WRN WRN RecQ like helicase [Homo sapiens (human)] - Gene

Summary

Official Symbol: WRNprovided by HGNC
Official Full Name: WRN RecQ like helicaseprovided by HGNC
Primary source: HGNC:HGNC:12791
See related: Ensembl:ENSG00000165392 MIM:604611; AllianceGenome:HGNC:12791
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RECQ3; RECQL2; RECQL3
Summary: This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in bone marrow (RPKM 5.0), endometrium (RPKM 4.7) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 8p12

Exon count:: 37

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (31033810..31176138)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (31314935..31457266)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (30891326..31033654)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease.
Title: A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease.
Werner syndrome protein works as a dimer for unwinding and replication fork regression.
Title: Werner syndrome protein works as a dimer for unwinding and replication fork regression.
WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.
Title: WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.
R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.
Title: R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.
Characterization of Stress Responses in a Drosophila Model of Werner Syndrome.
Title: Characterization of Stress Responses in a Drosophila Model of Werner Syndrome.
WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.
Title: WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.
The Impact of Vitamin C on Different System Models of Werner Syndrome.
Title: The Impact of Vitamin C on Different System Models of Werner Syndrome.
Human WRN is an intrinsic inhibitor of progerin, abnormal splicing product of lamin A.
Title: Human WRN is an intrinsic inhibitor of progerin, abnormal splicing product of lamin A.
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.
Title: Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.
HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN.
Title: HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN.

Submit: New GeneRIF Correction See all GeneRIFs (242)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Werner syndrome MedGen: C0043119 OMIM: 277700 GeneReviews: Werner Syndrome	Compare labs

EBI GWAS Catalog

Description
Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Werner syndrome helicase co-localizes with Tat in central nervous system tissue (thalamus and basal ganglia)	PubMed
	tat	Werner syndrome helicase cooperates with HIV-1 Tat to transactivate the HIV-1 LTR. The helicase K577M mutant inhibits Tat-dependent LTR transactivation in a dose-dependent manner	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH64913 (e-PCR)
- UniSTS:86304

PMC109206P1 (e-PCR)
- UniSTS:270155

WI-17945 (e-PCR)
- UniSTS:23392

SHGC-111489 (e-PCR)
- UniSTS:184679

SHGC-106496 (e-PCR)
- UniSTS:169897

D8S2234 (e-PCR)
- UniSTS:473787

D8S2233 (e-PCR)
- UniSTS:473788

csnpwrn-pcr13-1 (e-PCR)
- UniSTS:243166

csnpwrn-pcr14-1 (e-PCR)
- UniSTS:243167

csnpwrn-pcr15-1 (e-PCR)
- UniSTS:243168

csnpwrn-pcr18-1 (e-PCR)
- UniSTS:243169

csnpwrn-pcr2-1 (e-PCR)
- UniSTS:243170

csnpwrn-pcr20-1 (e-PCR)
- UniSTS:243171

csnpwrn-pcr21-1 (e-PCR)
- UniSTS:243172

csnpwrn-pcr22-1 (e-PCR)
- UniSTS:243173

csnpwrn-pcr23-1 (e-PCR)
- UniSTS:243174

csnpwrn-pcr25-1 (e-PCR)
- UniSTS:243175

csnpwrn-pcr26-1 (e-PCR)
- UniSTS:243176

csnpwrn-pcr27-1 (e-PCR)
- UniSTS:243177

csnpwrn-pcr29-1 (e-PCR)
- UniSTS:243178

csnpwrn-pcr30-1 (e-PCR)
- UniSTS:243179

csnpwrn-pcr31-1 (e-PCR)
- UniSTS:243180

csnpwrn-pcr34-1 (e-PCR)
- UniSTS:243181

csnpwrn-pcr4-1 (e-PCR)
- UniSTS:243182

PMC117198P1 (e-PCR)
- UniSTS:270319

csnpwrn-pcr5-1 (e-PCR)
- UniSTS:243183

csnpwrn-pcr6-1 (e-PCR)
- UniSTS:243184

csnpwrn-pcr7-1 (e-PCR)
- UniSTS:243185

G63421 (e-PCR)
- UniSTS:140533

SHGC-37564 (e-PCR)
- UniSTS:77823

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3'-5' DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables 3'-5' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables 3'-5' DNA helicase activity	TAS Traceable Author Statement more info
enables 3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables 3'-flap-structured DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables 8-hydroxy-2'-deoxyguanosine DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA helicase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables G-quadruplex DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables MutLalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
enables Y-form DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables bubble DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables exonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables forked DNA-dependent helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables four-way junction DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables four-way junction helicase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables four-way junction helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables manganese ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables telomeric D-loop binding	IDA Inferred from Direct Assay more info	PubMed
enables telomeric G-quadruplex DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA duplex unwinding	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA synthesis involved in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA unwinding involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in G-quadruplex DNA unwinding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in G-quadruplex DNA unwinding	IDA Inferred from Direct Assay more info	PubMed
involved_in G-quadruplex DNA unwinding	ISS Inferred from Sequence or Structural Similarity more info
involved_in base-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to gamma radiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of adult lifespan	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of strand invasion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein localization to nucleolus	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of growth rate	IEA Inferred from Electronic Annotation more info
involved_in replication fork processing	IDA Inferred from Direct Assay more info	PubMed
involved_in replication fork processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in replicative senescence	IEA Inferred from Electronic Annotation more info
involved_in response to UV-C	IDA Inferred from Direct Assay more info	PubMed
involved_in response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in t-circle formation	TAS Traceable Author Statement more info	PubMed
involved_in telomere maintenance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telomere maintenance	TAS Traceable Author Statement more info	PubMed
involved_in telomere maintenance via semi-conservative replication	TAS Traceable Author Statement more info
involved_in telomeric D-loop disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in telomeric D-loop disassembly	IGI Inferred from Genetic Interaction more info	PubMed
involved_in telomeric D-loop disassembly	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in chromosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in replication fork	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Go to the top of the page Help

Preferred Names: bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

Names: DNA helicase, RecQ-like type 3; Werner syndrome ATP-dependent helicase; Werner syndrome RecQ like helicase; Werner syndrome protein; Werner syndrome, RecQ helicase-like; exonuclease WRN; recQ protein-like 2

NP_000544.2

EC 3.6.4.12

XP_011542941.1

EC 3.6.4.12

XP_011542942.1

EC 3.6.4.12

XP_054217155.1

EC 3.6.4.12

XP_054217156.1

EC 3.6.4.12

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008870.1 RefSeqGene

Range

5001..145500

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_524

mRNA and Protein(s)

NM_000553.6 → NP_000544.2 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

See identical proteins and their annotated locations for NP_000544.2

Status: REVIEWED

Source sequence(s)

AC009563, AC084736

Consensus CDS

CCDS6082.1

UniProtKB/Swiss-Prot

A1KYY9, Q14191

Related

ENSP00000298139.5, ENST00000298139.7

Conserved Domains (8) summary

smart00341
Location:1156 → 1229

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:538 → 1010

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:61 → 229

RNaseD_like; DEDDy 3'-5' exonuclease domain of RNase D, WRN, and similar proteins

smart00956
Location:958 → 1051

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:759 → 867

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:551 → 712

DEAD; DEAD/DEAH box helicase

pfam14493
Location:1261 → 1351

HTH_40; Helix-turn-helix domain

pfam16124
Location:872 → 939

RecQ_Zn_bind; RecQ zinc-binding

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

31033810..31176138

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544639.4 → XP_011542941.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X1

See identical proteins and their annotated locations for XP_011542941.1

Conserved Domains (8) summary

smart00341
Location:1129 → 1202

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:511 → 983

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:61 → 229

RNaseD_like; DEDDy 3'-5' exonuclease domain of RNase D, WRN, and similar proteins

smart00956
Location:931 → 1024

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:732 → 840

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:524 → 685

DEAD; DEAD/DEAH box helicase

pfam14493
Location:1234 → 1324

HTH_40; Helix-turn-helix domain

pfam16124
Location:845 → 912

RecQ_Zn_bind; RecQ zinc-binding
XM_011544640.2 → XP_011542942.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X2

UniProtKB/TrEMBL

Q59F09

Conserved Domains (7) summary

smart00341
Location:623 → 696

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:42 → 477

recQ_fam; ATP-dependent DNA helicase, RecQ family

smart00956
Location:425 → 518

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:226 → 334

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:42 → 179

DEAD; DEAD/DEAH box helicase

pfam14493
Location:728 → 818

HTH_40; Helix-turn-helix domain

pfam16124
Location:339 → 406

RecQ_Zn_bind; RecQ zinc-binding

RNA

XR_949472.4 RNA Sequence
XR_949471.4 RNA Sequence
XR_949470.4 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

31314935..31457266

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054361180.1 → XP_054217155.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X1
XM_054361181.1 → XP_054217156.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X2

UniProtKB/TrEMBL

Q59F09