Developmental and epileptic encephalopathy 110

disease

On this page

Summary

Developmental and epileptic encephalopathy 110 (MONDO:0859327) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 110
Mondo ID	MONDO:0859327
OMIM	620149
DOID	DOID:0070395
UMLS	C5774265
MedGen	1824038
GARD	0026700
Is cancer (heuristic)	no

Data availability: 6 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 110

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

6 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802179	NM_000722.4(CACNA2D1):c.818_821dup (p.Ser275fs)	CACNA2D1	Pathogenic	no assertion criteria provided
1802180	NM_000722.4(CACNA2D1):c.13_23dup (p.Leu9fs)	CACNA2D1	Pathogenic	no assertion criteria provided
1802181	NM_000722.4(CACNA2D1):c.626G>A (p.Gly209Asp)	CACNA2D1	Pathogenic	no assertion criteria provided
4277370	NM_000722.4(CACNA2D1):c.295-2080_354+3407del	CACNA2D1	Likely pathogenic	criteria provided, single submitter
2450727	NM_000722.4(CACNA2D1):c.469C>T (p.Arg157Ter)	CACNA2D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064709	NM_000722.4(CACNA2D1):c.3152A>G (p.Asn1051Ser)	CACNA2D1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
CACNA2D1	Limited	Autosomal dominant	genetic developmental and epileptic encephalopathy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CACNA2D1	Orphanet:130	Brugada syndrome
CACNA2D1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CACNA2D1	Orphanet:51083	Congenital short QT 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
CACNA2D1	HGNC:1399	ENSG00000153956	P54289	Voltage-dependent calcium channel subunit alpha-2/delta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNA2D1	Voltage-dependent calcium channel subunit alpha-2/delta-1	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.

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)
CACNA2D1	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu

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
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNA2D1	261	ubiquitous	marker	biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CACNA2D1	2,002

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CACNA2D1	P54289	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	671.8×	0.004	CACNA2D1
Cellular responses to mechanical stimuli	1	259.6×	0.006	CACNA2D1
Cellular responses to stimuli	1	31.5×	0.032	CACNA2D1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
calcium ion transmembrane transport via high voltage-gated calcium channel	1	5617.3×	7e-04	CACNA2D1
membrane depolarization during bundle of His cell action potential	1	5617.3×	7e-04	CACNA2D1
regulation of membrane repolarization during action potential	1	5617.3×	7e-04	CACNA2D1
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	1685.2×	0.002	CACNA2D1
calcium ion transport into cytosol	1	1203.7×	0.002	CACNA2D1
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.002	CACNA2D1
regulation of calcium ion transport	1	802.5×	0.002	CACNA2D1
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	CACNA2D1
calcium ion import across plasma membrane	1	543.6×	0.002	CACNA2D1
cellular response to amyloid-beta	1	391.9×	0.003	CACNA2D1
regulation of heart rate by cardiac conduction	1	374.5×	0.003	CACNA2D1
calcium ion transport	1	181.2×	0.006	CACNA2D1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CACNA2D1	PREGABALIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA2D1	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PREGABALIN	4	CACNA2D1
GABAPENTIN	4	CACNA2D1
NIMODIPINE	4	CACNA2D1
TACRINE	4	CACNA2D1
Z160	2	CACNA2D1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CACNA2D1	47	Binding:45, ADMET:1, 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

5 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)
PREGABALIN	4	CACNA2D1
GABAPENTIN	4	CACNA2D1
NIMODIPINE	4	CACNA2D1
TACRINE	4	CACNA2D1
Z160	2	CACNA2D1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CACNA2D1
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	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.

Cohort genes: CACNA2D1