Developmental and epileptic encephalopathy, 38

disease

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Also known as ARV1 early infantile epileptic encephalopathyDEE38developmental and epileptic encephalopathy 38early infantile epileptic encephalopathy caused by mutation in ARV1EIEE38epileptic encephalopathy, early infantile, 38epileptic encephalopathy, early infantile, type 38

Summary

Developmental and epileptic encephalopathy, 38 (MONDO:0014868) is a disease caused by ARV1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ARV1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 38
Mondo ID	MONDO:0014868
OMIM	617020
DOID	DOID:0080417
UMLS	C4310762
MedGen	934729
GARD	0016175
Is cancer (heuristic)	no

Also known as: ARV1 early infantile epileptic encephalopathy · DEE38 · developmental and epileptic encephalopathy 38 · early infantile epileptic encephalopathy caused by mutation in ARV1 · EIEE38 · epileptic encephalopathy, early infantile, 38 · epileptic encephalopathy, early infantile, 38; EIEE38 · epileptic encephalopathy, early infantile, type 38

Data availability: 21 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy, 38

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

21 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 5 likely pathogenic, 4 pathogenic, 2 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1343148	NM_022786.3(ARV1):c.175-3_175-2inv	ARV1	Pathogenic	criteria provided, single submitter
224496	NM_022786.3(ARV1):c.294+1G>A	ARV1	Pathogenic	criteria provided, multiple submitters, no conflicts
3775589	NM_022786.3(ARV1):c.384del (p.Asp129fs)	ARV1	Pathogenic	criteria provided, single submitter
839151	NM_022786.3(ARV1):c.518dup (p.Pro174fs)	ARV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775294	NM_022786.3(ARV1):c.99dup (p.Cys34fs)	LOC129932761	Pathogenic	criteria provided, single submitter
1028780	NM_022786.3(ARV1):c.175-2A>G	ARV1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
183341	NM_022786.3(ARV1):c.565G>A (p.Gly189Arg)	ARV1	Likely pathogenic	criteria provided, single submitter
1878578	NM_022786.3(ARV1):c.573_574del (p.Leu192fs)	ARV1	Likely pathogenic	criteria provided, single submitter
2663891	NM_022786.3(ARV1):c.594_595del (p.Ile198fs)	ARV1	Likely pathogenic	criteria provided, single submitter
982604	NM_022786.3(ARV1):c.363_364del (p.Ser122fs)	ARV1	Likely pathogenic	criteria provided, single submitter
520804	NM_022786.3(ARV1):c.674-2A>T	ARV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034010	NM_022786.3(ARV1):c.29A>G (p.Gln10Arg)	ARV1	Uncertain significance	criteria provided, single submitter
2439213	NM_022786.3(ARV1):c.691C>T (p.Arg231Cys)	ARV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2580659	NM_022786.3(ARV1):c.*4+1G>A	ARV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3129976	NM_022786.3(ARV1):c.179C>A (p.Ser60Tyr)	ARV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4078021	NM_022786.3(ARV1):c.701C>T (p.Ser234Phe)	ARV1	Uncertain significance	criteria provided, single submitter
4292068	NM_022786.3(ARV1):c.637G>C (p.Val213Leu)	ARV1	Uncertain significance	criteria provided, single submitter
843659	NM_022786.3(ARV1):c.101G>A (p.Cys34Tyr)	ARV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
982891	NM_022786.3(ARV1):c.292_294+1del	ARV1	Uncertain significance	criteria provided, single submitter
1192479	NM_022786.3(ARV1):c.175-11T>C	ARV1	Benign	criteria provided, multiple submitters, no conflicts
789436	NM_022786.3(ARV1):c.302G>A (p.Gly101Glu)	ARV1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
ARV1	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 38	2

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
ARV1	HGNC:29561	ENSG00000173409	Q9H2C2	Protein ARV1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARV1	Protein ARV1	Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis.

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)
ARV1	Other/Unknown	no		Arv1

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
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARV1	258	ubiquitous	marker	cardiac muscle of right atrium, myocardium, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARV1	476

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARV1	Q9H2C2	82.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cholesterol biosynthesis	1	1142.0×	0.004	ARV1
Metabolism of steroids	1	137.6×	0.015	ARV1
Metabolism of lipids	1	31.6×	0.042	ARV1
Metabolism	1	11.6×	0.086	ARV1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of plasma membrane sterol distribution	1	16852.0×	5e-04	ARV1
regulation of intracellular cholesterol transport	1	4213.0×	9e-04	ARV1
intracellular sterol transport	1	3370.4×	9e-04	ARV1
regulation of cholesterol metabolic process	1	1123.5×	0.002	ARV1
sphingolipid metabolic process	1	991.3×	0.002	ARV1
bile acid metabolic process	1	991.3×	0.002	ARV1
sterol metabolic process	1	842.6×	0.002	ARV1
cholesterol transport	1	732.7×	0.002	ARV1
cholesterol biosynthetic process	1	421.3×	0.002	ARV1

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
ARV1	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	ARV1

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)
ARV1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ARV1