RAD54B

Summary

RAD54B (RAD54 homolog B, HGNC:17228) is a protein-coding gene on chromosome 8q22.1, encoding DNA repair and recombination protein RAD54B (Q9Y620). Multifunctional ATPase that could play with RAD54, a redundant role in homologous recombination (HR), a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks.

The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer.

Source: NCBI Gene 25788 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 146 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_012415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17228
Approved symbol	RAD54B
Name	RAD54 homolog B
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RDH54
Ensembl gene	ENSG00000197275
Ensembl biotype	protein_coding
OMIM	604289
Entrez	25788

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297592, ENST00000336148, ENST00000463267, ENST00000518358, ENST00000518998, ENST00000519348, ENST00000523192, ENST00000523839, ENST00000871949, ENST00000911512, ENST00000911513, ENST00000911514, ENST00000911515, ENST00000911516, ENST00000911517, ENST00000911518, ENST00000911519

RefSeq mRNA: 3 — MANE Select: NM_012415 NM_001205262, NM_001205263, NM_012415

CCDS: CCDS56546, CCDS6262

Canonical transcript exons

ENST00000336148 — 15 exons

Exon	Start	End
ENSE00001131862	94371960	94372387
ENSE00001725574	94458268	94458436
ENSE00002126484	94475001	94475115
ENSE00002583857	94467405	94467555
ENSE00003574412	94407439	94407720
ENSE00003611816	94411121	94411315
ENSE00003792272	94399414	94399621
ENSE00003792466	94393743	94393882
ENSE00003793791	94380145	94380406
ENSE00003794699	94378568	94378634
ENSE00003795021	94400238	94400463
ENSE00003796414	94404077	94404239
ENSE00003797544	94378180	94378380
ENSE00003797965	94391609	94391899
ENSE00003798830	94386984	94387159

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 88.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8536 / max 243.9932, expressed in 1353 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93989	4.9444	1121
93988	4.0792	1030
93990	2.9025	1076
93986	0.0067	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.44	gold quality
ventricular zone	UBERON:0003053	84.93	gold quality
oocyte	CL:0000023	83.30	gold quality
secondary oocyte	CL:0000655	82.32	gold quality
ganglionic eminence	UBERON:0004023	81.77	gold quality
lower esophagus mucosa	UBERON:0035834	81.54	gold quality
endometrium	UBERON:0001295	80.24	gold quality
embryo	UBERON:0000922	80.05	gold quality
pigmented layer of retina	UBERON:0001782	77.67	gold quality
right lobe of liver	UBERON:0001114	77.55	gold quality
cerebellar hemisphere	UBERON:0002245	76.34	gold quality
adrenal tissue	UBERON:0018303	76.27	gold quality
tibial nerve	UBERON:0001323	76.15	gold quality
cerebellar cortex	UBERON:0002129	76.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.80	gold quality
pituitary gland	UBERON:0000007	75.78	gold quality
cortical plate	UBERON:0005343	75.27	gold quality
stromal cell of endometrium	CL:0002255	75.21	gold quality
mucosa of transverse colon	UBERON:0004991	74.97	gold quality
caudate nucleus	UBERON:0001873	74.76	gold quality
cerebellum	UBERON:0002037	74.51	gold quality
metanephros cortex	UBERON:0010533	74.02	gold quality
sural nerve	UBERON:0015488	73.88	gold quality
right frontal lobe	UBERON:0002810	73.79	gold quality
seminal vesicle	UBERON:0000998	73.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.62	gold quality
esophagus mucosa	UBERON:0002469	73.49	gold quality
right adrenal gland cortex	UBERON:0035827	73.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	186.17
E-ANND-3	no	3.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting RAD54B, 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-5692A	100.00	74.40	6850
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052

Literature-anchored findings (GeneRIF, showing 23)

• Rad54B is a DNA-dependent ATPase and has biochemical properties different from its structural homolog in yeast, Tid1/Rdh54 (PMID:11884632)
• Rad54B enhanced the DNA strand-exchange activity of Dmc1 by stabilizing the Dmc1-single-stranded DNA complex. (PMID:16945962)
• the loss of heterozygosity (LOH) in the 8q12-q24.1 chromosomal region, containing RAD54B gene isn’t predictive for breast cancer (PMID:17585536)
• S100A11 targets Rad54B to sites of DNA DSB repair sites and has a role in p21-based regulation of cell cycle (PMID:18463164)
• RAD54B binding may affect the quaternary structure of DMC1. (PMID:18718930)
• RAD54B-deficient human colorectal cancer cells are sensitive to synthetic lethal killing by reduced FEN1 expression, while isogenic RAD54B proficient cells are not (PMID:19218431)
• These results suggest that hINO80 assists double-strand break repair by positively regulating the expression of the Rad54B and XRCC3 genes. (PMID:20687897)
• RAD54B and GREB1 gene polymorphisms may not be associated with PCOS in the Han Chinese population. (PMID:23876972)
• RAD54B-deficient cells are selectively killed relative to controls via siRNA-based silencing of SOD1 (PMID:24002644)
• The scaffolding function of Rad54B dynamically regulates the maintenance of genome integrity by limiting checkpoint strength. (PMID:25384516)
• support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in tumor cells (PMID:25765654)
• RAD54B expression has potential to serve as a novel prognostic biomarker, particularly for distant recurrence in colorectal cancer (PMID:26046797)
• Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis. (PMID:26431531)
• Review of structural aspects of RAD54B, molecular functions associated with its cellular roles in preventing genome instability, and how aberrant function contributes to oncogenesis. (PMID:28295846)
• High RAD54B expression is associated with hepatoma. (PMID:29956808)
• Results demonstrate that the patched 1 protein (PTCH1) rs10512248 and DNA repair and recombination protein RAD54B (RAD54B) rs12681366 were significantly associated with non-syndromic orofacial clefts (NSOC) in a Northern Chinese population. (PMID:30172247)
• miR-139-3p target genes ISG20L2, RAD54B, KIAA0101, and PIGS were significantly negatively correlated with miR-139-3p expression in patients with hepatocellular carcinoma. (PMID:30394818)
• the biological role of RAD54B in the neoplastic process of luminal A breast cancer, is reported. (PMID:31545289)
• RAD54B exerts an oncogenic role in lung cancer cell proliferation. (PMID:31558081)
• Integrated study of miR-215 promoting breast cancer cell apoptosis by targeting RAD54B. (PMID:33635591)
• RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors. (PMID:35952757)
• RNA-sequencing analysis reveals the potential molecular mechanism of RAD54B in the proliferation of inflamed human dental pulp cells. (PMID:36196684)
• RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/beta-catenin pathway. (PMID:38378037)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad54b	ENSDARG00000092134
mus_musculus	Rad54b	ENSMUSG00000078773
rattus_norvegicus	Rad54b	ENSRNOG00000039949
caenorhabditis_elegans		WBGENE00013792

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), 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), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

DNA repair and recombination protein RAD54B — Q9Y620 (reviewed: Q9Y620)

Alternative names: RAD54 homolog B

All UniProt accessions (4): E5RHN9, E5RI14, E5RJF7, Q9Y620

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional ATPase that could play with RAD54, a redundant role in homologous recombination (HR), a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Could act as a molecular motor during the homology search and guide RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Once DNA strand exchange occured, could dissociate RAD51 from nucleoprotein filaments formed on dsDNA. May also function as a molecular adapter, promoting MDM2-MDM4 heterodimerization to facilitate the ubiquitin-dependent degradation of p53, thereby modulating the cellular decision between cell cycle arrest and progression in response to DNA damage.

Subunit / interactions. Probable monomer. Interacts with RAD51; stimulates the DNA remodeling activity of RAD54B. Interacts with MDM2 and MDM4; enhances the ubiquitin ligase activity of MDM2 on TP53 by promoting MDM2-MDM4 heterodimerization.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Abundantly expressed in testis and spleen. Relatively low levels observed in thymus, prostate, ovary and colon.

Induction. Up-regulated by genotoxic stress in the early phases of DNA damage response (DDR) (at protein level).

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y620-1	1	yes
Q9Y620-2	2

RefSeq proteins (3): NP_001192191, NP_001192192, NP_036547* (*=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 (18 total): sequence variant 6, domain 2, splice variant 2, region of interest 2, chain 1, mutagenesis site 1, short sequence motif 1, compositionally biased region 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9TRM	ELECTRON MICROSCOPY	2.4
9SRZ	ELECTRON MICROSCOPY	2.61
9SSL	ELECTRON MICROSCOPY	2.9
9TRL	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y620-F1	71.80	0.21

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): 326–333

Post-translational modifications (1): 14

Mutagenesis-validated functional residues (1):

Position	Phenotype
332	loss of dsdna-dependent atpase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 258 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KAUFFMANN_DNA_REPAIR_GENES, KEGG_HOMOLOGOUS_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, WEI_MYCN_TARGETS_WITH_E_BOX, ONKEN_UVEAL_MELANOMA_UP, GOBP_ORGANELLE_FISSION, DOANE_RESPONSE_TO_ANDROGEN_DN, GROSS_HYPOXIA_VIA_ELK3_DN, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION, LIAO_METASTASIS, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), reciprocal meiotic recombination (GO:0007131), determination of adult lifespan (GO:0008340), response to xenobiotic stimulus (GO:0009410), response to ionizing radiation (GO:0010212), homologous recombination (GO:0035825), negative regulation of signal transduction by p53 class mediator (GO:1901797), DNA repair (GO:0006281), mitotic recombination (GO:0006312), DNA damage response (GO:0006974)

GO Molecular Function (11): DNA binding (GO:0003677), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), DNA translocase activity (GO:0015616), hydrolase activity (GO:0016787), protein-macromolecule adaptor activity (GO:0030674), nucleotide binding (GO:0000166), DNA helicase activity (GO:0003678), RNA helicase activity (GO:0003724), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), site of double-strand break (GO:0035861)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA recombination	2
ATP-dependent activity	2
ATP-dependent activity, acting on DNA	2
helicase activity	2
recombinational repair	1
double-strand break repair	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
signal transduction by p53 class mediator	1
regulation of signal transduction by p53 class mediator	1
negative regulation of intracellular signal transduction	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
DNA binding	1
catalytic activity	1
protein binding	1
molecular adaptor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
site of DNA damage	1

Protein interactions and networks

STRING

2633 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD54B	RAD51	Q06609	980
RAD54B	ATRX	P46100	979
RAD54B	RAD52	P43351	951
RAD54B	BRCA2	P51587	835
RAD54B	BRCA1	P38398	778
RAD54B	WRN	Q14191	726
RAD54B	LIG4	P49917	718
RAD54B	XRCC3	O43542	695
RAD54B	XRCC5	P13010	675
RAD54B	RAD51C	O43502	648
RAD54B	MUS81	Q96NY9	630
RAD54B	EXO1	Q9UQ84	630
RAD54B	SH2D2A	Q9NP31	622
RAD54B	FANCM	Q8IYD8	607
RAD54B	FEN1	P39748	598

IntAct

29 interactions, top by confidence:

A	B	Type	Score
LNX1	RAD54B	psi-mi:“MI:0915”(physical association)	0.670
RAD54B	LNX1	psi-mi:“MI:0915”(physical association)	0.670
ATXN1	RAD54B	psi-mi:“MI:0915”(physical association)	0.560
RIBC2	RAD54B	psi-mi:“MI:0915”(physical association)	0.550
RAD54B	RIBC2	psi-mi:“MI:0915”(physical association)	0.550
MAF1	POLR3A	psi-mi:“MI:0914”(association)	0.530
RAD54B	CCDC33	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	ZNF580	psi-mi:“MI:0915”(physical association)	0.370
CDC23	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	GORASP2	psi-mi:“MI:0915”(physical association)	0.370
PSMA1	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	MYO15B	psi-mi:“MI:0915”(physical association)	0.370
DYRK2	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
CSNK1E	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
UBE2I	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	TRAPPC6A	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
SUMO1	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	BAAT	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	TRMO	psi-mi:“MI:0915”(physical association)	0.370
IGFBP3	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
CPNE5	NCK2	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
NOLC1	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
RAD54B	LNX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (81): RAD54B (Affinity Capture-MS), RAD54B (Two-hybrid), RAD54B (Two-hybrid), RAD54B (Two-hybrid), RAD54B (Two-hybrid), GMCL1 (Two-hybrid), MYO15B (Two-hybrid), ENKD1 (Two-hybrid), ANKRD36BP1 (Two-hybrid), ATPAF2 (Two-hybrid), TCEANC (Two-hybrid), RAD54B (Affinity Capture-Western), RAD54B (Affinity Capture-Western), MDM2 (Affinity Capture-Western), RAD54B (Reconstituted Complex)

ESM2 similar proteins: A0A0P0V4R0, A0A1D5PRR9, A4IG62, A9UMG5, B4JNS2, F1R345, F4HQE2, F4KFV7, O75417, P0C928, P42285, Q14527, Q16X92, Q28E61, Q2VPA6, Q43093, Q56YN3, Q5JK52, Q5U2U7, Q5W9E7, Q5ZJT0, Q5ZLV4, Q60446, Q642J4, Q6PCL9, Q6PCN7, Q6PFE3, Q7XT07, Q8CGS6, Q8H2D5, Q8IYB8, Q8IYD8, Q8K394, Q94BR5, Q95216, Q9BWT3, Q9CZU3, Q9DG67, Q9FF61, Q9FT73

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	90
Likely benign	10
Benign	26

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
5639	NM_012415.3(RAD54B):c.1252G>T (p.Asp418Tyr)	Pathogenic
870770	NM_012415.3(RAD54B):c.1413del (p.Phe471fs)	Likely pathogenic

SpliceAI

3589 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94378177:AACCT:A	donor_loss	1.0000
8:94378178:A:AC	donor_gain	1.0000
8:94378178:A:AG	donor_loss	1.0000
8:94378179:C:CA	donor_loss	1.0000
8:94378179:C:CC	donor_gain	1.0000
8:94378378:TAC:T	acceptor_gain	1.0000
8:94378381:C:CC	acceptor_gain	1.0000
8:94378381:CTAAA:C	acceptor_loss	1.0000
8:94393737:TTATA:T	donor_loss	1.0000
8:94393738:TATA:T	donor_loss	1.0000
8:94393739:ATACC:A	donor_loss	1.0000
8:94393740:TA:T	donor_loss	1.0000
8:94393741:A:AG	donor_loss	1.0000
8:94393742:C:CG	donor_loss	1.0000
8:94400232:TCTTA:T	donor_loss	1.0000
8:94400233:CTTAC:C	donor_loss	1.0000
8:94400234:TTAC:T	donor_loss	1.0000
8:94400235:TACCT:T	donor_loss	1.0000
8:94400236:ACCTG:A	donor_loss	1.0000
8:94400237:C:CG	donor_loss	1.0000
8:94400460:CATT:C	acceptor_gain	1.0000
8:94400464:C:CC	acceptor_gain	1.0000
8:94404241:T:C	acceptor_gain	1.0000
8:94404241:T:TC	acceptor_gain	1.0000
8:94407437:A:AC	donor_gain	1.0000
8:94407438:C:CC	donor_gain	1.0000
8:94407438:CTTGG:C	donor_gain	1.0000
8:94407544:T:A	donor_gain	1.0000
8:94407581:T:TA	donor_gain	1.0000
8:94407582:C:A	donor_gain	1.0000

AlphaMissense

6022 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94400300:A:G	W370R	0.999
8:94400300:A:T	W370R	0.999
8:94399565:A:C	S409R	0.998
8:94399565:A:T	S409R	0.998
8:94399567:T:G	S409R	0.998
8:94380168:A:G	W742R	0.997
8:94380168:A:T	W742R	0.997
8:94380295:C:A	R699S	0.997
8:94380295:C:G	R699S	0.997
8:94399488:C:G	R435P	0.997
8:94400326:A:T	V361D	0.997
8:94378614:T:A	R756S	0.996
8:94378614:T:G	R756S	0.996
8:94378615:C:G	R756T	0.996
8:94380206:A:G	L729P	0.996
8:94380323:A:G	L690P	0.996
8:94378615:C:A	R756I	0.995
8:94380235:A:C	S719R	0.995
8:94380235:A:T	S719R	0.995
8:94380237:T:G	S719R	0.995
8:94380296:C:G	R699T	0.995
8:94399566:C:A	S409I	0.995
8:94400332:A:G	L359P	0.995
8:94380284:A:T	V703D	0.994
8:94391862:A:G	L519P	0.994
8:94399497:T:A	E432V	0.994
8:94399504:A:G	C430R	0.994
8:94399512:A:G	L427P	0.994
8:94400298:C:A	W370C	0.994
8:94400298:C:G	W370C	0.994

dbSNP variants (sampled 300 via entrez): RS1000017168 (8:94466444 G>A), RS1000057469 (8:94419438 G>T), RS1000068116 (8:94466698 C>G,T), RS1000099743 (8:94371851 G>A), RS1000134321 (8:94447936 T>C), RS1000153069 (8:94396719 C>G), RS1000166095 (8:94445578 T>C), RS1000210868 (8:94430080 G>A), RS1000275485 (8:94389264 A>G), RS1000290325 (8:94440915 G>A), RS1000347621 (8:94405124 CTT>C), RS1000381786 (8:94432931 A>G), RS1000382375 (8:94454573 G>T), RS1000388587 (8:94382089 G>A), RS1000410842 (8:94452287 G>T)

Disease associations

OMIM: gene MIM:604289 | disease phenotypes: MIM:114500

GenCC curated gene-disease

Mondo (3): colorectal cancer (MONDO:0005575), non-Hodgkin lymphoma (MONDO:0018908), colon carcinoma (MONDO:0002032)

Orphanet (2): Non-Hodgkin lymphoma (Orphanet:547), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002665	Lymphoma
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004166_49	Nonsyndromic cleft lip with cleft palate	2.000000e-10
GCST90000047_162	Age at first sexual intercourse	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008228	Lymphoma, Non-Hodgkin	C04.557.386.480; C15.604.515.569.480; C20.683.515.761.480

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression	3
bisphenol S	affects methylation, affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	affects cotreatment, increases expression, decreases expression	2
afuresertib	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	decreases expression, increases activity, affects binding	1
4-biphenylamine	decreases expression, decreases reaction	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
sodium arsenite	affects methylation	1
ochratoxin A	decreases acetylation, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KT99	HeLa SilenciX Rad54B	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer