Developmental and epileptic encephalopathy 103

disease

On this page

Also known as DEE103

Summary

Developmental and epileptic encephalopathy 103 (MONDO:0030957) is a disease caused by KCNC2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: KCNC2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 103
Mondo ID	MONDO:0030957
OMIM	619913
DOID	DOID:0070389
UMLS	C5677002
MedGen	1809962
GARD	0025667
Is cancer (heuristic)	no

Also known as: DEE103 · developmental and epileptic encephalopathy 103

Data availability: 23 ClinVar variants · 3 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 103

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

23 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 7 pathogenic, 5 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1411978	NM_139137.4(KCNC2):c.1052G>A (p.Arg351Lys)	KCNC2	Pathogenic	criteria provided, single submitter
1693470	NM_139137.4(KCNC2):c.1411G>C (p.Val471Leu)	KCNC2	Pathogenic	no assertion criteria provided
1693471	NM_139137.4(KCNC2):c.499G>T (p.Asp167Tyr)	KCNC2	Pathogenic	no assertion criteria provided
1693472	NM_139137.4(KCNC2):c.375C>G (p.Cys125Trp)	KCNC2	Pathogenic	no assertion criteria provided
1693473	NM_139137.4(KCNC2):c.404A>G (p.Glu135Gly)	KCNC2	Pathogenic	no assertion criteria provided
1693475	NM_139137.4(KCNC2):c.1309A>G (p.Thr437Ala)	KCNC2	Pathogenic	no assertion criteria provided
2413122	NM_139137.4(KCNC2):c.1163T>C (p.Phe388Ser)	KCNC2	Pathogenic	criteria provided, single submitter
3061800	NM_139137.4(KCNC2):c.487G>A (p.Glu163Lys)	KCNC2	Likely pathogenic	criteria provided, single submitter
3234060	NM_139137.4(KCNC2):c.1210G>A (p.Glu404Lys)	KCNC2	Likely pathogenic	criteria provided, single submitter
3773727	NM_139137.4(KCNC2):c.1181T>C (p.Leu394Ser)	KCNC2	Likely pathogenic	criteria provided, single submitter
3775571	NM_139137.4(KCNC2):c.1405G>C (p.Val469Leu)	KCNC2	Likely pathogenic	criteria provided, single submitter
3778672	NM_139137.4(KCNC2):c.879T>A (p.Phe293Leu)	KCNC2	Likely pathogenic	no assertion criteria provided
872705	NM_139137.4(KCNC2):c.1408C>T (p.Pro470Ser)	KCNC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2431912	NM_139137.4(KCNC2):c.1408C>A (p.Pro470Thr)	KCNC2	Uncertain significance	criteria provided, single submitter
3376848	NM_139137.4(KCNC2):c.347A>G (p.Asn116Ser)	KCNC2	Uncertain significance	criteria provided, single submitter
3377239	NM_139137.4(KCNC2):c.914C>A (p.Pro305His)	KCNC2	Uncertain significance	criteria provided, single submitter
3731524	NM_139137.4(KCNC2):c.1647G>C (p.Glu549Asp)	KCNC2	Uncertain significance	criteria provided, single submitter
3773696	NM_139137.4(KCNC2):c.1476A>C (p.Lys492Asn)	KCNC2	Uncertain significance	criteria provided, single submitter
3897954	NM_139137.4(KCNC2):c.437C>A (p.Thr146Asn)	KCNC2	Uncertain significance	criteria provided, single submitter
4279635	NM_139137.4(KCNC2):c.92G>A (p.Gly31Glu)	KCNC2	Uncertain significance	criteria provided, single submitter
4292721	NM_139137.4(KCNC2):c.1495C>T (p.Pro499Ser)	KCNC2	Uncertain significance	criteria provided, single submitter
4293042	NM_139137.4(KCNC2):c.1420A>G (p.Asn474Asp)	KCNC2	Uncertain significance	criteria provided, single submitter
4293674	NM_139137.4(KCNC2):c.620G>C (p.Arg207Pro)	KCNC2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
KCNC2	Strong	Autosomal dominant	developmental and epileptic encephalopathy 103	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNC2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
KCNC2	HGNC:6234	ENSG00000166006	Q96PR1	Voltage-gated potassium channel KCNC2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNC2	Voltage-gated potassium channel KCNC2	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain.

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNC2	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv

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
Brodmann (1909) area 9	1
anterior cingulate cortex	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNC2	69	tissue_specific	marker	prefrontal cortex, Brodmann (1909) area 9, anterior cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNC2	2,436

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNC2	Q96PR1	68.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.010	KCNC2
Voltage gated Potassium channels	1	243.0×	0.010	KCNC2
Regulation of insulin secretion	1	219.6×	0.010	KCNC2
Integration of energy metabolism	1	175.7×	0.010	KCNC2
Potassium Channels	1	134.3×	0.010	KCNC2
Neuronal System	1	44.3×	0.026	KCNC2
Metabolism	1	11.6×	0.086	KCNC2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of action potential firing rate	1	5617.3×	0.001	KCNC2
response to nerve growth factor	1	5617.3×	0.001	KCNC2
globus pallidus development	1	3370.4×	0.001	KCNC2
cellular response to ammonium ion	1	3370.4×	0.001	KCNC2
response to kainic acid	1	2407.4×	0.001	KCNC2
response to light intensity	1	2106.5×	0.001	KCNC2
response to amine	1	1872.4×	0.001	KCNC2
membrane hyperpolarization	1	1872.4×	0.001	KCNC2
nitric oxide-cGMP-mediated signaling	1	1532.0×	0.001	KCNC2
response to magnesium ion	1	1404.3×	0.001	KCNC2
cellular response to toxic substance	1	1404.3×	0.001	KCNC2
optic nerve development	1	1203.7×	0.001	KCNC2
protein heterooligomerization	1	1053.2×	0.001	KCNC2
positive regulation of potassium ion transmembrane transport	1	991.3×	0.001	KCNC2
cellular response to nitric oxide	1	936.2×	0.001	KCNC2
action potential	1	358.6×	0.003	KCNC2
potassium ion transport	1	191.5×	0.006	KCNC2
response to ethanol	1	146.5×	0.008	KCNC2
potassium ion transmembrane transport	1	135.9×	0.008	KCNC2
protein homooligomerization	1	122.1×	0.008	KCNC2

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
KCNC2	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
KCNC2	32	Binding:31, Toxicity:1

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	1	KCNC2
E	Difficult family or no structure, no drug	0

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)
KCNC2	32	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KCNC2