Intellectual disability, autosomal recessive 61

Summary

Intellectual disability, autosomal recessive 61 (MONDO:0030915) is a disease caused by RUSC2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RUSC2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 61
Mondo ID	MONDO:0030915
OMIM	617773
DOID	DOID:0080239
UMLS	C4540424
MedGen	1622296
GARD	0025660
Is cancer (heuristic)	no

Also known as: autosomal recessive mental retardation 61 · intellectual disability, autosomal recessive 61 · mental retardation, autosomal recessive 61 · MRT61

Data availability: 41 ClinVar variants · 3 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 disability, autosomal recessive 61

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 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 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

41 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 5 conflicting classifications of pathogenicity, 3 pathogenic, 2 benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2793514	NM_014806.5(RUSC2):c.4177C>T (p.Arg1393Ter)	RUSC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3251326	NM_014806.5(RUSC2):c.4227G>A (p.Trp1409Ter)	RUSC2	Pathogenic	criteria provided, single submitter
446385	NM_014806.5(RUSC2):c.2596C>T (p.Arg866Ter)	RUSC2	Pathogenic	criteria provided, single submitter
446386	NM_014806.5(RUSC2):c.3952C>T (p.Arg1318Ter)	RUSC2	Pathogenic	no assertion criteria provided
931076	NM_014806.5(RUSC2):c.2773C>T (p.Arg925Ter)	RUSC2	Likely pathogenic	criteria provided, single submitter
1380751	NM_014806.5(RUSC2):c.2245G>A (p.Glu749Lys)	RUSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419441	NM_014806.5(RUSC2):c.3511G>A (p.Asp1171Asn)	RUSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1958339	NM_014806.5(RUSC2):c.242T>C (p.Ile81Thr)	RUSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2176544	NM_014806.5(RUSC2):c.752G>A (p.Arg251His)	RUSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
787071	NM_014806.5(RUSC2):c.1418C>T (p.Pro473Leu)	RUSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027718	NM_014806.5(RUSC2):c.119C>A (p.Thr40Lys)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027719	NM_014806.5(RUSC2):c.2132G>A (p.Arg711Gln)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027720	NM_014806.5(RUSC2):c.2959T>G (p.Ser987Ala)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027721	NM_014806.5(RUSC2):c.3044G>A (p.Arg1015Gln)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027722	NM_014806.5(RUSC2):c.380C>T (p.Thr127Ile)	RUSC2	Uncertain significance	criteria provided, single submitter
1027723	NM_014806.5(RUSC2):c.61C>T (p.His21Tyr)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031865	NM_014806.5(RUSC2):c.1568G>A (p.Arg523His)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031866	NM_014806.5(RUSC2):c.1747C>T (p.Arg583Trp)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031867	NM_014806.5(RUSC2):c.2324C>T (p.Ser775Leu)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031868	NM_014806.5(RUSC2):c.2614C>T (p.Arg872Trp)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031869	NM_014806.5(RUSC2):c.3557G>A (p.Arg1186Gln)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031870	NM_014806.5(RUSC2):c.3877C>T (p.Arg1293Cys)	RUSC2	Uncertain significance	criteria provided, single submitter
1031871	NM_014806.5(RUSC2):c.3908A>G (p.Lys1303Arg)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031872	NM_014806.5(RUSC2):c.4078C>T (p.Arg1360Trp)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031873	NM_014806.5(RUSC2):c.567C>A (p.His189Gln)	RUSC2	Uncertain significance	criteria provided, single submitter
1298339	NM_014806.5(RUSC2):c.2626G>A (p.Glu876Lys)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1358977	NM_014806.5(RUSC2):c.737G>A (p.Gly246Glu)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1432689	NM_014806.5(RUSC2):c.1528C>T (p.Arg510Cys)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434340	NM_014806.5(RUSC2):c.4079G>A (p.Arg1360Gln)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1445209	NM_014806.5(RUSC2):c.438C>G (p.Phe146Leu)	RUSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
RUSC2	Strong	Autosomal recessive	intellectual disability, autosomal recessive 61	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
RUSC2	HGNC:23625	ENSG00000198853	Q8N2Y8	AP-4 complex accessory subunit RUSC2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUSC2	AP-4 complex accessory subunit RUSC2	Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RUSC2	Scaffold/PPI	no		SH3_domain, Run_dom, SH3-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
cortical plate	1
popliteal artery	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RUSC2	237	ubiquitous	marker	cortical plate, right frontal lobe, popliteal artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RUSC2	1,916

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RUSC2	Q8N2Y8	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
RUSC2	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	RUSC2

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)
RUSC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.