RAD54L

Chr 1ADSomatic

RAD54 like

Also known as: HR54, RAD54A, hHR54, hRAD54

The RAD54L protein is a multifunctional ATPase that repairs DNA double-strand breaks through homologous recombination and acts as a molecular motor to guide RAD51 during the homology search process. Mutations cause autosomal dominant predisposition to adult-onset cancers including invasive ductal breast cancer, colonic adenocarcinoma, and non-Hodgkin lymphoma. The gene shows minimal constraint against loss-of-function variants in the population, consistent with its role as a cancer predisposition gene rather than a cause of severe developmental disorders.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/SomaticLOEUF 0.973 OMIM phenotypes
Clinical SummaryRAD54L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.71
OE 0.71 (0.530.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.25Z-score
OE missense 1.04 (0.951.12)
424 obs / 409.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.530.97)
00.351.4
Missense OE1.04 (0.951.12)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 29 / 40.8Missense obs/exp: 424 / 409.6Syn Z: -0.27
DN
0.6842th %ile
GOF
0.4678th %ile
LOF
0.3648th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RAD54L · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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