Intellectual disability, autosomal dominant 24

Summary

Intellectual disability, autosomal dominant 24 (MONDO:0014357) is a disease caused by DEAF1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: DEAF1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 82

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 24
Mondo ID	MONDO:0014357
OMIM	615828
DOID	DOID:0070054
UMLS	C4014414
MedGen	862851
GARD	0016467
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 24 · autosomal dominant non-syndromic intellectual disability caused by mutation in DEAF1 · DEAF1 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 24 · intellectual disability, autosomal dominant type 24 · mental retardation, autosomal dominant 24 · mental retardation, autosomal dominant type 24 · MRD24

Data availability: 82 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 › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 24

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 38, 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

82 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 11 pathogenic, 10 likely pathogenic, 8 conflicting classifications of pathogenicity, 8 benign, 7 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
133291	NM_021008.4(DEAF1):c.683T>G (p.Ile228Ser)	DEAF1	Pathogenic	no assertion criteria provided
133293	NM_021008.4(DEAF1):c.670C>T (p.Arg224Trp)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
133294	NM_021008.4(DEAF1):c.762A>C (p.Arg254Ser)	DEAF1	Pathogenic	criteria provided, single submitter
1342716	NM_021008.4(DEAF1):c.719T>C (p.Phe240Ser)	DEAF1	Pathogenic	criteria provided, single submitter
1677014	NM_021008.4(DEAF1):c.926del (p.Leu309fs)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685692	NM_021008.4(DEAF1):c.883A>G (p.Arg295Gly)	DEAF1	Pathogenic	criteria provided, single submitter
1687234	NM_021008.4(DEAF1):c.674G>A (p.Gly225Glu)	DEAF1	Pathogenic	criteria provided, single submitter
1695344	NM_021008.4(DEAF1):c.748A>G (p.Lys250Glu)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2034753	NM_021008.4(DEAF1):c.671G>C (p.Arg224Pro)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376599	NM_021008.4(DEAF1):c.637A>C (p.Thr213Pro)	DEAF1	Pathogenic	criteria provided, single submitter
3383244	NM_021008.4(DEAF1):c.664+2T>A	DEAF1	Pathogenic	criteria provided, single submitter
375554	NM_021008.4(DEAF1):c.634G>A (p.Gly212Ser)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437396	NM_021008.4(DEAF1):c.737G>C (p.Arg246Thr)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802647	NM_021008.4(DEAF1):c.34_35dup (p.Leu13fs)	DEAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
915949	NM_021008.4(DEAF1):c.640C>G (p.Leu214Val)	DEAF1	Pathogenic	no assertion criteria provided
915950	NM_021008.4(DEAF1):c.826G>C (p.Ala276Pro)	DEAF1	Pathogenic	no assertion criteria provided
915951	NM_021008.4(DEAF1):c.664+1G>T	DEAF1	Pathogenic	no assertion criteria provided
915952	NM_021008.4(DEAF1):c.815_817delinsG (p.Leu272_Asn273delinsTer)	DEAF1	Pathogenic	no assertion criteria provided
1297022	NM_021008.4(DEAF1):c.613G>C (p.Val205Leu)	DEAF1	Likely pathogenic	criteria provided, single submitter
1685295	NM_021008.4(DEAF1):c.682A>T (p.Ile228Phe)	DEAF1	Likely pathogenic	criteria provided, single submitter
1710462	NM_021008.4(DEAF1):c.664G>A (p.Gly222Ser)	DEAF1	Likely pathogenic	criteria provided, single submitter
3377443	NM_021008.4(DEAF1):c.761G>C (p.Arg254Thr)	DEAF1	Likely pathogenic	criteria provided, single submitter
3779564	NM_021008.4(DEAF1):c.1628C>G (p.Ser543Ter)	DEAF1	Likely pathogenic	criteria provided, single submitter
3897851	NM_021008.4(DEAF1):c.613G>T (p.Val205Leu)	DEAF1	Likely pathogenic	criteria provided, single submitter
437398	NM_021008.4(DEAF1):c.700T>A (p.Trp234Arg)	DEAF1	Likely pathogenic	criteria provided, single submitter
4533265	NM_021008.4(DEAF1):c.1126+1G>C	DEAF1	Likely pathogenic	criteria provided, single submitter
802645	NM_021008.4(DEAF1):c.880G>C (p.Val294Leu)	DEAF1	Likely pathogenic	criteria provided, single submitter
976339	NM_021008.4(DEAF1):c.842G>C (p.Cys281Ser)	DEAF1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1089738	NM_021008.4(DEAF1):c.1640C>G (p.Thr547Ser)	DEAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376145	NM_021008.4(DEAF1):c.754T>C (p.Trp252Arg)	DEAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 2 · 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
DEAF1	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 24	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DEAF1	Orphanet:468620	Intellectual disability-epilepsy-extrapyramidal syndrome
DEAF1	Orphanet:714385	Global developmental delay-high pain tolerance-intellectual disability syndrome

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
DEAF1	HGNC:14677	ENSG00000177030	O75398	Deformed epidermal autoregulatory factor 1 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DEAF1	Deformed epidermal autoregulatory factor 1 homolog	Transcription factor that binds to sequence with multiple copies of 5’-TTC[CG]G-3’ present in its own promoter and that of the HNRPA2B1 gene.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DEAF1	Transcription factor	no		SAND_dom, Znf_MYND, SAND-like_dom_sf

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
Ammon’s horn	1
amygdala	1
temporal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DEAF1	134	ubiquitous	marker	amygdala, temporal lobe, Ammon’s horn

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DEAF1	784

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DEAF1	O75398	3

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
regulation of mammary gland epithelial cell proliferation	1	2808.7×	0.004	DEAF1
germ cell development	1	455.5×	0.008	DEAF1
behavioral fear response	1	432.1×	0.008	DEAF1
embryonic skeletal system development	1	391.9×	0.008	DEAF1
visual learning	1	306.4×	0.008	DEAF1
neural tube closure	1	187.2×	0.011	DEAF1
anatomical structure morphogenesis	1	139.3×	0.012	DEAF1
transcription by RNA polymerase II	1	70.5×	0.021	DEAF1
negative regulation of DNA-templated transcription	1	31.6×	0.042	DEAF1
positive regulation of DNA-templated transcription	1	27.9×	0.043	DEAF1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.062	DEAF1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	DEAF1

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
DEAF1	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	DEAF1

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)
DEAF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.