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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
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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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