Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Summary

Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (MONDO:0033572) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies
Mondo ID	MONDO:0033572
OMIM	619031
UMLS	C5436646
MedGen	1759589
GARD	0018529
Is cancer (heuristic)	no

Also known as: IDDEBF · intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Data availability: 18 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › ALG14-congenital disorder of glycosylation › intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Related subtypes (2): congenital myasthenic syndrome 15, myopathy, epilepsy, and progressive cerebral atrophy

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

18 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1356542	NM_144988.4(ALG14):c.16G>A (p.Val6Ile)	ALG14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
978234	NM_144988.4(ALG14):c.420+6_420+9del	ALG14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045564	NM_144988.4(ALG14):c.599C>T (p.Pro200Leu)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1304004	NM_144988.4(ALG14):c.323G>A (p.Ser108Asn)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1361709	NM_144988.4(ALG14):c.248C>A (p.Ser83Tyr)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1364291	NM_144988.4(ALG14):c.181A>G (p.Asn61Asp)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1411371	NM_144988.4(ALG14):c.532G>A (p.Val178Ile)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1505343	NM_144988.4(ALG14):c.535G>A (p.Glu179Lys)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1931369	NM_144988.4(ALG14):c.626C>T (p.Ser209Leu)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
379351	NM_144988.4(ALG14):c.326G>A (p.Arg109Gln)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
383072	NM_144988.4(ALG14):c.140G>T (p.Gly47Val)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
390702	NM_144988.4(ALG14):c.179C>G (p.Ser60Cys)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
542122	NM_144988.4(ALG14):c.182A>G (p.Asn61Ser)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
652328	NM_144988.4(ALG14):c.422T>G (p.Val141Gly)	ALG14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1486917	NM_144988.4(ALG14):c.288+4A>G	ALG14-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1170538	NM_144988.4(ALG14):c.288+11A>G	ALG14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
376840	NM_144988.4(ALG14):c.31G>A (p.Ala11Thr)	ALG14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
516659	NM_144988.4(ALG14):c.137-18T>A	ALG14-AS1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALG14	Orphanet:353327	Congenital myasthenic syndrome with glycosylation defect

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
ALG14	HGNC:28287	ENSG00000172339	Q96F25	UDP-N-acetylglucosamine transferase subunit ALG14	clinvar
CNN3-DT	HGNC:54176	ENSG00000235501		CNN3 divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALG14	UDP-N-acetylglucosamine transferase subunit ALG14	Part of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.

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)
ALG14	Other/Unknown	no		Oligosacch_biosynth_Alg14
CNN3-DT	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
colonic mucosa	1
corpus epididymis	1
jejunal mucosa	1
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALG14	235	ubiquitous	marker	corpus epididymis, jejunal mucosa, colonic mucosa
CNN3-DT	189	ubiquitous	marker	right adrenal gland, left adrenal gland cortex, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALG14	708
CNN3-DT	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG14	Q96F25	91.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Defective ALG14 causes ALG14-CMS	1	5710.0×	0.002	ALG14
Diseases associated with N-glycosylation of proteins	1	634.4×	0.007	ALG14
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.014	ALG14
Diseases of glycosylation	1	131.3×	0.017	ALG14
Diseases of metabolism	1	80.4×	0.022	ALG14
Asparagine N-linked glycosylation	1	60.1×	0.025	ALG14
Post-translational protein modification	1	19.2×	0.067	ALG14
Disease	1	13.1×	0.081	ALG14
Metabolism of proteins	1	12.4×	0.081	ALG14

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
dolichol-linked oligosaccharide biosynthetic process	1	842.6×	0.002	ALG14
protein N-linked glycosylation	1	263.3×	0.004	ALG14

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
ALG14	0	0
CNN3-DT	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	2	ALG14, CNN3-DT

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)
ALG14	0	—
CNN3-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.