Intellectual developmental disorder, autosomal recessive 67

Summary

Intellectual developmental disorder, autosomal recessive 67 (MONDO:0032662) is a disease caused by EIF3F (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EIF3F (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 67
Mondo ID	MONDO:0032662
OMIM	618295
DOID	DOID:0081228
UMLS	C4749019
MedGen	1648350
GARD	0025716
Is cancer (heuristic)	no

Also known as: MRT67

Data availability: 12 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 67

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 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

12 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1697326	NM_003754.3(EIF3F):c.861dup (p.Gln288fs)	EIF3F	Pathogenic	no assertion criteria provided
617475	NM_003754.3(EIF3F):c.694T>G (p.Phe232Val)	EIF3F	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3359241	NM_003754.3(EIF3F):c.181C>T (p.Gln61Ter)	EIF3F	Likely pathogenic	no assertion criteria provided
988781	NM_003754.3(EIF3F):c.671C>T (p.Pro224Leu)	EIF3F	Likely pathogenic	no assertion criteria provided
1028654	NM_003754.3(EIF3F):c.908C>T (p.Thr303Ile)	EIF3F	Uncertain significance	criteria provided, multiple submitters, no conflicts
1710038	NM_003754.3(EIF3F):c.916C>T (p.Arg306Cys)	EIF3F	Uncertain significance	criteria provided, multiple submitters, no conflicts
3362634	NM_003754.3(EIF3F):c.1025A>G (p.Asn342Ser)	EIF3F	Uncertain significance	criteria provided, single submitter
3891928	NM_003754.3(EIF3F):c.41C>T (p.Thr14Met)	EIF3F	Uncertain significance	criteria provided, single submitter
978126	NM_003754.3(EIF3F):c.263G>A (p.Gly88Asp)	EIF3F	Uncertain significance	criteria provided, single submitter
996992	NM_003754.3(EIF3F):c.653+3G>T	EIF3F	Uncertain significance	criteria provided, single submitter
1255378	NM_003754.3(EIF3F):c.561C>T (p.His187=)	EIF3F	Benign	criteria provided, multiple submitters, no conflicts
1255379	NM_003754.3(EIF3F):c.*24C>T	EIF3F	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
EIF3F	Strong	Autosomal recessive	intellectual developmental disorder, autosomal recessive 67	4

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
EIF3F	HGNC:3275	ENSG00000175390	O00303	Eukaryotic translation initiation factor 3 subunit F	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EIF3F	Eukaryotic translation initiation factor 3 subunit F	Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation 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)
EIF3F	Other/Unknown	no		JAMM/MPN+_dom, EIF3F/CSN6-like_C, eIF3f

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
ganglionic eminence	1
left ovary	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EIF3F	261	ubiquitous	marker	primordial germ cell in gonad, ganglionic eminence, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EIF3F	4,287

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EIF3F	O00303	27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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 ternary complex, and subsequently, the 43S complex	1	215.5×	0.010	EIF3F
Translation initiation complex formation	1	190.3×	0.010	EIF3F
Ribosomal scanning and start codon recognition	1	190.3×	0.010	EIF3F
Formation of a pool of free 40S subunits	1	112.0×	0.010	EIF3F
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.010	EIF3F
GTP hydrolysis and joining of the 60S ribosomal subunit	1	100.2×	0.010	EIF3F

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
IRES-dependent viral translational initiation	1	1532.0×	0.002	EIF3F
formation of cytoplasmic translation initiation complex	1	1123.5×	0.002	EIF3F
translational initiation	1	358.6×	0.004	EIF3F
proteolysis	1	34.2×	0.029	EIF3F

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
EIF3F	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
EIF3F	4	Binding:4

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	EIF3F

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)
EIF3F	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.