Developmental and epileptic encephalopathy, 83

disease

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Also known as DEE83developmental and epileptic encephalopathy 83EIEE83EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 83

Summary

Developmental and epileptic encephalopathy, 83 (MONDO:0032895) is a disease caused by UGP2 (GenCC Strong), with 3 cohort genes.

At a glance

Causal gene: UGP2 (GenCC Strong)
Cohort genes: 3
ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 83
Mondo ID	MONDO:0032895
OMIM	618744
DOID	DOID:0112218
UMLS	C5231487
MedGen	1684784
GARD	0025767
Is cancer (heuristic)	no

Also known as: DEE83 · developmental and epileptic encephalopathy 83 · EIEE83 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 83 · epileptic encephalopathy, early infantile, 83

Data availability: 10 ClinVar variants · 4 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, 83

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

10 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 2 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
805980	NM_006759.4(UGP2):c.34A>G (p.Met12Val)	UGP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300129	NM_001242896.3(DEPDC5):c.1460G>A (p.Arg487Gln)	DEPDC5	Uncertain significance	criteria provided, multiple submitters, no conflicts
4278365	NM_182543.5(NSUN6):c.976T>C (p.Cys326Arg)	NSUN6	Uncertain significance	criteria provided, single submitter
3186088	NM_006759.4(UGP2):c.154A>C (p.Lys52Gln)	UGP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3359117	NM_001001521.2(UGP2):c.-15+1G>A	UGP2	Uncertain significance	criteria provided, single submitter
3359140	NM_006759.4(UGP2):c.1419_1419+14del	UGP2	Uncertain significance	criteria provided, single submitter
3586845	NM_006759.4(UGP2):c.1091dup (p.Asn364fs)	UGP2	Uncertain significance	criteria provided, single submitter
3731372	NM_006759.4(UGP2):c.1265G>A (p.Arg422Gln)	UGP2	Uncertain significance	criteria provided, single submitter
1684237	NM_006759.4(UGP2):c.255+44G>A	UGP2	Benign	criteria provided, multiple submitters, no conflicts
3068684	NM_006759.4(UGP2):c.1089G>A (p.Leu363=)	UGP2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
UGP2	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 83	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DEPDC5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
DEPDC5	Orphanet:98784	Sleep-related hypermotor epilepsy
DEPDC5	Orphanet:98820	Familial focal epilepsy with variable foci

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
UGP2	HGNC:12527	ENSG00000169764	Q16851	UTP–glucose-1-phosphate uridylyltransferase	gencc,clinvar
DEPDC5	HGNC:18423	ENSG00000100150	O75140	GATOR1 complex protein DEPDC5	clinvar
NSUN6	HGNC:23529	ENSG00000241058	Q8TEA1	tRNA (cytosine(72)-C(5))-methyltransferase NSUN6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UGP2	UTP–glucose-1-phosphate uridylyltransferase	UTP–glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.
DEPDC5	GATOR1 complex protein DEPDC5	As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway.
NSUN6	tRNA (cytosine(72)-C(5))-methyltransferase NSUN6	S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA).

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UGP2	Enzyme (other)	yes	2.7.7.9	UDPGP_fam, UDPGP_trans, Nucleotide-diphossugar_trans
DEPDC5	Other/Unknown	no		DEP_dom, IML1, WH-like_DNA-bd_sf
NSUN6	Enzyme (other)	yes	2.1.1.202	MeTrfase_RsmB-F_NOP2_dom, PUA-like_sf, RsmB/NOL1/NOP2-like_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
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
frontal pole	1
middle frontal gyrus	1
paraflocculus	1
oviduct epithelium	1
right lobe of liver	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UGP2	295	ubiquitous	marker	skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis, biceps brachii
DEPDC5	236	ubiquitous	marker	paraflocculus, frontal pole, middle frontal gyrus
NSUN6	216	ubiquitous	marker	oviduct epithelium, sperm, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UGP2	2,190
NSUN6	1,977
DEPDC5	1,273

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DEPDC5	O75140	11
NSUN6	Q8TEA1	5
UGP2	Q16851	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Formation of the active cofactor, UDP-glucuronate	1	761.3×	0.005	UGP2
Glycogen synthesis	1	271.9×	0.007	UGP2
tRNA modification in the nucleus and cytosol	1	97.6×	0.014	NSUN6
Amino acids regulate mTORC1	1	66.8×	0.015	DEPDC5

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA C5-cytosine methylation	1	5617.3×	0.001	NSUN6
glucose 1-phosphate metabolic process	1	5617.3×	0.001	UGP2
UDP-glucuronate biosynthetic process	1	2808.7×	0.002	UGP2
UDP-alpha-D-glucose metabolic process	1	1872.4×	0.002	UGP2
RNA methylation	1	561.7×	0.005	NSUN6
glycogen biosynthetic process	1	312.1×	0.007	UGP2
tRNA modification	1	200.6×	0.009	NSUN6
tRNA methylation	1	193.7×	0.009	NSUN6
glycogen metabolic process	1	175.5×	0.009	UGP2
negative regulation of TORC1 signaling	1	108.0×	0.012	DEPDC5
cellular response to amino acid starvation	1	106.0×	0.012	DEPDC5
positive regulation of autophagy	1	69.3×	0.017	DEPDC5
brain development	1	26.5×	0.040	UGP2
intracellular signal transduction	1	12.7×	0.077	DEPDC5

Therapeutics

Drug target analysis

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

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
UGP2	0	0
DEPDC5	0	0
NSUN6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
NSUN6	3	Binding:3
UGP2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UGP2	2.7.7.9	UTP-glucose-1-phosphate uridylyltransferase
NSUN6	2.1.1.202	multisite-specific tRNA:(cytosine-C5)-methyltransferase

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

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	2	UGP2, NSUN6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DEPDC5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UGP2	1	—
DEPDC5	0	—
NSUN6	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: UGP2, DEPDC5, NSUN6