RAD54B

Chr 8

RAD54 homolog B

Also known as: RDH54

The protein is an ATPase that functions in homologous recombination for repairing DNA double-strand breaks and guides RAD51 during the DNA repair process. Mutations cause colon cancer and non-Hodgkin lymphoma through somatic inheritance patterns. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its association with somatic rather than germline developmental disorders.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Colon cancer, somaticMIM #114500
Lymphoma, non-Hodgkin, somaticMIM #605027
0
Active trials
12
Pubs (1 yr)
40
P/LP submissions
3%
P/LP missense
0.86
LOEUF
DN
Mechanism· predicted
Clinical SummaryRAD54B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 92 VUS of 186 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.27
OE 0.62 (0.450.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.88 (0.810.95)
402 obs / 457.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.450.86)
00.351.4
Missense OE0.88 (0.810.95)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 26 / 41.9Missense obs/exp: 402 / 457.7Syn Z: 0.68
DN
0.74top 25%
GOF
0.4282th %ile
LOF
0.3164th %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

186 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic2
VUS92
Likely Benign10
Benign26
38
Pathogenic
2
Likely Pathogenic
92
VUS
10
Likely Benign
26
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
37
0
38
Likely Pathogenic
1
0
1
0
2
VUS
0
90
2
0
92
Likely Benign
1
8
0
1
10
Benign
0
3
20
3
26
Total2102604168

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

View in ClinVar →

Protein Context — Lollipop Plot

RAD54B · protein map & ClinVar variants

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

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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