Intellectual disability, autosomal dominant 38

Summary

Intellectual disability, autosomal dominant 38 (MONDO:0014617) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 38
Mondo ID	MONDO:0014617
OMIM	616393
DOID	DOID:0070068
UMLS	C4225343
MedGen	895359
GARD	0016469
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 38 · autosomal dominant non-syndromic intellectual disability caused by mutation in EEF1A2 · EEF1A2 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 38 · intellectual disability, autosomal dominant type 38 · mental retardation, autosomal dominant 38 · mental retardation, autosomal dominant type 38 · MRD38 · PRELDS · psychomotor retardation, epilepsy, and language disability syndrome

Data availability: 31 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 38

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

31 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 5 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 4 likely pathogenic, 3 pathogenic, 2 likely benign, 2 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100782	NM_001958.5(EEF1A2):c.208G>A (p.Gly70Ser)	EEF1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
192252	NM_001958.5(EEF1A2):c.364G>A (p.Glu122Lys)	EEF1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664000	NM_001958.5(EEF1A2):c.286C>T (p.Arg96Cys)	EEF1A2	Pathogenic	criteria provided, single submitter
279803	NM_001958.5(EEF1A2):c.271G>A (p.Asp91Asn)	EEF1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
280924	NM_001958.5(EEF1A2):c.370G>A (p.Glu124Lys)	EEF1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449242	NM_001958.5(EEF1A2):c.796C>T (p.Arg266Trp)	EEF1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
830077	NM_001958.5(EEF1A2):c.1295C>T (p.Thr432Met)	EEF1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775659	NM_001958.5(EEF1A2):c.797G>A (p.Arg266Gln)	EEF1A2	Likely pathogenic	criteria provided, single submitter
3897818	NM_001958.5(EEF1A2):c.823G>C (p.Gly275Arg)	EEF1A2	Likely pathogenic	criteria provided, single submitter
4277778	NM_001958.5(EEF1A2):c.1027C>A (p.Gln343Lys)	EEF1A2	Likely pathogenic	criteria provided, single submitter
620070	NM_001958.5(EEF1A2):c.821C>T (p.Pro274Leu)	EEF1A2	Likely pathogenic	criteria provided, single submitter
1595477	NM_001958.5(EEF1A2):c.667G>A (p.Ala223Thr)	EEF1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1661415	NM_001958.5(EEF1A2):c.332G>A (p.Cys111Tyr)	EEF1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192251	NM_001958.5(EEF1A2):c.754G>C (p.Asp252His)	EEF1A2	Conflicting classifications of pathogenicity	no assertion criteria provided
422192	NM_001958.5(EEF1A2):c.71C>T (p.Thr24Met)	EEF1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
941751	NM_001958.5(EEF1A2):c.1136T>C (p.Ile379Thr)	EEF1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015458	NM_001958.5(EEF1A2):c.1345G>A (p.Gly449Ser)	EEF1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1333252	NM_001958.5(EEF1A2):c.47T>C (p.Val16Ala)	EEF1A2	Uncertain significance	criteria provided, single submitter
1679617	NM_001958.5(EEF1A2):c.653G>A (p.Arg218His)	EEF1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1709392	NM_001958.5(EEF1A2):c.1379A>G (p.Lys460Arg)	EEF1A2	Uncertain significance	criteria provided, single submitter
2431392	NM_001958.5(EEF1A2):c.958A>G (p.Ile320Val)	EEF1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500024	NM_001958.5(EEF1A2):c.1286T>G (p.Met429Arg)	EEF1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3254760	NM_001958.5(EEF1A2):c.1052G>A (p.Gly351Glu)	EEF1A2	Uncertain significance	criteria provided, single submitter
3376277	NM_001958.5(EEF1A2):c.962G>A (p.Arg321Gln)	EEF1A2	Uncertain significance	criteria provided, single submitter
625937	NM_001958.5(EEF1A2):c.532A>T (p.Ile178Phe)	EEF1A2	Uncertain significance	criteria provided, single submitter
1805716	NM_001958.5(EEF1A2):c.866T>C (p.Val289Ala)	EEF1A2	Likely benign	criteria provided, single submitter
379689	NM_001958.5(EEF1A2):c.594T>C (p.Gly198=)	EEF1A2	Benign	criteria provided, multiple submitters, no conflicts
382763	NM_001958.5(EEF1A2):c.1266C>A (p.Gly422=)	EEF1A2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
386473	NM_001958.5(EEF1A2):c.183C>T (p.Asp61=)	EEF1A2	Likely benign	criteria provided, multiple submitters, no conflicts
386730	NM_001958.5(EEF1A2):c.1182G>T (p.Leu394=)	EEF1A2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EEF1A2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
EEF1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
EEF1A2	HGNC:3192	ENSG00000101210	Q05639	Elongation factor 1-alpha 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EEF1A2	Elongation factor 1-alpha 2	Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EEF1A2	Other/Unknown	no		T_Tr_GTP-bd_dom, EFTu-like_2, Transl_elong_EF1A_euk/arc

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
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EEF1A2	247	ubiquitous	marker	gastrocnemius, apex of heart, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EEF1A2	745

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EEF1A2	Q05639	2

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
Eukaryotic Translation Elongation	1	278.5×	0.004	EEF1A2

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
positive regulation of lipid kinase activity	1	16852.0×	3e-04	EEF1A2
regulation of chaperone-mediated autophagy	1	3370.4×	7e-04	EEF1A2
translational elongation	1	1203.7×	0.001	EEF1A2
translation	1	102.8×	0.012	EEF1A2
positive regulation of apoptotic process	1	56.7×	0.018	EEF1A2

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
EEF1A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EEF1A2	8	Binding:8

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	EEF1A2

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)
EEF1A2	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.