Intellectual disability, autosomal recessive 13

Summary

Intellectual disability, autosomal recessive 13 (MONDO:0013173) is a disease caused by TRAPPC9 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: TRAPPC9 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 121

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 13
Mondo ID	MONDO:0013173
MeSH	C567714
OMIM	613192
DOID	DOID:0081098
UMLS	C2750791
MedGen	442564
GARD	0022548
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in TRAPPC9 · intellectual disability, autosomal recessive 13 · intellectual disability, autosomal recessive type 13 · mental retardation, autosomal recessive 13 · mental retardation, autosomal recessive type 13 · MRT13 · TRAPPC9 autosomal recessive non-syndromic intellectual disability

Data availability: 121 ClinVar variants · 4 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 13

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 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

121 retrieved; paginated sample, class counts are floors:

47 uncertain significance, 25 pathogenic, 19 conflicting classifications of pathogenicity, 13 likely pathogenic, 9 benign, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
915964	GRCh37/hg19 8q24.3(chr8:140852548-140953922)	C8orf17	Pathogenic	no assertion criteria provided
130637	NM_001160372.4(TRAPPC9):c.367G>T (p.Glu123Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1323708	NM_031466.8(TRAPPC9):c.-124dup	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1452925	NM_001160372.4(TRAPPC9):c.289G>T (p.Glu97Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1679936	NM_001160372.4(TRAPPC9):c.2699+1G>A	TRAPPC9	Pathogenic	criteria provided, single submitter
1686272	NM_001160372.4(TRAPPC9):c.3279+1G>A	TRAPPC9	Pathogenic	criteria provided, single submitter
1709594	NM_001160372.4(TRAPPC9):c.1840C>T (p.Arg614Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1805300	NM_001160372.4(TRAPPC9):c.175del (p.His59fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
191233	NM_001160372.4(TRAPPC9):c.3034C>T (p.Gln1012Ter)	TRAPPC9	Pathogenic	criteria provided, single submitter
2637918	NM_001160372.4(TRAPPC9):c.2186del (p.Gly729fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
2778686	NM_001160372.4(TRAPPC9):c.2841dup (p.Glu948Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
3063740	NM_001160372.4(TRAPPC9):c.203G>A (p.Trp68Ter)	TRAPPC9	Pathogenic	criteria provided, single submitter
3064394	NM_001160372.4(TRAPPC9):c.2520dup (p.Glu841fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
3250477	NM_001160372.4(TRAPPC9):c.2167dup (p.Ser723fs)	TRAPPC9	Pathogenic	no assertion criteria provided
3764586	NM_001160372.4(TRAPPC9):c.2513del (p.Asn838fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
3902333	NM_001160372.4(TRAPPC9):c.643C>T (p.Gln215Ter)	TRAPPC9	Pathogenic	criteria provided, single submitter
41419	NM_001160372.4(TRAPPC9):c.2557-2A>C	TRAPPC9	Pathogenic	no assertion criteria provided
437051	NM_001160372.4(TRAPPC9):c.531dup (p.Leu178fs)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
437052	NM_001160372.4(TRAPPC9):c.370_373dup (p.Val125fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
446015	NM_001160372.4(TRAPPC9):c.2854G>T (p.Glu952Ter)	TRAPPC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4536723	NM_001160372.4(TRAPPC9):c.865C>T (p.Gln289Ter)	TRAPPC9	Pathogenic	criteria provided, single submitter
694658	NM_001160372.4(TRAPPC9):c.2491C>T (p.Arg831Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
758	NM_001160372.4(TRAPPC9):c.1129C>T (p.Arg377Ter)	TRAPPC9	Pathogenic	criteria provided, multiple submitters, no conflicts
759	NM_001160372.4(TRAPPC9):c.1414C>T (p.Arg472Ter)	TRAPPC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
760	NM_001160372.4(TRAPPC9):c.2019_2022del (p.Leu674fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
977824	NM_001160372.4(TRAPPC9):c.2920C>T (p.Arg974Ter)	TRAPPC9	Pathogenic	criteria provided, single submitter
981432	NM_001160372.4(TRAPPC9):c.151C>T (p.Arg51Ter)	TRAPPC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982269	NM_001160372.4(TRAPPC9):c.2458_2459del (p.Leu820fs)	TRAPPC9	Pathogenic	criteria provided, single submitter
545512	NM_031466.7(TRAPPC9):c.[2415_2416insC];[3349+1G>A]		Likely pathogenic	criteria provided, single submitter
1723256	NM_001160372.4(TRAPPC9):c.1928del (p.Tyr643fs)	TRAPPC9	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
TRAPPC9	Definitive	Autosomal recessive	intellectual disability, autosomal recessive 13	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAPPC9	Orphanet:352530	Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome
TRAPPC9	Orphanet:88616	Autosomal recessive non-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
TRAPPC9	HGNC:30832	ENSG00000167632	Q96Q05	Trafficking protein particle complex subunit 9	gencc,clinvar
C8orf17	HGNC:17737	ENSG00000250733	Q9NRJ1	Protein MOST-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAPPC9	Trafficking protein particle complex subunit 9	Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex.
C8orf17	Protein MOST-1	May be involved in cell survival, proliferation and progression of cancer cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRAPPC9	Other/Unknown	no		Trs120_TRAPPC9, Trs120_TRAPPC9_N, TPR_TRAPPC9_Trs120
C8orf17	Other/Unknown	no

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)	1
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
bone marrow cell	1
pancreatic ductal cell	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAPPC9	258	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, apex of heart
C8orf17	4		yes	pancreatic ductal cell, tibialis anterior, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAPPC9	1,987
C8orf17	2

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAPPC9	Q96Q05	82.98
C8orf17	Q9NRJ1	54.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
COPII-mediated vesicle transport	1	163.1×	0.008	TRAPPC9
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.008	TRAPPC9

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
vesicle coat assembly	1	766.0×	0.007	TRAPPC9
obsolete vesicle tethering	1	495.6×	0.007	TRAPPC9
cerebral cortex development	1	102.8×	0.023	TRAPPC9
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.026	TRAPPC9
neuron differentiation	1	50.1×	0.028	TRAPPC9
negative regulation of apoptotic process	1	17.4×	0.059	C8orf17
positive regulation of cell population proliferation	1	16.8×	0.059	C8orf17

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
TRAPPC9	0	0
C8orf17	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	TRAPPC9, C8orf17

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TRAPPC9	0	—
C8orf17	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.