Intellectual developmental disorder, autosomal dominant 75

Summary

Intellectual developmental disorder, autosomal dominant 75 (MONDO:0975838) is a disease caused by DHX9 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DHX9 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 75
Mondo ID	MONDO:0975838
OMIM	620988
DOID	DOID:0061048
UMLS	C5975482
MedGen	1875012
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 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 developmental disorder, autosomal dominant 75

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 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 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2505168	NM_001357.5(DHX9):c.1240G>A (p.Gly414Arg)	DHX9	Pathogenic/Likely pathogenic	no assertion criteria provided
3367218	NM_001357.5(DHX9):c.3497G>C (p.Arg1166Pro)	DHX9	Pathogenic	no assertion criteria provided
3367220	NM_001357.5(DHX9):c.685C>T (p.Arg229Ter)	DHX9	Pathogenic	no assertion criteria provided
3367217	NM_001357.5(DHX9):c.422G>A (p.Arg141Gln)	DHX9	Likely pathogenic	criteria provided, single submitter
2505473	NM_001357.5(DHX9):c.3488A>G (p.Lys1163Arg)	DHX9	Conflicting classifications of pathogenicity	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DHX9	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 75	3

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
DHX9	HGNC:2750	ENSG00000135829	Q08211	ATP-dependent RNA helicase A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DHX9	ATP-dependent RNA helicase A	Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3’ to 5’ direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DHX9	Enzyme (other)	yes	3.6.4.13	Helicase_C-like, DNA/RNA_helicase_DEAH_CS, Helicase-assoc_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DHX9	295	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DHX9	6,255

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DHX9	Q08211	6

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
DEx/H-box helicases activate type I IFN and inflammatory cytokines production	1	1631.4×	0.004	DHX9
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.004	DHX9
PKR-mediated signaling	1	141.0×	0.014	DHX9
mRNA Polyadenylation	1	87.8×	0.017	DHX9
mRNA Splicing - Major Pathway	1	54.6×	0.022	DHX9
Dengue Virus-Host Interactions	1	45.7×	0.022	DHX9

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
DNA-templated viral transcription	1	16852.0×	0.002	DHX9
regulation of cytoplasmic translation	1	8426.0×	0.002	DHX9
positive regulation of viral transcription	1	5617.3×	0.002	DHX9
positive regulation of RNA export from nucleus	1	3370.4×	0.002	DHX9
positive regulation of response to cytokine stimulus	1	2407.4×	0.002	DHX9
positive regulation of interleukin-18 production	1	2106.5×	0.002	DHX9
regulation of defense response to virus by host	1	2106.5×	0.002	DHX9
protein localization to cytoplasmic stress granule	1	2106.5×	0.002	DHX9
negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1	1872.4×	0.002	DHX9
DNA-templated transcription termination	1	1532.0×	0.002	DHX9
RISC complex assembly	1	1532.0×	0.002	DHX9
CRD-mediated mRNA stabilization	1	1404.3×	0.002	DHX9
miRNA-mediated post-transcriptional gene silencing	1	1296.3×	0.002	DHX9
cellular response to exogenous dsRNA	1	1053.2×	0.002	DHX9
positive regulation of cytoplasmic translation	1	991.3×	0.002	DHX9
regulation of mRNA processing	1	887.0×	0.003	DHX9
alternative mRNA splicing, via spliceosome	1	674.1×	0.003	DHX9
positive regulation of interferon-alpha production	1	648.1×	0.003	DHX9
positive regulation of DNA replication	1	581.1×	0.003	DHX9
positive regulation of innate immune response	1	526.6×	0.003	DHX9
pyroptotic inflammatory response	1	510.7×	0.003	DHX9
positive regulation of interferon-beta production	1	391.9×	0.004	DHX9
positive regulation of DNA repair	1	358.6×	0.004	DHX9
positive regulation of fibroblast proliferation	1	295.6×	0.005	DHX9
mRNA transport	1	263.3×	0.006	DHX9
rhythmic process	1	251.5×	0.006	DHX9
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	DHX9
positive regulation of interleukin-6 production	1	166.8×	0.008	DHX9
DNA replication	1	165.2×	0.008	DHX9
positive regulation of tumor necrosis factor production	1	153.2×	0.008	DHX9

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
DHX9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DHX9	10	Binding:10

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DHX9	3.6.4.13	RNA helicase

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	1	DHX9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DHX9	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.