UMAD1

Chr 7

UBAP1-MVB12-associated (UMA) domain containing 1

Also known as: RPA3-AS1, RPA3OS

NCBI Gene: 729852 ENSG00000219545 UniProt: C9J7I0

UMAD1 encodes a component of the mitotic spindle assembly checkpoint that ensures proper chromosome segregation during cell division. Mutations cause autosomal recessive megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, characterized by brain malformations including enlarged brain size, abnormal cortical folding, extra digits, and fluid accumulation in the brain. This condition typically presents in the neonatal period with developmental abnormalities affecting the central nervous system and limbs.

Research

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.44

Clinical Summary— UMAD1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

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ClinVar Variants

2 total variants — no pathogenic classifications of 2 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.44LOEUF

pLI 0.225

Z-score 1.10

OE 0.32 (0.11–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.70Z-score

OE missense 0.74 (0.57–0.95)

41 obs / 55.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.11–1.44)

0≤0.351.4

Missense OE?0.74 (0.57–0.95)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 1 / 3.1Missense obs/exp: 41 / 55.7Syn Z: 0.53

This gene — mechanism propensity

0.5673th %ile

GOF

0.6931th %ile

LOF

0.3259th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

2 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign1

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	1	1
Benign	0	0
Total	1	1

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap UMAD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →