Intellectual disability, autosomal recessive 7

Summary

Intellectual disability, autosomal recessive 7 (MONDO:0012615) is a disease caused by TUSC3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TUSC3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 89

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 7
Mondo ID	MONDO:0012615
MeSH	C567016
OMIM	611093
DOID	DOID:0081183
UMLS	C1970197
MedGen	370847
GARD	0022543
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in TUSC3 · intellectual disability, autosomal recessive 7 · intellectual disability, autosomal recessive type 7 · mental retardation, autosomal recessive 22 · mental retardation, autosomal recessive 7 · mental retardation, autosomal recessive type 7 · MRT7 · TUSC3 autosomal recessive non-syndromic intellectual disability

Data availability: 89 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 7

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 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 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

89 retrieved; paginated sample, class counts are floors:

31 likely benign, 28 uncertain significance, 9 pathogenic, 7 likely pathogenic, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2603687	NM_006765.4(TUSC3):c.529C>T (p.Gln177Ter)	TUSC3	Pathogenic	criteria provided, multiple submitters, no conflicts
3245514	NC_000008.10:g.(?15397940)(15615318_?)del	TUSC3	Pathogenic	criteria provided, single submitter
3340901	NM_006765.4(TUSC3):c.279dup (p.Gln94fs)	TUSC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3778770	NM_006765.4(TUSC3):c.567+1G>C	TUSC3	Pathogenic	criteria provided, single submitter
449114	NM_006765.4(TUSC3):c.1028G>C (p.Ser343Thr)	TUSC3	Pathogenic	criteria provided, single submitter
4687305	NC_000008.10:g.(15531346_15588174)_(15615365_15621711)del	TUSC3	Pathogenic	criteria provided, single submitter
495148	NM_006765.4(TUSC3):c.225del (p.Lys75fs)	TUSC3	Pathogenic	no assertion criteria provided
560138	Single allele	TUSC3	Pathogenic	criteria provided, single submitter
8183	NM_006765.4(TUSC3):c.786dup (p.Asn263fs)	TUSC3	Pathogenic	no assertion criteria provided
95432	NM_006765.4(TUSC3):c.992C>A (p.Ser331Ter)	TUSC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973756	NM_006765.4(TUSC3):c.420dup (p.Gln141fs)	TUSC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1325320	NM_006765.4(TUSC3):c.220C>T (p.Arg74Ter)	TUSC3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333604	NM_006765.4(TUSC3):c.568-2A>G	TUSC3	Likely pathogenic	criteria provided, single submitter
1710460	NM_006765.4(TUSC3):c.55_69delinsGC (p.Tyr19fs)	TUSC3	Likely pathogenic	criteria provided, single submitter
2503415	NM_006765.4(TUSC3):c.119dup (p.Gly41fs)	TUSC3	Likely pathogenic	no assertion criteria provided
30177	NM_006765.4(TUSC3):c.163C>T (p.Gln55Ter)	TUSC3	Likely pathogenic	criteria provided, single submitter
3381904	NM_006765.4(TUSC3):c.327T>A (p.Tyr109Ter)	TUSC3	Likely pathogenic	criteria provided, single submitter
4813718	NM_006765.4(TUSC3):c.286C>T (p.Gln96Ter)	TUSC3	Likely pathogenic	criteria provided, single submitter
1770299	NM_006765.4(TUSC3):c.1029-5G>C	TUSC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362313	NM_006765.4(TUSC3):c.768T>C (p.Tyr256=)	TUSC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362314	NM_006765.4(TUSC3):c.937+11G>C	TUSC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
437172	NM_006765.4(TUSC3):c.1029-8T>C	TUSC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910173	NM_006765.4(TUSC3):c.568-15A>G	TUSC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1022009	NM_006765.4(TUSC3):c.670T>G (p.Phe224Val)	TUSC3	Uncertain significance	criteria provided, single submitter
1034307	NM_006765.4(TUSC3):c.308+3A>G	TUSC3	Uncertain significance	criteria provided, single submitter
1059475	NM_006765.4(TUSC3):c.53G>A (p.Arg18Gln)	TUSC3	Uncertain significance	criteria provided, single submitter
1062649	NC_000008.10:g.(?15588155)(15615318_?)del	TUSC3	Uncertain significance	criteria provided, single submitter
1325580	NM_006765.4(TUSC3):c.19C>T (p.Pro7Ser)	TUSC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1400888	NC_000008.10:g.(?15397940)(15615318_?)dup	TUSC3	Uncertain significance	criteria provided, single submitter
1517661	NM_006765.4(TUSC3):c.187C>T (p.Arg63Cys)	TUSC3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TUSC3	Definitive	Autosomal recessive	intellectual disability	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUSC3	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
TUSC3	HGNC:30242	ENSG00000104723	Q13454	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TUSC3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUSC3	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TUSC3	Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consens…

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)
TUSC3	Other/Unknown	no		MAGT1/OST3/OST6, Thioredoxin-like_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
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUSC3	266	ubiquitous	marker	type B pancreatic cell, cortical plate, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUSC3	1,346

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUSC3	Q13454	4

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
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	519.1×	0.006	TUSC3
Miscellaneous transport and binding events	1	439.2×	0.006	TUSC3
Maturation of spike protein	1	265.6×	0.006	TUSC3
Maturation of DENV proteins	1	211.5×	0.006	TUSC3
Asparagine N-linked glycosylation	1	60.1×	0.017	TUSC3

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
magnesium ion transmembrane transport	1	4213.0×	0.001	TUSC3
magnesium ion transport	1	1203.7×	0.002	TUSC3
obsolete protein N-linked glycosylation via asparagine	1	674.1×	0.003	TUSC3
cognition	1	285.6×	0.005	TUSC3
protein N-linked glycosylation	1	263.3×	0.005	TUSC3
transmembrane transport	1	168.5×	0.006	TUSC3

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
TUSC3	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	TUSC3

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)
TUSC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.