Developmental and epileptic encephalopathy, 81

disease

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Also known as DEE81developmental and epileptic encephalopathy 81EIEE81EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 81

Summary

Developmental and epileptic encephalopathy, 81 (MONDO:0032858) is a disease caused by DMXL2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: DMXL2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 36

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 81
Mondo ID	MONDO:0032858
OMIM	618663
DOID	DOID:0112217
UMLS	C5231450
MedGen	1684681
GARD	0025760
Is cancer (heuristic)	no

Also known as: DEE81 · developmental and epileptic encephalopathy 81 · EIEE81 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 81 · epileptic encephalopathy, early infantile, 81

Data availability: 36 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, 81

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

36 retrieved; paginated sample, class counts are floors:

12 benign, 12 uncertain significance, 6 pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3775539	NM_001378457.1(DMXL2):c.3295G>T (p.Glu1099Ter)	DMXL2	Pathogenic	criteria provided, single submitter
694529	NM_001378457.1(DMXL2):c.6257_6258insTTACATGA (p.Glu2086fs)	DMXL2	Pathogenic	no assertion criteria provided
694530	NM_001378457.1(DMXL2):c.4478C>A (p.Ser1493Ter)	DMXL2	Pathogenic	no assertion criteria provided
694531	NM_001378457.1(DMXL2):c.4478C>G (p.Ser1493Ter)	DMXL2	Pathogenic	no assertion criteria provided
694532	NM_001378457.1(DMXL2):c.5135C>T (p.Ala1712Val)	DMXL2	Pathogenic	no assertion criteria provided
694533	NM_001378457.1(DMXL2):c.7521-1G>A	DMXL2	Pathogenic	criteria provided, single submitter
3236826	NM_001378457.1(DMXL2):c.4784-1G>A	DMXL2	Likely pathogenic	criteria provided, single submitter
4845702	NM_001378457.1(DMXL2):c.2911dup (p.Ile971fs)	DMXL2	Likely pathogenic	criteria provided, single submitter
1397986	NM_001378457.1(DMXL2):c.3108G>T (p.Glu1036Asp)	DMXL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2062918	NM_001378457.1(DMXL2):c.6035A>C (p.Gln2012Pro)	DMXL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342372	NM_001378457.1(DMXL2):c.7312C>T (p.Pro2438Ser)	DMXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342373	NM_001378457.1(DMXL2):c.358C>T (p.Pro120Ser)	DMXL2	Uncertain significance	criteria provided, single submitter
1402171	NM_001378457.1(DMXL2):c.1339G>A (p.Asp447Asn)	DMXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1431479	NM_001378457.1(DMXL2):c.7148C>G (p.Ala2383Gly)	DMXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1471673	NM_001378457.1(DMXL2):c.7543A>G (p.Met2515Val)	DMXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698793	NM_001378457.1(DMXL2):c.418G>A (p.Asp140Asn)	DMXL2	Uncertain significance	criteria provided, single submitter
2203460	NM_001378457.1(DMXL2):c.2314+6T>G	DMXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2429473	NM_001378457.1(DMXL2):c.2522A>G (p.Asn841Ser)	DMXL2	Uncertain significance	criteria provided, single submitter
2583121	NM_001378457.1(DMXL2):c.352T>C (p.Trp118Arg)	DMXL2	Uncertain significance	criteria provided, single submitter
2672165	NM_001378457.1(DMXL2):c.3172G>A (p.Gly1058Arg)	DMXL2	Uncertain significance	criteria provided, single submitter
3577360	NM_001378457.1(DMXL2):c.5393G>A (p.Arg1798His)	DMXL2	Uncertain significance	criteria provided, single submitter
4682495	NM_001378457.1(DMXL2):c.3495C>G (p.Ile1165Met)	DMXL2	Uncertain significance	criteria provided, single submitter
1178042	NM_001378457.1(DMXL2):c.2823C>T (p.Asn941=)	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1227653	NM_001378457.1(DMXL2):c.27A>G (p.Gly9=)	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1233890	NM_001378457.1(DMXL2):c.1346-39A>G	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1234931	NM_001378457.1(DMXL2):c.6833+11del	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1239392	NM_001378457.1(DMXL2):c.-36A>C	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1242526	NM_001378457.1(DMXL2):c.8077-22C>T	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1248420	NM_001378457.1(DMXL2):c.1490C>T (p.Thr497Met)	DMXL2	Benign	criteria provided, multiple submitters, no conflicts
1255508	NM_001378457.1(DMXL2):c.7520+35del	DMXL2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
DMXL2	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 81	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMXL2	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
DMXL2	Orphanet:453533	Polyendocrine-polyneuropathy syndrome
DMXL2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
DMXL2	HGNC:2938	ENSG00000104093	Q8TDJ6	DmX-like protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DMXL2	DmX-like protein 2	May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMXL2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, Rav1p_C

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMXL2	269	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DMXL2	1,090

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DMXL2	Q8TDJ6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
vacuolar acidification	1	732.7×	0.001	DMXL2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
DMXL2	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	0
E	Difficult family or no structure, no drug	1	DMXL2

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)
DMXL2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: DMXL2