RECQL5

Summary

RECQL5 (RecQ like helicase 5, HGNC:9950) is a protein-coding gene on chromosome 17q25, encoding ATP-dependent DNA helicase Q5 (O94762). DNA helicase that plays an important role in DNA replication, transcription and repair.

The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9400 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coronary artery disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 281 total
• MANE Select transcript: NM_004259

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9950
Approved symbol	RECQL5
Name	RecQ like helicase 5
Location	17q25
Locus type	gene with protein product
Status	Approved
Aliases	RecQ5, FLJ90603
Ensembl gene	ENSG00000108469
Ensembl biotype	protein_coding
OMIM	603781
Entrez	9400

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 18 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000317905, ENST00000340830, ENST00000420326, ENST00000423245, ENST00000443199, ENST00000578201, ENST00000578865, ENST00000579265, ENST00000579274, ENST00000579739, ENST00000580078, ENST00000580707, ENST00000581825, ENST00000581827, ENST00000582464, ENST00000582548, ENST00000583673, ENST00000584999, ENST00000585205, ENST00000910739, ENST00000910740, ENST00000910741, ENST00000919294, ENST00000919295, ENST00000919296, ENST00000941132, ENST00000941133

RefSeq mRNA: 3 — MANE Select: NM_004259 NM_001003715, NM_001003716, NM_004259

CCDS: CCDS32735, CCDS42380, CCDS45777

Canonical transcript exons

ENST00000317905 — 20 exons

Exon	Start	End
ENSE00000744463	75660955	75661066
ENSE00000744466	75661606	75661708
ENSE00000744469	75662479	75662997
ENSE00000744471	75665051	75665172
ENSE00001325232	75626854	75627522
ENSE00001368387	75666428	75666571
ENSE00002312029	75651186	75651265
ENSE00003466316	75628218	75628442
ENSE00003482739	75630779	75630837
ENSE00003542084	75631150	75631249
ENSE00003567565	75631450	75631668
ENSE00003581246	75628934	75629475
ENSE00003581511	75629708	75629842
ENSE00003589385	75630184	75630277
ENSE00003602514	75630974	75631010
ENSE00003604259	75630619	75630692
ENSE00003641159	75627623	75627692
ENSE00003672679	75628672	75628762
ENSE00003674196	75658298	75658460
ENSE00003844989	75667044	75667154

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8043 / max 128.7205, expressed in 1792 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168087	7.6644	1741
168086	5.8971	1648
168085	0.1648	99
168084	0.0779	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.66	gold quality
right lobe of thyroid gland	UBERON:0001119	97.92	gold quality
right uterine tube	UBERON:0001302	97.74	gold quality
left lobe of thyroid gland	UBERON:0001120	97.53	gold quality
metanephros cortex	UBERON:0010533	97.32	gold quality
thyroid gland	UBERON:0002046	96.27	gold quality
esophagus mucosa	UBERON:0002469	95.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.88	gold quality
left testis	UBERON:0004533	94.87	gold quality
adenohypophysis	UBERON:0002196	94.85	gold quality
right testis	UBERON:0004534	94.82	gold quality
sural nerve	UBERON:0015488	94.05	gold quality
pituitary gland	UBERON:0000007	93.66	gold quality
skin of abdomen	UBERON:0001416	93.49	gold quality
body of stomach	UBERON:0001161	93.44	gold quality
skin of leg	UBERON:0001511	93.38	gold quality
mucosa of transverse colon	UBERON:0004991	93.17	gold quality
transverse colon	UBERON:0001157	93.12	gold quality
right lobe of liver	UBERON:0001114	93.04	gold quality
minor salivary gland	UBERON:0001830	92.91	gold quality
left ovary	UBERON:0002119	92.86	gold quality
gall bladder	UBERON:0002110	92.80	gold quality
small intestine	UBERON:0002108	92.78	gold quality
right ovary	UBERON:0002118	92.56	gold quality
apex of heart	UBERON:0002098	92.13	gold quality
granulocyte	CL:0000094	92.08	gold quality
spleen	UBERON:0002106	92.03	gold quality
testis	UBERON:0000473	91.86	gold quality
ectocervix	UBERON:0012249	91.65	gold quality
esophagus	UBERON:0001043	91.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33
E-ENAD-17	no	140.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting RECQL5, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-631	97.05	66.93	602
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-541-3P	96.07	66.11	1271

Literature-anchored findings (GeneRIF, showing 40)

• RECQ5 is a protein with DNA helicase and strand-annealing activities in a single polypeptide. (PMID:15241474)
• RECQ5beta promotes strand exchange between arms of synthetic forked DNA structures resembling a stalled replication fork in a reaction dependent on ATP hydrolysis. (PMID:17003056)
• RECQL5 binds the Rad51 recombinase and inhibits Rad51-mediated D-loop formation. (PMID:18003859)
• The novel intramolecular modulation of RECQ5beta catalytic activity mediated by the zinc-binding motif may represent a universal regulation mode for all RecQ family helicases. (PMID:18290761)
• RecQ5beta has suppressive roles in events associated with RNAP II-dependent transcription (PMID:18419580)
• RECQ5 appears to be the only member of the human RECQ family of helicases that associates with RNAPII. (PMID:18562274)
• RECQL5 inhibits reconstituted, promoter-driven RNAPII transcription in a dose-dependent manner. (PMID:19570979)
• RECQL5beta dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. (PMID:20081208)
• Data suggest that RecQL5 promotes genome stabilization by participation in homologous recombination-dependent DNA repair as a RecQ helicase and by regulating the initiation of Pol II to reduce replication impairment and recombination. (PMID:20231364)
• Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity. (PMID:20348101)
• propose that RECQL5 stabilises the replication fork allowing replication to overcome the effects of thymidine and complete the cell cycle (PMID:20643585)
• RECQL5 as a major determinant for camptothecin resistance in colorectal cancer cells. (PMID:21210765)
• study provides novel insights into a mechanism by which RECQ5 regulates the transcription machinery via its dynamic interaction with RNAPII, thereby preventing genome instability (PMID:21402780)
• the recruitment of RECQL5 to laser-induced DSB sites is independent of functional activities of its interacting partners, MRE11 and RNA polymerase II. (PMID:22633600)
• Data indicate taht BRC repeat is a common RAD51 recombinase interaction module that can either promote homologous recombination (HR), as in the case of BRCA2, or to suppress HR, as in RECQL5 helicase. (PMID:22645136)
• RECQL5 modulates and/or directly participates in base excision repair of endogenous DNA damage. (PMID:22973052)
• The study provides insight into the recruitment and retention dynamics of RECQL5 at DNA double-strand breaks sites and its functional interplay with BLM protein and Werner syndrome protein. (PMID:23180761)
• This article reviews the established roles of RECQL5 at the cross roads of DNA replication, recombination and transcription, and propose that human RECQL5 provides important backup functions in the absence of other DNA helicases.[review] (PMID:23627586)
• RECQL5 contacts the Rpb1 jaw domain of Pol II at a site that overlaps with the binding site for the transcription elongation factor TFIIS. Binding of RECQL5 to Pol II interferes with the ability of TFIIS to promote transcriptional read-through in vitro. (PMID:23748380)
• The present study indicated that RECQL5 genetic polymorphism and haplotypes were associated with larynx cancer in a Chinese population. (PMID:24213927)
• RECQL5 genetic polymorphisms were associated with osteosarcoma in a Chinese population. (PMID:24287950)
• The findings suggest that RECQ5 acts during the post-synaptic phase of synthesis-dependent strand annealing to prevent formation of aberrant RAD51 filaments on the extended invading strand, thus limiting its channeling into potentially hazardous crossover pathway of homologous recombination. (PMID:24319145)
• The data presented here provide evidence that RECQL5 plays a general role in the control of transcript elongation in human cells. In its absence, transcript elongation rates increase, the distribution profile of RNAPII is markedly altered across the genome, and higher levels of RNAPII pausing or arrest (i.e., transcription stress) are detected. (PMID:24836610)
• The present study indicated that the RECQL5 genetic polymorphism and haplotypes were associated with breast cancer in a Chinese population. (PMID:25394896)
• RecQ5 prevents transcription associated genome instability by facilitating PIAS1-SRSF1 ligase complex sumoylation of DNA topoisomerase 1. (PMID:25851487)
• The RECQL5 genetic polymorphism was associated with osteosarcoma in a Chinese population. (PMID:25867335)
• PARylation is involved in the recruitment of RECQL5 and WRN to laser-induced DNA damage and RECQL5 and WRN have differential responses to PARylated PARP1 and Poly(ADP-ribose). (PMID:26391948)
• results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment (PMID:26499077)
• Expression of RECQL5 in breast cancer can drive proliferation supporting an oncogenic function for RECQL5 in breast cancer. RECQL5 is a promising biomarker in breast cancer. (PMID:26586793)
• RECQL5 is a critical regulator of genome stability in myeloproliferative neoplasms and demonstrate that replication stress-associated cytotoxicity can be amplified specifically in JAK2V617F mutant cells through RECQL5-targeted synthetic lethality. (PMID:26686625)
• RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins (PMID:26717024)
• mutation associated with early myocardial infarction (PMID:26844521)
• Study characterized the G-quadruplex (GQ) unfolding activity of RECQ5 for different DNA constructs under different salt conditions, showed that RECQ5 is overall a weak GQ destabilizer compared to Bloom and Werner (PMID:27332117)
• interaction between RECQ5 and proliferating cell nuclear antigen (PCNA) promotes RAD18-dependent PCNA ubiquitination and the helicase activity of RECQ5 promotes the processing of replication intermediates. (PMID:27502483)
• we have shown that increased expression of RECQL5 protein occurs and is likely to contribute to tumourigenesis in UCC and that the pharmacological targeting of the helicase activity of RECQL5 is a strong target for future small molecule inhibitor development. (PMID:27764811)
• the open and closed forms of RECQL5 were used together with a quantitative comparison of all current RecQ family structures to construct a mechanistic model for RECQL5 helicase activity (PMID:28100692)
• RECQ5 removes RAD51 filaments stabilizing stalled replication forks at common fragile sites and hence facilitates CFS cleavage by MUS81-EME1. (PMID:28575661)
• It has been shown that conjugation of SUMO2, but not SUMO1 or SUMO3, to the essential replication factor PCNA is induced on transcribed chromatin by the RNAPII-bound helicase RECQ5. (PMID:30006506)
• increased RECQ5 levels stimulated ‘alternative’ HDR by single-stranded DNA donors, which is normally suppressed by RAD51; this was accompanied by stimulation of mutagenic end-joining. These results suggest that in some tumors, RECQ5 gene amplification may have profound consequences for genomic instability (PMID:30107528)
• These results prompt us to propose RECQL5 as a gene that would be worth to analyze in larger studies to explore its possible implication in BC susceptibility. (PMID:30817846)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	recql5	ENSDARG00000059556
mus_musculus	Recql5	ENSMUSG00000020752
rattus_norvegicus	Recql5	ENSRNOG00000005107
drosophila_melanogaster	RecQ5	FBGN0027375
caenorhabditis_elegans		WBGENE00004322

Paralogs (4): RECQL (ENSG00000004700), RECQL4 (ENSG00000160957), WRN (ENSG00000165392), BLM (ENSG00000197299)

Protein

Protein identifiers

ATP-dependent DNA helicase Q5 — O94762 (reviewed: O94762)

Alternative names: DNA 3’-5’ helicase RecQ5, DNA helicase, RecQ-like type 5, RecQ protein-like 5

All UniProt accessions (7): O94762, J3KRM6, J3KS37, J3KSL7, J3KSV9, J3KTQ2, J3QLU0

UniProt curated annotations — full annotation on UniProt →

Function. DNA helicase that plays an important role in DNA replication, transcription and repair. Probably unwinds DNA in a 3’-5’ direction. Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability. Also associates with POLR1A and enforces the stability of ribosomal DNA arrays. Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress. Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis. Required for efficient DNA repair, including repair of inter-strand cross-links. Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. A core helicase fragment (residues 11-609) binds preferentially to splayed duplex, looped and ssDNA.

Subunit / interactions. Monomer. Interacts with TOP2A, TOP3A and TOP3B. Isoform beta interacts with RNA polymerase II subunit POLR2A. Identified in a complex with the RNA polymerase II core bound to DNA. Interacts (via C-terminus) with POLR1A. Isoform beta interacts with RAD51. Interacts with WRN; this interaction stimulates WRN helicase activity on DNA fork duplexes. Interacts with MUS1; this interaction promotes MUS81-dependent mitotic DNA synthesis.

Subcellular location. Nucleus. Nucleoplasm. Nucleus Cytoplasm Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by CDK1 at Ser-727; this phosphorylation is required for RECQL5-mediated disruption of RAD51 filaments on stalled replication forks.

Cofactor. Binds a Zn(2+) ion per subunit.

Domain organisation. The alpha-helix immediately C-terminal to the Zn(2+)-binding site (residues 438-453, characterized in C-terminally truncated contructs) is required for helicase activity, is positively charged, and may play a role in DNA-binding and choice of substrates.

Similarity. Belongs to the helicase family. RecQ subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O94762-1	Beta	yes
O94762-2	Alpha, RecQ5b
O94762-3	Gamma, RecQ5a
O94762-4	4

RefSeq proteins (3): NP_001003715, NP_001003716, NP_004250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR004589	DNA_helicase_ATP-dep_RecQ	Family
IPR010716	RECQ5	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR013257	SRI	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032284	RecQ_Zn-bd	Domain

Pfam: PF00270, PF00271, PF06959, PF08236, PF16124

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (107 total): helix 25, mutagenesis site 19, strand 19, binding site 14, turn 6, region of interest 6, modified residue 5, splice variant 4, compositionally biased region 3, domain 2, sequence variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
5LB3	X-RAY DIFFRACTION	1.8
4BK0	X-RAY DIFFRACTION	1.9
5LB5	X-RAY DIFFRACTION	2
9HVQ	ELECTRON MICROSCOPY	2
7ZMV	X-RAY DIFFRACTION	2
7ZMT	X-RAY DIFFRACTION	2.3
5LBA	X-RAY DIFFRACTION	2.5
7ZMM	X-RAY DIFFRACTION	2.5
7ZMQ	X-RAY DIFFRACTION	2.7
7ZMS	X-RAY DIFFRACTION	2.7
7ZML	X-RAY DIFFRACTION	2.79
9EI2	ELECTRON MICROSCOPY	2.8
9HVO	ELECTRON MICROSCOPY	2.8
8RLA	ELECTRON MICROSCOPY	3.03
8RL6	ELECTRON MICROSCOPY	3.18
7ZMN	X-RAY DIFFRACTION	3.2
9EI1	ELECTRON MICROSCOPY	3.2
9EI3	ELECTRON MICROSCOPY	3.2
8RL9	ELECTRON MICROSCOPY	3.22
7ZMR	X-RAY DIFFRACTION	3.3
5LB8	X-RAY DIFFRACTION	3.4
9HWG	ELECTRON MICROSCOPY	3.5
7ZMP	X-RAY DIFFRACTION	3.63
9EI4	ELECTRON MICROSCOPY	3.7
7ZMO	X-RAY DIFFRACTION	3.75
8RL5	ELECTRON MICROSCOPY	3.79
8QQ2	ELECTRON MICROSCOPY	4.2
8QW9	ELECTRON MICROSCOPY	4.3
8QW8	ELECTRON MICROSCOPY	7.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94762-F1	70.91	0.40

Antibody-complex structures (SAbDab): 13 — 7ZML, 7ZMM, 7ZMN, 7ZMO, 7ZMP, 7ZMQ, 7ZMR, 7ZMS, 7ZMT, 7ZMV, 8RL5, 8RL9, 8RLA

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 (14): 26; 28; 30; 34; 53; 55; 56; 57; 58; 59; 411; 427 …

Post-translational modifications (5): 488, 491, 727, 815, 839

Mutagenesis-validated functional residues (19):

Position	Phenotype
157	abolishes helicase activity.
165	loss of helicase activity, reduced dna-binding (in a residue 11-526 fragment).
167	loss of helicase activity, reduced dna-binding (in a residue 11-526 fragment).
345	loss of helicase activity, reduced dna-binding (in a residue 11-526 fragment).
352	loss of helicase activity (in a residue 11-526 fragment).
504	abolishes interaction with polr2a.
508	abolishes interaction with polr2a.
515	abolishes interaction with polr2a.
516	abolishes interaction with polr2a.
550	impairs protein folding and abolishes interaction with polr2a.
552	abolishes interaction with polr2a.
556	abolishes interaction with polr2a.
584	abolishes interaction with polr2a.
597	reduces interaction with polr2a.
598	abolishes interaction with polr2a.
602	abolishes interaction with polr2a.
603	abolishes interaction with polr2a.
666	abolishes interaction with rad51.
727	loss of phosphorylation in early mitosis.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_CHROMOSOME_SEPARATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, KAUFFMANN_DNA_REPAIR_GENES, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_DNA_REPAIR, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, MODULE_118, GOBP_RESPONSE_TO_ALKALOID, MODULE_379

GO Biological Process (18): mitotic cell cycle (GO:0000278), double-strand break repair via homologous recombination (GO:0000724), DNA metabolic process (GO:0006259), DNA replication (GO:0006260), DNA repair (GO:0006281), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), cell division (GO:0051301), chromosome separation (GO:0051304), cellular response to xenobiotic stimulus (GO:0071466), cellular response to camptothecin (GO:0072757), replication-born double-strand break repair via sister chromatid exchange (GO:1990414), mitotic DNA-templated DNA replication (GO:1990506), negative regulation of double-strand break repair via homologous recombination (GO:2000042), DNA recombination (GO:0006310), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974), negative regulation of macromolecule metabolic process (GO:0010605), negative regulation of nucleobase-containing compound metabolic process (GO:0045934)

GO Molecular Function (17): RNA polymerase II complex binding (GO:0000993), DNA binding (GO:0003677), DNA helicase activity (GO:0003678), helicase activity (GO:0004386), ATP binding (GO:0005524), four-way junction helicase activity (GO:0009378), ATP hydrolysis activity (GO:0016887), identical protein binding (GO:0042802), 3’-5’ DNA helicase activity (GO:0043138), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853), catalytic activity, acting on DNA (GO:0140097), catalytic activity, acting on a nucleic acid (GO:0140640)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), chromosome (GO:0005694), cytoplasm (GO:0005737), cytosol (GO:0005829), transcription preinitiation complex (GO:0097550)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	3
catalytic activity	3
double-strand break repair via homologous recombination	2
negative regulation of metabolic process	2
catalytic activity, acting on a nucleic acid	2
ATP-dependent activity	2
DNA helicase activity	2
binding	2
cell cycle	1
mitotic nuclear division	1
recombinational repair	1
double-strand break repair	1
nucleic acid metabolic process	1
DNA biosynthetic process	1
DNA damage response	1
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
cellular process	1
chromosome segregation	1
cell cycle process	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
cellular response to alkaloid	1
cellular response to alcohol	1
response to camptothecin	1
mitotic DNA replication	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1
nucleobase-containing compound metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
RNA polymerase core enzyme binding	1

Protein interactions and networks

STRING

1766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RECQL5	TOP3A	Q13472	835
RECQL5	FEN1	P39748	823
RECQL5	FBH1	Q8NFZ0	823
RECQL5	RAD51	Q06609	819
RECQL5	DNA2	P51530	807
RECQL5	FANCM	Q8IYD8	733
RECQL5	RTEL1	Q9NZ71	731
RECQL5	MUS81	Q96NY9	728
RECQL5	EXO1	Q9UQ84	723
RECQL5	RAD52	P43351	705
RECQL5	BRIP1	Q9BX63	695
RECQL5	SLX4	Q8IY92	691
RECQL5	RMI1	Q9H9A7	687
RECQL5	RPAP2	Q8IXW5	665
RECQL5	XRCC6	P12956	657

IntAct

90 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
POLR2G	RECQL5	psi-mi:“MI:0914”(association)	0.730
RPRD1B	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	RECQL5	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
PIN1	POLR2D	psi-mi:“MI:0914”(association)	0.640
DXO	RECQL5	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530

BioGRID (185): RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS), DHX36 (Co-fractionation), EIF2D (Co-fractionation), RECQL5 (Co-fractionation), RECQL5 (Co-fractionation), RECQL5 (Synthetic Growth Defect), RECQL5 (Proximity Label-MS), RECQL5 (Proximity Label-MS), RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS), RECQL5 (Affinity Capture-MS)

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: A2XVF7, A3AVH5, A4RK80, A8WK63, D4ACP5, G2TRN7, O09053, O18017, O34748, O88700, O93530, O94761, O94762, P0CQ88, P0CQ89, P15043, P35187, P40724, P46063, P50729, P54132, P71359, P73421, Q09811, Q0WVW7, Q14191, Q19546, Q5RF63, Q5UPX0, Q6AYJ1, Q75NR7, Q7RZH4, Q8L840, Q8VID5, Q9CL21, Q9DEY9, Q9FT70, Q9FT72, Q9FT73, Q9FT74

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FGFR2 mutant receptor activation	8	93.7×	2e-12
Signaling by FGFR2 IIIa TM	8	74.0×	3e-12
Abortive elongation of HIV-1 transcript in the absence of Tat	8	61.1×	1e-11
FGFR2 alternative splicing	9	58.6×	2e-12
Signaling by FGFR2	9	56.5×	2e-12
Signaling by FGFR in disease	8	52.1×	5e-11
MicroRNA (miRNA) biogenesis	7	49.2×	2e-09
RNA Polymerase III Chain Elongation	5	48.8×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	5	19.3×	2e-03
RNA polymerase II preinitiation complex assembly	5	17.4×	2e-03
transcription by RNA polymerase II	8	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	177
Likely benign	52
Benign	29

Top pathogenic / likely-pathogenic (0)

SpliceAI

4483 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75628214:CTAC:C	donor_loss	1.0000
17:75628215:TAC:T	donor_loss	1.0000
17:75628216:ACC:A	donor_loss	1.0000
17:75628217:C:A	donor_loss	1.0000
17:75628237:T:TA	donor_gain	1.0000
17:75628262:TGACC:T	donor_gain	1.0000
17:75628282:T:TA	donor_gain	1.0000
17:75629744:A:AC	donor_gain	1.0000
17:75630157:C:A	donor_gain	1.0000
17:75630179:CCCA:C	donor_loss	1.0000
17:75630181:CA:C	donor_loss	1.0000
17:75630182:A:C	donor_loss	1.0000
17:75630183:C:T	donor_loss	1.0000
17:75630183:CCTT:C	donor_gain	1.0000
17:75630186:T:A	donor_gain	1.0000
17:75630273:CAGCT:C	acceptor_gain	1.0000
17:75630274:AGCT:A	acceptor_gain	1.0000
17:75630275:GCT:G	acceptor_gain	1.0000
17:75630276:CT:C	acceptor_gain	1.0000
17:75630276:CTC:C	acceptor_gain	1.0000
17:75630276:CTCTG:C	acceptor_loss	1.0000
17:75630277:TCT:T	acceptor_gain	1.0000
17:75630278:C:A	acceptor_gain	1.0000
17:75630278:C:CC	acceptor_gain	1.0000
17:75630280:G:C	acceptor_gain	1.0000
17:75630284:G:C	acceptor_gain	1.0000
17:75630284:G:GC	acceptor_gain	1.0000
17:75630287:C:CT	acceptor_gain	1.0000
17:75630617:A:AC	donor_gain	1.0000
17:75630618:C:CC	donor_gain	1.0000

AlphaMissense

6470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75660987:A:C	S318R	1.000
17:75660987:A:T	S318R	1.000
17:75660989:T:G	S318R	1.000
17:75658412:C:A	Q345H	0.999
17:75658412:C:G	Q345H	0.999
17:75660982:C:T	G320E	0.999
17:75660984:A:C	F319L	0.999
17:75660984:A:T	F319L	0.999
17:75660986:A:G	F319L	0.999
17:75660997:G:T	A315E	0.999
17:75662743:A:C	F169L	0.999
17:75662743:A:T	F169L	0.999
17:75662745:A:G	F169L	0.999
17:75662757:A:G	W165R	0.999
17:75662757:A:T	W165R	0.999
17:75658455:A:T	V331D	0.998
17:75660958:A:T	V328D	0.998
17:75660979:A:G	M321T	0.998
17:75660998:C:G	A315P	0.998
17:75661028:A:G	W305R	0.998
17:75661028:A:T	W305R	0.998
17:75661047:T:A	R298S	0.998
17:75661047:T:G	R298S	0.998
17:75661615:A:C	Y289D	0.998
17:75661664:A:C	C272W	0.998
17:75662755:C:A	W165C	0.998
17:75662755:C:G	W165C	0.998
17:75662777:T:A	E158V	0.998
17:75658370:G:C	C359W	0.997
17:75658392:C:A	R352M	0.997

dbSNP variants (sampled 300 via entrez): RS1000031005 (17:75658176 A>G,T), RS1000045499 (17:75632266 G>A), RS1000059605 (17:75635014 C>T), RS1000127169 (17:75627935 C>T), RS1000140249 (17:75646101 C>A), RS1000225625 (17:75664688 G>A), RS1000276971 (17:75630003 G>T), RS1000278223 (17:75667385 A>T), RS1000309258 (17:75667610 G>T), RS1000333509 (17:75640066 T>C), RS1000612496 (17:75668682 T>C), RS1000645018 (17:75668999 T>C), RS1000649609 (17:75631387 C>T), RS1000725901 (17:75667867 G>T), RS1000740986 (17:75644486 G>C)

Disease associations

OMIM: gene MIM:603781 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
coronary artery disorder	Limited	Autosomal recessive
breast cancer	Limited	Autosomal dominant

Mondo (3): myoepithelial tumor (MONDO:0002380), coronary artery disorder (MONDO:0005010), breast cancer (MONDO:0007254)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010396_229	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-06
GCST010726_68	Periventricular white matter hyperintensities	2.000000e-07
GCST010727_39	Deep white matter hyperintensities	2.000000e-07
GCST90000025_620	Appendicular lean mass	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003324	Coronary Artery Disease	C14.280.647.250.260; C14.907.137.126.339; C14.907.585.250.260
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Tobacco Smoke Pollution	decreases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	increases expression	1
Decitabine	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Leflunomide	decreases expression	1
Caffeine	decreases phosphorylation	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Ethinyl Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
Selenium	increases expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00025766	PHASE4	COMPLETED	Angioplasty and Heart Stents to Treat Individuals With an Occluded Artery Following a Heart Attack
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00111566	PHASE4	COMPLETED	BRIEF-PCI: Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention
NCT00129038	PHASE4	COMPLETED	Modified-release Dipyridamole/Aspirin (200mg/25mg bd) Versus Aspirin (75mg) in Aspirin-resistant Patients
NCT00133003	PHASE4	COMPLETED	Abciximab, Clopidogrel and Percutaneous Coronary Intervention in Acute Coronary Syndrome (ISAR-REACT-2)
NCT00133237	PHASE4	COMPLETED	Drug-eluting-stents for Unprotected Left Main Stem Disease (ISAR-LEFT-MAIN)
NCT00133692	PHASE4	COMPLETED	INVEST: INternational VErapamil SR Trandolapril STudy
NCT00139386	PHASE4	COMPLETED	Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
NCT00140465	PHASE4	COMPLETED	75 or 150 mg Clopidogrel Maintenance Doses Following PCI (ISAR-CHOICE-2)
NCT00140530	PHASE4	COMPLETED	Nonpolymer- and Polymer-Based Drug-Eluting Stents for Restenosis (ISAR-TEST-1)
NCT00146575	PHASE4	COMPLETED	Sirolimus- and Paclitaxel-Eluting Stents for Small Vessels (ISAR-SMART-3)
NCT00152308	PHASE4	TERMINATED	Non-Polymer-Based, Rapamycin-Eluting Stents to Prevent Restenosis
NCT00155350	PHASE4	UNKNOWN	Treatment of Coronary Atherosclerosis by Insulin Sensitizers in Insulin-Resistant Patients
NCT00162370	PHASE4	COMPLETED	A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease
NCT00163202	PHASE4	COMPLETED	Comparative Atorvastatin Pleiotropic Effects
NCT00169819	PHASE4	COMPLETED	EArly Discharge After Transradial Stenting of CoronarY Arteries: The EASY Study
NCT00171275	PHASE4	COMPLETED	Fluvastatin in the Therapy of Acute Coronary Syndrome
NCT00175240	PHASE4	COMPLETED	Enhancing the Secondary Prevention of Coronary Artery Disease
NCT00180388	PHASE4	TERMINATED	VENEK: Healing in Different Vein Harvesting Methods During Aortocoronary Coronary Artery Bypass Graft Surgery (CABG)
NCT00180583	PHASE4	COMPLETED	Vision II: Evaluation of GALILEO Intravascular Radiotherapy System
NCT00189215	PHASE4	COMPLETED	Long-Term Cognitive Decline After Coronary Artery Bypass Grafting: is Off-Pump Surgery Beneficial?
NCT00200629	PHASE4	TERMINATED	Both Exercise and Adenosine Stress Testing
NCT00202904	PHASE4	COMPLETED	Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)
NCT00209404	PHASE4	COMPLETED	Iodixanol in Multidetector-Row Computed Tomography-Coronary Angiography (MDCT-CA)
NCT00209430	PHASE4	COMPLETED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Coronary Angiography
NCT00220558	PHASE4	UNKNOWN	GISSOC II: Sirolimus Eluting Stent Versus Bare Metal Stent in Chronic Total Coronary Occlusions
NCT00222261	PHASE4	COMPLETED	Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
NCT00229528	PHASE4	COMPLETED	Effect of Paroxetine on COAT-Platelet Production in Normal Volunteers and Patients With Cardiovascular Disease
NCT00232804	PHASE4	COMPLETED	The BRIDGE Registry: Safety and Efficacy Registry of Bx Cypher Stent
NCT00232856	PHASE4	COMPLETED	A Study of the Cypher SES to Treat Restenotic Native Coronary Artery Lesions.
NCT00235066	PHASE4	COMPLETED	The CYPHER™ Stent Study in Patients With Small de Novo Coronary Artery Lesions.
NCT00235092	PHASE4	COMPLETED	The REALITY Study - Head-to-Head Comparison Between Cypher and Taxus
NCT00235950	PHASE4	COMPLETED	Assessment of the Lipid Lowering Effect of Rosuvastatin Compared to Atorvastatin in Subjects With Coronary Heart Disease
NCT00238004	PHASE4	UNKNOWN	The Low HDL On Six Weeks Statin Therapy (LOW) Study
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00242944	PHASE4	COMPLETED	Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)
NCT00243477	PHASE4	COMPLETED	MOTIV Study- Effect of Antidepressive Treatment by Escitalopram in Patients Undergoing Coronary Artery Bypass Grafting
NCT00244530	PHASE4	COMPLETED	Prophylactic Effect of Nifedipine on Further Decline in Renal Function in Patients Undergoing Open-Heart Surgery
NCT00245401	PHASE4	COMPLETED	CYPHERTM Stent Post-Marketing Surveillance Registry (US-PMS)