Developmental and epileptic encephalopathy, 84

disease

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Also known as DEE84developmental and epileptic encephalopathy 84EIEE84EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 84UGDH-Related Disorder

Summary

Developmental and epileptic encephalopathy, 84 (MONDO:0032918) is a disease caused by UGDH (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: UGDH (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, 84
Mondo ID	MONDO:0032918
OMIM	618792
DOID	DOID:0112219
UMLS	C5394081
MedGen	1720141
GARD	0025774
NORD	102487
Is cancer (heuristic)	no

Also known as: DEE84 · developmental and epileptic encephalopathy 84 · EIEE84 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 84 · epileptic encephalopathy, early infantile, 84 · UGDH-Related Disorder

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, 84

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:

12 uncertain significance, 5 pathogenic/likely pathogenic, 4 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
592087	NM_003359.4(UGDH):c.950G>A (p.Arg317Gln)	UGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
810646	NM_003359.4(UGDH):c.1100A>G (p.Tyr367Cys)	UGDH	Pathogenic/Likely pathogenic	no assertion criteria provided
810656	NM_003359.4(UGDH):c.244G>A (p.Ala82Thr)	UGDH	Pathogenic/Likely pathogenic	no assertion criteria provided
810657	NM_003359.4(UGDH):c.214T>G (p.Ser72Ala)	UGDH	Pathogenic/Likely pathogenic	no assertion criteria provided
810658	NM_003359.4(UGDH):c.193C>T (p.Arg65Ter)	UGDH	Pathogenic	criteria provided, multiple submitters, no conflicts
810659	NM_003359.4(UGDH):c.131C>T (p.Ala44Val)	UGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376216	NM_003359.4(UGDH):c.528_531del (p.Asp176fs)	UGDH	Likely pathogenic	criteria provided, single submitter
4072030	NM_003359.4(UGDH):c.1084G>A (p.Ala362Thr)	UGDH	Likely pathogenic	criteria provided, single submitter
4072031	NM_003359.4(UGDH):c.742G>C (p.Val248Leu)	UGDH	Likely pathogenic	criteria provided, single submitter
810645	NM_003359.4(UGDH):c.1177C>T (p.Arg393Trp)	UGDH	Likely pathogenic	criteria provided, single submitter
1804342	NM_003359.4(UGDH):c.949C>T (p.Arg317Trp)	UGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1699071	NM_003359.4(UGDH):c.311C>T (p.Ala104Val)	UGDH	Uncertain significance	criteria provided, single submitter
2690415	NM_003359.4(UGDH):c.304C>T (p.Arg102Trp)	UGDH	Uncertain significance	criteria provided, single submitter
3233379	NM_003359.4(UGDH):c.927C>G (p.Tyr309Ter)	UGDH	Uncertain significance	criteria provided, single submitter
3367062	NM_003359.4(UGDH):c.1136A>T (p.Asp379Val)	UGDH	Uncertain significance	criteria provided, single submitter
3376215	NM_003359.4(UGDH):c.1066T>C (p.Tyr356His)	UGDH	Uncertain significance	criteria provided, single submitter
3776194	NM_003359.4(UGDH):c.1009G>A (p.Ala337Thr)	UGDH	Uncertain significance	criteria provided, single submitter
3892812	NM_003359.4(UGDH):c.38G>C (p.Gly13Ala)	UGDH	Uncertain significance	criteria provided, single submitter
4075731	NM_003359.4(UGDH):c.563G>A (p.Gly188Asp)	UGDH	Uncertain significance	criteria provided, multiple submitters, no conflicts
4076290	NM_003359.4(UGDH):c.1364T>C (p.Ile455Thr)	UGDH	Uncertain significance	criteria provided, single submitter
4076291	NM_003359.4(UGDH):c.264+5G>A	UGDH	Uncertain significance	criteria provided, single submitter
4846956	NM_003359.4(UGDH):c.852G>T (p.Leu284Phe)	UGDH	Uncertain significance	criteria provided, single submitter
810662	NM_003359.4(UGDH):c.41A>G (p.Tyr14Cys)	UGDH	Uncertain significance	criteria provided, single submitter

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
UGDH	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 84	3

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
UGDH	HGNC:12525	ENSG00000109814	O60701	UDP-glucose 6-dehydrogenase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UGDH	UDP-glucose 6-dehydrogenase	Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UGDH	Enzyme (other)	yes	1.1.1.22	UDP-Glc/GDP-Man_DH_N, 6-PGluconate_DH-like_C_sf, UDP-Glc/GDP-Man_DH_dimer

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
colonic mucosa	1
islet of Langerhans	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UGDH	278	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UGDH	2,637

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UGDH	O60701	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Formation of the active cofactor, UDP-glucuronate	1	2284.0×	4e-04	UGDH

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
UDP-glucuronate biosynthetic process	1	8426.0×	8e-04	UGDH
protein hexamerization	1	1404.3×	0.002	UGDH
gastrulation with mouth forming second	1	936.2×	0.002	UGDH
glycosaminoglycan biosynthetic process	1	842.6×	0.002	UGDH
chondroitin sulfate proteoglycan biosynthetic process	1	624.1×	0.002	UGDH
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.002	UGDH
neuron development	1	255.3×	0.004	UGDH

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
UGDH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
UGDH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UGDH	1.1.1.22	UDP-glucose 6-dehydrogenase

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	1	UGDH
D	Druggable family + AlphaFold only, no drug	0
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)
UGDH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: UGDH