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

Summary

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Official Symbol: WRNprovided by HGNC
Official Full Name: Werner syndrome, RecQ helicase-likeprovided by HGNC
Primary source: HGNC:12791
See related: Ensembl:ENSG00000165392; HPRD:05212; MIM:604611; Vega:OTTHUMG00000163894
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 and the DEAH (Asp-Glu-Ala-His) subfamily of DNA and RNA helicases. DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. This protein contains a nuclear localization signal in the C-terminus and shows a predominant nucleolar localization. It possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease. Based on interactions between this protein and Ku70/80 heterodimer in DNA end processing, this protein may be involved in the repair of double strand DNA breaks. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by premature aging. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 8p12

Sequence :: Chromosome: 8; NC_000008.10 (30890778..31031277)

See WRN in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

a relationship between the methylation of the WRN gene and sensitivity to CPT-11 in cervical cancer
Title: Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells.
we show that the WRN protein, a member of the human RecQ helicases, is necessary to sustain replication fork progression in response to oncogene-induced replication stress.
Title: The WRN and MUS81 proteins limit cell death and genome instability following oncogene activation.
We concluded that WRN genes might be involved in age related cataract pathogenesis in the Han Chinese population.
Title: The associations between single nucleotide polymorphisms of DNA repair genes, DNA damage, and age-related cataract: Jiangsu Eye Study.
HSF4 and WRN CNVs might be involved in ARC pathogenesis in the Han Chinese.
Title: Copy number variations of DNA repair genes and the age-related cataract: Jiangsu Eye Study.
the Arg-993 and Phe-1037 in the RQC domain play essential roles in catalytic activity, and in functional interactions mediated by WRN.
Title: DNA binding residues in the RQC domain of Werner protein are critical for its catalytic activities.
WRN improves the efficiency and fidelity of hpol eta to promote more effective replication of DNA.
Title: Enhancement of human DNA polymerase η activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.
WRN prevents large deletions and rearrangements during replication, especially within telomeric regions.
Title: Werner syndrome protein suppresses the formation of large deletions during the replication of human telomeric sequences.
The data presented show that the W-V cell line, lacking the WRN protein, does not form the complex telomere mutations derived from inter-telomeric processes.
Title: The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres.
Quantitative analysis of WRN exonuclease activity by isotope dilution mass spectrometry.
Title: Quantitative analysis of WRN exonuclease activity by isotope dilution mass spectrometry.
WRN stimulates (CTG)(n) HPR on the template DNA strand by resolving the hairpin so that it can be efficiently used as a template for repair or replicative synthesis.
Title: The Werner syndrome protein promotes CAG/CTG repeat stability by resolving large (CAG)(n)/(CTG)(n) hairpins.

Submit: New GeneRIF Correction See all (160)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.

Diagnosis Testing

Clinical diagnostic criteria have been proposed. WRN is the only gene in which mutations are known to cause Werner syndrome. Mutations in WRN are identified in approximately 90% of individuals with Werner syndrome. Molecular genetic testing for WRN is available.

Genetic Counseling

Werner syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3. Prenatal testing for WRN mutations is possible.

References

PMID: 20301687

NHGRI GWAS Catalog

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

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Tat, p14	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 Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000544.1	NP_000048.1	BLM	BIND	PubMed	BLM interacts with WRN.
NP_000544.1	NP_478102.1	CDKN2A	BIND	PubMed	p14 interacts with WRN.
NP_000544.1	NP_001609.1	PARP1	BIND	PubMed	WRN interacts with PARP1.
NP_000544.1	NP_002870.2	RAD52	BIND	PubMed	WRN interacts with RAD52.
NP_000544.1	NP_005643.1	TERF2	BIND	PubMed	Wrn interacts with TRF2.
NP_000544.1	NP_000537.2	TP53	BIND	PubMed	WRN interacts with p53.
NP_000544.1	NP_001460.1	XRCC6	BIND	PubMed	WRN interacts with G22P1 (Ku70) as part of a complex.
Q14191	Q13315	ATM	HPRD	PubMed
Q14191	P54132	BLM	HPRD	PubMed
Q14191	Q8N726	CDKN2A	HPRD	PubMed
Q14191	P39748	FEN1	HPRD	PubMed
Q14191	P16104	H2AFX	HPRD	PubMed
Q14191	P09874	PARP1	HPRD	PubMed
Q14191	P12004	PCNA	HPRD	PubMed
Q14191	P49005	POLD2	HPRD	PubMed
Q14191	O15160	POLR1C	HPRD	PubMed
Q14191	P31321	PRKAR1B	HPRD	PubMed
Q14191	P78527	PRKDC	HPRD	PubMed
Q14191	P43351	RAD52	HPRD	PubMed
Q14191	P27694	RPA1	HPRD	PubMed
Q14191	Q15554	TERF2	HPRD	PubMed
Q14191	P04637	TP53	HPRD	PubMed
Q14191	P55072	VCP	HPRD	PubMed
Q14191	Q96S55	WRNIP1	HPRD	PubMed
Q14191	P13010	XRCC5	HPRD	PubMed
Q14191	P12956	XRCC6	HPRD	PubMed
BioGRID:113323	BioGRID:106962	ATM	BioGRID	PubMed	Protein-peptide
BioGRID:113323	BioGRID:107027	ATR	BioGRID	PubMed	Affinity Capture-Western; Protein-peptide
BioGRID:113323	BioGRID:107028	ATRX	BioGRID	PubMed	Far Western
BioGRID:113323	BioGRID:107110	BLM	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:107424	CDC5L	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:107463	CDKN2A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:115349	CHAF1A	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Far Western
BioGRID:113323	BioGRID:108025	DHX9	BioGRID	PubMed	Affinity Capture-Western; Co-purification; Reconstituted Complex
BioGRID:113323	BioGRID:34435	EXO1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:108528	FEN1	BioGRID	PubMed	Affinity Capture-Luminescence; Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:32151	GIS1	BioGRID	PubMed	Two-hybrid
BioGRID:113323	BioGRID:109268	H2AFX	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:115014	MDC1	BioGRID	PubMed	Protein-peptide
BioGRID:113323	BioGRID:110763	NBN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:106652	PARP1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:111142	PCNA	BioGRID	PubMed	Affinity Capture-Western; FRET; Reconstituted Complex
BioGRID:113323	BioGRID:111384	PML	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:111419	POLB	BioGRID	PubMed	Far Western
BioGRID:113323	BioGRID:114909	POLR1C	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:117417	POT1	BioGRID	PubMed	Phenotypic Enhancement
BioGRID:113323	BioGRID:111577	PRKDC	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Protein-peptide
BioGRID:113323	BioGRID:35589	RAD50	BioGRID	PubMed	Dosage Rescue
BioGRID:113323	BioGRID:111825	RAD51	BioGRID	PubMed	Affinity Capture-Western; Far Western; Reconstituted Complex
BioGRID:113323	BioGRID:111830	RAD52	BioGRID	PubMed	Affinity Capture-Western; FRET; Far Western; Reconstituted Complex; Two-hybrid
BioGRID:113323	BioGRID:117321	RAD54B	BioGRID	PubMed	Far Western
BioGRID:113323	BioGRID:116983	SIRT1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:113323	BioGRID:113188	SUMO1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113323	BioGRID:112873	TERF2	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Reconstituted Complex
BioGRID:113323	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113323	BioGRID:971471	UL29	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:113258	VCP	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113323	BioGRID:121649	WDR48	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113323	BioGRID:113323	WRN	BioGRID	PubMed	Reconstituted Complex
BioGRID:113323	BioGRID:121227	WRNIP1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:113323	BioGRID:113353	XRCC5	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:113323	BioGRID:108822	XRCC6	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex

Pathways from BioSystems

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Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
Regulation of Telomerase, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Telomerase, organism-specific biosystem
Regulation of Telomerase

General gene information

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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

Genotypes

See WRN SNP Geneview Report
See WRN SNP Genotype Report
See WRN SNP Variation Viewer Report

Homology

Homologs of the WRN gene: The WRN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

DKFZp686C2056

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
3'-5' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
ATP binding	IEA Inferred from Electronic Annotation more info
ATP-dependent 3'-5' DNA helicase activity	IEA Inferred from Electronic Annotation more info
ATP-dependent DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
ATPase activity	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
DNA helicase activity	IMP Inferred from Mutant Phenotype more info	PubMed
G-quadruplex DNA binding	IDA Inferred from Direct Assay more info	PubMed
Y-form DNA binding	IDA Inferred from Direct Assay more info	PubMed
bubble DNA binding	IDA Inferred from Direct Assay more info	PubMed
exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
four-way junction helicase activity	IDA Inferred from Direct Assay more info	PubMed
helicase activity	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
manganese ion binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein complex binding	IDA Inferred from Direct Assay more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
ATP catabolic process	IDA Inferred from Direct Assay more info	PubMed
DNA duplex unwinding	IDA Inferred from Direct Assay more info	PubMed
DNA duplex unwinding	IMP Inferred from Mutant Phenotype more info	PubMed
DNA metabolic process	IDA Inferred from Direct Assay more info	PubMed
DNA recombination	IEA Inferred from Electronic Annotation more info
DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
DNA synthesis involved in DNA repair	IDA Inferred from Direct Assay more info	PubMed
aging	NAS Non-traceable Author Statement more info	PubMed
base-excision repair	IDA Inferred from Direct Assay more info	PubMed
cell aging	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to gamma radiation	IDA Inferred from Direct Assay more info
cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
double-strand break repair	IMP Inferred from Mutant Phenotype more info
multicellular organismal aging	IMP Inferred from Mutant Phenotype more info	PubMed
nucleolus to nucleoplasm transport	IDA Inferred from Direct Assay more info	PubMed
positive regulation of hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
regulation of growth rate	IEA Inferred from Electronic Annotation more info
replication fork processing	IDA Inferred from Direct Assay more info	PubMed
replication fork processing	IMP Inferred from Mutant Phenotype more info	PubMed
replicative cell aging	IEA Inferred from Electronic Annotation more info
response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
response to UV-C	IDA Inferred from Direct Assay more info	PubMed
response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with MutLalpha complex	IDA Inferred from Direct Assay more info	PubMed
centrosome	IDA Inferred from Direct Assay more info	PubMed
nucleolus	IDA Inferred from Direct Assay more info	PubMed
NOT nucleolus	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: Werner syndrome ATP-dependent helicase

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

NP_000544.2

EC 3.6.4.12

NCBI Reference Sequences (RefSeq)

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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)

mRNA and Protein(s)

NM_000553.4 → NP_000544.2 Werner syndrome ATP-dependent helicase

Status: REVIEWED

Source sequence(s)

AB209652, AC084736, AF091214, BP279291

Consensus CDS

CCDS6082.1

UniProtKB/Swiss-Prot

Q14191

UniProtKB/TrEMBL

Q59F09

Related

ENSP00000298139, OTTHUMP00000225301, ENST00000298139, OTTHUMT00000376248

Conserved Domains (6) summary

cd00046
Location:565 – 705
Blast Score: 183

DEXDc; DEAD-like helicases superfamily. A diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

cd00079
Location:758 – 867
Blast Score: 266

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 ...

smart00341
Location:1156 – 1229
Blast Score: 190

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:538 – 1010
Blast Score: 2151

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:61 – 229
Blast Score: 624

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

smart00956
Location:958 – 1051
Blast Score: 263

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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p10 Primary Assembly

Range

30890778..31031277

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

29435610..29576278

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018919.1 Alternate CHM1_1.0

Range

31127817..31268296

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB003173.1	None
genomic	ABBA01023642.1 (86736..104363)	None
genomic	ABBA01023643.1	None
genomic	ABBA01023644.1	None
genomic	ABBA01023645.1	None
genomic	AC009563.12 (92239..117254)	None
genomic	AC084736.5 (64615..180098)	None
genomic	AF032113.1	None
genomic	AF181896.1	AAF06162.1
genomic	AF181897.1	AAF06162.1
genomic	AMYH01018623.1	None
genomic	AY442327.1	AAR05448.1
genomic	CH471080.2	EAW63424.1
		EAW63425.1
		EAW63426.1
genomic	L76937.1	AAC41981.1
mRNA	AB209652.1	BAD92889.1
mRNA	AF091214.1	AAC63361.1
mRNA	AL833572.1	None
mRNA	AY818673.1	AAX21098.1
mRNA	BP279291.1	None