The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duple... See more...

Aliases for RNASEH2A Gene

Aliases for RNASEH2A Gene

  • Ribonuclease H2 Subunit A 2 3 4 5
  • RNASEHI 2 3 4
  • RNHIA 2 3 4
  • AGS4 2 3 4
  • Aicardi-Goutieres Syndrome 4 Protein 3 4
  • Ribonuclease H2, Large Subunit 2 3
  • Ribonuclease HI Large Subunit 3 4
  • Ribonuclease HI Subunit A 3 4
  • RNase HI Large Subunit 3 4
  • RNase H2 Subunit A 3 4
  • RNase H(35) 3 4
  • EC 3.1.26.4 4 51
  • RNHL 2 3
  • Aicardi-Goutieres Syndrome 4 2
  • Ribonuclease H2, Subunit A 2
  • RNASEH2A 5
  • THSD8 3
  • JUNB 3

External Ids for RNASEH2A Gene

Previous GeneCards Identifiers for RNASEH2A Gene

  • GC19P013048
  • GC19P013140
  • GC19P012762
  • GC19P012778
  • GC19P012918
  • GC19P012489
  • GC19P012804

Summaries for RNASEH2A Gene

Entrez Gene Summary for RNASEH2A Gene

  • The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duplexes. Mutations in this gene cause Aicardi-Goutieres Syndrome (AGS), a an autosomal recessive neurological disorder characterized by progressive microcephaly and psychomotor retardation, intracranial calcifications, elevated levels of interferon-alpha and white blood cells in the cerebrospinal fluid.[provided by RefSeq, Aug 2009]

GeneCards Summary for RNASEH2A Gene

RNASEH2A (Ribonuclease H2 Subunit A) is a Protein Coding gene. Diseases associated with RNASEH2A include Aicardi-Goutieres Syndrome 4 and Aicardi-Goutieres Syndrome. Among its related pathways are Telomere C-strand (Lagging Strand) Synthesis. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and ribonuclease activity.

UniProtKB/Swiss-Prot Summary for RNASEH2A Gene

  • Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.

Gene Wiki entry for RNASEH2A Gene

Additional gene information for RNASEH2A Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RNASEH2A Gene

Genomics for RNASEH2A Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RNASEH2A Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RNASEH2A on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RNASEH2A

Top Transcription factor binding sites by QIAGEN in the RNASEH2A gene promoter:
  • ATF-2
  • c-Jun
  • SRF (504 AA)
  • STAT1

Genomic Locations for RNASEH2A Gene

Genomic Locations for RNASEH2A Gene
chr19:12,806,584-12,813,640
(GRCh38/hg38)
Size:
7,057 bases
Orientation:
Plus strand
chr19:12,917,394-12,924,462
(GRCh37/hg19)
Size:
7,069 bases
Orientation:
Plus strand

Genomic View for RNASEH2A Gene

Genes around RNASEH2A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNASEH2A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNASEH2A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNASEH2A Gene

Proteins for RNASEH2A Gene

  • Protein details for RNASEH2A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75792-RNH2A_HUMAN
    Recommended name:
    Ribonuclease H2 subunit A
    Protein Accession:
    O75792
    Secondary Accessions:
    • B2RCY1
    • Q96F11

    Protein attributes for RNASEH2A Gene

    Size:
    299 amino acids
    Molecular mass:
    33395 Da
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.

    Three dimensional structures from OCA and Proteopedia for RNASEH2A Gene

neXtProt entry for RNASEH2A Gene

Selected DME Specific Peptides for RNASEH2A Gene

O75792:
  • GVDEAGRG
  • DEAGRGPV
  • DLEALKVADSKTL

Post-translational modifications for RNASEH2A Gene

  • Ubiquitination at Lys26, Lys64, Lys165, Lys167, Lys192, Lys198, Lys215, Lys221, and Lys267
  • Modification sites at PhosphoSitePlus

Other Protein References for RNASEH2A Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for RNASEH2A

Domains & Families for RNASEH2A Gene

Gene Families for RNASEH2A Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for RNASEH2A Gene

Suggested Antigen Peptide Sequences for RNASEH2A Gene

GenScript: Design optimal peptide antigens:
  • Ribonuclease (Q6UQL6_HUMAN)
  • Ribonuclease HI subunit A (RNH2A_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O75792

UniProtKB/Swiss-Prot:

RNH2A_HUMAN :
  • Belongs to the RNase HII family. Eukaryotic subfamily.
Family:
  • Belongs to the RNase HII family. Eukaryotic subfamily.
genes like me logo Genes that share domains with RNASEH2A: view

Function for RNASEH2A Gene

Molecular function for RNASEH2A Gene

UniProtKB/Swiss-Prot Function:
Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000269|PubMed:21177858};.

Enzyme Numbers (IUBMB) for RNASEH2A Gene

Phenotypes From GWAS Catalog for RNASEH2A Gene

Gene Ontology (GO) - Molecular Function for RNASEH2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003723 RNA binding IEA --
GO:0004518 nuclease activity IEA --
GO:0004519 endonuclease activity IEA --
GO:0004523 RNA-DNA hybrid ribonuclease activity IEA,IDA 21177858
genes like me logo Genes that share ontologies with RNASEH2A: view
genes like me logo Genes that share phenotypes with RNASEH2A: view

Human Phenotype Ontology for RNASEH2A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for RNASEH2A

CRISPR Products

miRNA for RNASEH2A Gene

Transcription Factor Targets for RNASEH2A Gene

Selected GeneGlobe predicted Target genes for RNASEH2A

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNASEH2A

No data available for Animal Models and HOMER Transcription for RNASEH2A Gene

Localization for RNASEH2A Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNASEH2A Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RNASEH2A gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RNASEH2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol IDA --
GO:0032299 ribonuclease H2 complex IBA,IDA 21177858
genes like me logo Genes that share ontologies with RNASEH2A: view

Pathways & Interactions for RNASEH2A Gene

PathCards logo

SuperPathways for RNASEH2A Gene

SuperPathway Contained pathways
1 Telomere C-strand (Lagging Strand) Synthesis
genes like me logo Genes that share pathways with RNASEH2A: view

Pathways by source for RNASEH2A Gene

1 KEGG pathway for RNASEH2A Gene

Gene Ontology (GO) - Biological Process for RNASEH2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006260 DNA replication TAS 21177858
GO:0006298 mismatch repair IDA 23603115
GO:0006401 RNA catabolic process TAS,IDA 21177858
GO:0016070 RNA metabolic process IEA --
GO:0043137 DNA replication, removal of RNA primer IBA 21873635
genes like me logo Genes that share ontologies with RNASEH2A: view

No data available for SIGNOR curated interactions for RNASEH2A Gene

Drugs & Compounds for RNASEH2A Gene

(2) Drugs for RNASEH2A Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
Manganese Approved Nutra 56
genes like me logo Genes that share compounds with RNASEH2A: view

Transcripts for RNASEH2A Gene

mRNA/cDNA for RNASEH2A Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNASEH2A

Alternative Splicing Database (ASD) splice patterns (SP) for RNASEH2A Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8
SP1: - -
SP2: - -
SP3: -
SP4: -
SP5:

Relevant External Links for RNASEH2A Gene

GeneLoc Exon Structure for
RNASEH2A

Expression for RNASEH2A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RNASEH2A Gene

Protein differential expression in normal tissues from HIPED for RNASEH2A Gene

This gene is overexpressed in Peripheral blood mononuclear cells (15.7), Lymph node (13.4), and Monocytes (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RNASEH2A Gene



Protein tissue co-expression partners for RNASEH2A Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RNASEH2A

SOURCE GeneReport for Unigene cluster for RNASEH2A Gene:

Hs.532851

Evidence on tissue expression from TISSUES for RNASEH2A Gene

  • Nervous system(4.5)
  • Skin(3.1)
  • Lung(2.9)
  • Blood(2.3)
  • Intestine(2.2)
  • Lymph node(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RNASEH2A Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • meninges
  • mouth
  • neck
  • nose
  • outer ear
  • skull
Thorax:
  • chest wall
Abdomen:
  • abdominal wall
  • liver
  • spleen
  • stomach
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with RNASEH2A: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for RNASEH2A Gene

Orthologs for RNASEH2A Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for RNASEH2A Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RNASEH2A 30 31
  • 98.77 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RNASEH2A 30 31
  • 86.8 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RNASEH2A 30 31
  • 86.69 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rnaseh2a 30
  • 82.77 (n)
Mouse
(Mus musculus)
Mammalia Rnaseh2a 30 17 31
  • 81.94 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RNASEH2A 31
  • 66 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RNASEH2A 31
  • 62 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RNASEH2A 31
  • 64 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rnaseh2a 30
  • 63.48 (n)
MGC76169 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.8314 30
Zebrafish
(Danio rerio)
Actinopterygii rnaseh2a 30 31
  • 64.66 (n)
OneToOne
wufa92h07 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2178 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG13690 30 31 32
  • 54.98 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007741 30
  • 53.72 (n)
Worm
(Caenorhabditis elegans)
Secernentea rnh-2 30 31 32
  • 49.63 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AER363W 30
  • 53.91 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RNH201 30 31 33
  • 51.45 (n)
OneToOne
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F04774g 30
  • 50 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT2G25100 30
  • 55.27 (n)
Rice
(Oryza sativa)
Liliopsida Os11g0153900 30
  • 54.17 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU09608 30
  • 53.5 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 52 (a)
OneToOne
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes rnh201 30
  • 48.17 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.1877 30
Species where no ortholog for RNASEH2A was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for RNASEH2A Gene

ENSEMBL:
Gene Tree for RNASEH2A (if available)
TreeFam:
Gene Tree for RNASEH2A (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RNASEH2A: view image

Paralogs for RNASEH2A Gene

(1) SIMAP similar genes for RNASEH2A Gene using alignment to 2 proteins:

  • RNH2A_HUMAN
  • Q6UQL6_HUMAN
genes like me logo Genes that share paralogs with RNASEH2A: view

No data available for Paralogs for RNASEH2A Gene

Variants for RNASEH2A Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RNASEH2A Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
636354 Pathogenic: not provided 12,810,354(+) TG/T FRAMESHIFT_VARIANT
641095 Uncertain Significance: Aicardi Goutieres syndrome 4 12,810,333(+) C/A MISSENSE_VARIANT
645703 Uncertain Significance: Aicardi Goutieres syndrome 4 12,813,148(+) C/T MISSENSE_VARIANT
657197 Uncertain Significance: Aicardi Goutieres syndrome 4 12,807,281(+) C/T MISSENSE_VARIANT
659767 Uncertain Significance: Aicardi Goutieres syndrome 4 12,813,160(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for RNASEH2A Gene

Structural Variations from Database of Genomic Variants (DGV) for RNASEH2A Gene

Variant ID Type Subtype PubMed ID
dgv138n111 CNV deletion 26073780
nsv1160586 CNV duplication 26073780
nsv513711 OTHER inversion 21212237
nsv513712 OTHER inversion 21212237
nsv953977 CNV deletion 24416366

Variation tolerance for RNASEH2A Gene

Residual Variation Intolerance Score: 54.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.31; 53.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RNASEH2A Gene

Human Gene Mutation Database (HGMD)
RNASEH2A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNASEH2A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNASEH2A Gene

Disorders for RNASEH2A Gene

MalaCards: The human disease database

(12) MalaCards diseases for RNASEH2A Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
aicardi-goutieres syndrome 4
  • aicardi-goutieres syndrome 1
aicardi-goutieres syndrome
  • aicardi-goutieres syndrome 1
vasculopathy, retinal, with cerebral leukodystrophy
  • rvcl
sting-associated vasculopathy with onset in infancy
  • sting-associated vasculopathy, infantile-onset
chilblain lupus 1
  • chbl1
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RNH2A_HUMAN
  • Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269 PubMed:16845400, ECO:0000269 PubMed:17846997, ECO:0000269 PubMed:20131292}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for RNASEH2A

genes like me logo Genes that share disorders with RNASEH2A: view

No data available for Genatlas for RNASEH2A Gene

Publications for RNASEH2A Gene

  1. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. (PMID: 16845400) Crow YJ … Jackson AP (Nature genetics 2006) 2 3 4 23
  2. Cloning of the cDNA encoding the large subunit of human RNase HI, a homologue of the prokaryotic RNase HII. (PMID: 9789007) Frank P … Büsen W (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4
  3. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects. (PMID: 21177858) Figiel M … Nowotny M (The Journal of biological chemistry 2011) 3 4
  4. Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome. (PMID: 20131292) Ramantani G … Lee-Kirsch MA (Arthritis and rheumatism 2010) 4 23
  5. Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. (PMID: 19015152) Chon H … Cerritelli SM (Nucleic acids research 2009) 3 23

Products for RNASEH2A Gene

Sources for RNASEH2A Gene