RAD9A

Chr 11

RAD9 checkpoint clamp component A

Also known as: RAD9

NCBI Gene: 5883 ENSG00000172613 UniProt: Q99638 OMIM: 603761

RAD9A encodes a component of the 9-1-1 cell cycle checkpoint complex that functions as a sliding clamp platform for DNA repair proteins and possesses 3' to 5' exonuclease activity for sensing and repairing DNA damage. Mutations cause autosomal recessive developmental delays, intellectual disability, and microcephaly with onset in early childhood. The gene shows minimal constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.41

OE 0.64 (0.40–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.90–1.11)

246 obs / 245.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.40–1.05)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 11 / 17.3Missense obs/exp: 246 / 245.7Syn Z: -1.96

Background carrier burden — how many people carry a rare variant somewhere in RAD9A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

553 rare PASS variants

Rare truncating (LoF)

1 in 2,800

93 rare PASS variants

Rare synonymous (reference)

1 in 190

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAD9A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 3,100
South Asian	~43k	1 in 72	1 in 3,300
Remaining (unassigned)	~30k	1 in 81	1 in 3,000
European (Finnish)	~27k	1 in 340	1 in 4,300
Admixed American	~22k	1 in 100	1 in 3,100
African / African American	~21k	1 in 82	1 in 1,300
East Asian	~20k	1 in 100	1 in 3,300
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 5,800
Middle Eastern	~2,884	1 in 64	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓