Developmental and epileptic encephalopathy, 5

Summary

Developmental and epileptic encephalopathy, 5 (MONDO:0013277) is a disease caused by SPTAN1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: SPTAN1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 364

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 5
Mondo ID	MONDO:0013277
OMIM	613477
DOID	DOID:0080438
UMLS	C3150731
MedGen	462081
GARD	0012949
Is cancer (heuristic)	no

Also known as: DEE5 · developmental and epileptic encephalopathy 5 · early infantile epileptic encephalopathy caused by mutation in SPTAN1 · EIEE5 · epileptic encephalopathy, early infantile, 5 · epileptic encephalopathy, early infantile, type 5 · SPTAN1 early infantile epileptic encephalopathy

Data availability: 364 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › infantile spasms › developmental and epileptic encephalopathy, 5

Related subtypes (7): developmental and epileptic encephalopathy, 2, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 12, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 40

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

364 retrieved; paginated sample, class counts are floors:

121 conflicting classifications of pathogenicity, 95 uncertain significance, 78 benign/likely benign, 24 likely pathogenic, 19 benign, 10 pathogenic/likely pathogenic, 9 pathogenic, 8 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
160024	NM_001130438.3(SPTAN1):c.6616GAG[1] (p.Glu2207del)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160028	NM_001130438.3(SPTAN1):c.6899ACCAGCTGG[3] (p.2300DQL[3])	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686228	NM_001130438.3(SPTAN1):c.6905_6946dup (p.Leu2302_Gln2315dup)	SPTAN1	Pathogenic	criteria provided, single submitter
1701629	NM_001130438.3(SPTAN1):c.7229C>T (p.Ser2410Phe)	SPTAN1	Pathogenic	criteria provided, single submitter
1707716	NC_000009.11:g.(?131382516)(131393966_?)del	SPTAN1	Pathogenic	criteria provided, single submitter
1804130	NM_001130438.3(SPTAN1):c.6924_6929dup (p.Met2309_Gln2310insHisMet)	SPTAN1	Pathogenic	criteria provided, single submitter
207360	NM_001130438.3(SPTAN1):c.6922C>T (p.Arg2308Cys)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207370	NM_001130438.3(SPTAN1):c.6917GCATGC[3] (p.Arg2308_Met2309dup)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207380	NM_001130438.3(SPTAN1):c.6899ACCAGCTGG[1] (p.2300DQL[1])	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2628105	NM_001130438.3(SPTAN1):c.466C>T (p.Arg156Ter)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3066357	NM_001130438.3(SPTAN1):c.3014G>A (p.Trp1005Ter)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35483	NM_001130438.3(SPTAN1):c.6605_6607del (p.Gln2202del)	SPTAN1	Pathogenic	criteria provided, single submitter
429871	NM_001130438.3(SPTAN1):c.4828C>T (p.Arg1610Trp)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
632592	NM_001130438.3(SPTAN1):c.4813C>T (p.His1605Tyr)	SPTAN1	Pathogenic	no assertion criteria provided
844981	NM_001130438.3(SPTAN1):c.6241AAG[2] (p.Lys2083del)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929476	NM_001130438.3:c.(?1225)(1572_?)del	SPTAN1	Pathogenic	criteria provided, single submitter
976410	NM_001130438.3(SPTAN1):c.4936C>T (p.Gln1646Ter)	SPTAN1	Pathogenic	criteria provided, single submitter
986935	NM_001130438.3(SPTAN1):c.6811G>A (p.Glu2271Lys)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996072	NM_001130438.3(SPTAN1):c.4343A>C (p.Gln1448Pro)	SPTAN1	Pathogenic	criteria provided, single submitter
4278421	NM_138761.4(BAX):c.474+50_474+63del	BAX	Likely pathogenic	criteria provided, single submitter
3338457	GRCh37/hg19 9q34.11(chr9:131295791-131419128)x1	DYNC2I2	Likely pathogenic	no assertion criteria provided
1027548	NM_001130438.3(SPTAN1):c.4640T>A (p.Leu1547Gln)	SPTAN1	Likely pathogenic	no assertion criteria provided
1065462	NM_001130438.3(SPTAN1):c.415C>T (p.Arg139Ter)	SPTAN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325793	NM_001130438.3(SPTAN1):c.6622_6624del (p.Asn2208del)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1325794	NM_001130438.3(SPTAN1):c.6850_6852del (p.Asp2284del)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1325795	NM_001130438.3(SPTAN1):c.6910_6918del (p.Gln2304_Gly2306del)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1325796	NM_001130438.3(SPTAN1):c.533G>A (p.Gly178Asp)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1325797	NM_001130438.3(SPTAN1):c.917C>T (p.Ala306Val)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1331519	NM_001130438.3(SPTAN1):c.840dup (p.Asp281Ter)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1676440	NM_001130438.3(SPTAN1):c.1210C>T (p.Gln404Ter)	SPTAN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
SPTAN1	Definitive	Autosomal dominant	genetic developmental and epileptic encephalopathy	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTAN1	Orphanet:697160	Infantile epileptic spasms syndrome
DYNC2I2	Orphanet:474	Jeune syndrome
DYNC2I2	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPTAN1	HGNC:11273	ENSG00000197694	Q13813	Spectrin alpha chain, non-erythrocytic 1	gencc,clinvar
DYNC2I2	HGNC:28296	ENSG00000119333	Q96EX3	Cytoplasmic dynein 2 intermediate chain 2	clinvar
BAX	HGNC:959	ENSG00000087088	Q07812	Apoptosis regulator BAX	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTAN1	Spectrin alpha chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
DYNC2I2	Cytoplasmic dynein 2 intermediate chain 2	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i…
BAX	Apoptosis regulator BAX	Plays a role in the mitochondrial apoptotic process.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Scaffold/PPI	2	11.5×	0.019
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTAN1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
DYNC2I2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
BAX	Other/Unknown	no		Bcl2-like, Bcl2_BH1_motif_CS, Bcl2_BH2_motif_CS

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
apex of heart	1
pancreatic ductal cell	1
right uterine tube	1
granulocyte	1
mucosa of transverse colon	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTAN1	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
DYNC2I2	238	ubiquitous	marker	right uterine tube, pancreatic ductal cell, apex of heart
BAX	244	ubiquitous	marker	mucosa of transverse colon, stromal cell of endometrium, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTAN1	3,083
DYNC2I2	1,099
BAX	543

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BAX	Q07812	37
SPTAN1	Q13813	7
DYNC2I2	Q96EX3	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Apoptosis	2	112.0×	0.004	SPTAN1, BAX
Programmed Cell Death	2	97.6×	0.004	SPTAN1, BAX
Activation, translocation and oligomerization of BAX	1	1903.3×	0.010	BAX
NTRK3 as a dependence receptor	1	1268.9×	0.011	BAX
Release of apoptotic factors from the mitochondria	1	543.8×	0.021	BAX
Signaling by NTRK3 (TRKC)	1	380.7×	0.022	BAX
Caspase-mediated cleavage of cytoskeletal proteins	1	317.2×	0.022	SPTAN1
Apoptotic factor-mediated response	1	292.8×	0.022	BAX
Regulated Necrosis	1	237.9×	0.022	BAX
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	200.3×	0.022	BAX
TP53 Regulates Transcription of Cell Death Genes	1	181.3×	0.022	BAX
TP53 Regulates Transcription of Cell Cycle Genes	1	181.3×	0.022	BAX
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	181.3×	0.022	BAX
Apoptotic cleavage of cellular proteins	1	158.6×	0.022	SPTAN1
Nephrin family interactions	1	158.6×	0.022	SPTAN1
Apoptotic execution phase	1	158.6×	0.022	SPTAN1
Pyroptosis	1	141.0×	0.024	BAX
Interaction between L1 and Ankyrins	1	122.8×	0.026	SPTAN1
Sensory processing of sound	1	102.9×	0.027	SPTAN1
Intrinsic Pathway for Apoptosis	1	97.6×	0.027	BAX
RHOV GTPase cycle	1	95.2×	0.027	SPTAN1
RHOU GTPase cycle	1	92.8×	0.027	SPTAN1
NCAM signaling for neurite out-growth	1	90.6×	0.027	SPTAN1
Transcriptional regulation by RUNX2	1	84.6×	0.028	BAX
Sensory processing of sound by outer hair cells of the cochlea	1	68.0×	0.033	SPTAN1
Intraflagellar transport	1	66.8×	0.033	DYNC2I2
Signaling by NTRKs	1	60.4×	0.035	BAX
Sensory processing of sound by inner hair cells of the cochlea	1	54.4×	0.037	SPTAN1
Cell-Cell communication	1	45.9×	0.042	SPTAN1
ER to Golgi Anterograde Transport	1	44.3×	0.042	SPTAN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
T cell homeostatic proliferation	1	5617.3×	0.003	BAX
release of matrix enzymes from mitochondria	1	5617.3×	0.003	BAX
positive regulation of developmental pigmentation	1	5617.3×	0.003	BAX
B cell negative selection	1	2808.7×	0.003	BAX
B cell homeostatic proliferation	1	2808.7×	0.003	BAX
regulation of nitrogen utilization	1	2808.7×	0.003	BAX
development of animal secondary sexual characteristics	1	2808.7×	0.003	BAX
B cell receptor apoptotic signaling pathway	1	2808.7×	0.003	BAX
positive regulation of motor neuron apoptotic process	1	2808.7×	0.003	BAX
retinal cell programmed cell death	1	1872.4×	0.003	BAX
apoptotic process involved in mammary gland involution	1	1872.4×	0.003	BAX
apoptotic process involved in embryonic digit morphogenesis	1	1872.4×	0.003	BAX
regulation of mitochondrial membrane permeability involved in programmed necrotic cell death	1	1872.4×	0.003	BAX
positive regulation of B cell apoptotic process	1	1404.3×	0.003	BAX
post-embryonic camera-type eye morphogenesis	1	1404.3×	0.003	BAX
protein insertion into mitochondrial membrane	1	1404.3×	0.003	BAX
positive regulation of apoptotic process involved in mammary gland involution	1	1404.3×	0.003	BAX
positive regulation of mitochondrial membrane permeability involved in apoptotic process	1	1404.3×	0.003	BAX
positive regulation of reproductive process	1	1404.3×	0.003	BAX
establishment or maintenance of transmembrane electrochemical gradient	1	936.2×	0.004	BAX
negative regulation of endoplasmic reticulum calcium ion concentration	1	936.2×	0.004	BAX
regulation of mammary gland epithelial cell proliferation	1	936.2×	0.004	BAX
Sertoli cell proliferation	1	936.2×	0.004	BAX
apoptotic process involved in blood vessel morphogenesis	1	936.2×	0.004	BAX
positive regulation of apoptotic DNA fragmentation	1	936.2×	0.004	BAX
glycosphingolipid metabolic process	1	802.5×	0.004	BAX
myeloid cell homeostasis	1	702.2×	0.005	BAX
positive regulation of IRE1-mediated unfolded protein response	1	702.2×	0.005	BAX
response to salt stress	1	624.1×	0.005	BAX
spermatid differentiation	1	561.7×	0.006	BAX

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPTAN1	1	2
BAX	1	1
DYNC2I2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SPTAN1
ABT 737	1	BAX

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BAX	49	Binding:47, Functional:2
SPTAN1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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	SPTAN1
ABT 737	1	BAX

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	2	SPTAN1, BAX
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DYNC2I2

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)
DYNC2I2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.