MAD1L1

Chr 7AR

mitotic arrest deficient 1 like 1

Also known as: MAD1, MVA7, PIG9, TP53I9, TXBP181

NCBI Gene: 8379ENSG00000002822UniProt: Q9Y6D9

MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1. MAD1L1 may play a role in cell cycle control and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Primary Disease Associations & Inheritance

Lymphoma, B-cell, somatic
Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predispositionMIM #620189
AR
Prostate cancer, somaticMIM #176807
0
Active trials
45
Pathogenic / LP
211
ClinVar variants
26
Pubs (1 yr)
0.0
Missense Z
0.97
LOEUF
Clinical Summary— MAD1L1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 146 VUS of 211 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.71
OE 0.71 (0.53–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 1.00 (0.92–1.08)
460 obs / 461.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.71 (0.53–0.97)
0≤0.351.4
Missense OE1.00 (0.92–1.08)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 30 / 42.0Missense obs/exp: 460 / 461.5Syn Z: -0.81
DN
DN
0.6839th %ile
GOF
0.4875th %ile
LOF
0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

211 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic3
VUS146
Likely Benign14
Benign6
42
Pathogenic
3
Likely Pathogenic
146
VUS
14
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
41
0
42
Likely Pathogenic
0
0
3
0
3
VUS
0
120
26
0
146
Likely Benign
1
4
3
6
14
Benign
0
0
3
3
6
Total2124769211

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

MAD1L1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients