Developmental and epileptic encephalopathy, 80

Summary

Developmental and epileptic encephalopathy, 80 (MONDO:0032822) is a disease caused by PIGB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PIGB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 80
Mondo ID	MONDO:0032822
OMIM	618580
DOID	DOID:0112216
UMLS	C5231418
MedGen	1684779
GARD	0025754
Is cancer (heuristic)	no

Also known as: DEE80 · developmental and epileptic encephalopathy 80 · EIEE80 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 80 · epileptic encephalopathy, early infantile, 80

Data availability: 24 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 › inborn errors of metabolism › inherited lipid metabolism disorder › developmental and epileptic encephalopathy, 80

Related subtypes (28): cortisone reductase deficiency, familial hyperlipidemia, hypolipoproteinemia, steroid inherited metabolic disorder, corticosterone methyloxidase type 1 deficiency, lipoid proteinosis, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, vitamin D hydroxylation-deficient rickets, type 1B, mitochondrial trifunctional protein deficiency, pancreatic triacylglycerol lipase deficiency, glucocorticoid resistance, syndromic dyslipidemia, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of plasmalogens biosynthesis, disorder of phospholipids, sphingolipids and fatty acids biosynthesis, inborn disorder of ketolysis, lysosomal lipid storage disorder, sterol metabolism disorder, disorder of sphingolipid biosynthesis, glycosylphosphatidylinositol biosynthesis defect 18, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 55, inherited fatty acid metabolism disorder, glycosylphosphatidylinositol biosynthesis defect 16, glycosylphosphatidylinositol biosynthesis defect 15, glycosylphosphatidylinositol biosynthesis defect 17, CYP7B1-related disorder of oxysterol accumulation

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

24 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 6 pathogenic, 3 conflicting classifications of pathogenicity, 3 benign, 2 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
976715	NM_004855.5(PIGB):c.1611A>G (p.Ile537Met)	CCPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1943029	NM_004855.5(PIGB):c.91A>T (p.Lys31Ter)	PIGB	Pathogenic	criteria provided, multiple submitters, no conflicts
689514	NM_004855.5(PIGB):c.212G>A (p.Arg71Gln)	PIGB	Pathogenic	no assertion criteria provided
689515	NM_004855.5(PIGB):c.1162G>C (p.Ala388Pro)	PIGB	Pathogenic	no assertion criteria provided
689516	NM_004855.5(PIGB):c.856G>C (p.Val286Leu)	PIGB	Pathogenic	no assertion criteria provided
689517	NM_004855.5(PIGB):c.695G>A (p.Arg232His)	PIGB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689519	NM_004855.5(PIGB):c.847-10A>G	PIGB	Pathogenic	criteria provided, multiple submitters, no conflicts
976714	NM_004855.5(PIGB):c.392T>G (p.Leu131Ter)	PIGB	Pathogenic	criteria provided, multiple submitters, no conflicts
1098618	NM_004855.5(PIGB):c.795-1G>C	PIGB	Likely pathogenic	criteria provided, multiple submitters, no conflicts
995863	NM_004855.5(PIGB):c.463G>C (p.Asp155His)	PIGB	Likely pathogenic	criteria provided, single submitter
2434836	NM_004855.5(PIGB):c.1594C>T (p.Arg532Ter)	CCPG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028306	NM_004855.5(PIGB):c.1432C>G (p.Leu478Val)	PIGB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2776210	NM_004855.5(PIGB):c.522+1G>T	PIGB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1712511	NM_004855.5(PIGB):c.1016G>A (p.Arg339Gln)	PIGB	Uncertain significance	criteria provided, single submitter
2434832	NM_004855.5(PIGB):c.996T>A (p.Tyr332Ter)	PIGB	Uncertain significance	criteria provided, single submitter
2434833	NM_004855.5(PIGB):c.334C>G (p.Leu112Val)	PIGB	Uncertain significance	criteria provided, single submitter
2434834	NM_004855.5(PIGB):c.832A>G (p.Ile278Val)	PIGB	Uncertain significance	criteria provided, single submitter
2434835	NM_004855.5(PIGB):c.643T>G (p.Ser215Ala)	PIGB	Uncertain significance	criteria provided, single submitter
2580204	NM_004855.5(PIGB):c.1334A>G (p.Tyr445Cys)	PIGB	Uncertain significance	criteria provided, single submitter
3602744	NM_004855.5(PIGB):c.1484C>T (p.Pro495Leu)	PIGB	Uncertain significance	criteria provided, single submitter
561082	NM_004855.5(PIGB):c.1220A>G (p.His407Arg)	PIGB	Uncertain significance	criteria provided, single submitter
1179234	NM_004855.5(PIGB):c.896G>T (p.Trp299Leu)	PIGB	Benign	criteria provided, multiple submitters, no conflicts
1327019	NM_004855.5(PIGB):c.-16A>G	PIGB	Benign	criteria provided, multiple submitters, no conflicts
1327020	NM_004855.5(PIGB):c.523-33T>C	PIGB	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
PIGB	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 80	3

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PIGB	HGNC:8959	ENSG00000069943	Q92521	GPI alpha-1,2-mannosyltransferase 3	gencc,clinvar
CCPG1	HGNC:24227	ENSG00000260916	Q9ULG6	Cell cycle progression protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIGB	GPI alpha-1,2-mannosyltransferase 3	Alpha-1,2-mannosyltransferase that catalyzes the transfer of the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to a 2-acyl-6-[alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha…
CCPG1	Cell cycle progression protein 1	Acts as an assembly platform for Rho protein signaling complexes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIGB	Other/Unknown	no		GPI_mannosylTrfase
CCPG1	Other/Unknown	no		CCPG1/PBIP1

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
calcaneal tendon	2
blood	1
granulocyte	1
body of pancreas	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIGB	254	ubiquitous	marker	granulocyte, blood, calcaneal tendon
CCPG1	223	ubiquitous	marker	calcaneal tendon, colonic epithelium, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCPG1	1,609
PIGB	690

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCPG1	Q9ULG6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PIGB	Q92521	88.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Synthesis of glycosylphosphatidylinositol (GPI)	1	634.4×	0.002	PIGB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reticulophagy	1	351.1×	0.008	CCPG1
GPI anchor biosynthetic process	1	247.8×	0.008	PIGB
positive regulation of cell cycle	1	221.7×	0.008	CCPG1
positive regulation of cell population proliferation	1	16.8×	0.073	CCPG1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CCPG1

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
PIGB	0	0
CCPG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
E	Difficult family or no structure, no drug	2	PIGB, CCPG1

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)
PIGB	0	—
CCPG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.