Intellectual developmental disorder, autosomal dominant 73

Summary

Intellectual developmental disorder, autosomal dominant 73 (MONDO:0957536) is a disease caused by TAF4 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TAF4 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 73
Mondo ID	MONDO:0957536
OMIM	620450
DOID	DOID:0061046
UMLS	C5830636
MedGen	1841272
GARD	0026856
Is cancer (heuristic)	no

Data availability: 21 ClinVar variants · 2 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 dominant non-syndromic intellectual disability › intellectual developmental disorder, autosomal dominant 73

Related subtypes (25): intellectual disability, autosomal dominant 22, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language, intellectual disability, autosomal dominant 33, intellectual disability, autosomal dominant 34, intellectual disability, autosomal dominant 41, intellectual disability, autosomal dominant 43, intellectual disability, autosomal dominant 58, intellectual disability, autosomal dominant 45, intellectual disability, autosomal dominant 46, intellectual disability, autosomal dominant 47, Clark-Baraitser syndrome, intellectual disability, autosomal dominant 50, intellectual disability, autosomal dominant 51, intellectual disability, autosomal dominant 52, intellectual disability, autosomal dominant 53, intellectual disability, autosomal dominant 54, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 61, intellectual developmental disorder 59, intellectual developmental disorder 60 with seizures, intellectual developmental disorder 62, intellectual developmental disorder, autosomal dominant 63, with macrocephaly, Coffin-Siris syndrome 6, intellectual disability, autosomal dominant 57

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

21 retrieved; paginated sample, class counts are floors:

8 likely pathogenic, 7 pathogenic, 4 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3242345	NM_003185.4(TAF4):c.2845C>T (p.Gln949Ter)	TAF4	Pathogenic	no assertion criteria provided
3242346	NM_003185.4(TAF4):c.1348C>T (p.Gln450Ter)	TAF4	Pathogenic	criteria provided, single submitter
3242347	NM_003185.4(TAF4):c.2185C>T (p.Gln729Ter)	TAF4	Pathogenic	no assertion criteria provided
3242348	NM_003185.4(TAF4):c.2453dup (p.Asn818fs)	TAF4	Pathogenic	no assertion criteria provided
3242349	NM_003185.4(TAF4):c.2664del (p.Lys888fs)	TAF4	Pathogenic	no assertion criteria provided
4818966	NM_003185.4(TAF4):c.2425dup (p.Ser809fs)	TAF4	Pathogenic	criteria provided, single submitter
4819103	NM_003185.4(TAF4):c.633dup (p.Ala212fs)	TAF4	Pathogenic	criteria provided, single submitter
1687439	NM_003185.4(TAF4):c.853_860del (p.Gly285fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3236097	NM_003185.4(TAF4):c.213_268del (p.Gly72fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3376435	NM_003185.4(TAF4):c.808_818del (p.Pro270fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3587593	NM_003185.4(TAF4):c.962del (p.Gly321fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3765856	NM_003185.4(TAF4):c.1290del (p.Val431fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3767129	NM_003185.4(TAF4):c.1529del (p.Gly510fs)	TAF4	Likely pathogenic	criteria provided, single submitter
3773682	NM_003185.4(TAF4):c.3160_3163del (p.Arg1054fs)	TAF4	Likely pathogenic	criteria provided, single submitter
4291844	NM_003185.4(TAF4):c.756del (p.Ala253fs)	TAF4	Likely pathogenic	criteria provided, single submitter
1526080	NM_003185.4(TAF4):c.296del (p.Gly99fs)	TAF4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4086153	NM_006386.5(DDX17):c.1447+4T>C	DDX17	Uncertain significance	criteria provided, single submitter
3235955	NM_003185.4(TAF4):c.3052_3053del (p.Arg1018fs)	TAF4	Uncertain significance	criteria provided, single submitter
3242534	NM_003185.4(TAF4):c.308A>G (p.Gln103Arg)	TAF4	Uncertain significance	criteria provided, single submitter
3376452	NM_003185.4(TAF4):c.1631C>T (p.Pro544Leu)	TAF4	Uncertain significance	criteria provided, single submitter
4795862	NM_003185.4(TAF4):c.674_700del (p.Leu225_Ala233del)	TAF4	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
TAF4	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 73	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAF4	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TAF4	HGNC:11537	ENSG00000130699	O00268	Transcription initiation factor TFIID subunit 4	gencc,clinvar
DDX17	HGNC:2740	ENSG00000100201	Q92841	Probable ATP-dependent RNA helicase DDX17	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAF4	Transcription initiation factor TFIID subunit 4	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
DDX17	Probable ATP-dependent RNA helicase DDX17	As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAF4	Other/Unknown	no		TAFH_NHR1, TAF4_C, Histone-fold
DDX17	Enzyme (other)	yes	3.6.4.13	RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
testis	1
endothelial cell	1
middle temporal gyrus	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAF4	139	ubiquitous	yes	right testis, left testis, testis
DDX17	306	ubiquitous	marker	tibia, middle temporal gyrus, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX17	5,248
TAF4	1,749

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAF4	O00268	31
DDX17	Q92841	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SUMOylation of transcription cofactors	1	121.5×	0.025	DDX17
HIV Transcription Initiation	1	116.5×	0.025	TAF4
RNA Polymerase II HIV Promoter Escape	1	116.5×	0.025	TAF4
RNA Polymerase II Promoter Escape	1	116.5×	0.025	TAF4
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	116.5×	0.025	TAF4
RNA Polymerase II Transcription Initiation	1	116.5×	0.025	TAF4
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	116.5×	0.025	TAF4
Transcription of the HIV genome	1	86.5×	0.025	TAF4
Late Phase of HIV Life Cycle	1	84.0×	0.025	TAF4
HIV Life Cycle	1	80.4×	0.025	TAF4
RNA Polymerase II Pre-transcription Events	1	68.8×	0.025	TAF4
Regulation of TP53 Activity	1	66.4×	0.025	TAF4
HIV Infection	1	59.5×	0.025	TAF4
Regulation of TP53 Activity through Phosphorylation	1	58.9×	0.025	TAF4
Transcriptional Regulation by TP53	1	31.0×	0.045	TAF4
Viral Infection Pathways	1	15.4×	0.084	TAF4
Infectious disease	1	12.4×	0.098	TAF4
RNA Polymerase II Transcription	1	11.3×	0.101	TAF4
Gene expression (Transcription)	1	8.9×	0.120	TAF4
Generic Transcription Pathway	1	7.5×	0.134	TAF4
Disease	1	6.5×	0.147	TAF4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 skeletal muscle cell differentiation	1	1404.3×	0.009	DDX17
miRNA metabolic process	1	702.2×	0.009	DDX17
DNA-templated transcription initiation	1	468.1×	0.009	TAF4
myoblast differentiation	1	421.3×	0.009	DDX17
estrogen receptor signaling pathway	1	366.4×	0.009	DDX17
androgen receptor signaling pathway	1	351.1×	0.009	DDX17
alternative mRNA splicing, via spliceosome	1	337.0×	0.009	DDX17
regulatory ncRNA-mediated gene silencing	1	337.0×	0.009	DDX17
ovarian follicle development	1	195.9×	0.010	TAF4
immune system process	1	195.9×	0.010	DDX17
transcription initiation at RNA polymerase II promoter	1	187.2×	0.010	TAF4
mRNA transcription by RNA polymerase II	1	165.2×	0.010	TAF4
epithelial to mesenchymal transition	1	156.0×	0.010	DDX17
regulation of DNA repair	1	138.1×	0.010	TAF4
RNA polymerase II preinitiation complex assembly	1	135.9×	0.010	TAF4
positive regulation of transcription initiation by RNA polymerase II	1	135.9×	0.010	TAF4
regulation of transcription by RNA polymerase II	2	11.7×	0.010	TAF4, DDX17
regulation of alternative mRNA splicing, via spliceosome	1	122.1×	0.011	DDX17
RNA processing	1	109.4×	0.012	DDX17
rRNA processing	1	70.8×	0.017	DDX17
transcription by RNA polymerase II	1	35.3×	0.031	TAF4
defense response to virus	1	34.7×	0.031	DDX17
positive regulation of DNA-templated transcription	1	14.0×	0.073	TAF4
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	DDX17

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDX17	1	2
TAF4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DDX17

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DDX17	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DDX17	3.6.4.13	RNA helicase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	DDX17

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	1	DDX17
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TAF4

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)
TAF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.