Intellectual developmental disorder, autosomal recessive 81

Summary

Intellectual developmental disorder, autosomal recessive 81 (MONDO:0958204) is a disease caused by ASCC3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ASCC3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 81
Mondo ID	MONDO:0958204
OMIM	620700
UMLS	C5882758
MedGen	1844192
GARD	0026975
Is cancer (heuristic)	no

Data availability: 16 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 recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 81

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 67, 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 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

16 retrieved; paginated sample, class counts are floors:

9 pathogenic, 3 uncertain significance, 3 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2691800	NM_006828.4(ASCC3):c.4690T>C (p.Ser1564Pro)	ASCC3	Pathogenic	no assertion criteria provided
2691801	NM_006828.4(ASCC3):c.4553G>A (p.Arg1518His)	ASCC3	Pathogenic	no assertion criteria provided
2691804	NM_006828.4(ASCC3):c.4415G>A (p.Arg1472Gln)	ASCC3	Pathogenic	no assertion criteria provided
2691806	NM_006828.4(ASCC3):c.3631C>T (p.Gln1211Ter)	ASCC3	Pathogenic	no assertion criteria provided
2691808	NM_006828.4(ASCC3):c.5281C>T (p.Arg1761Ter)	ASCC3	Pathogenic	no assertion criteria provided
2691809	NM_006828.4(ASCC3):c.4955G>A (p.Gly1652Asp)	ASCC3	Pathogenic	no assertion criteria provided
2691810	NM_006828.4(ASCC3):c.4984A>T (p.Ile1662Phe)	ASCC3	Pathogenic	no assertion criteria provided
2691811	NM_006828.4(ASCC3):c.3522dup (p.Cys1175fs)	ASCC3	Pathogenic	no assertion criteria provided
3233652	NM_006828.4(ASCC3):c.5769_5770del (p.Cys1924fs)	ASCC3	Pathogenic	criteria provided, single submitter
2691852	NM_006828.4(ASCC3):c.1597-2A>G	ASCC3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3629890	NM_006828.4(ASCC3):c.802-2A>C	ASCC3	Likely pathogenic	criteria provided, single submitter
931384	NM_006828.4(ASCC3):c.801+1G>T	ASCC3	Likely pathogenic	criteria provided, single submitter
2691853	NM_006828.4(ASCC3):c.5996T>C (p.Leu1999Pro)	ASCC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2580575	NM_006828.4(ASCC3):c.4280C>T (p.Thr1427Met)	ASCC3	Uncertain significance	criteria provided, single submitter
422281	NM_006828.4(ASCC3):c.3434del (p.Lys1145fs)	ASCC3	Uncertain significance	criteria provided, single submitter
931383	NM_006828.4(ASCC3):c.5693A>G (p.His1898Arg)	ASCC3	Uncertain significance	criteria provided, single submitter

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
ASCC3	Strong	Autosomal recessive	intellectual developmental disorder, autosomal recessive 81	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
ASCC3	HGNC:18697	ENSG00000112249	Q8N3C0	Activating signal cointegrator 1 complex subunit 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASCC3	Activating signal cointegrator 1 complex subunit 3	ATPase involved both in DNA repair and rescue of stalled ribosomes. 3’-5’ DNA helicase involved in repair of alkylated DNA: promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylate…

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)
ASCC3	Other/Unknown	no		Helicase_C-like, AAA+_ATPase, Sec63-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
calcaneal tendon	1
decidua	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASCC3	278	ubiquitous	marker	decidua, secondary oocyte, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASCC3	2,898

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASCC3	Q8N3C0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
ALKBH3 mediated reversal of alkylation damage	1	2855.0×	0.001	ASCC3
DNA Damage Reversal	1	1631.4×	0.001	ASCC3
Reversal of alkylation damage by DNA dioxygenases	1	1631.4×	0.001	ASCC3
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.010	ASCC3
DNA Repair	1	98.5×	0.010	ASCC3

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
ribosome-associated ubiquitin-dependent protein catabolic process	1	2407.4×	0.002	ASCC3
DNA alkylation repair	1	1532.0×	0.002	ASCC3
ribosome disassembly	1	991.3×	0.002	ASCC3
rescue of stalled cytosolic ribosome	1	481.5×	0.003	ASCC3
DNA replication	1	165.2×	0.006	ASCC3

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
ASCC3	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	ASCC3

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)
ASCC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.