Mosaic variegated aneuploidy syndrome 3

Summary

Mosaic variegated aneuploidy syndrome 3 (MONDO:0054736) is a disease caused by TRIP13 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TRIP13 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic variegated aneuploidy syndrome 3
Mondo ID	MONDO:0054736
OMIM	617598
DOID	DOID:0080689
UMLS	C4539839
MedGen	1616382
GARD	0016240
Is cancer (heuristic)	no

Also known as: MVA3

Data availability: 12 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › mosaic variegated aneuploidy syndrome › mosaic variegated aneuploidy syndrome 3

Related subtypes (6): mosaic variegated aneuploidy syndrome 1, mosaic variegated aneuploidy syndrome 2, mosaic variegated aneuploidy syndrome 4, mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition, Atelis syndrome 1, Atelis syndrome 2

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

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 benign, 2 pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
431045	NM_004237.4(TRIP13):c.1060C>T (p.Arg354Ter)	TRIP13	Pathogenic	no assertion criteria provided
431046	NM_004237.4(TRIP13):c.673-1G>C	TRIP13	Pathogenic	no assertion criteria provided
4070948	NM_004237.4(TRIP13):c.1021-1G>C	TRIP13	Likely pathogenic	criteria provided, single submitter
977641	NM_004237.4(TRIP13):c.77A>G (p.His26Arg)	TRIP13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031392	NM_004237.4(TRIP13):c.712G>A (p.Asp238Asn)	TRIP13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805147	NM_004237.4(TRIP13):c.1016T>C (p.Met339Thr)	TRIP13	Uncertain significance	criteria provided, single submitter
1805254	NM_004237.4(TRIP13):c.759+1G>T	TRIP13	Uncertain significance	criteria provided, single submitter
3592818	NM_004237.4(TRIP13):c.140A>G (p.Asn47Ser)	TRIP13	Uncertain significance	criteria provided, single submitter
3592838	NM_004237.4(TRIP13):c.955A>G (p.Ile319Val)	TRIP13	Uncertain significance	criteria provided, single submitter
4796589	NM_004237.4(TRIP13):c.1070A>G (p.Glu357Gly)	TRIP13	Uncertain significance	criteria provided, single submitter
1225568	NM_004237.4(TRIP13):c.258+48del	TRIP13	Benign	criteria provided, multiple submitters, no conflicts
1241500	NM_004237.4(TRIP13):c.608+39T>G	TRIP13	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
TRIP13	Strong	Autosomal recessive	mosaic variegated aneuploidy syndrome 3	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIP13	Orphanet:1052	Mosaic variegated aneuploidy syndrome
TRIP13	Orphanet:654	Nephroblastoma

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
TRIP13	HGNC:12307	ENSG00000071539	Q15645	Pachytene checkpoint protein 2 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIP13	Pachytene checkpoint protein 2 homolog	Plays a key role in chromosome recombination and chromosome structure development during meiosis.

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)
TRIP13	Other/Unknown	no		ClpA/B, AAA+_ATPase, ATPase_AAA_core

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
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIP13	212	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIP13	4,676

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRIP13	Q15645	6

Function

Pathway analysis

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

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
meiotic recombination checkpoint signaling	1	5617.3×	0.002	TRIP13
female meiosis I	1	1872.4×	0.003	TRIP13
synaptonemal complex assembly	1	648.1×	0.003	TRIP13
oocyte maturation	1	601.9×	0.003	TRIP13
male meiosis I	1	581.1×	0.003	TRIP13
mitotic spindle assembly checkpoint signaling	1	561.7×	0.003	TRIP13
reciprocal meiotic recombination	1	561.7×	0.003	TRIP13
oogenesis	1	383.0×	0.004	TRIP13
double-strand break repair	1	203.0×	0.007	TRIP13
spermatid development	1	145.3×	0.008	TRIP13
transcription by RNA polymerase II	1	70.5×	0.015	TRIP13
spermatogenesis	1	35.2×	0.028	TRIP13

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
TRIP13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRIP13	9	Binding:9

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	TRIP13

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)
TRIP13	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.