RAD54L

Chr 1ADSomatic

RAD54 like

Also known as: HR54, RAD54A, hHR54, hRAD54

NCBI Gene: 8438ENSG00000085999UniProt: Q92698

The protein encoded by this gene belongs to the DEAD-like helicase superfamily, and shares similarity with Saccharomyces cerevisiae Rad54, a protein known to be involved in the homologous recombination and repair of DNA. This protein has been shown to play a role in homologous recombination related repair of DNA double-strand breaks. The binding of this protein to double-strand DNA induces a DNA topological change, which is thought to facilitate homologous DNA paring, and stimulate DNA recombination. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

{Breast cancer, invasive ductal}MIM #114480
ADSomatic
Adenocarcinoma, colonic, somatic
Lymphoma, non-Hodgkin, somaticMIM #605027
380
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— RAD54L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 257 VUS of 380 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.000
Z-score 1.71
OE 0.71 (0.53–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.25Z-score
OE missense 1.04 (0.95–1.12)
424 obs / 409.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.53–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.95–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 29 / 40.8Missense obs/exp: 424 / 409.6Syn Z: -0.27

ClinVar Variant Classifications

380 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic3
VUS257
Likely Benign118
Conflicting1
1
Pathogenic
3
Likely Pathogenic
257
VUS
118
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
1
0
2
0
3
VUS
1
256
0
0
257
Likely Benign
1
14
0
103
118
Benign
0
0
0
0
0
Conflicting
—1
Total32703103380

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
RAD54-LIKE; RAD54L
MIM #603615 · *

{Breast cancer, invasive ductal}

MIM #114480

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Adenocarcinoma, colonic, somatic

Molecular basis of disorder known

Lymphoma, non-Hodgkin, somatic

MIM #605027

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RAD54L promotes progression of hepatocellular carcinoma via the homologous recombination repair pathway.
Li H et al.·Funct Integr Genomics
2023
Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial.
Thiery-Vuillemin A et al.·Lancet Oncol
2022Clinical trial
Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L.
Nathansen J et al.·Oncogene
2021
Radiation-Induced Synchronous Parathyroid Carcinoma and Papillary Thyroid Carcinoma: Clinical, Morphological, and Genetic Insights.
Iványi G et al.·Int J Mol Sci
2025Case report
Ovarian high-grade serous carcinoma with transitional-like (SET) morphology: a homologous recombination-deficient tumor.
D'Angelo E et al.·Hum Pathol
2023
Pan-cancer analysis of homologous recombination deficiency and homologous recombination repair-associated gene alterations in solid tumors from a large Asian cohort.
Ren L et al.·BMC Cancer
2025Cohort
Clinicopathological features of Chinese ovarian cancer patients with double heterozygosity for cancer-predisposed genes.
Jin Y et al.·BMC Cancer
2025Cohort
Contributions of DNA double strand break repair pathways to DNA crosslink repair.
van de Kamp G et al.·DNA Repair (Amst)
2025
Exome sequencing reveals new insights into the germline landscape of inflammatory breast cancer among Tunisian patients.
Boujemaa M et al.·J Transl Med
2025Cohort
Germline RAD54L with somatic POLE defect implicated in Hypermutation phenotype: case report.
Zohud BA et al.·BMC Gastroenterol
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Renal Cell CarcinomaMetastatic Renal Cell CarcinomaKidney Cancer

Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations

RECRUITING
NCT03786796Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2019-06-03
Olaparib
Advanced or Metastatic Solid TumorsBreast CancerOvarian Cancer

A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors

RECRUITING
NCT05787587Phase PHASE1IDEAYA BiosciencesStarted 2023-04-18
IDE-161Pembrolizumab

External Resources

Links to major genomics databases and tools