.296G>A (p.Arg99His)	ARF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343802	NM_001658.4(ARF1):c.103T>G (p.Tyr35Asp)	LOC126806039	Pathogenic	criteria provided, single submitter
1343801	NM_001658.4(ARF1):c.55C>T (p.Arg19Cys)	ARF1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343805	NM_001658.4(ARF1):c.295C>T (p.Arg99Cys)	ARF1	Likely pathogenic	criteria provided, single submitter
3420237	NM_001658.4(ARF1):c.208G>A (p.Gly70Ser)	ARF1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
690284	NM_001658.4(ARF1):c.143C>T (p.Thr48Ile)	ARF1	Likely pathogenic	criteria provided, single submitter
1343800	NM_001658.4(ARF1):c.392C>T (p.Pro131Leu)	ARF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343804	NM_001658.4(ARF1):c.278A>G (p.Asp93Gly)	ARF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343290	NM_001658.4(ARF1):c.214del (p.Asp72fs)	ARF1	Uncertain significance	criteria provided, single submitter
1709793	NM_001658.4(ARF1):c.201C>G (p.Asp67Glu)	ARF1	Uncertain significance	criteria provided, single submitter
3024252	NM_001658.4(ARF1):c.238C>T (p.His80Tyr)	ARF1	Uncertain significance	criteria provided, single submitter
3242410	NM_001658.4(ARF1):c.509T>C (p.Leu170Pro)	ARF1	Uncertain significance	no assertion criteria provided

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
ARF1	Definitive	Autosomal dominant	periventricular nodular heterotopia	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARF1	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
ARF1	HGNC:652	ENSG00000143761	P84077	ADP-ribosylation factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARF1	ADP-ribosylation factor 1	Small GTPase involved in protein trafficking between different compartments.

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)
ARF1	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF

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
adult organism	1
ileal mucosa	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARF1	295	ubiquitous	marker	adult organism, ileal mucosa, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARF1	485

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARF1	P84077	40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. 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
Glycosphingolipid transport	1	1427.5×	0.012	ARF1
Nef Mediated CD4 Down-regulation	1	1268.9×	0.012	ARF1
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.012	ARF1
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.012	ARF1
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.012	ARF1
Interleukin-12 family signaling	1	475.8×	0.012	ARF1
Interleukin-12 signaling	1	407.9×	0.012	ARF1
PI Metabolism	1	356.9×	0.012	ARF1
Host Interactions of HIV factors	1	335.9×	0.012	ARF1
Lysosome Vesicle Biogenesis	1	326.3×	0.012	ARF1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.012	ARF1
Intra-Golgi traffic	1	259.6×	0.012	ARF1
trans-Golgi Network Vesicle Budding	1	253.8×	0.012	ARF1
Synthesis of PIPs at the plasma membrane	1	211.5×	0.012	ARF1
Phospholipid metabolism	1	200.3×	0.012	ARF1
Golgi Associated Vesicle Biogenesis	1	200.3×	0.012	ARF1
ER to Golgi Anterograde Transport	1	132.8×	0.016	ARF1
Golgi-to-ER retrograde transport	1	132.8×	0.016	ARF1
HIV Infection	1	119.0×	0.016	ARF1
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.016	ARF1
COPI-mediated anterograde transport	1	109.8×	0.016	ARF1
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.016	ARF1
Transport to the Golgi and subsequent modification	1	102.9×	0.016	ARF1
MHC class II antigen presentation	1	89.2×	0.018	ARF1
Signaling by Interleukins	1	64.2×	0.024	ARF1
Asparagine N-linked glycosylation	1	60.1×	0.025	ARF1
Cytokine Signaling in Immune system	1	40.8×	0.035	ARF1
Membrane Trafficking	1	37.1×	0.038	ARF1
Vesicle-mediated transport	1	34.8×	0.039	ARF1
Metabolism of lipids	1	31.6×	0.041	ARF1

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
mitotic cleavage furrow ingression	1	16852.0×	5e-04	ARF1
dendritic spine organization	1	4213.0×	0.001	ARF1
regulation of receptor internalization	1	2407.4×	0.001	ARF1
regulation of Arp2/3 complex-mediated actin nucleation	1	1053.2×	0.002	ARF1
intracellular copper ion homeostasis	1	936.2×	0.002	ARF1
long-term synaptic depression	1	887.0×	0.002	ARF1
cellular response to virus	1	200.6×	0.006	ARF1
vesicle-mediated transport	1	96.3×	0.012	ARF1
intracellular protein transport	1	64.8×	0.015	ARF1

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
ARF1	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
ARF1	4	Binding: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	ARF1

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)
ARF1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.