RECQL

Summary

RECQL (RecQ like helicase, HGNC:9948) is a protein-coding gene on chromosome 12p12.1, encoding ATP-dependent DNA helicase Q1 (P46063). DNA helicase that plays a role in DNA damage repair and genome stability.

The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer.

Source: NCBI Gene 5965 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RECON progeroid syndrome (Moderate, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,596 total — 10 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 37 tissues, sQTL in 15 (q < 0.05)
• Phenotypes (HPO): 38
• ChEMBL bioactivity: 115 clinical-phase molecules tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.24 (unconstrained)
• MANE Select transcript: NM_002907
• Notable: 1,596 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9948
Approved symbol	RECQL
Name	RecQ like helicase
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	RecQ1, RecQL1
Ensembl gene	ENSG00000004700
Ensembl biotype	protein_coding
OMIM	600537
Entrez	5965

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 5 nonsense_mediated_decay

MANE Select: ENST00000444129

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 2, TSL 4: 1, TSL 5: 3

ENST00000444129, ENST00000314748, ENST00000396093, ENST00000421138, ENST00000536240, ENST00000536964, ENST00000539672, ENST00000542432, ENST00000887707, ENST00000887708, ENST00000887709, ENST00000887710, ENST00000965021, ENST00000965022, ENST00000965023, ENST00000965024, ENST00000988862, ENST00000988863, ENST00001030934, ENST00001030936, ENST00001081911, ENST00001106701, ENST00001114731, ENST00001143116

RefSeq mRNA: 2 — MANE Select: NM_002907 NM_002907, NM_032941

CCDS: CCDS31756

Canonical transcript exons

ENST00000444129 — 15 exons

Exon	Start	End
ENSE00000822265	21491519	21491716
ENSE00001233896	21499555	21499615
ENSE00001349501	21468910	21470346
ENSE00001373746	21501170	21501635
ENSE00001616825	21475676	21475824
ENSE00001626384	21486479	21486585
ENSE00001641465	21473551	21473642
ENSE00001652439	21483376	21483574
ENSE00001663080	21476911	21476992
ENSE00001739619	21471428	21471647
ENSE00001743716	21477803	21477969
ENSE00001756630	21475468	21475585
ENSE00001760414	21474841	21474979
ENSE00001777089	21470969	21471098
ENSE00003789652	21490199	21490378

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.8685 / max 620.4743, expressed in 1796 samples.

Highest expression (Bgee): buccal mucosa cell, tibia, calcaneal tendon, parietal pleura, pleura.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RECQL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 52 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	2.5e-26	+0.80	12:21501473:G:A
Cells EBV-transformed lymphocytes	sqtl	1.4e-22	+1.02	12:21501897:G:T
Skin Sun Exposed Lower leg	eqtl	1.2e-20	+0.26	12:21501473:G:A
Spleen	eqtl	4.8e-18	+0.38	12:21501473:G:A
Adipose Subcutaneous	eqtl	4.5e-16	+0.25	12:21501473:G:A
Brain Cerebellar Hemisphere	sqtl	6.1e-16	-2.06	12:21437069:C:T
Skin Not Sun Exposed Suprapubic	eqtl	9.1e-16	+0.27	12:21501473:G:A
Nerve Tibial	eqtl	1.5e-14	+0.21	12:21501897:G:T
Adipose Subcutaneous	sqtl	2.1e-14	-0.60	12:21501473:G:A
Colon Transverse	eqtl	1.5e-11	+0.20	12:21501473:G:A
Lung	eqtl	4.1e-11	+0.23	12:21456346:C:A
Testis	sqtl	4.4e-11	-1.87	12:21437069:C:T
Stomach	eqtl	3.5e-10	+0.27	12:21501897:G:T
Artery Tibial	eqtl	4.1e-09	+0.18	12:21494403:T:C
Esophagus Gastroesophageal Junction	eqtl	7.7e-09	+0.18	12:21501897:G:T
Adipose Visceral Omentum	eqtl	1.1e-08	+0.20	12:21501473:G:A
Artery Aorta	eqtl	1.4e-08	+0.17	12:21450943:G:A
Nerve Tibial	sqtl	1.8e-08	-0.51	12:21501473:G:A
Artery Tibial	sqtl	5.2e-08	-0.47	12:21501897:G:T
Brain Cerebellum	sqtl	1.5e-07	-1.69	12:21437069:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130026	23.1557	1786
130024	5.5264	1518
130025	1.1864	724

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.76	gold quality
tibia	UBERON:0000979	97.21	gold quality
calcaneal tendon	UBERON:0003701	96.65	gold quality
parietal pleura	UBERON:0002400	96.40	gold quality
pleura	UBERON:0000977	96.12	gold quality
visceral pleura	UBERON:0002401	96.05	gold quality
superficial temporal artery	UBERON:0001614	95.70	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.32	gold quality
tendon	UBERON:0000043	94.29	gold quality
esophagus squamous epithelium	UBERON:0006920	93.96	gold quality
synovial joint	UBERON:0002217	93.85	gold quality
oral cavity	UBERON:0000167	93.73	gold quality
skin of hip	UBERON:0001554	93.68	gold quality
hair follicle	UBERON:0002073	93.16	gold quality
cauda epididymis	UBERON:0004360	92.32	gold quality
layer of synovial tissue	UBERON:0007616	92.30	gold quality
trabecular bone tissue	UBERON:0002483	92.19	gold quality
stromal cell of endometrium	CL:0002255	92.14	gold quality
lymph node	UBERON:0000029	92.02	gold quality
vermiform appendix	UBERON:0001154	91.91	gold quality
cartilage tissue	UBERON:0002418	91.64	gold quality
blood vessel layer	UBERON:0004797	91.23	gold quality
monocyte	CL:0000576	91.11	gold quality
endometrium	UBERON:0001295	91.11	gold quality
mononuclear cell	CL:0000842	91.07	gold quality
leukocyte	CL:0000738	90.97	gold quality
smooth muscle tissue	UBERON:0001135	90.94	gold quality
palpebral conjunctiva	UBERON:0001812	90.93	gold quality
epithelium of esophagus	UBERON:0001976	90.86	gold quality
upper leg skin	UBERON:0004262	90.86	gold quality
germinal epithelium of ovary	UBERON:0001304	90.77	gold quality
corpus epididymis	UBERON:0004359	90.65	gold quality
penis	UBERON:0000989	90.50	gold quality
secondary oocyte	CL:0000655	90.46	gold quality
decidua	UBERON:0002450	90.46	gold quality
caput epididymis	UBERON:0004358	90.46	gold quality
amniotic fluid	UBERON:0000173	90.43	gold quality
islet of Langerhans	UBERON:0000006	90.41	gold quality
epithelium of nasopharynx	UBERON:0001951	90.33	gold quality
caecum	UBERON:0001153	90.29	gold quality
pericardium	UBERON:0002407	90.24	gold quality
descending thoracic aorta	UBERON:0002345	89.94	gold quality
ventricular zone	UBERON:0003053	89.85	gold quality
lower lobe of lung	UBERON:0008949	89.48	gold quality
jejunal mucosa	UBERON:0000399	89.43	gold quality
mammary duct	UBERON:0001765	89.35	gold quality
epithelium of mammary gland	UBERON:0003244	89.33	gold quality
thoracic aorta	UBERON:0001515	89.28	gold quality
tendon of biceps brachii	UBERON:0008188	89.14	gold quality
ascending aorta	UBERON:0001496	89.13	gold quality
urethra	UBERON:0000057	89.07	gold quality
gall bladder	UBERON:0002110	89.05	gold quality
aorta	UBERON:0000947	88.95	gold quality
seminal vesicle	UBERON:0000998	88.93	gold quality
mammalian vulva	UBERON:0000997	88.91	gold quality
mammary gland	UBERON:0001911	88.88	gold quality
thoracic mammary gland	UBERON:0005200	88.88	gold quality
periodontal ligament	UBERON:0008266	88.86	gold quality
connective tissue	UBERON:0002384	88.74	gold quality
squamous epithelium	UBERON:0006914	88.69	gold quality
popliteal artery	UBERON:0002250	88.67	gold quality
tibial artery	UBERON:0007610	88.66	gold quality
adipose tissue	UBERON:0001013	88.51	gold quality
left coronary artery	UBERON:0001626	88.51	gold quality
coronary artery	UBERON:0001621	88.45	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.33	gold quality
cranial nerve II	UBERON:0000941	88.30	gold quality
rectum	UBERON:0001052	88.07	gold quality
ganglionic eminence	UBERON:0004023	88.01	gold quality
saphenous vein	UBERON:0007318	87.97	gold quality
endothelial cell	CL:0000115	87.96	gold quality
uterus	UBERON:0000995	87.93	gold quality
lung	UBERON:0002048	87.89	gold quality
tonsil	UBERON:0002372	87.78	gold quality
right coronary artery	UBERON:0001625	87.66	gold quality
pylorus	UBERON:0001166	87.54	gold quality
urinary bladder	UBERON:0001255	87.43	gold quality
placenta	UBERON:0001987	87.43	gold quality
jejunum	UBERON:0002115	87.43	gold quality
embryo	UBERON:0000922	87.37	gold quality
myometrium	UBERON:0001296	87.32	gold quality
renal glomerulus	UBERON:0000074	87.23	gold quality
upper arm skin	UBERON:0004263	87.00	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.95	gold quality
right lung	UBERON:0002167	86.94	gold quality
metanephric glomerulus	UBERON:0004736	86.93	gold quality
bone marrow	UBERON:0002371	86.87	gold quality
gingiva	UBERON:0001828	86.72	gold quality
omental fat pad	UBERON:0010414	86.62	gold quality
granulocyte	CL:0000094	86.61	gold quality
peritoneum	UBERON:0002358	86.60	gold quality
adrenal tissue	UBERON:0018303	86.51	gold quality
heart right ventricle	UBERON:0002080	86.43	gold quality
bronchial epithelial cell	CL:0002328	86.19	gold quality
metanephros	UBERON:0000081	86.17	gold quality
bone marrow cell	CL:0002092	86.00	gold quality
mucosa of urinary bladder	UBERON:0001259	85.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.27
E-MTAB-5061	no	3.53

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lymph node	tissue	38.2	medium
Tonsil	tissue	36.0	medium
Appendix	tissue	32.0	low
Thymus	tissue	31.9
Spleen	tissue	29.7	low
Smooth muscle	tissue	28.3	medium
Adipose tissue	tissue	27.1	medium
Heart muscle	tissue	25.2	medium
Urinary bladder	tissue	24.4	medium
Lung	tissue	21.5	low
Endometrium 1	tissue	20.8	medium
Placenta	tissue	20.8	medium
Gallbladder	tissue	19.3	low
Esophagus	tissue	18.6	low
Tongue	tissue	18.4
Cervix	tissue	18.0	medium
Bone marrow	tissue	17.7	medium
Skin 1	tissue	17.5	medium
Breast	tissue	17.4	medium
Rectum	tissue	17.1	low
Ovary	tissue	16.9	medium
Seminal vesicle	tissue	16.8	low
Adrenal gland	tissue	16.2	medium
Thyroid gland	tissue	15.5	medium
Prostate	tissue	15.0	not detected
Liver	tissue	14.7	medium
Colon	tissue	14.0	low
Fallopian tube	tissue	14.0	medium
Kidney	tissue	13.9	medium
Stomach 1	tissue	13.7	low
Epididymis	tissue	12.9	medium
Choroid plexus	tissue	12.9
Caudate putamen	tissue	12.9
Small intestine	tissue	12.7	low
Frontal cortex	tissue	12.3
Skeletal muscle	tissue	10.9	low
Duodenum	tissue	10.7	low
Corpus callosum	tissue	10.3
Parathyroid gland	tissue	10.1	medium
Testis	tissue	9.8	high
Salivary gland	tissue	9.5	low
Vagina	tissue	9.4	low
Locus coeruleus	tissue	9.4
Pancreas	tissue	9.3	low
Nucleus accumbens	tissue	9.3
Retina	tissue	9.1
Hippocampus	tissue	8.4	medium
Postcentral gyrus	tissue	7.7
Spinal cord	tissue	7.3
Cerebellum	tissue	7.2	high
Putamen	tissue	6.8
Olfactory bulb	tissue	6.8
Medulla oblongata	tissue	6.7
Substantia nigra	tissue	6.7
Midbrain	tissue	6.5
Hippocampal formation	tissue	6.4
Ventral forebrain	tissue	6.4
Pons	tissue	6.1
Amygdala	tissue	6.1
Periaqueductal gray	tissue	6.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (21.8), Nucleus raphe pallidus (16.5), Lateral funiculus (white matter) (16.4), Corpus callosum, splenium (white matter) (15.2), Medial olivary nucleus (15.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, E2F6

miRNA regulators (miRDB)

Targeting RECQL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 73 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-1283	99.69	72.42	3009

Functional genomics

gnomAD constraint: pLI 1.07e-19, LOEUF 1.24, missense Z 1.08 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000444129 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:21,470,197–21,470,969	30 / 58.6	0.51	no
12:21,470,970–21,499,570	669 / 713.5	0.94	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Molecular cloning of a splicing variant of human RECQL helicase. (PMID:12419324)
• characterization of DNA-unwinding activity (PMID:12419808)
• RECQ1 alone is able to unwind short DNA duplexes (<110 bp), whereas considerably longer substrates (501 bp) can be unwound only in the presence of human replication protein A (hRPA) (PMID:15096578)
• RECQ1 has a role in a pathway involving mismatch repair factors (PMID:15886194)
• analysis of enzymatic properties of the RECQ1 helicase and DNA unwinding and strand annealing activities (PMID:15899892)
• Identification of RecQL1 as a predominant ATP-dependent, Holliday junction branch migrator present in human nuclear extracts. (PMID:16260474)
• Our findings suggest that higher-order oligomers are associated with DNA strand annealing, and lower-order oligomers with DNA unwinding. (PMID:17227144)
• RecQ DNA helicase resolves genetic recombination and suppressive aberrant recombination. (PMID:17483412)
• Results support that endogenous DNA damage that occurs during DNA replication and remains unrepaired in cancer cells due to RecQL1 silencing induces cancer cell-specific mitotic catastrophe through a less-strict checkpoint in cancer than in normal cells. (PMID:17953710)
• results provide the first evidence for a role of human RECQ1 in the response to DNA damage and chromosomal stability maintenance and point to the vital importance of RECQ1 in genome homeostasis (PMID:18074021)
• Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities (PMID:18448429)
• properties of the RECQ1 helicase may have important implications for the function of RECQ1 in maintenance of genomic stability (PMID:18495662)
• A crystal structure of a truncated form of the human RECQ1 protein with Mg-ADP, is presented. (PMID:19151156)
• Topoisomerase I and RecQL1 promote the lytic reactivation of Epstein-Barr virus. (PMID:19494003)
• These results indicate that RECQ1 and RECQ4 are integral components of the human replication complex and play distinct roles in DNA replication initiation and replication fork progression in vivo. (PMID:20065033)
• Histological data reveal the potential of RecQL1 as a biological marker predicting the malignancy and progression of liver cancer. (PMID:20198302)
• The beta-hairpin is a key structural element that controls not only the enzymatic activity of RECQ1, but also the balance between the multiple oligomeric states of the protein. (PMID:21059676)
• RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas. (PMID:21752281)
• RAD54 that lacks helicase activity is more efficient in DNA heterology bypass than BLM or REQ1 helicases. (PMID:22356911)
• Data show that RECQ1 associates with PARP-1 in nuclear extracts and exhibits direct protein interaction in vitro. (PMID:22542292)
• The data suggested that HomolD-containing promoters require the RNA polymerase II machinery and the proteins DDB1 and RECQL for accurate transcription. (PMID:22705827)
• RECQ1 might have a similar role to that of WRN in helping cells deal with stalled replication forks. (PMID:23095637)
• RECQ1 promotes restart of DNA replication forks reversed by DNA topoisomerase I inhibition. (PMID:23396353)
• a crucial role for RECQ1 at naturally occurring fork stalling sites and implicate RECQ1 in mechanisms underlying common fragile site instability in cancer. (PMID:23601052)
• An interaction of RECQ1 with Ku70/80 and a role of the human RecQ helicase in double-strand break repair through nonhomologous end-joining. (PMID:23650516)
• RECQL1 expression was exceptionally high in rapidly growing ovarian cancer cells. (PMID:23951333)
• RECQL1 may participate in the same pathway as WRN, probably in telomere replication. (PMID:24623817)
• results indicate that RECQL1 plays an important regulatory role in cancer cell proliferation and tumor progression (PMID:24854846)
• The stimulation of helicase-catalyzed protein displacement is observed with the DNA helicase RECQ1, suggesting a conserved functional interaction of RPA-interacting helicases. (PMID:24895130)
• our results provide first indication of nonredundant participation of WRN and RECQ1 in protection from the potentially carcinogenic effects (PMID:25228686)
• RECQL1 is a prognostic factor for epithelial ovarian cancer and contributes to potential malignancy by inhibiting apoptosis. (PMID:25424877)
• A novel function of RECQ1 is identified: in gene regulation and indicates that RECQ1 contributes to tumor development and progression, in part, by regulating the expression of key genes that promote cancer cell migration, invasion and metastasis. (PMID:25483193)
• we show that RECQ1 can form what appears to be a flat, homotetrameric complex and propose that RECQ1 tetramers are involved in Holliday junction recognition (PMID:25831490)
• RECQL is a breast cancer susceptibility gene. (PMID:25915596)
• RECQL is a potential breast cancer susceptibility gene; mutations in this gene contribute to familial breast cancer development. (PMID:25945795)
• RECQL is a new breast cancer susceptibility gene. (PMID:26125302)
• RECQL is a DNA helicase in breast cancer [editorial] (PMID:26387136)
• To better understand the roles of RECQ1, two AL mutants (W227A and F231A) in full-length RECQ1 were characterized biochemically and genetically (PMID:26455304)
• RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. (PMID:26725729)
• Study detected five different RECQL mutation in six unrelated breast cancer patients. The identified mutations include one frame-shift deletion, two splicing site mutation and one nonsense mutation. (PMID:27125668)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	recql	ENSDARG00000007175
mus_musculus	Recql	ENSMUSG00000030243
rattus_norvegicus	Recql	ENSRNOG00000012602
caenorhabditis_elegans		WBGENE00019334

Paralogs (4): RECQL5 (ENSG00000108469), RECQL4 (ENSG00000160957), WRN (ENSG00000165392), BLM (ENSG00000197299)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103021) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
elevated level of mitotic sister chromatid exchange	1
abnormal chromosome morphology	1
aneuploidy	1
spontaneous chromosome breakage	1
decreased fibroblast proliferation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RF63	98.9%	Diamond
Escherichia coli K-12	P15043	94.7%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P40724	94.7%	Diamond
Caenorhabditis briggsae	A8WK63	80.7%	Diamond
Haemophilus influenzae Rd KW20	P71359	80.7%	Diamond
Pasteurella multocida subsp. multocida str. Pm70	Q9CL21	80.7%	Diamond
Arabidopsis thaliana	Q8L840	70.4%	Diamond
Xenopus laevis	Q9DEY9	58.2%	Diamond
Gallus gallus	Q9I920	58.0%	Diamond
Schizosaccharomyces pombe 972h-	Q09811	55.0%	Diamond
Drosophila melanogaster	Q9VGI8	48.8%	Diamond
Saccharomyces cerevisiae S288C	P35187	43.3%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P50729	42.7%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P73421	40.6%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UPX0	40.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLCO1B1	protein-coding	10599
IAPP	protein-coding	3375
GOLT1B	protein-coding	51026
SLCO1A2	protein-coding	6579
PYROXD1	protein-coding	79912
GYS2	protein-coding	2998
SPX	protein-coding	80763
KCNJ8-AS1	ncRNA	105369689
LDHB	protein-coding	3945

Protein

Protein identifiers

ATP-dependent DNA helicase Q1 — P46063 (reviewed: P46063)

Alternative names: DNA 3’-5’ helicase Q1, DNA helicase, RecQ-like type 1, DNA-dependent ATPase Q1, RecQ protein-like 1

All UniProt accessions (7): P46063, F5GYB7, F5H2L2, F5H3W0, F5H4P4, F8WA66, F8WD97

UniProt curated annotations — full annotation on UniProt →

Function. DNA helicase that plays a role in DNA damage repair and genome stability. Exhibits a Mg(2+)- and ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3’-5’ direction. Full-length protein unwinds forked DNA substrates, resolves Holliday junctions, and has DNA strand annealing activity. Plays a role in restoring regressed replication forks. Required to restart stalled replication forks induced by abortive topoisomerase 1 and 2 lesions. Does not unwind G-quadruplex DNA. May play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens.

Subunit / interactions. May form homodimers or higher order oligomers. Forms a dimer in complex with tailed duplex DNA; the DNA only mkaes contact with one of the monomers. Probably forms flat tetramers on Holliday junction DNA. Interacts with EXO1. Interacts with MLH1. Interacts with PARP1.

Subcellular location. Nucleus.

Tissue specificity. High expression in heart, lung, skeletal muscle and kidney, low expression in brain.

Disease relevance. RECON progeroid syndrome (RECON) [MIM:620370] An autosomal recessive syndrome characterized by short stature, progeroid facial features, a hypoplastic nose, xeroderma, skin photosensitivity, muscle wasting with reduced subcutaneous fat, and slender elongated thumbs. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Zn(2+) per monomer.

Domain organisation. A helical hairpin (residues 554-573) in the winged-helix proble DNA-binding domain couples the ATPase (and probably ssDNA translocation) to DNA unwinding. The isolated WH domain (residues 481-624) anneals DNA as well as full-length protein.

Similarity. Belongs to the helicase family. RecQ subfamily.

RefSeq proteins (2): NP_002898, NP_116559 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR004589	DNA_helicase_ATP-dep_RecQ	Family
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032284	RecQ_Zn-bd	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily

Pfam: PF00270, PF00271, PF16124

Enzyme classification (BRENDA)

• EC 5.6.2.4 — DNA 3’-5’ helicase (BRENDA: 32 organisms, 185 substrates, 89 inhibitors, 54 Km, 46 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	41
2’(3’)-O-(N-METHYLANTHRANILOYL)ATP	0.0026–0.006	2
DATP	0.25	1

Catalyzed reactions (Rhea)

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• dATP + H2O = dADP + phosphate + H(+) (RHEA:51908)

UniProt features (93 total): helix 27, strand 20, binding site 11, mutagenesis site 6, modified residue 5, sequence variant 5, sequence conflict 5, compositionally biased region 4, turn 3, domain 2, region of interest 2, chain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
2V1X	Crystal structure of human RECQ-like DNA helicase	X-RAY DIFFRACTION	2
9I22	Structure of Human helicase RecQ1- Myc G-quadruplex - ADP complex	X-RAY DIFFRACTION	2.42
8YRS	Crystal structure of human RECQ1 helicase containing a flexible linker in complex with …	X-RAY DIFFRACTION	2.43
6JTZ	Crystal Structure of hRecQ1_D2-Zn-WH containing mutation on beta-hairpin	X-RAY DIFFRACTION	2.8
2WWY	Structure of human RECQ-like helicase in complex with a DNA substrate	X-RAY DIFFRACTION	2.9
4U7D	Structure of human RECQ-like helicase in complex with an oligonucleotide	X-RAY DIFFRACTION	3.4
9I23	Structure of Human helicase RecQ1- 795-2T G-quadruplex - ADP complex	X-RAY DIFFRACTION	3.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46063-F1	86.55	0.69

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
119

Ligand- & substrate-binding residues (11)

Position	Role
91	ATP
93	ATP
96	ATP
116	ATP
118	ATP
119	ATP
120	ATP
453	Zn(2+)
471	Zn(2+)
475	Zn(2+)
478	Zn(2+)

Post-translational modifications (5)

Type	Positions
N6-acetyllysine	514, 522
Phosphoserine	597, 602, 634

Mutagenesis-validated functional residues (6)

Position	Phenotype
119	abrogates helicase activity.
511–514	considerably reduced dna unwinding and branch migration on holliday junctions, small change in dna annealing.
528	reduced dna unwinding and branch migration on holliday junctions, small change in dna annealing.
555–572	complete loss of dna fork unwinding, retains atpase activity (in a 49-616 residue fragment).
560–567	complete loss of dna fork unwinding, retains atpase activity (in a 49-616 residue fragment).
564	nearly complete loss of dna fork unwinding, retains atpase activity (in a 49-616 residue fragment).

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 264 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MORF_BRCA1, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_UP, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, KORKOLA_EMBRYONAL_CARCINOMA_UP, DAZARD_RESPONSE_TO_UV_SCC_UP, GOBP_DNA_DAMAGE_RESPONSE, HIF1_Q3, SANSOM_APC_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, HAHTOLA_SEZARY_SYNDROM_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (5): double-strand break repair via homologous recombination (GO:0000724), DNA replication (GO:0006260), DNA repair (GO:0006281), replication fork processing (GO:0031297), DNA recombination (GO:0006310)

GO Molecular Function (15): DNA helicase activity (GO:0003678), ATP binding (GO:0005524), four-way junction helicase activity (GO:0009378), ATP hydrolysis activity (GO:0016887), double-stranded DNA helicase activity (GO:0036121), 3’-5’ DNA helicase activity (GO:0043138), metal ion binding (GO:0046872), DNA/DNA annealing activity (GO:1990814), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

30 GO namespaces:

Category	Terms
DNA metabolic process	3
DNA helicase activity	3
cellular anatomical structure	3
ATP-dependent activity	2
binding	2
catalytic activity	2
recombinational repair	1
double-strand break repair	1
DNA biosynthetic process	1
DNA damage response	1
DNA-templated DNA replication maintenance of fidelity	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ribonucleoside triphosphate phosphatase activity	1
cation binding	1
single-stranded DNA binding	1
catalytic activity, acting on DNA	1
annealing activity	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
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
replication fork processing	BP	direct assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
3’-5’ DNA helicase activity	MF	direct assay
DNA helicase activity	MF	direct assay
DNA/DNA annealing activity	MF	direct assay
double-stranded DNA helicase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,550 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RECQL	DNA2	P51530	871
RECQL	EXO1	Q9UQ84	787
RECQL	RAD51	Q06609	765
RECQL	SMARCAL1	Q9NZC9	750
RECQL	FEN1	P39748	733
RECQL	TOP3A	Q13472	699
RECQL	KPNA4	O00629	689
RECQL	RAD50	Q92878	687
RECQL	FANCM	Q8IYD8	682
RECQL	ZRANB3	Q5FWF4	680
RECQL	BRCA2	P51587	675
RECQL	KPNA2	P52292	657
RECQL	MUS81	Q96NY9	652
RECQL	RAD52	P43351	645
RECQL	BRIP1	Q9BX63	641

IntAct

Human interaction partners of RECQL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
PARP1	direct interaction	0.750	8
KPNA2	physical association	0.510	2
KPNA4	physical association	0.510	2
SCRT2	association	0.350	1
TRAF3IP1	physical association	0.000	1

BioGRID (345 interactions; top human partners by supporting records): CYP1A1 (Affinity Capture-MS; 3 records), PARP1 (Affinity Capture-MS; 3 records), DDB1 (Affinity Capture-Western; 2 records), E2F4 (Reconstituted Complex; 2 records), FOXC1 (Affinity Capture-MS; 2 records), HIST1H2BG (Proximity Label-MS; 2 records), HSPA1A (Proximity Label-MS; 2 records), KPNA2 (Two-hybrid; 2 records), KPNA4 (Two-hybrid; 2 records), MSH2 (Co-fractionation; 2 records), MYC (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PML (Proximity Label-MS; 2 records), PSMC5 (Affinity Capture-MS; 2 records), SNRNP27 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for RECQL: 1,596 ClinVar records (10 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

1,596 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	10
Uncertain significance	1036
Likely benign	412
Benign	51

Top pathogenic / likely-pathogenic (10)

Showing all 10 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
584813	NM_002907.4(RECQL):c.676delinsGATGTAGCATGT (p.Gln226fs)	Likely pathogenic	criteria provided, single submitter	1
801376	NM_002907.4(RECQL):c.1099-2A>G	Likely pathogenic	criteria provided, single submitter	1
801380	NM_002907.4(RECQL):c.677_678insTGTA (p.Gln226fs)	Likely pathogenic	criteria provided, single submitter	1
801381	NM_002907.4(RECQL):c.675_676insGATGTAG (p.Gln226fs)	Likely pathogenic	criteria provided, single submitter	1
801388	NM_002907.4(RECQL):c.215-20_223del	Likely pathogenic	criteria provided, single submitter	1
801391	NM_002907.4(RECQL):c.-45-1G>A	Likely pathogenic	criteria provided, single submitter	1
1685425	NM_002907.4(RECQL):c.502-2A>G	Likely pathogenic	criteria provided, single submitter	1
2581010	NM_002907.4(RECQL):c.1082C>A (p.Ser361Ter)	Likely pathogenic	criteria provided, single submitter	1
4845850	NM_002907.4(RECQL):c.1241_1242del (p.Cys414fs)	Likely pathogenic	criteria provided, single submitter	1
4850460	NM_002907.4(RECQL):c.439C>T (p.Gln147Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore RECQL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,554):

Position(s)	Effect	Δscore	Sites
12:21471426–21471427	donor_loss	1.0000	4
12:21471431	donor_gain	1.0000
12:21471650	acceptor_gain	1.0000
12:21473549–21473550	donor_loss	1.0000	5
12:21473653–21473655	acceptor_gain	1.0000	2
12:21480354	donor_gain	1.0000
12:21483575–21483576	acceptor_loss	1.0000	4
12:21486477–21486478	donor_loss	1.0000	5
12:21486586–21486587	acceptor_loss	1.0000	5
12:21490197–21490198	donor_loss	1.0000	5

AlphaMissense

1,487 missense substitutions predicted likely pathogenic (of 4,317 scored), across 371 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M376	9	0.906	0.998
D219	8	0.993	0.997
F374	8	0.990	0.999
D230	8	0.987	0.995
H222	8	0.982	0.997
H388	8	0.979	0.998
D146	8	0.976	0.995
F231	8	0.976	1.000
F462	8	0.966	0.989
D422	8	0.964	0.991
D476	8	0.931	0.987
S120	8	0.930	0.997
D264	8	0.928	0.965
H229	8	0.923	0.987
D408	8	0.923	0.987
S225	8	0.920	0.999
H345	8	0.910	0.975
D234	8	0.902	0.963
F424	8	0.881	0.976
M144	8	0.861	0.980

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	0.000214

Disease associations

OMIM: gene MIM:600537 | disease phenotypes: MIM:620370, MIM:614561

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
RECON progeroid syndrome	Moderate	Autosomal recessive	2
breast cancer	Disputed Evidence	Autosomal dominant
familial ovarian cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
hereditary breast carcinoma	Disputed	AD
familial ovarian cancer	No Known Disease Relationship	AD

Mondo (6): cancer (MONDO:0004992), RECON progeroid syndrome (MONDO:0957266), leukoencephalopathy with calcifications and cysts (MONDO:0013803), hereditary neoplastic syndrome (MONDO:0015356), breast cancer (MONDO:0007254), familial ovarian cancer (MONDO:0016248)

Orphanet (2): Leukoencephalopathy with calcifications and cysts (Orphanet:542310), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

38 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000311	Round face
HP:0000319	Smooth philtrum
HP:0000418	Narrow nasal ridge
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000678	Dental crowding
HP:0000696	Delayed eruption of permanent teeth
HP:0000958	Dry skin
HP:0000963	Thin skin
HP:0000992	Cutaneous photosensitivity
HP:0001007	Hirsutism
HP:0001097	Keratoconjunctivitis sicca
HP:0001166	Arachnodactyly
HP:0001382	Joint hypermobility
HP:0001510	Growth delay
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0002719	Recurrent infections
HP:0003202	Skeletal muscle atrophy
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0005328	Progeroid facial appearance
HP:0007646	Absent lower eyelashes
HP:0008407	Hyperconvex thumb nails
HP:0008551	Microtia
HP:0009623	Proximal placement of thumb
HP:0009907	Attached earlobe
HP:0010759	Prominence of the premaxilla
HP:0025337	Red eye
HP:0032152	Keratosis pilaris
HP:0032524	Long thumb
HP:0033505	Livedo reticularis
HP:0040189	Scaling skin

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_1758	Blood protein levels	9e-27

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C000598644	Leukoencephalopathy Brain Calcifications and Cysts *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293236 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,225,128 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 115 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL600	ACETYLCYSTEINE	4	96,284
CHEMBL184	ACYCLOVIR	4	98,123
CHEMBL1046	AMINOCAPROIC ACID	4	96,126
CHEMBL174	AMPICILLIN	4	336,569
CHEMBL1200758	AMPICILLIN SODIUM	4	5,652
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,317
CHEMBL1200522	AVOBENZONE	4	34,310
CHEMBL388590	BENZBROMARONE	4	8,286
CHEMBL1023	BEXAROTENE	4	41,527
CHEMBL290106	BITHIONOL	4	6,490
CHEMBL1447476	BITHIONOLATE SODIUM	4	326
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL1010	CEFOTAXIME SODIUM	4	4,963
CHEMBL1201043	CEPHAPIRIN SODIUM	4	3,320
CHEMBL311498	CIANIDANOL	4	60,179
CHEMBL11359	CISPLATIN	4
CHEMBL61593	CYCLOTHIAZIDE	4	4,424
CHEMBL1554	DACTINOMYCIN	4	177,038
CHEMBL178	DAUNORUBICIN	4	205,873
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	29,081
CHEMBL333826	DEQUALINIUM	4
CHEMBL121663	DEQUALINIUM CHLORIDE	4
CHEMBL75435	DEXKETOPROFEN	4
CHEMBL1751	DIGOXIN	4
CHEMBL421701	DITHIAZANINE IODIDE	4
CHEMBL1477036	DOCUSATE	4
CHEMBL59	DOPAMINE	4
CHEMBL1557	DOPAMINE HYDROCHLORIDE	4
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4
CHEMBL1201049	ECONAZOLE NITRATE	4
CHEMBL679	EPINEPHRINE	4
CHEMBL135	ESTRADIOL	4
CHEMBL456	ETHACRYNIC ACID	4
CHEMBL588	FENOLDOPAM	4
CHEMBL1057	FLUORESCEIN	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL537	HYDROQUINONE	4
CHEMBL1117	IDARUBICIN	4
CHEMBL12856	INAMRINONE	4
CHEMBL1009	LEVODOPA	4
CHEMBL677	LEVONORDEFRIN	4
CHEMBL313972	MASOPROCOL	4
CHEMBL704	MESALAMINE	4
CHEMBL2146123	METHACYCLINE HYDROCHLORIDE	4
CHEMBL459	METHYLDOPA	4
CHEMBL550495	METHYLENE BLUE	4
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4
CHEMBL191083	METHYLENE BLUE CATION	4
CHEMBL1201356	METHYLERGONOVINE	4
CHEMBL1065	METHYSERGIDE	4
CHEMBL1200938	METHYSERGIDE MALEATE	4
CHEMBL1559	MICONAZOLE NITRATE	4
CHEMBL58	MITOXANTRONE	4
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4
CHEMBL521606	NADOLOL	4
CHEMBL1437	NOREPINEPHRINE	4
CHEMBL1133	OXYBUTYNIN CHLORIDE	4
CHEMBL1517	OXYTETRACYCLINE	4
CHEMBL428647	PACLITAXEL	4

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

2 measured of 6 human assays (7 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM
1-(3,4-Dichloro-phenyl)-3-(5-pyridin-4-yl-[1,3,4]thiadiazol-2-yl)-urea	IC50	1560 nM

ChEMBL bioactivities

1727 potent at pChembl≥5 of 5018 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Potency	1	nM	ACTINONIN
8.00	Potency	10	nM	CHEMBL1383575
7.80	Potency	15.8	nM	CHEMBL1367444
7.70	Potency	20	nM	CHEMBL1445279
7.65	Potency	22.4	nM	CHEMBL1427696
7.65	Potency	22.4	nM	CHEMBL3212668
7.60	Potency	25.1	nM	CHEMBL1373063
7.60	Potency	25.1	nM	CHEMBL1374949
7.60	Potency	25.1	nM	CHEMBL1565317
7.60	Potency	25.1	nM	CHEMBL1502893
7.60	Potency	25.1	nM	CHEMBL1439221
7.60	Potency	25.1	nM	CHEMBL1608986
7.60	Potency	25.1	nM	CHEMBL1526090
7.60	Potency	25.1	nM	CHEMBL3208086
7.60	Potency	25.1	nM	CHEMBL1417273
7.60	Potency	25.1	nM	CHEMBL1573985
7.60	Potency	25.1	nM	CHEMBL1348698
7.60	Potency	25.1	nM	CHEMBL1418131
7.60	Potency	25.1	nM	CHEMBL1311130
7.60	Potency	25.1	nM	CHEMBL446240
7.55	Kd	28.13	nM	CHEMBL3752910
7.55	Potency	28.2	nM	CHEMBL1372612
7.55	Potency	28.2	nM	CHEMBL1578026
7.55	Potency	28.2	nM	CHEMBL1491039
7.55	Potency	28.2	nM	TYRPHOSTIN 47
7.55	Potency	28.2	nM	CHEMBL1334855
7.55	Potency	28.2	nM	CHEMBL1576131
7.55	Potency	28.2	nM	CHEMBL1480560
7.55	Potency	28.2	nM	CHEMBL1335249
7.55	Potency	28.2	nM	MICONAZOLE NITRATE
7.55	Potency	28.2	nM	CHEMBL1571837
7.55	Potency	28.2	nM	CHEMBL1420974
7.55	Potency	28.2	nM	CHEMBL1599050
7.55	Potency	28.2	nM	TICLOPIDINE HYDROCHLORIDE
7.55	Potency	28.2	nM	CHEMBL1521482
7.55	Potency	28.2	nM	CHEMBL1443429
7.55	Potency	28.2	nM	CHEMBL1534809
7.55	Potency	28.2	nM	CHEMBL408850
7.55	Potency	28.2	nM	CHEMBL1445414
7.55	Potency	28.2	nM	CHEMBL1500912
7.52	ED50	30.43	nM	CHEMBL3752910
7.50	Potency	31.6	nM	CHEMBL1450895
7.50	Potency	31.6	nM	CHEMBL1461262
7.50	Potency	31.6	nM	CHEMBL1504207
7.50	Potency	31.6	nM	CHEMBL1466446
7.50	Potency	31.6	nM	CHEMBL1586490
7.50	Potency	31.6	nM	CHEMBL1485734
7.45	Potency	35.5	nM	CHEMBL1331485
7.45	Potency	35.5	nM	CHEMBL1324333
7.40	Potency	39.8	nM	CHEMBL1572517

PubChem BioAssay actives

1 with measured affinity, of 13 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149214: Binding affinity to human RECQL incubated for 45 mins by Kinobead based pull down assay	kd	0.0281	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
kojic acid	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
1,2,5,6-dibenzanthracene	increases expression	1
pentanal	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
bisphenol B	increases expression	1
trans-10,cis-12-conjugated linoleic acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 4 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613829	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of RecQ-Like Dna Helicase 1 (RECQ1). (Class of assay: confirmatory) [Related pubchem assays: 594 (Rhodamine region spectral profiling screen), 593 (Fluorescein region spectral profiling screen), 2	PubChem BioAssay data set
CHEMBL2428259	Binding	Inhibition of RECQ1 (unknown origin) by gel-based DNA unwinding assay	Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1QC	Abcam K-562 RECQL KO	Cancer cell line	Female
CVCL_D2LY	Abcam Raji RECQL KO	Cancer cell line	Male
CVCL_TI69	HAP1 RECQL (-) 1	Cancer cell line	Male
CVCL_TI70	HAP1 RECQL (-) 2	Cancer cell line	Male
CVCL_WQ46	Abcam Jurkat RECQL KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 599 trials:

NCT	Phase	Status	Title
NCT00014638	Phase 4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	Phase 4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	Phase 4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	Phase 4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	Phase 4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	Phase 4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	Phase 4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	Phase 4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	Phase 4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	Phase 4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	Phase 4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	Phase 4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	Phase 4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	Phase 4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	Phase 4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	Phase 4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	Phase 4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	Phase 4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	Phase 4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	Phase 4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	Phase 4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	Phase 4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	Phase 4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	Phase 4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	Phase 4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	Phase 4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	Phase 4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	Phase 4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	Phase 4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	Phase 4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	Phase 4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	Phase 4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	Phase 4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	Phase 4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	Phase 4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer
NCT00756717	Phase 4	COMPLETED	Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer
NCT00766532	Phase 4	COMPLETED	Do Aromatase Inhibitors (AIs) Decrease Intestinal Calcium Absorption?
NCT00768222	Phase 4	COMPLETED	Coated VICRYL* Plus Suture Compared to Chinese Silk in Scheduled Breast Cancer Surgery
NCT00772824	Phase 4	COMPLETED	Study of the Effect of Glutamine Supplementation on Chemotherapy Induced Toxicities in Breast Cancer Patients
NCT00774241	Phase 4	WITHDRAWN	PRIMADOS Study:A Study of Avastin (Bevacizumab) Plus Docetaxel for First Line Treatment of Patients With Metastatic Breast Cancer
NCT00812864	Phase 4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00872859	Phase 4	COMPLETED	The BREASTrial:Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial
NCT00882089	Phase 4	COMPLETED	Use of the Contura™ Catheter in Intermediate-Risk, Pathological Stage 0, I, or II (Up to 3.0 cm) Breast Cancer Patients
NCT00882596	Phase 4	COMPLETED	Use of the Contura™ Catheter to Deliver Accelerated Partial Breast Irradiation to Low-risk Breast Cancer Patients
NCT00904410	Phase 4	COMPLETED	Early Assessment of the Response to Neo-adjuvant Chemotherapy in Breast Cancer Patients With FDG-PET
NCT00912639	Phase 4	UNKNOWN	A Clinical Trial of Paclitaxel Loaded Polymeric Micelle in Patients With Taxane-Pretreated Recurrent Breast Cancer
NCT00912938	Phase 4	UNKNOWN	Evaluate the Relationship of Bone Remodeling Markers for Skeletal Complications in Metastatic Breast Cancer Patients
NCT01035099	Phase 4	COMPLETED	RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF
NCT01049295	Phase 4	UNKNOWN	Omega-3 Fatty Acids and Chemotherapy-induced Neuropathy and Inflammation in Breast Cancer
NCT01072318	Phase 4	UNKNOWN	Extended Adjuvant Treatment With Letrozole in Breast Cancer Who Complete 5 Years of Toremifene
NCT01094184	Phase 4	COMPLETED	A Study of Bevacizumab With Taxane Therapy in Participants With Triple Negative Breast Cancer
NCT01156961	Phase 4	WITHDRAWN	A Study of The Safety Profile of First-line Avastin (Bevacizumab) in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Her2-negative Breast Cancer (AVATAX)
NCT01199432	Phase 4	COMPLETED	Comparative Efficiency of Three Regimen, CEFci, CEF and EC as Neoadjuvant Chemotherapy for Primary Breast Cancer
NCT01216254	Phase 4	UNKNOWN	Clinical Trial Comparing Outcomes of Breast Conserving Operations With Classic v High-frequency Electrocoagulation
NCT01231204	Phase 4	COMPLETED	Prevention of Post-Mastectomy Breast Pain Using Ambulatory Continuous Paravertebral Blocks

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RECQL across ~30M SureChEMBL compounds — explore on Sugi Predict.