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    TCN2 transcobalamin 2 [ Homo sapiens (human) ]

    Gene ID: 6948, updated on 3-Nov-2024

    Summary

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    Official Symbol
    TCN2provided by HGNC
    Official Full Name
    transcobalamin 2provided by HGNC
    Primary source
    HGNC:HGNC:11653
    See related
    Ensembl:ENSG00000185339 MIM:613441; AllianceGenome:HGNC:11653
    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
    II; TC; TC2; TC-2; TCII; TC II; D22S676; D22S750
    Summary
    This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
    Expression
    Broad expression in kidney (RPKM 50.7), gall bladder (RPKM 33.1) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TCN2 in Genome Data Viewer
    Location:
    22q12.2
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (30607174..30627271)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (31070745..31090856)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (31003161..31023258)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak4480 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30967053-30967554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30969210-30969891 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30969892-30970572 Neighboring gene galactose-3-O-sulfotransferase 1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:30982632-30983831 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:30987725-30988440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18840 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:31002947-31003526 Neighboring gene Sharpr-MPRA regulatory region 4664 Neighboring gene pescadillo ribosomal biogenesis factor 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:31030490-31031194 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13614 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:31042177-31042759 Neighboring gene solute carrier family 35 member E4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18842 Neighboring gene ribosomal protein L13a pseudogene 26 Neighboring gene dual specificity phosphatase 18 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13615 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13616 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:31112835-31114034 Neighboring gene oxysterol binding protein 2 Neighboring gene microRNA 3200

    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. Transcobalamin deficiency caused by compound heterozygosity for two novel mutations in the TCN2 gene: a study of two affected siblings, their brother, and their parents. Nissen PH, et al. J Inherit Metab Dis, 2010 Dec. PMID 20607612
    2. Function and stability of human transcobalamin II: role of intramolecular disulfide bonds C98-C291 and C147-C187. Kalra S, et al. Am J Physiol Cell Physiol, 2003 Jul. PMID 12660150
    3. Transcobalamin deficiency due to activation of an intra exonic cryptic splice site. Namour F, et al. Br J Haematol, 2003 Dec. PMID 14632784
    4. Population-based differences in frequency of the transcobalamin II Pro259Arg polymorphism. Bowen RA, et al. Clin Biochem, 2004 Feb. PMID 14725943
    5. Effects of TCN2 776C>G on vitamin B, folate, and total homocysteine levels in kidney transplant patients. Winkelmayer WC, et al. Kidney Int, 2004 May. PMID 15086930

    See all (145) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.
      Title: Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.
    2. Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.
      Title: Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.
    3. "Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".
      Title: "Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".
    4. Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women.
      Title: Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women.
    5. Transcobalamin II deficiency in twins with a novel variant in the TCN2 gene: case report and review of literature.
      Title: Transcobalamin II deficiency in twins with a novel variant in the TCN2 gene: case report and review of literature.
    6. Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter.
      Title: Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter.
    7. Relationship between cobalt transporter II gene rs9606756 site mutant and serum homocysteine level and recurrent cerebral infarction in young and middle-aged people.
      Title: Relationship between cobalt transporter II gene rs9606756 site mutant and serum homocysteine level and recurrent cerebral infarction in young and middle-aged people.
    8. 3'-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.
      Title: 3'-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.
    9. Association of single nucleotide polymorphisms of MTHFR, TCN2, RNF213 with susceptibility to hypertension and blood pressure.
      Title: Association of single nucleotide polymorphisms of MTHFR, TCN2, RNF213 with susceptibility to hypertension and blood pressure.
    10. A decreased risk of cleft for children carrying the 667G allele at TCN2 gene (P = 0.02).
      Title: Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq.
    Submit: New GeneRIF Correction See all GeneRIFs (74)

    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

    Associated conditions

    Description Tests
    Transcobalamin II deficiency
    MedGen: C0342701 OMIM: 275350 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies susceptibility loci for Wilms tumor.
    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

    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 cargo receptor ligand activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables cobalamin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cobalamin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cobalamin transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cobalamin transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cobalamin transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in cobalt ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    transcobalamin-2
    Names
    macrocytic anemia
    transcobalamin II
    transcobalamin II; macrocytic anemia
    vitamin B12-binding protein 2

    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

    1. NG_007263.1 RefSeqGene

      Range
      4910..24887
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_116

    mRNA and Protein(s)

    1. NM_000355.4 → NP_000346.2  transcobalamin-2 isoform 1 precursor

      See identical proteins and their annotated locations for NP_000346.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC005006, BC001176
      Consensus CDS
      CCDS13881.1
      UniProtKB/Swiss-Prot
      P20062, Q96FD4, Q9BVI8, Q9UCI5, Q9UCI6, Q9UDM0
      UniProtKB/TrEMBL
      A0A8V8TLM2, A0A8V8TN28
      Related
      ENSP00000215838.3, ENST00000215838.8
      Conserved Domains (2) summary
      pfam01122
      Location:19 → 316
      Cobalamin_bind; Eukaryotic cobalamin-binding protein
      pfam14478
      Location:353 → 426
      DUF4430; Domain of unknown function (DUF4430)

    2. NM_001184726.2 → NP_001171655.1  transcobalamin-2 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001171655.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC005006, BC011239
      Consensus CDS
      CCDS54519.1
      UniProtKB/TrEMBL
      A0A8V8TLM2, A0A8V8TN28
      Related
      ENSP00000384914.3, ENST00000407817.3
      Conserved Domains (2) summary
      pfam01122
      Location:19 → 297
      Cobalamin_bind; Eukaryotic cobalamin-binding protein
      pfam14478
      Location:326 → 399
      DUF4430; Domain of unknown function (DUF4430)

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      30607174..30627271
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      31070745..31090856
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001190420.1: Suppressed sequence

      Description
      NM_001190420.1: This RefSeq was permanently suppressed because the splice pattern is likely only found in rare individuals with a polymorphic splice site (rs9606756).
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20062.3 GenPept UniProtKB/Swiss-Prot:P20062

    Gene LinkOut

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

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