Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition

Summary

Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition (MONDO:0859346) is a cancer with 1 cohort gene.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition
Mondo ID	MONDO:0859346
OMIM	620189
DOID	DOID:0060982
UMLS	C5774284
MedGen	1824057
GARD	0026709
Is cancer (heuristic)	yes

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

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 7 with inflammation and tumor predisposition

Related subtypes (6): mosaic variegated aneuploidy syndrome 1, mosaic variegated aneuploidy syndrome 2, mosaic variegated aneuploidy syndrome 3, mosaic variegated aneuploidy syndrome 4, 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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443777	NM_001013836.2(MAD1L1):c.196C>T (p.Gln66Ter)	MAD1L1	Pathogenic	no assertion criteria provided
2443778	NM_001013836.2(MAD1L1):c.1882G>T (p.Glu628Ter)	MAD1L1	Pathogenic	no assertion criteria provided
4690248	NM_001013836.2(MAD1L1):c.244C>T (p.Arg82Ter)	MAD1L1	Likely pathogenic	criteria provided, single submitter
3238790	NM_001013836.2(MAD1L1):c.1948C>T (p.Arg650Trp)	MAD1L1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
MAD1L1	Limited	Autosomal recessive	mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition	2

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
MAD1L1	HGNC:6762	ENSG00000002822	Q9Y6D9	Mitotic spindle assembly checkpoint protein MAD1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAD1L1	Mitotic spindle assembly checkpoint protein MAD1	Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate.

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)
MAD1L1	Other/Unknown	no		Mad1

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
left testis	1
right testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAD1L1	137	ubiquitous	marker	sural nerve, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAD1L1	2,947

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAD1L1	Q9Y6D9	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Amplification of signal from the kinetochores	1	196.9×	0.023	MAD1L1
Mitotic Spindle Checkpoint	1	158.6×	0.023	MAD1L1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.023	MAD1L1
Mitotic Metaphase and Anaphase	1	96.8×	0.023	MAD1L1
Mitotic Anaphase	1	96.8×	0.023	MAD1L1
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.023	MAD1L1
Cell Cycle Checkpoints	1	88.5×	0.023	MAD1L1
Resolution of Sister Chromatid Cohesion	1	86.5×	0.023	MAD1L1
RHO GTPases Activate Formins	1	77.7×	0.023	MAD1L1
Mitotic Prometaphase	1	69.2×	0.023	MAD1L1
RHO GTPase Effectors	1	68.0×	0.023	MAD1L1
M Phase	1	66.0×	0.023	MAD1L1
Separation of Sister Chromatids	1	60.7×	0.023	MAD1L1
Cell Cycle, Mitotic	1	48.2×	0.027	MAD1L1
Cell Cycle	1	36.0×	0.032	MAD1L1
Signaling by Rho GTPases	1	34.2×	0.032	MAD1L1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.032	MAD1L1
Signal Transduction	1	10.2×	0.098	MAD1L1

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
deactivation of mitotic spindle assembly checkpoint	1	5617.3×	0.001	MAD1L1
regulation of metaphase plate congression	1	3370.4×	0.001	MAD1L1
positive regulation of mitotic cell cycle spindle assembly checkpoint	1	1532.0×	0.002	MAD1L1
attachment of mitotic spindle microtubules to kinetochore	1	1053.2×	0.002	MAD1L1
mitotic spindle assembly checkpoint signaling	1	561.7×	0.003	MAD1L1
thymus development	1	337.0×	0.003	MAD1L1
negative regulation of T cell proliferation	1	330.4×	0.003	MAD1L1
cell division	1	46.2×	0.022	MAD1L1

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
MAD1L1	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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	MAD1L1

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)
MAD1L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.