RAD54L

Summary

RAD54L (RAD54 like, HGNC:9826) is a protein-coding gene on chromosome 1p34.1, encoding DNA repair and recombination protein RAD54-like (Q92698). Multifunctional ATPase that plays a role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. In precision oncology, RAD54L Mutation confers sensitivity to Olaparib in Castration-resistant Prostate Carcinoma (CIViC Level A).

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.

Source: NCBI Gene 8438 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 922 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_003579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9826
Approved symbol	RAD54L
Name	RAD54 like
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	hHR54, hRAD54, RAD54A
Ensembl gene	ENSG00000085999
Ensembl biotype	protein_coding
OMIM	603615
Entrez	8438

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 19 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000371975, ENST00000442598, ENST00000459678, ENST00000463715, ENST00000469835, ENST00000472889, ENST00000473251, ENST00000476687, ENST00000487700, ENST00000488942, ENST00000493032, ENST00000493985, ENST00000655446, ENST00000657122, ENST00000661174, ENST00000661701, ENST00000664182, ENST00000668390, ENST00000668565, ENST00000669994, ENST00000671528, ENST00000932539, ENST00000932540, ENST00000932541, ENST00000932542, ENST00000932543, ENST00000932544, ENST00000932545, ENST00000932546, ENST00000932547

RefSeq mRNA: 3 — MANE Select: NM_003579 NM_001142548, NM_001370766, NM_003579

CCDS: CCDS532

Canonical transcript exons

ENST00000371975 — 18 exons

Exon	Start	End
ENSE00001456595	46278072	46278473
ENSE00001456599	46247763	46248408
ENSE00003462978	46267459	46267609
ENSE00003550653	46261261	46261385
ENSE00003556760	46273355	46273465
ENSE00003681522	46260727	46261015
ENSE00003691897	46270659	46270785
ENSE00003703892	46260542	46260611
ENSE00003704858	46248512	46248598
ENSE00003704996	46272672	46272802
ENSE00003705958	46258686	46258746
ENSE00003706535	46274138	46274216
ENSE00003706873	46274538	46274717
ENSE00003708705	46272466	46272540
ENSE00003709550	46273624	46273747
ENSE00003710014	46277817	46277980
ENSE00003710087	46259964	46260099
ENSE00003711467	46250000	46250119

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 88.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4367 / max 196.8402, expressed in 1289 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2731	17.0616	1262
2730	0.8786	474
2729	0.3059	180
2732	0.1907	83

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	88.47	gold quality
right testis	UBERON:0004534	88.37	gold quality
ventricular zone	UBERON:0003053	88.11	gold quality
ganglionic eminence	UBERON:0004023	87.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.35	gold quality
testis	UBERON:0000473	85.72	gold quality
mucosa of transverse colon	UBERON:0004991	85.17	gold quality
embryo	UBERON:0000922	83.64	gold quality
lower esophagus mucosa	UBERON:0035834	82.08	gold quality
cerebellar hemisphere	UBERON:0002245	78.92	gold quality
cerebellar cortex	UBERON:0002129	78.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.46	gold quality
gastrocnemius	UBERON:0001388	78.38	gold quality
stromal cell of endometrium	CL:0002255	77.99	gold quality
secondary oocyte	CL:0000655	77.86	gold quality
rectum	UBERON:0001052	77.86	gold quality
esophagus mucosa	UBERON:0002469	77.77	gold quality
endometrium epithelium	UBERON:0004811	77.60	silver quality
muscle of leg	UBERON:0001383	77.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.75	gold quality
pancreatic ductal cell	CL:0002079	76.30	silver quality
cerebellum	UBERON:0002037	75.42	gold quality
vermiform appendix	UBERON:0001154	74.46	gold quality
right frontal lobe	UBERON:0002810	73.88	gold quality
spinal cord	UBERON:0002240	73.20	gold quality
metanephros cortex	UBERON:0010533	73.15	gold quality
thymus	UBERON:0002370	73.06	silver quality
Brodmann (1909) area 9	UBERON:0013540	72.86	gold quality
nucleus accumbens	UBERON:0001882	72.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

10 targeting RAD54L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 20)

• The RAD54L polymorphism (2290C/T) can be used as a genetic marker inside the consensus deletion region at 1p32 in human meningiomas. (PMID:12614485)
• Shortened telomeres in murine scid cells expressing mutant RAD54L coincide wirth reduction in recombination at telomeres. (PMID:15975611)
• hRad54, a Swi2/Snf2 protein, binds HJ-like structures with high specificity and promotes their bidirectional branch migration in an ATPase-dependent manner (PMID:16862129)
• Some immortal cells use the alternative lengthening of telomeres (ALT) pathway to maintain their telomeres instead of telomerase. This is the first genetic evidence that Rad54 is dispensable for the ALT pathway. (PMID:17054727)
• RAD54 is recruited by RAD51-ssDNA filament to the chromatin of the intact chromosome and it remodels that chromatin to facilitate accessibility for strand exchange (PMID:17417655)
• analysis of human rad54 protein interactions with branched DNA molecules (PMID:17545145)
• Rad54 protein causes dissociation of joint molecules by ATP-dependent branch-migration and therefore plays an important role in double strand DNA break repair. (PMID:17660833)
• germline mutations in RAD51, RAD51AP1, RAD51L1, RAD51L3, RAD52 and RAD54L are unlikely to be causal of an inherited predisposition to CLL. (PMID:18203022)
• Rad51 protein stimulates the branch migration activity of Rad54 protein.( (PMID:18617519)
• Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. (PMID:24798879)
• support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in tumor cells (PMID:25765654)
• TAF12 and NFYC are transcription factors that regulate the epigenome, whereas RAD54L plays a central role in DNA repair (PMID:25965574)
• Data show that the RAD54 N-terminal domain (NTD) is responsible for initiation of branch migration (BM) through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. (PMID:29295984)
• Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1-related genes and impairs DNA double-strand break recognition. (PMID:32333827)
• E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair. (PMID:33261027)
• Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L. (PMID:34079088)
• Association of MTHFR, MTRR and RAD54L Gene Variations with Meningioma and Correlation with Tumor’s Histopathological Characteristics on Turkish Cohort. (PMID:34169999)
• Rad54L promotes bladder cancer progression by regulating cell cycle and cell senescence. (PMID:36071250)
• DNA repair/recombination protein 54L promotes the progression of lung adenocarcinoma by activating mTORC1 pathway. (PMID:36454390)
• Overexpression of RAD54L attenuates osteoarthritis by suppressing the HIF-1alpha/VEGF signaling pathway: Bioinformatics analysis and experimental validation. (PMID:38593124)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad54l	ENSDARG00000018623
mus_musculus	Rad54l	ENSMUSG00000028702
rattus_norvegicus	Rad54l	ENSRNOG00000013148
drosophila_melanogaster	okr	FBGN0002989
caenorhabditis_elegans	rad-54.L	WBGENE00004298

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

DNA repair and recombination protein RAD54-like — Q92698 (reviewed: Q92698)

Alternative names: RAD54 homolog

All UniProt accessions (13): Q92698, A0A087WTB0, A0A087WV39, A0A087WVW5, A0A087WW72, A0A087WWG5, A0A087X124, A0A590UJ71, A0A590UJ90, A0A590UJJ7, A0A590UJQ8, V9GYD3, V9GYX6

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional ATPase that plays a role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Also plays an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA.

Subunit / interactions. Homohexamer. Interacts (via N-terminus) with RAD51; RAD51 nucleoprotein filament stimulate RAD54L ATPase activity. Interacts with NAP1L1. Interacts with BRD9; this interaction orchestrates RAD51-RAD54 complex formation.

Subcellular location. Nucleus.

Post-translational modifications. Acetylated. Acetylation promotes interaction with BRD9, and subsequently with RAD54, which is essential for homologous recombination (HR). Phosphorylated. Phosphorylation at Ser-572 by NEK1 specifically in G2 phase allows efficient removal of RAD51 filaments from DNA.

Induction. Expression increases approximately 3-fold in late G1 phase compared to other phases of the cell cycle.

Similarity. Belongs to the SNF2/RAD54 helicase family.

RefSeq proteins (3): NP_001136020, NP_001357695, NP_003570* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR050496	SNF2_RAD54_helicase_repair	Family

Pfam: PF00176, PF00271

Enzyme classification (BRENDA):

• EC 3.6.4.B9 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (25 total): sequence variant 10, mutagenesis site 4, modified residue 3, domain 2, region of interest 2, chain 1, sequence conflict 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9TYY	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92698-F1	80.64	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 183–190

Post-translational modifications (3): 38, 515, 572

Mutagenesis-validated functional residues (4):

Position	Phenotype
189	loss of dsdna-dependent atpase activity. loss of function in double-strand break repair based on complementation assays
515	loss of acetylation.
572	defect in homologous recombination (hr).
572	promotes homologous recombination (hr), but causes rad51 removal from chromatin.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 288 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, GOBP_RESPONSE_TO_IONIZING_RADIATION, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC2, MODULE_16, KAUFFMANN_DNA_REPAIR_GENES, KONG_E2F3_TARGETS, KEGG_HOMOLOGOUS_RECOMBINATION, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, LI_WILMS_TUMOR_ANAPLASTIC_UP, MUELLER_PLURINET, GOBP_ORGANELLE_FISSION

GO Biological Process (12): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), DNA recombination (GO:0006310), reciprocal meiotic recombination (GO:0007131), determination of adult lifespan (GO:0008340), response to xenobiotic stimulus (GO:0009410), response to ionizing radiation (GO:0010212), double-strand break repair via synthesis-dependent strand annealing (GO:0045003), chromosome organization (GO:0051276), meiotic cell cycle (GO:0051321), double-strand break repair (GO:0006302), DNA damage response (GO:0006974)

GO Molecular Function (12): DNA helicase activity (GO:0003678), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), DNA translocase activity (GO:0015616), ATP hydrolysis activity (GO:0016887), ATP-dependent DNA/DNA annealing activity (GO:0036310), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), DNA binding (GO:0003677), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), site of double-strand break (GO:0035861)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity, acting on DNA	3
ATP-dependent activity	3
DNA metabolic process	2
recombinational repair	1
double-strand break repair	1
DNA damage response	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
multicellular organismal process	1
response to chemical	1
response to radiation	1
double-strand break repair via homologous recombination	1
organelle organization	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
DNA repair	1
cellular response to stress	1
helicase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
DNA binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA/DNA annealing activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

2885 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD54L	RAD51	Q06609	904
RAD54L	RAD52	P43351	900
RAD54L	K7EN88	K7EN88	796
RAD54L	RAD51D	O75771	795
RAD54L	RAD51C	O43502	765
RAD54L	ATM	Q13315	744
RAD54L	RAD51B	O15315	740
RAD54L	BRCA2	P51587	723
RAD54L	MRE11	P49959	680
RAD54L	XRCC3	O43542	677
RAD54L	BRCA1	P38398	666
RAD54L	FANCL	Q9NW38	665
RAD54L	RAD51AP1	Q96B01	655
RAD54L	CHEK2	O96017	653
RAD54L	PALB2	Q86YC2	651

IntAct

18 interactions, top by confidence:

A	B	Type	Score
NTAQ1	RAD54L	psi-mi:“MI:0915”(physical association)	0.740
RAD54L	NTAQ1	psi-mi:“MI:0915”(physical association)	0.740
RAD54L	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.590
RAD54L	TNKS2	psi-mi:“MI:0915”(physical association)	0.590
TNKS2	STRN	psi-mi:“MI:0914”(association)	0.520
EME1	RAD54L	psi-mi:“MI:0915”(physical association)	0.400
RAD51	RAD54L	psi-mi:“MI:0915”(physical association)	0.370
Tecpr2	PUF60	psi-mi:“MI:0914”(association)	0.350
LIMK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
NCK1	APBB2	psi-mi:“MI:0914”(association)	0.350
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
NTAQ1	SBNO1	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
NTAQ1	TRIM24	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): WDYHV1 (Two-hybrid), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Positive Genetic), RAD54L (Affinity Capture-MS), RAD54L (Affinity Capture-MS), RAD54L (Negative Genetic), RAD54L (Negative Genetic), NDUFA9 (Negative Genetic), PFDN5 (Negative Genetic), RAD54L (Positive Genetic)

ESM2 similar proteins: A0A1D5PRR9, A4IHD2, A4PBL4, B4F769, D4ACP5, F4HQE2, I3XHK1, O09053, O12944, O75417, O94762, P0DOY1, P56960, P70270, Q08D35, Q0PCS3, Q1LWH4, Q2VPA6, Q3B7N1, Q3UWM4, Q5NC05, Q5QJC2, Q5RDL2, Q5RHD1, Q5SXJ3, Q5ZJF6, Q6NU40, Q6NZP1, Q6NZQ2, Q6PFE3, Q6ZMT4, Q80Y44, Q8BGE5, Q8CGS6, Q8GT06, Q8IYD8, Q8TDG4, Q8VID5, Q92698, Q99NG0

Diamond homologs: A0A0P0WGX7, A2A8L1, A2BGR3, A3KFM7, A6QQR4, A7Z019, A9X4T1, B0R0I6, B0XPE7, B3NAN8, B4GS98, B5BT18, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, F1Q8K0, F4I2H2, F4IV45, F4J9M5, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EF53, O12944, O13682, O14139, O14646, O14981, O43065, O76460, P0CO16, P0CO17, P28370, P31380, P32333

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK2	“down-regulates activity”	RAD54L	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

922 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	557
Likely benign	324
Benign	3

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
6191	NM_003579.4(RAD54L):c.188C>A (p.Pro63His)	Pathogenic
6192	NM_003579.4(RAD54L):c.1331T>A (p.Val444Glu)	Pathogenic
6193	NM_003579.4(RAD54L):c.973G>A (p.Gly325Arg)	Pathogenic
208693	NM_003579.4(RAD54L):c.1033G>T (p.Gly345Cys)	Likely pathogenic
225054	NM_003579.4(RAD54L):c.1624C>T (p.Arg542Cys)	Likely pathogenic
2671642	NM_003579.4(RAD54L):c.1298del (p.Pro433fs)	Likely pathogenic
3362666	NM_003579.4(RAD54L):c.267T>G (p.Tyr89Ter)	Likely pathogenic

SpliceAI

3402 predictions. Top by Δscore:

Variant	Effect	Δscore
1:46248596:GTG:G	donor_gain	1.0000
1:46249998:A:AG	acceptor_gain	1.0000
1:46249999:G:GG	acceptor_gain	1.0000
1:46250116:GCAT:G	donor_gain	1.0000
1:46250120:G:GG	donor_gain	1.0000
1:46260100:G:GG	donor_gain	1.0000
1:46260994:G:GT	donor_gain	1.0000
1:46261011:GCTGG:G	donor_gain	1.0000
1:46261012:C:G	donor_gain	1.0000
1:46261259:A:AG	acceptor_gain	1.0000
1:46261259:AGAAG:A	acceptor_gain	1.0000
1:46261260:G:GA	acceptor_gain	1.0000
1:46261260:GAA:G	acceptor_gain	1.0000
1:46261260:GAAGG:G	acceptor_gain	1.0000
1:46261357:G:GT	donor_gain	1.0000
1:46261357:G:T	donor_gain	1.0000
1:46261381:ACGAG:A	donor_gain	1.0000
1:46267563:GCT:G	donor_gain	1.0000
1:46267565:T:G	donor_gain	1.0000
1:46267565:T:TG	donor_gain	1.0000
1:46267578:C:G	donor_gain	1.0000
1:46270657:AG:A	acceptor_gain	1.0000
1:46270658:GG:G	acceptor_gain	1.0000
1:46270781:AATAG:A	donor_gain	1.0000
1:46272751:A:G	donor_gain	1.0000
1:46272803:G:GG	donor_gain	1.0000
1:46274533:TCCA:T	acceptor_loss	1.0000
1:46274534:CCA:C	acceptor_loss	1.0000
1:46274536:A:AG	acceptor_gain	1.0000
1:46274536:AG:A	acceptor_loss	1.0000

AlphaMissense

4898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:46260605:G:C	Q157H	1.000
1:46260605:G:T	Q157H	1.000
1:46260736:T:C	F163L	1.000
1:46260738:C:A	F163L	1.000
1:46260738:C:G	F163L	1.000
1:46260803:T:C	M185T	1.000
1:46260804:G:A	M185I	1.000
1:46260804:G:C	M185I	1.000
1:46260804:G:T	M185I	1.000
1:46260805:G:C	G186R	1.000
1:46260811:G:A	G188R	1.000
1:46260811:G:C	G188R	1.000
1:46260812:G:A	G188E	1.000
1:46260812:G:T	G188V	1.000
1:46260910:A:C	S221R	1.000
1:46260912:C:A	S221R	1.000
1:46260912:C:G	S221R	1.000
1:46260914:T:C	L222P	1.000
1:46260925:T:A	W226R	1.000
1:46260925:T:C	W226R	1.000
1:46261381:A:C	D296A	1.000
1:46261381:A:T	D296V	1.000
1:46261383:G:A	E297K	1.000
1:46261384:A:C	E297A	1.000
1:46261384:A:T	E297V	1.000
1:46261385:G:C	E297D	1.000
1:46261385:G:T	E297D	1.000
1:46267469:T:C	L301P	1.000
1:46267473:G:C	K302N	1.000
1:46267473:G:T	K302N	1.000

dbSNP variants (sampled 300 via entrez): RS1000014491 (1:46246560 T>C), RS1000072834 (1:46277559 G>A), RS1000087776 (1:46257326 C>T), RS1000268852 (1:46249789 G>A), RS1000418508 (1:46270559 G>C), RS1000491961 (1:46276600 A>C), RS1000520969 (1:46275687 C>T), RS1000523346 (1:46257030 G>T), RS1000614462 (1:46270019 G>A), RS1000666993 (1:46269743 T>C), RS1000844787 (1:46249411 T>C,G), RS1000933325 (1:46276923 A>C), RS1000936133 (1:46249027 C>T), RS1000983278 (1:46262238 C>T), RS1001002565 (1:46255871 T>C)

Disease associations

OMIM: gene MIM:603615 | disease phenotypes: MIM:114480, MIM:605027

GenCC curated gene-disease

Mondo (11): hereditary breast ovarian cancer syndrome (MONDO:0003582), hereditary breast carcinoma (MONDO:0016419), polymorphous low grade neuroepithelial tumor of the young (MONDO:0858959), hereditary diffuse gastric adenocarcinoma (MONDO:0007648), germ cell tumor (MONDO:0005040), lymphoma, non-Hodgkin, familial (MONDO:0011508), pilocytic astrocytoma (MONDO:0016691), colon adenocarcinoma (MONDO:0002271), non-Hodgkin lymphoma (MONDO:0018908), breast ductal adenocarcinoma (MONDO:0005590), primary ovarian failure (MONDO:0005387)

Orphanet (6): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Hereditary breast cancer (Orphanet:227535), Hereditary diffuse gastric cancer (Orphanet:26106), Pilocytic astrocytoma (Orphanet:251612), Non-Hodgkin lymphoma (Orphanet:547), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002665	Lymphoma
HP:0003002	Breast carcinoma

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005312_2	Menopause (age at onset)	7.000000e-09
GCST005951_37	Body mass index	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0004340	body mass index

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008228	Lymphoma, Non-Hodgkin	C04.557.386.480; C15.604.515.569.480; C20.683.515.761.480
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146297 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,337 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11417	STREPTONIGRIN	2	43,337

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
RAD54L Mutation	Olaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID11207

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
(+)-JQ1 compound	decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression, affects expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
AM 251	decreases expression	1
CPG-oligonucleotide	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
biflorin	affects expression	1
riccardin D	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114783	Functional	PubChem BioAssay. Identification of Rad54 Inhibitors - Ruling Out Fluorescence Quenchers Measured in Biochemical System Using Plate Reader - 2159-03_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3377968	Binding	Inhibition of RAD54 (unknown origin) ATPase activity assessed as generation of reactive oxygen species	Targeting the homologous recombination pathway by small molecule modulators. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9U93	Delta-Rad54+hRad54-DT40	Cancer cell line	Female
CVCL_C7YL	HAP1 RAD54L (-) 1	Cancer cell line	Male
CVCL_C7YM	HAP1 RAD54L (-) 2	Cancer cell line	Male
CVCL_D9Q8	Ubigene HEK293 RAD54L KO	Transformed cell line	Female
CVCL_HE08	NALM-6 RAD54L(-/-)	Cancer cell line	Male
CVCL_KT98	HeLa SilenciX Rad54A	Cancer cell line	Female
CVCL_LH54	DT40-ATM(-/-)-RAD5L(-/-) hRad54	Cancer cell line	Female

Clinical trials (associated diseases)

290 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00168727	PHASE4	COMPLETED	Zevalin® Followed by Rituxan® Maintenance in Previously Treated Low Grade Non-Hodgkin’s Lymphoma
NCT03229200	PHASE4	ACTIVE_NOT_RECRUITING	Extended Treatment Protocol for Subjects Continuing to Benefit From Ibrutinib.
NCT04083079	PHASE4	UNKNOWN	Cost-Effectiveness Study of PEG-rhG-CSF in Prophylactic Treatment of Neutropenia After Chemotherapy in Lymphoma
NCT04460235	PHASE4	RECRUITING	Clinical Trial Assessing the Immunogenicity of an Anti-pneumococcal Vaccination Strategy (PCV13+PPV23 Versus PREVENAR20) in Adult Patients Treated for a Lymphoma
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00572572	PHASE3	COMPLETED	Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT02582697	PHASE3	RECRUITING	Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours
NCT03067181	PHASE3	RECRUITING	Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
NCT05874063	PHASE3	RECRUITING	Thromboprophylaxis in Good and Intermediate Prognosis Advanced Germ Cell Tumors
NCT00000658	PHASE3	COMPLETED	A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin’s Lymphoma
NCT00006434	PHASE3	COMPLETED	Tumor Lysate Pulsed-Dendritic Cell Vaccines After High-Dose Chemotherapy for Non-Hodgkin’s Lymphoma
NCT00088530	PHASE3	COMPLETED	BBR 2778 for Relapsed, Aggressive Non-Hodgkin’s Lymphoma (NHL)
NCT00103610	PHASE3	COMPLETED	Mobilization of Stem Cells With AMD3100 (Plerixafor) in Non-Hodgkin’s Lymphoma Patients
NCT00154440	PHASE3	UNKNOWN	Helicobacter - Lymphoma - Radiation Part I: Eradication, Part II: Radiation
NCT00185393	PHASE3	COMPLETED	Treatment With [90]Y-Ibritumomab Tiuxetan Versus no Treatment in Patients With Follicular Non Hodgkin Lymphoma (Stage III or IV) Having Achieved a Partial or Complete Remission After First Line Chemotherapy
NCT00186823	PHASE3	COMPLETED	Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00261677	PHASE3	COMPLETED	A Study to Evaluate the Effect of Weekly PROCRIT (Epoetin Alfa) or Placebo on Anemia and Quality of Life in Children With Cancer Undergoing Chemotherapy
NCT00268983	PHASE3	COMPLETED	Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
NCT00319332	PHASE3	WITHDRAWN	A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen
NCT00329030	PHASE3	COMPLETED	Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin’s Lymphoma (BMTCTN0401)
NCT01232556	PHASE3	TERMINATED	A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy
NCT01938001	PHASE3	COMPLETED	Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin’s Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
NCT01987505	PHASE3	COMPLETED	MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma
NCT01996865	PHASE3	COMPLETED	Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.
NCT02369016	PHASE3	COMPLETED	Phase III Copanlisib in Rituximab-refractory iNHL
NCT02417129	PHASE3	TERMINATED	BI 695500 vs Rituxan First Line Treatment in Patients With Low Tumor Burden Follicular Lymphoma
NCT02626455	PHASE3	TERMINATED	Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin’s Lymphoma (iNHL)
NCT02703272	PHASE3	TERMINATED	A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
NCT02747043	PHASE3	COMPLETED	Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03575351	PHASE3	COMPLETED	A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
NCT05431179	PHASE3	WITHDRAWN	A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
NCT05556720	PHASE3	ACTIVE_NOT_RECRUITING	Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries