Developmental and epileptic encephalopathy, 70

Summary

Developmental and epileptic encephalopathy, 70 (MONDO:0032663) is a disease caused by PHACTR1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PHACTR1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 70
Mondo ID	MONDO:0032663
OMIM	618298
DOID	DOID:0112206
UMLS	C4749023
MedGen	1648407
GARD	0016336
Is cancer (heuristic)	no

Also known as: DEE70 · developmental and epileptic encephalopathy 70 · EIEE70 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 70 · epileptic encephalopathy, early infantile, 70

Data availability: 34 ClinVar variants · 4 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, 70

Related subtypes (104): developmental and epileptic encephalopathy, 9, developmental and epileptic encephalopathy, 8, developmental and epileptic encephalopathy, 2, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 3, developmental and epileptic encephalopathy, 4, microcephaly, seizures, and developmental delay, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 7, developmental and epileptic encephalopathy, 11, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 14, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 17, developmental and epileptic encephalopathy, 18, developmental and epileptic encephalopathy, 19, developmental and epileptic encephalopathy, 23, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 50, developmental and epileptic encephalopathy, 35, developmental and epileptic encephalopathy, 37, developmental and epileptic encephalopathy, 38, developmental and epileptic encephalopathy, 40, developmental and epileptic encephalopathy, 48, developmental and epileptic encephalopathy, 49, developmental and epileptic encephalopathy, 51, Lennox-Gastaut syndrome, developmental and epileptic encephalopathy 91, developmental and epileptic encephalopathy 92, developmental and epileptic encephalopathy 93, developmental and epileptic encephalopathy 96, developmental and epileptic encephalopathy, 90, developmental and epileptic encephalopathy, 85, with or without midline brain defects, developmental and epileptic encephalopathy, 67, developmental and epileptic encephalopathy, 86, developmental and epileptic encephalopathy, 87, developmental and epileptic encephalopathy, 88, developmental and epileptic encephalopathy 6B, developmental and epileptic encephalopathy 97, developmental and epileptic encephalopathy 98, developmental and epileptic encephalopathy 99, developmental and epileptic encephalopathy 100, developmental and epileptic encephalopathy 101, developmental and epileptic encephalopathy 89, developmental and epileptic encephalopathy 102, developmental and epileptic encephalopathy 103, developmental and epileptic encephalopathy 104, developmental and epileptic encephalopathy 105 with hypopituitarism, developmental and epileptic encephalopathy 106, developmental and epileptic encephalopathy 107, developmental and epileptic encephalopathy, 68, developmental and epileptic encephalopathy, 69, developmental and epileptic encephalopathy, 71, developmental and epileptic encephalopathy, 72, developmental and epileptic encephalopathy, 74, developmental and epileptic encephalopathy, 75, developmental and epileptic encephalopathy, 76, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 78, developmental and epileptic encephalopathy, 79, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 81, developmental and epileptic encephalopathy, 82, developmental and epileptic encephalopathy, 83, developmental and epileptic encephalopathy, 84, developmental and epileptic encephalopathy, 52, developmental and epileptic encephalopathy, 53, developmental and epileptic encephalopathy, 54, developmental and epileptic encephalopathy, 55, developmental and epileptic encephalopathy, 56, developmental and epileptic encephalopathy, 57, developmental and epileptic encephalopathy, 58, developmental and epileptic encephalopathy, 59, developmental and epileptic encephalopathy, 60, developmental and epileptic encephalopathy, 61, developmental and epileptic encephalopathy, 62, developmental and epileptic encephalopathy, 63, developmental and epileptic encephalopathy, 64, developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 73, developmental and epileptic encephalopathy, 66, developmental and epileptic encephalopathy, 6A, non-neonatal early infantile epileptic encephalopathy, Dravet syndrome, neonatal-onset developmental and epileptic encephalopathy, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, DNM1-encephalopathy and neurodevelopmental disorder, TMEM63B-related developmental and epileptic encephalopathy with anemia, developmental and epileptic encephalopathy 108, developmental and epileptic encephalopathy 109, developmental and epileptic encephalopathy 110, developmental and epileptic encephalopathy 111, developmental and epileptic encephalopathy 112, developmental and epileptic encephalopathy 113, developmental and epileptic encephalopathy 114, developmental and epileptic encephalopathy 115, developmental and epileptic encephalopathy 116, developmental and epileptic encephalopathy 118, developmental and epileptic encephalopathy 120, developmental and epileptic encephalopathy 121, developmental and epileptic encephalopathy 119

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

34 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 3 pathogenic, 3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
617491	NM_030948.6(PHACTR1):c.1499T>C (p.Leu500Pro)	LOC100130357	Pathogenic	criteria provided, single submitter
1679588	NM_030948.6(PHACTR1):c.1396C>A (p.Leu466Met)	PHACTR1	Pathogenic	criteria provided, single submitter
617492	NM_030948.6(PHACTR1):c.1436A>T (p.Asn479Ile)	PHACTR1	Pathogenic	no assertion criteria provided
1704279	NM_030948.6(PHACTR1):c.1278C>G (p.Ile426Met)	PHACTR1	Likely pathogenic	no assertion criteria provided
2584340	NM_030948.6(PHACTR1):c.209C>G (p.Pro70Arg)	PHACTR1	Likely pathogenic	criteria provided, single submitter
3068777	NM_030948.6(PHACTR1):c.190C>G (p.Arg64Gly)	PHACTR1	Likely pathogenic	criteria provided, single submitter
2596788	NM_030948.6(PHACTR1):c.1688C>G (p.Thr563Ser)	LOC100130357	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1699256	NM_030948.6(PHACTR1):c.1454A>G (p.Asn485Ser)	LOC100130357	Uncertain significance	criteria provided, single submitter
2627780	NM_030948.6(PHACTR1):c.1643C>G (p.Ala548Gly)	LOC100130357	Uncertain significance	no assertion criteria provided
3377117	NM_030948.6(PHACTR1):c.1555C>G (p.Leu519Val)	LOC100130357	Uncertain significance	criteria provided, single submitter
1184319	NM_030948.6(PHACTR1):c.250+8924C>G	PHACTR1	Uncertain significance	criteria provided, single submitter
1184391	NM_030948.6(PHACTR1):c.664+2178C>G	PHACTR1	Uncertain significance	criteria provided, single submitter
1341741	NM_030948.6(PHACTR1):c.664+2260T>A	PHACTR1	Uncertain significance	criteria provided, single submitter
1341821	NM_030948.6(PHACTR1):c.275C>T (p.Ala92Val)	PHACTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341876	NM_030948.6(PHACTR1):c.1252G>T (p.Val418Phe)	PHACTR1	Uncertain significance	criteria provided, single submitter
1342493	NM_030948.6(PHACTR1):c.163A>G (p.Ile55Val)	PHACTR1	Uncertain significance	criteria provided, single submitter
2434676	NM_030948.6(PHACTR1):c.1043G>A (p.Gly348Asp)	PHACTR1	Uncertain significance	criteria provided, single submitter
2434677	NM_030948.6(PHACTR1):c.917_918delinsTT (p.His306Leu)	PHACTR1	Uncertain significance	criteria provided, single submitter
2434678	NM_030948.6(PHACTR1):c.206C>A (p.Thr69Lys)	PHACTR1	Uncertain significance	criteria provided, single submitter
2434679	NM_030948.6(PHACTR1):c.1388C>T (p.Thr463Ile)	PHACTR1	Uncertain significance	criteria provided, single submitter
2434680	NM_030948.6(PHACTR1):c.920C>T (p.Pro307Leu)	PHACTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2538117	NM_030948.6(PHACTR1):c.964A>G (p.Met322Val)	PHACTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689688	NM_030948.6(PHACTR1):c.1000G>C (p.Val334Leu)	PHACTR1	Uncertain significance	criteria provided, single submitter
3064903	NM_030948.6(PHACTR1):c.251-39420G>T	PHACTR1	Uncertain significance	criteria provided, single submitter
3341456	NM_030948.6(PHACTR1):c.259G>A (p.Val87Met)	PHACTR1	Uncertain significance	criteria provided, single submitter
3367052	NM_030948.6(PHACTR1):c.580C>G (p.Leu194Val)	PHACTR1	Uncertain significance	criteria provided, single submitter
3393281	NM_030948.6(PHACTR1):c.323G>A (p.Arg108His)	PHACTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4056711	NM_030948.6(PHACTR1):c.1162T>G (p.Ser388Ala)	PHACTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079546	NM_030948.6(PHACTR1):c.1509+3A>C	PHACTR1	Uncertain significance	criteria provided, single submitter
4292944	NM_030948.6(PHACTR1):c.218C>G (p.Ala73Gly)	PHACTR1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PHACTR1	Strong	Autosomal dominant	developmental and epileptic encephalopathy, 70	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHACTR1	Orphanet:697160	Infantile epileptic spasms syndrome

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
PHACTR1	HGNC:20990	ENSG00000112137	Q9C0D0	Phosphatase and actin regulator 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHACTR1	Phosphatase and actin regulator 1	Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula…

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)
PHACTR1	Other/Unknown	no		RPEL_repeat

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
cortical plate	1
nucleus accumbens	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHACTR1	210	ubiquitous	marker	cortical plate, postcentral gyrus, nucleus accumbens

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHACTR1	986

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHACTR1	Q9C0D0	6

Function

Pathway analysis

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

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
dendrite arborization	1	1872.4×	0.003	PHACTR1
stress fiber assembly	1	766.0×	0.003	PHACTR1
regulation of neuron migration	1	624.1×	0.003	PHACTR1
actomyosin structure organization	1	561.7×	0.003	PHACTR1
cell motility	1	401.2×	0.003	PHACTR1
cerebral cortex development	1	205.5×	0.006	PHACTR1
actin cytoskeleton organization	1	79.1×	0.013	PHACTR1

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
PHACTR1	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	PHACTR1

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)
PHACTR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.