Developmental and epileptic encephalopathy, 48

Summary

Developmental and epileptic encephalopathy, 48 (MONDO:0015000) is a disease caused by AP3B2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: AP3B2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 48
Mondo ID	MONDO:0015000
OMIM	617276
DOID	DOID:0080448
UMLS	C4310637
MedGen	934604
GARD	0016218
Is cancer (heuristic)	no

Also known as: AP3B2 early infantile epileptic encephalopathy · DEE48 · developmental and epileptic encephalopathy 48 · early infantile epileptic encephalopathy caused by mutation in AP3B2 · EIEE48 · epileptic encephalopathy, early infantile, 48 · epileptic encephalopathy, early infantile, 48; EIEE48 · epileptic encephalopathy, early infantile, type 48

Data availability: 48 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, 48

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, 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, 70, 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

48 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 9 likely pathogenic, 8 pathogenic, 7 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 2 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031455	NM_001278512.2(AP3B2):c.940C>T (p.Gln314Ter)	AP3B2	Pathogenic	criteria provided, single submitter
1279926	NM_001278512.2(AP3B2):c.445_448del (p.Ala149fs)	AP3B2	Pathogenic	criteria provided, multiple submitters, no conflicts
1457064	NM_001278512.2(AP3B2):c.2515C>T (p.Gln839Ter)	AP3B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2028168	NM_001278512.2(AP3B2):c.1958_1959del (p.Val653fs)	AP3B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2435024	NM_001278512.2(AP3B2):c.2929C>T (p.Arg977Ter)	AP3B2	Pathogenic	criteria provided, multiple submitters, no conflicts
2577043	NM_001278512.2(AP3B2):c.641delinsATG (p.Ile214fs)	AP3B2	Pathogenic	criteria provided, single submitter
374848	NM_001278512.2(AP3B2):c.1489-245_1665+2029del	AP3B2	Pathogenic	no assertion criteria provided
374849	NM_001278512.2(AP3B2):c.2579_2582del (p.Leu860fs)	AP3B2	Pathogenic	no assertion criteria provided
374850	NM_001278512.2(AP3B2):c.199C>T (p.Arg67Ter)	AP3B2	Pathogenic	no assertion criteria provided
374851	NM_001278512.2(AP3B2):c.1837del (p.Glu613fs)	AP3B2	Pathogenic	criteria provided, single submitter
987398	NM_001278512.2(AP3B2):c.2978_2979del (p.Pro993fs)	AP3B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323917	NM_001278512.2(AP3B2):c.454G>T (p.Glu152Ter)	AP3B2	Likely pathogenic	criteria provided, single submitter
2434281	NM_001278512.2(AP3B2):c.1750C>T (p.Gln584Ter)	AP3B2	Likely pathogenic	criteria provided, single submitter
3362285	NM_001278512.2(AP3B2):c.1129del (p.Tyr376_Leu377insTer)	AP3B2	Likely pathogenic	criteria provided, single submitter
374846	NM_001278512.2(AP3B2):c.1182G>A (p.Lys394=)	AP3B2	Likely pathogenic	criteria provided, single submitter
374847	NM_001278512.2(AP3B2):c.1110+1G>C	AP3B2	Likely pathogenic	criteria provided, single submitter
4759258	NM_001278512.2(AP3B2):c.2262-34_2268del	AP3B2	Likely pathogenic	criteria provided, single submitter
800531	NM_001278512.2(AP3B2):c.674_675del (p.Leu224_Cys225insTer)	AP3B2	Likely pathogenic	criteria provided, single submitter
803113	NM_001278512.2(AP3B2):c.392_394del (p.Leu131del)	AP3B2	Likely pathogenic	criteria provided, single submitter
983350	NM_001278512.2(AP3B2):c.66C>G (p.Tyr22Ter)	LOC130057772	Likely pathogenic	criteria provided, single submitter
1034104	NM_001278512.2(AP3B2):c.1183-19T>G	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034106	NM_001278512.2(AP3B2):c.2633G>A (p.Arg878Gln)	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1367208	NM_001278512.2(AP3B2):c.3125G>A (p.Arg1042His)	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1442192	NM_001278512.2(AP3B2):c.1767C>A (p.Ser589=)	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679661	NM_001278512.2(AP3B2):c.1379-6C>G	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
786277	NM_001278512.2(AP3B2):c.3143C>A (p.Ser1048Tyr)	AP3B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
444351	NM_001278512.2(AP3B2):c.2261+2T>C	CPEB1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031454	NM_001278512.2(AP3B2):c.3293C>A (p.Ala1098Asp)	AP3B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034105	NM_001278512.2(AP3B2):c.1636G>C (p.Ala546Pro)	AP3B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034107	NM_001278512.2(AP3B2):c.2679C>G (p.Asp893Glu)	AP3B2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
AP3B2	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 48	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP3B2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AP3B2	HGNC:567	ENSG00000103723	Q13367	AP-3 complex subunit beta-2	gencc,clinvar
CPEB1-AS1	HGNC:27523	ENSG00000259462		CPEB1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP3B2	AP-3 complex subunit beta-2	Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AP3B2	Antibody/Immunoglobulin	yes		Clathrin/coatomer_adapt-like_N, ARM-like, Clathrin_app_Ig-like_sf
CPEB1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
C1 segment of cervical spinal cord	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP3B2	202	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CPEB1-AS1	143	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, sural nerve, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AP3B2	1,738
CPEB1-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AP3B2	Q13367	75.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
synaptic vesicle coating	1	3370.4×	0.001	AP3B2
clathrin-coated vesicle cargo loading, AP-3-mediated	1	2407.4×	0.001	AP3B2
synaptic vesicle recycling	1	1203.7×	0.002	AP3B2
anterograde synaptic vesicle transport	1	991.3×	0.002	AP3B2
anterograde axonal transport	1	581.1×	0.002	AP3B2
vesicle-mediated transport	1	96.3×	0.012	AP3B2
intracellular protein transport	1	64.8×	0.015	AP3B2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
AP3B2	0	0
CPEB1-AS1	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	1	AP3B2
E	Difficult family or no structure, no drug	1	CPEB1-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AP3B2	0	—
CPEB1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.