Epilepsy, early-onset, with or without developmental delay

Summary

Epilepsy, early-onset, with or without developmental delay (MONDO:0030005) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 58

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, early-onset, with or without developmental delay
Mondo ID	MONDO:0030005
OMIM	618832
DOID	DOID:0070471
UMLS	C5882670
MedGen	1845576
Is cancer (heuristic)	no

Also known as: EPEDD · EPILEPSY, EARLY-ONSET, WITH OR WITHOUT DEVELOPMENTAL DELAY · epilepsy, early-onset, with or without developmental delay

Data availability: 58 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 › epilepsy, early-onset › epilepsy, early-onset, with or without developmental delay

Related subtypes (2): epilepsy, early-onset, vitamin B6-dependent, epilepsy, early-onset, 3, with or without developmental delay

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

58 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1709342	NM_014712.3(SETD1A):c.2968C>T (p.Arg990Ter)	SETD1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2609891	NM_014712.3(SETD1A):c.2002C>T (p.Arg668Ter)	SETD1A	Pathogenic	criteria provided, multiple submitters, no conflicts
417721	NM_014712.3(SETD1A):c.4582-2_4582-1del	SETD1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
834091	NM_014712.3(SETD1A):c.806A>G (p.Gln269Arg)	SETD1A	Pathogenic	no assertion criteria provided
834092	NM_014712.3(SETD1A):c.4105G>A (p.Gly1369Arg)	SETD1A	Pathogenic	no assertion criteria provided
976774	NM_014712.3(SETD1A):c.1287dup (p.Ser430fs)	SETD1A	Pathogenic	criteria provided, single submitter
1678536	NM_014712.3(SETD1A):c.2512C>T (p.Gln838Ter)	SETD1A	Likely pathogenic	criteria provided, single submitter
2664066	NM_014712.3(SETD1A):c.2665C>T (p.Arg889Trp)	SETD1A	Likely pathogenic	criteria provided, single submitter
834090	NM_014712.3(SETD1A):c.2737C>T (p.Arg913Cys)	SETD1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
973880	NM_014712.3(SETD1A):c.46C>T (p.Gln16Ter)	SETD1A	Likely pathogenic	criteria provided, single submitter
1176348	NM_014712.3(SETD1A):c.4636G>A (p.Ala1546Thr)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342416	NM_014712.3(SETD1A):c.3680G>A (p.Arg1227Gln)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2361531	NM_014712.3(SETD1A):c.5100G>T (p.Glu1700Asp)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2646429	NM_014712.3(SETD1A):c.1361AAG[1] (p.Glu455del)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892403	NM_014712.3(SETD1A):c.2119C>T (p.Pro707Ser)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930684	NM_014712.3(SETD1A):c.3358+5G>A	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930685	NM_014712.3(SETD1A):c.4169G>A (p.Arg1390Gln)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992747	NM_014712.3(SETD1A):c.3236C>T (p.Pro1079Leu)	SETD1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1184383	NM_014712.3(SETD1A):c.3613C>T (p.Arg1205Trp)	SETD1A	Uncertain significance	criteria provided, single submitter
1333205	NM_014712.3(SETD1A):c.2842C>G (p.Arg948Gly)	SETD1A	Uncertain significance	criteria provided, single submitter
1341789	NM_014712.3(SETD1A):c.3536C>G (p.Pro1179Arg)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341796	NM_014712.3(SETD1A):c.3673G>T (p.Val1225Leu)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341940	NM_014712.3(SETD1A):c.3689G>A (p.Arg1230Gln)	SETD1A	Uncertain significance	criteria provided, single submitter
1342473	NM_014712.3(SETD1A):c.667G>C (p.Asp223His)	SETD1A	Uncertain significance	criteria provided, single submitter
1342591	NM_014712.3(SETD1A):c.1064C>T (p.Ser355Leu)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342592	NM_014712.3(SETD1A):c.1345C>G (p.Pro449Ala)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342909	NM_014712.3(SETD1A):c.4513A>G (p.Lys1505Glu)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1701627	NM_014712.3(SETD1A):c.4298C>T (p.Ser1433Leu)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2404727	NM_014712.3(SETD1A):c.1381C>T (p.Arg461Cys)	SETD1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2443344	NM_014712.3(SETD1A):c.1503del (p.Lys502fs)	SETD1A	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
SETD1A	Limited	Autosomal dominant	epilepsy, early-onset, with or without developmental delay	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SETD1A	Orphanet:528084	Non-specific syndromic intellectual disability

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
SETD1A	HGNC:29010	ENSG00000099381	O15047	Histone-lysine N-methyltransferase SETD1A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SETD1A	Histone-lysine N-methyltransferase SETD1A	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SETD1A	Enzyme (other)	yes	2.1.1.354	RRM_dom, SET_dom, Post-SET_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
paraflocculus	1
parotid gland	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SETD1A	234	ubiquitous	marker	paraflocculus, sural nerve, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SETD1A	3,862

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SETD1A	O15047	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Formation of WDR5-containing histone-modifying complexes	1	265.6×	0.018	SETD1A
PKMTs methylate histone lysines	1	160.8×	0.018	SETD1A
Epigenetic regulation by WDR5-containing histone modifying complexes	1	154.3×	0.018	SETD1A
Transcriptional regulation by RUNX1	1	146.4×	0.018	SETD1A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.018	SETD1A
Chromatin organization	1	81.6×	0.019	SETD1A
Chromatin modifying enzymes	1	72.3×	0.019	SETD1A
Epigenetic regulation of gene expression	1	71.4×	0.019	SETD1A
RNA Polymerase II Transcription	1	22.5×	0.054	SETD1A
Gene expression (Transcription)	1	17.8×	0.062	SETD1A
Generic Transcription Pathway	1	15.1×	0.066	SETD1A

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
regulation of hematopoietic stem cell differentiation	1	1532.0×	0.002	SETD1A
regulation of chromatin organization	1	1532.0×	0.002	SETD1A
methylation	1	170.2×	0.010	SETD1A
brain development	1	79.5×	0.016	SETD1A
DNA damage response	1	53.5×	0.019	SETD1A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

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
SETD1A	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SETD1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SETD1A	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SETD1A	2.1.1.354	[histone H3]-lysine4 N-trimethyltransferase

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SETD1A

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	1	SETD1A
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.