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    FHIT fragile histidine triad diadenosine triphosphatase [ Homo sapiens (human) ]

    Gene ID: 2272, updated on 2-Nov-2024

    Summary

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    Official Symbol
    FHITprovided by HGNC
    Official Full Name
    fragile histidine triad diadenosine triphosphataseprovided by HGNC
    Primary source
    HGNC:HGNC:3701
    See related
    Ensembl:ENSG00000189283 MIM:601153; AllianceGenome:HGNC:3701
    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
    FRA3B; AP3Aase
    Summary
    The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]
    Expression
    Ubiquitous expression in gall bladder (RPKM 2.2), lymph node (RPKM 1.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FHIT in Genome Data Viewer
    Location:
    3p14.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (59747277..61251452, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (59787636..61294609, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (59733003..61237126, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene CFAP20DC divergent transcript Neighboring gene Sharpr-MPRA regulatory region 3507 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:59599597-59599768 Neighboring gene SNRPB2 pseudogene 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:59703433-59704161 Neighboring gene hCG1813818 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:59784329-59785528 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59793929-59794564 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59795199-59795832 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59795833-59796466 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:59803658-59804857 Neighboring gene uncharacterized LOC105377113 Neighboring gene uncharacterized LOC105377112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14494 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:60040744-60040947 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20017 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20018 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20019 Neighboring gene uncharacterized LOC107986015 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:60349391-60349588 Neighboring gene origin of replication at fragile site FRA3B Neighboring gene NANOG hESC enhancer GRCh37_chr3:60645689-60646190 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60657785-60658608 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60655264-60656034 Neighboring gene MTERF1 pseudogene 1 Neighboring gene microRNA 548bb Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60758024-60758879 Neighboring gene peptidylprolyl isomerase A pseudogene 70 Neighboring gene small nucleolar RNA U3 Neighboring gene TMED2 pseudogene 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:60921018-60922217 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:60938928-60940127 Neighboring gene uncharacterized LOC124906244 Neighboring gene uncharacterized LOC105377111 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:61015791-61016990 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:61027375-61028574 Neighboring gene Sharpr-MPRA regulatory region 1919 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:61127340-61127863 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:61126817-61127339 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20020 Neighboring gene Sharpr-MPRA regulatory region 15147 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20022 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20024 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20026 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20027 Neighboring gene Sharpr-MPRA regulatory region 9847 Neighboring gene uncharacterized LOC124909387 Neighboring gene uncharacterized LOC105377114 Neighboring gene uncharacterized LOC105377115 Neighboring gene Sharpr-MPRA regulatory region 1523

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Fragile histidine triad (FHIT) gene is overexpressed in colorectal cancer. Wierzbicki PM, et al. J Physiol Pharmacol, 2009 Oct. PMID 20083853
    2. Association of 5'-CpG island hypermethylation of the FHIT gene with lung cancer in southern-central Chinese population. Li W, et al. Cancer Biol Ther, 2010 Nov 15. PMID 20814237
    3. Restoration of fragile histidine triad (FHIT) expression inhibits cell growth and induces apoptosis in cutaneous T-cell lymphoma cell line. Song X, et al. Cancer Invest, 2010 Dec. PMID 20690795
    4. Homozygous deletion but not mutation of exons 5 and 8 of the fragile histidine triad (FHIT) gene is associated with features of differentiated thyroid carcinoma. Yin DT, et al. Ann Clin Lab Sci, 2010 Summer. PMID 20689140
    5. Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma. Kameoka Y, et al. Oncogene, 2004 Dec 2. PMID 15480422

    See all (356) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Integrated analysis of FHIT gene alterations in cancer.
      Title: Integrated analysis of FHIT gene alterations in cancer.
    2. Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
      Title: Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
    3. The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
      Title: The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
    4. Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
      Title: Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
    5. System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
      Title: System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
    6. Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
      Title: Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
    7. rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
      Title: rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
    8. Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
      Title: Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
    9. Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
      Title: Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
    10. Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.
      Title: Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (270)

    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

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2018-10-24)

    ClinGen Genome Curation PagePubMed
    Haploinsufficency

    No evidence available (Last evaluated 2018-10-24)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    A genome-wide association study (GWAS) for bronchopulmonary dysplasia.
    EBI GWAS Catalog
    A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population.
    EBI GWAS Catalog
    Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.
    EBI GWAS Catalog
    Genetic variants associated with breast size also influence breast cancer risk.
    EBI GWAS Catalog
    Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts.
    EBI GWAS Catalog
    Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
    EBI GWAS Catalog
    Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.
    EBI GWAS Catalog
    Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
    EBI GWAS Catalog
    Genome-wide association study of maternal and inherited loci for conotruncal heart defects.
    EBI GWAS Catalog
    Genome-wide association study of recurrent early-onset major depressive disorder.
    EBI GWAS Catalog
    Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study.
    EBI GWAS Catalog
    Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.
    EBI GWAS Catalog
    Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D.
    EBI GWAS Catalog
    Variants in several genomic regions associated with asperger disorder.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat-fused fragile histidine triad (FHIT) can robustly inhibit growth and induce apoptosis of human hepatocellular carcinoma cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables adenosine 5'-monophosphoramidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables adenylylsulfatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables adenylylsulfate-ammonia adenylyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables bis(5'-adenosyl)-triphosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables bis(5'-adenosyl)-triphosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in diadenosine triphosphate catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in diadenosine triphosphate catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway by p53 class mediator IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway by p53 class mediator IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in purine nucleotide metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in purine nucleotide metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    bis(5'-adenosyl)-triphosphatase
    Names
    AP3A hydrolase
    adenosine 5'-monophosphoramidase FHIT
    adenylylsulfatase
    adenylylsulfate-ammonia adenylyltransferase
    diadenosine 5',5'''-P1,P3-triphosphate hydrolase
    dinucleosidetriphosphatase
    NP_001159715.1
    NP_001307828.1
    NP_001307829.1
    NP_001307830.1
    NP_001341518.1
    NP_001341519.1
    NP_002003.1

    NCBI Reference Sequences (RefSeq)

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    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

    1. NG_007551.2 RefSeqGene

      Range
      5008..1509183
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166243.3 → NP_001159715.1  bis(5'-adenosyl)-triphosphatase isoform 1

      See identical proteins and their annotated locations for NP_001159715.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), as well as variants 1, 3, and 4, encodes isoform 1.
      Source sequence(s)
      AC132808, BC032336, DB477833
      Consensus CDS
      CCDS2894.1
      UniProtKB/Swiss-Prot
      A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
      Related
      ENSP00000417557.1, ENST00000476844.5
      Conserved Domains (1) summary
      cd01275
      Location:5 → 124
      FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

    2. NM_001320899.2 → NP_001307828.1  bis(5'-adenosyl)-triphosphatase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), as well as variants 1, 2, and 4, encodes isoform 1.
      Source sequence(s)
      AC132808, AK289824, DB477833
      Consensus CDS
      CCDS2894.1
      UniProtKB/Swiss-Prot
      A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
      Related
      ENSP00000417480.1, ENST00000468189.5
      Conserved Domains (1) summary
      cd01275
      Location:5 → 124
      FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

    3. NM_001320900.2 → NP_001307829.1  bis(5'-adenosyl)-triphosphatase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), as well as variants 1-3, encodes isoform 1.
      Source sequence(s)
      AC096917, AC097357, AC098480, AC099536, AC099780, AC132808, AC138071
      Consensus CDS
      CCDS2894.1
      UniProtKB/Swiss-Prot
      A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
      Conserved Domains (1) summary
      cd01275
      Location:5 → 124
      FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

    4. NM_001320901.2 → NP_001307830.1  bis(5'-adenosyl)-triphosphatase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) encodes a protein with a shorter N-terminus than isoform 1.
      Source sequence(s)
      AC132808, BE246370, DB131595
      Conserved Domains (1) summary
      cl00228
      Location:4 → 68
      HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...

    5. NM_001354589.2 → NP_001341518.1  bis(5'-adenosyl)-triphosphatase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7), as well as variant 8, encodes isoform 3.
      Source sequence(s)
      AC096917, AC097357, AC099536, AC099780, AC132808, AC138071
      Conserved Domains (1) summary
      cl00228
      Location:5 → 92
      HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...

    6. NM_001354590.2 → NP_001341519.1  bis(5'-adenosyl)-triphosphatase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8), as well as variant 7, encodes isoform 3.
      Source sequence(s)
      AC096917, AC097357, AC099536, AC099780, AC132808, AC138071
      Conserved Domains (1) summary
      cl00228
      Location:5 → 92
      HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...

    7. NM_002012.4 → NP_002003.1  bis(5'-adenosyl)-triphosphatase isoform 1

      See identical proteins and their annotated locations for NP_002003.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1-4 all encode the same isoform (1).
      Source sequence(s)
      AC132808, DB477833, U46922
      Consensus CDS
      CCDS2894.1
      UniProtKB/Swiss-Prot
      A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
      Related
      ENSP00000418582.1, ENST00000492590.6
      Conserved Domains (1) summary
      cd01275
      Location:5 → 124
      FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

    RNA

    1. NR_135491.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) is represented as non-coding because the predicted ORF does not meet RefSeq quality criteria.
      Source sequence(s)
      AC099780, AC132808, AK127931, BE246370

    2. NR_148921.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC096917, AC097357, AC104164, AC138071

    3. NR_148922.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC096917, AC097357, AC138071

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      59747277..61251452 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      59787636..61294609 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49789.3 GenPept UniProtKB/Swiss-Prot:P49789

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools