RECQL5

protein-coding

RecQ like helicase 5, the group of RecQ like helicases

Gene summary

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. [provided by RefSeq, Jul 2011]

MANE transcript

NM_004259.7

Inheritance

AR, AD

ClinVar variants

U:191B:51

Top phenotype

RECQL5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr17:75,626,845-75,667,189

External References & Databases

Ensembl (ENSG00000108469)

Transcript & Mutation Effects

hg38 • Region Span ~40.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

coronary artery disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005010

Submitter: Ambry Genetics

breast cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007254

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RECQL5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 184

RECQL5-related disorderTotal: 94

not providedTotal: 16

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004259.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	21 clinvar	2 clinvar	25
missense			182 clinvar	19 clinvar	7 clinvar	208
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar	2 clinvar		6
Total	0	0	191	42	9	242

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004259.7	RefSeq	NP_004250.4	19	MANE Select
ENST00000317905.10	Ensembl	ENSP00000317636.5	19	MANE Select
NM_001003715.4	RefSeq	NP_001003715.1	8	Standard
NM_001003716.4	RefSeq	NP_001003716.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic sister chromatid segregation
mitotic cell cycle
double-strand break repair via homologous recombination
DNA metabolic process
DNA replication

Molecular Function

RNA polymerase II complex binding
DNA binding
DNA helicase activity
ATP binding
four-way junction helicase activity

Cellular Component

nucleus
nucleoplasm
chromosome
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317905
Coding exons: 19
Length: 40345
Individuals with no LoFs: 125660
Homozygous LoFs: 0
Heterozygous LoFs: 88
Defined: 125748
p: 0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00455	577	577	1.00	0.0000357	6399
Missense (PolyPhen)		154	169.66	0.9077		1873
Synonymous	0.215	227	231	0.982	0.0000143	1985
Loss of Function	1.68	34	46.3	0.734	0.00000235	549

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00048	0.00046	rare
European (Non-Finnish)	0.00037	0.00032	rare
South Asian	0.00062	0.00062	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform beta is a DNA helicase that plays an important role in DNA replication, transcription and repair. Inhibits elongation of stalled transcripts at DNA damage sites by binding to the RNA polymerase II subunit POLR2A and blocking the TCEA1 binding site. Required for mitotic chromosome separation after cross-over events and cell cycle progress. 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. {ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20643585, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22973052, ECO:0000269|PubMed:23715498, ECO:0000269|PubMed:23748380}.;

Recessive Scores

pRec: 0.226

Intolerance Scores

LoFtool: 0.891
RVIS EVS: 0.15
RVIS percentile EVS: 63.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.575

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium