U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

    POLA1 DNA polymerase alpha 1, catalytic subunit [ Homo sapiens (human) ]

    Gene ID: 5422, updated on 11-Apr-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    POLA1provided by HGNC
    Official Full Name
    DNA polymerase alpha 1, catalytic subunitprovided by HGNC
    Primary source
    HGNC:HGNC:9173
    See related
    Ensembl:ENSG00000101868 MIM:312040; AllianceGenome:HGNC:9173
    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
    NSX; PDR; POLA; p180; VEODS
    Summary
    This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]
    Expression
    Ubiquitous expression in lymph node (RPKM 2.6), bone marrow (RPKM 2.2) and 25 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See POLA1 in Genome Data Viewer
    Location:
    Xp22.11-p21.3
    Exon count:
    44
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (24693918..24996986)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (24278197..24581230)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (24712035..25015103)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene phosphate cytidylyltransferase 1B, choline Neighboring gene uncharacterized LOC124905262 Neighboring gene ribosomal protein L23 pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:24710004-24710504 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20721 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29507 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:24783273-24783773 Neighboring gene small Cajal body-specific RNA 23 Neighboring gene eukaryotic translation elongation factor 1 beta 2 pseudogene 3 Neighboring gene VISTA enhancer hs118 Neighboring gene VISTA enhancer hs119 Neighboring gene uncharacterized LOC124905263 Neighboring gene VISTA enhancer hs121 Neighboring gene VISTA enhancer hs122 Neighboring gene VISTA enhancer hs145 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:25021017-25021551 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:25022180-25022754 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:25022755-25023328 Neighboring gene aristaless related homeobox polyalanine expansion region Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:25038709-25039287 Neighboring gene PAFAH1B2 pseudogene 1 Neighboring gene aristaless related homeobox

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Pol α-primase dependent nuclear localization of the mammalian CST complex. Kelich JM, et al. Commun Biol, 2021 Mar 17. PMID 33731801, Free PMC Article
    2. Activity and fidelity of human DNA polymerase α depend on primer structure. Baranovskiy AG, et al. J Biol Chem, 2018 May 4. PMID 29555682, Free PMC Article
    3. Functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 due to X;6 translocation with an atypical X-inactivation pattern. Podolska A, et al. Am J Med Genet A, 2017 May. PMID 28371302
    4. Divalent ions attenuate DNA synthesis by human DNA polymerase α by changing the structure of the template/primer or by perturbing the polymerase reaction. Zhang Y, et al. DNA Repair (Amst), 2016 Jul. PMID 27235627, Free PMC Article
    5. Human DNA polymerase α in binary complex with a DNA:DNA template-primer. Coloma J, et al. Sci Rep, 2016 Apr 1. PMID 27032819, Free PMC Article

    See all (141) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Small tandem DNA duplications result from CST-guided Pol alpha-primase action at DNA break termini.
      Title: Small tandem DNA duplications result from CST-guided Pol α-primase action at DNA break termini.
    2. Pol alpha-primase dependent nuclear localization of the mammalian CST complex.
      Title: Pol α-primase dependent nuclear localization of the mammalian CST complex.
    3. Defective DNA Polymerase alpha-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism.
      Title: Defective DNA Polymerase α-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism.
    4. detailed structural comparison of Polalpha with other replicative DNA polymerases disclosed common features and some differences, which may reflect the specialization of each polymerase in genome replication
      Title: Activity and fidelity of human DNA polymerase α depend on primer structure.
    5. High POLA1 expression is associated with bladder cancer.
      Title: Exploring the FGFR3-related oncogenic mechanism in bladder cancer using bioinformatics strategy.
    6. Divalent ions attenuate DNA synthesis by human DNA polymerase alpha by changing the structure of the template/primer or by perturbing the polymerase reaction.
      Title: Divalent ions attenuate DNA synthesis by human DNA polymerase α by changing the structure of the template/primer or by perturbing the polymerase reaction.
    7. We propose that completely skewed XCI favoring the normal X chromosome resulted from death of cells with an active derivative X that was caused by a non-functional POLA1 gene. In summary, we conclude that functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 are responsible for the clinical phenotype of the patient
      Title: Functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 due to X;6 translocation with an atypical X-inactivation pattern.
    8. The first crystal structure of human Polalpha polymerase subunit in complex with a DNA:DNA helix shows that portion of the DNA:DNA helix in contact with the polymerase is not in a B-form but in a hybrid A-B form. The free energy cost of distorting DNA from B- to hybrid A-B form may augur the termination of primer synthesis.
      Title: Human DNA polymerase α in binary complex with a DNA:DNA template-primer.
    9. Data indicate that X-linked reticulate pigmentary disorder (XLPDR) is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-alpha.
      Title: DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis.
    10. Mutation in POLA1 is responsible for XLPDR (MIM: 312040) and demonstrates a role for this gene in interferon regulation
      Title: DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    Phenotypes

    Go to the top of the page Help

    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
    X-linked intellectual disability, van Esch type
    MedGen: C4305072 OMIM: 301030 GeneReviews: Not available
    		Compare labs
    X-linked reticulate pigmentary disorder
    MedGen: C1845050 OMIM: 301220 GeneReviews: Not available
    		Compare labs

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

    Go to the top of the page Help

    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr downregulates POLA1 in HeLa cells within 12 hours of exposure PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Clone Names

    • DKFZp686K1672

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA replication origin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-directed DNA polymerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-directed DNA polymerase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-directed DNA polymerase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleotide binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    NOT involved_in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA replication initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA replication, synthesis of primer IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA strand elongation involved in DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA synthesis involved in DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    NOT involved_in DNA synthesis involved in UV-damage excision repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in double-strand break repair via nonhomologous end joining IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in lagging strand elongation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in lagging strand elongation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in leading strand elongation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in leading strand elongation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitotic DNA replication initiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    NOT involved_in nucleotide-excision repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of type I interferon production IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of alpha DNA polymerase:primase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of alpha DNA polymerase:primase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of alpha DNA polymerase:primase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of alpha DNA polymerase:primase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear envelope IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

    Go to the top of the page Help
    Preferred Names
    DNA polymerase alpha catalytic subunit
    Names
    DNA polymerase alpha catalytic subunit p180
    polymerase (DNA directed), alpha 1, catalytic subunit
    polymerase (DNA) alpha 1, catalytic subunit
    polymerase (DNA-directed), alpha (70kD)
    NP_001317289.1
    NP_001365232.1
    NP_058633.2
    XP_011543842.1
    XP_011543843.1
    XP_016885083.1
    XP_016885084.1
    XP_016885085.1
    XP_024308160.1
    XP_047298136.1
    XP_047298137.1
    XP_047298138.1
    XP_047298139.1
    XP_054183220.1
    XP_054183221.1
    XP_054183222.1
    XP_054183223.1
    XP_054183224.1
    XP_054183225.1
    XP_054183226.1
    XP_054183227.1
    XP_054183228.1
    XP_054183229.1

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    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_016798.2 RefSeqGene

      Range
      4972..308040
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001330360.2 → NP_001317289.1  DNA polymerase alpha catalytic subunit isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC002504, AC004655, AC079375, AC135280, KF459037
      Consensus CDS
      CCDS83462.1
      UniProtKB/TrEMBL
      A6NMQ1
      Related
      ENSP00000368358.3, ENST00000379068.8
      Conserved Domains (5) summary
      cd05776
      Location:541 → 773
      DNA_polB_alpha_exo; inactive DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase alpha, a family-B DNA polymerase
      cd05532
      Location:838 → 1248
      POLBc_alpha; DNA polymerase type-B alpha subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) alpha is almost exclusively ...
      TIGR00592
      Location:56 → 1231
      pol2; DNA polymerase (pol2)
      pfam08996
      Location:1271 → 1461
      zf-DNA_Pol; DNA Polymerase alpha zinc finger
      pfam12254
      Location:41 → 101
      DNA_pol_alpha_N; DNA polymerase alpha subunit p180 N terminal

    2. NM_001378303.1 → NP_001365232.1  DNA polymerase alpha catalytic subunit isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC002504, AC004655, AC079375, AC135280, KF459037
      Conserved Domains (2) summary
      TIGR00592
      Location:56 → 1206
      pol2; DNA polymerase (pol2)
      pfam08996
      Location:1246 → 1436
      zf-DNA_Pol; DNA Polymerase alpha zinc finger

    3. NM_016937.4 → NP_058633.2  DNA polymerase alpha catalytic subunit isoform 2

      See identical proteins and their annotated locations for NP_058633.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC004655, BM664024, BU508486, BX648513, CN364591, X06745
      Consensus CDS
      CCDS14214.1
      UniProtKB/Swiss-Prot
      P09884, Q86UQ7
      Related
      ENSP00000368349.3, ENST00000379059.7
      Conserved Domains (5) summary
      cd05776
      Location:535 → 767
      DNA_polB_alpha_exo; inactive DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase alpha, a family-B DNA polymerase
      cd05532
      Location:832 → 1242
      POLBc_alpha; DNA polymerase type-B alpha subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) alpha is almost exclusively ...
      TIGR00592
      Location:50 → 1225
      pol2; DNA polymerase (pol2)
      pfam08996
      Location:1265 → 1455
      zf-DNA_Pol; DNA Polymerase alpha zinc finger
      pfam12254
      Location:35 → 95
      DNA_pol_alpha_N; DNA polymerase alpha subunit p180 N terminal

    RNA

    1. NR_165482.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC002504, AC004655, AC079375, AC135280
      Related
      ENST00000672178.1

    2. NR_165483.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC002504, AC004655, AC079375, AC135280, KF459037

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      24693918..24996986
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017029595.3 → XP_016885084.1  DNA polymerase alpha catalytic subunit isoform X2

    2. XM_017029594.3 → XP_016885083.1  DNA polymerase alpha catalytic subunit isoform X1

    3. XM_017029596.2 → XP_016885085.1  DNA polymerase alpha catalytic subunit isoform X3

    4. XM_011545540.4 → XP_011543842.1  DNA polymerase alpha catalytic subunit isoform X4

      Conserved Domains (5) summary
      cd05776
      Location:541 → 773
      DNA_polB_alpha_exo; inactive DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase alpha, a family-B DNA polymerase
      cd05532
      Location:838 → 1248
      POLBc_alpha; DNA polymerase type-B alpha subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) alpha is almost exclusively ...
      TIGR00592
      Location:56 → 1231
      pol2; DNA polymerase (pol2)
      pfam08996
      Location:1271 → 1349
      zf-DNA_Pol; DNA Polymerase alpha zinc finger
      pfam12254
      Location:41 → 101
      DNA_pol_alpha_N; DNA polymerase alpha subunit p180 N terminal

    5. XM_047442180.1 → XP_047298136.1  DNA polymerase alpha catalytic subunit isoform X5

    6. XM_024452392.2 → XP_024308160.1  DNA polymerase alpha catalytic subunit isoform X7

      Conserved Domains (1) summary
      TIGR00592
      Location:56 → 1187
      pol2; DNA polymerase (pol2)

    7. XM_011545541.3 → XP_011543843.1  DNA polymerase alpha catalytic subunit isoform X8

      Conserved Domains (5) summary
      cd05776
      Location:541 → 773
      DNA_polB_alpha_exo; inactive DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase alpha, a family-B DNA polymerase
      COG0417
      Location:615 → 856
      PolB; DNA polymerase elongation subunit (family B) [Replication, recombination and repair]
      cl10023
      Location:838 → 856
      POLBc; DNA polymerase type-B family catalytic domain. DNA-directed DNA polymerases elongate DNA by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA. DNA-directed DNA polymerases are multifunctional with both synthetic ...
      pfam03104
      Location:377 → 717
      DNA_pol_B_exo1; DNA polymerase family B, exonuclease domain
      pfam12254
      Location:41 → 101
      DNA_pol_alpha_N; DNA polymerase alpha subunit p180 N terminal

    8. XM_047442183.1 → XP_047298139.1  DNA polymerase alpha catalytic subunit isoform X9

    9. XM_047442181.1 → XP_047298137.1  DNA polymerase alpha catalytic subunit isoform X6

    10. XM_047442182.1 → XP_047298138.1  DNA polymerase alpha catalytic subunit isoform X6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      24278197..24581230
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327246.1 → XP_054183221.1  DNA polymerase alpha catalytic subunit isoform X2

    2. XM_054327245.1 → XP_054183220.1  DNA polymerase alpha catalytic subunit isoform X1

    3. XM_054327247.1 → XP_054183222.1  DNA polymerase alpha catalytic subunit isoform X3

    4. XM_054327248.1 → XP_054183223.1  DNA polymerase alpha catalytic subunit isoform X4

    5. XM_054327249.1 → XP_054183224.1  DNA polymerase alpha catalytic subunit isoform X5

    6. XM_054327252.1 → XP_054183227.1  DNA polymerase alpha catalytic subunit isoform X7

    7. XM_054327253.1 → XP_054183228.1  DNA polymerase alpha catalytic subunit isoform X8

    8. XM_054327254.1 → XP_054183229.1  DNA polymerase alpha catalytic subunit isoform X9

    9. XM_054327250.1 → XP_054183225.1  DNA polymerase alpha catalytic subunit isoform X6

    10. XM_054327251.1 → XP_054183226.1  DNA polymerase alpha catalytic subunit isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P09884.2 GenPept UniProtKB/Swiss-Prot:P09884

    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
    Miscellaneous