MAD2L1

Chr 4

mitotic arrest deficient 2 like 1

Also known as: HSMAD2, MAD2

MAD2L1 encodes a component of the mitotic spindle assembly checkpoint that prevents anaphase onset until all chromosomes are properly aligned at the metaphase plate by sequestering CDC20. Mutations cause mosaic variegated aneuploidy syndrome, characterized by constitutional mosaicism for various trisomies and monosomies, intellectual disability, growth retardation, and increased cancer risk, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
39
Pubs (1 yr)
21
P/LP submissions
0%
P/LP missense
0.94
LOEUF
Mechanism
Clinical SummaryMAD2L1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 16 VUS of 48 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.009
Z-score 1.73
OE 0.44 (0.230.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.06Z-score
OE missense 0.72 (0.600.86)
79 obs / 110.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.230.94)
00.351.4
Missense OE0.72 (0.600.86)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 5 / 11.2Missense obs/exp: 79 / 110.2Syn Z: 0.57

ClinVar Variant Classifications

48 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS16
Likely Benign4
Benign1
20
Pathogenic
1
Likely Pathogenic
16
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
0
12
4
0
16
Likely Benign
0
0
0
4
4
Benign
0
1
0
0
1
Total01325442

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

View in ClinVar →

Protein Context — Lollipop Plot

MAD2L1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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