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    ANKH ANKH inorganic pyrophosphate transport regulator [ Homo sapiens (human) ]

    Gene ID: 56172, updated on 11-Apr-2024

    Summary

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    Official Symbol
    ANKHprovided by HGNC
    Official Full Name
    ANKH inorganic pyrophosphate transport regulatorprovided by HGNC
    Primary source
    HGNC:HGNC:15492
    See related
    Ensembl:ENSG00000154122 MIM:605145; AllianceGenome:HGNC:15492
    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
    ANK; CMDJ; HANK; MANK; CCAL2; CPPDD; SLC62A1
    Summary
    This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in prostate (RPKM 21.9), brain (RPKM 17.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    5p15.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (14704800..14871778, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (14644272..14811218, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (14704909..14871887, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 13 Neighboring gene small nucleolar RNA, C/D box 141B Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:14663902-14664704 Neighboring gene Sharpr-MPRA regulatory region 4048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22409 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22411 Neighboring gene OTULIN divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22412 Neighboring gene OTU deubiquitinase with linear linkage specificity Neighboring gene uncharacterized LOC100130744 Neighboring gene uncharacterized LOC124900944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22413 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:14727488-14727682 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14727811-14728770 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14728771-14729729 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22414 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:14809578-14810777 Neighboring gene RBBP4 pseudogene 1 Neighboring gene microRNA 4637 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15944 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15945 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15946 Neighboring gene heterogeneous nuclear ribonucleoprotein K pseudogene 5 Neighboring gene ubiquinol-cytochrome c reductase binding protein pseudogene 3

    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
    • 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. Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. Vijen S, et al. Sci Rep, 2020 May 4. PMID 32366894, Free PMC Article
    2. Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts. Chen IP, et al. Stem Cell Reports, 2017 Nov 14. PMID 29056330, Free PMC Article
    3. The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface. Seifert W, et al. Hum Mol Genet, 2016 Sep 1. PMID 27466194
    4. The association between ANKH promoter polymorphism and chondrocalcinosis is independent of age and osteoarthritis: results of a case-control study. Abhishek A, et al. Arthritis Res Ther, 2014 Jan 27. PMID 24467728, Free PMC Article
    5. Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease. Uzuki M, et al. J Rheumatol, 2014 Jan. PMID 24293574, Free PMC Article

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP, Not Pyrophosphate.
      Title: The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP, Not Pyrophosphate.
    2. m(6)A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3pAQP1/ANKH axis.
      Title: m(6)A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3p‒AQP1/ANKH axis.
    3. Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1.
      Title: Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1.
    4. Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia.
      Title: Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia.
    5. We used human vascular smooth muscle cells (VSMCs) and a rat model of chronic renal failure (CRF), and observed a native protective mechanism by which VC is reduced via the activation of Wnt1 and its transcriptional target ANKH inorganic pyrophosphate transport regulator (ANKH) gene
      Title: Wnt1 inhibits vascular smooth muscle cell calcification by promoting ANKH expression.
    6. ANK/ANKH protein carrying craniometaphyseal dysplasia mutations is present only at low levels due to rapid protein degradation. Decreased amounts of functional ANKH and improper subcellular localization are likely to contribute to CMD although these findings do not fully explain the pathogenic mechanisms seen in patients or the mouse model.
      Title: Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia.
    7. Craniometaphyseal dysplasia mutations in ANKH diminish hiPSC differentiation into osteoclasts in vitro.
      Title: Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.
    8. our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD.
      Title: Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression.
    9. Results show that ANK localizes to the trans-Golgi network (TGN), clathrin-coated vesicles and the plasma membrane, and is required for endosomal function and endocytosis
      Title: The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface.
    10. This study validates the association between a functional polymorphism in the 5' UTR of ANKH and Chondrocalcinosis
      Title: The association between ANKH promoter polymorphism and chondrocalcinosis is independent of age and osteoarthritis: results of a case-control study.
    Submit: New GeneRIF Correction See all GeneRIFs (52)

    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
    Chondrocalcinosis 2
    MedGen: C0856830 OMIM: 118600 GeneReviews: Not available
    		Compare labs
    Craniometaphyseal dysplasia, autosomal dominant
    MedGen: C1852502 OMIM: 123000 GeneReviews: Craniometaphyseal Dysplasia, Autosomal Dominant
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-02-23)

    ClinGen Genome Curation Page
    Haploinsufficency

    No evidence available (Last evaluated 2022-02-23)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
    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

    Clone Names

    • FLJ27166

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables inorganic diphosphate transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables inorganic diphosphate transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables inorganic diphosphate transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables phosphate transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphate transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphate transmembrane transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in ATP export IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in bone mineralization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cementum mineralization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in diphosphate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inhibition of non-skeletal tissue mineralization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inorganic diphosphate transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in locomotory behavior NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in muscle cell cellular homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphate ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphate ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of bone mineralization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of bone mineralization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to sodium phosphate IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal system development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in outer membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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
    		 PubMed 
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    mineralization regulator ANKH; progressive ankylosis protein homolog
    Names
    ATP carrier protein ANKH
    ankylosis, progressive homolog

    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_008273.2 RefSeqGene

      Range
      5008..171986
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1362

    mRNA and Protein(s)

    1. NM_054027.6 → NP_473368.1  mineralization regulator ANKH

      See identical proteins and their annotated locations for NP_473368.1

      Status: REVIEWED

      Source sequence(s)
      AC010491, BC009835, BQ008340, BU193060, DA126651
      Consensus CDS
      CCDS3885.1
      UniProtKB/Swiss-Prot
      B2RCA7, B3KMG4, D3DTD4, Q9HCJ1, Q9NQW2
      UniProtKB/TrEMBL
      Q53HE9
      Related
      ENSP00000284268.6, ENST00000284268.8
      Conserved Domains (1) summary
      pfam07260
      Location:1 → 345
      ANKH; Progressive ankylosis protein (ANKH)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      14704800..14871778 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017009644.3 → XP_016865133.1  progressive ankylosis protein homolog isoform X1

      UniProtKB/TrEMBL
      Q53HE9

    2. XM_011514067.2 → XP_011512369.1  progressive ankylosis protein homolog isoform X2

      Conserved Domains (1) summary
      pfam07260
      Location:1 → 337
      ANKH; Progressive ankylosis protein (ANKH)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      14644272..14811218 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352936.1 → XP_054208911.1  progressive ankylosis protein homolog isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HCJ1.2 GenPept UniProtKB/Swiss-Prot:Q9HCJ1

    Gene LinkOut

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

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