This gene encodes the smallest subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein enhances the activity of DNA polymerase delta and plays a role in fork repair and stabilization through interactions with the DNA helicase Bloom syndrome prot... See more...

Aliases for POLD4 Gene

Aliases for POLD4 Gene

  • DNA Polymerase Delta 4, Accessory Subunit 2 3 5
  • POLDS 2 3 4
  • Polymerase (DNA-Directed), Delta 4, Accessory Subunit 2 3
  • Polymerase (DNA) Delta 4, Accessory Subunit 2 3
  • DNA Polymerase Delta Smallest Subunit P12 2 3
  • DNA Polymerase Delta Subunit 4 3 4
  • P12 2 3
  • DNA Polymerase Delta Subunit P12 4
  • POLD4 5

External Ids for POLD4 Gene

Previous GeneCards Identifiers for POLD4 Gene

  • GC11M069752
  • GC11M068815
  • GC11M067369
  • GC11M066894
  • GC11M066875
  • GC11M067119
  • GC11M063448

Summaries for POLD4 Gene

Entrez Gene Summary for POLD4 Gene

  • This gene encodes the smallest subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein enhances the activity of DNA polymerase delta and plays a role in fork repair and stabilization through interactions with the DNA helicase Bloom syndrome protein. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneCards Summary for POLD4 Gene

POLD4 (DNA Polymerase Delta 4, Accessory Subunit) is a Protein Coding gene. Diseases associated with POLD4 include Bloom Syndrome and Autosomal Recessive Non-Syndromic Intellectual Disability. Among its related pathways are Transcription-Coupled Nucleotide Excision Repair (TC-NER) and Telomere C-strand (Lagging Strand) Synthesis. Gene Ontology (GO) annotations related to this gene include DNA-directed DNA polymerase activity. An important paralog of this gene is ENSG00000256514.

UniProtKB/Swiss-Prot Summary for POLD4 Gene

  • As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480).

Gene Wiki entry for POLD4 Gene

Additional gene information for POLD4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for POLD4 Gene

Genomics for POLD4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for POLD4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around POLD4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for POLD4

Top Transcription factor binding sites by QIAGEN in the POLD4 gene promoter:
  • c-Rel
  • C/EBPalpha
  • FOXL1
  • GATA-2
  • Lmo2
  • MIF-1
  • NF-1
  • Sp1

Genomic Locations for POLD4 Gene

Genomic Locations for POLD4 Gene
chr11:67,350,765-67,356,972
(GRCh38/hg38)
Size:
6,208 bases
Orientation:
Minus strand
chr11:67,118,248-67,124,443
(GRCh37/hg19)
Size:
6,196 bases
Orientation:
Minus strand

Genomic View for POLD4 Gene

Genes around POLD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
POLD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for POLD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for POLD4 Gene

Proteins for POLD4 Gene

  • Protein details for POLD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HCU8-DPOD4_HUMAN
    Recommended name:
    DNA polymerase delta subunit 4
    Protein Accession:
    Q9HCU8
    Secondary Accessions:
    • F5H506

    Protein attributes for POLD4 Gene

    Size:
    107 amino acids
    Molecular mass:
    12433 Da
    Quaternary structure:
    • Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:16510448, PubMed:17317665, PubMed:22801543). Within this complex, directly interacts with POLD1 and POLD2 (PubMed:12403614, PubMed:16510448). Directly interacts with PCNA, as do POLD1 and POLD3; this interaction stimulates Pol-delta4 polymerase activity (PubMed:24022480). As POLD1 and POLD2, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity (PubMed:15670210). Upon genotoxic stress induced by DNA damaging agents or by replication stress, POLD4 is proteolytically degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) which has an increased proofreading activity (PubMed:22801543, PubMed:17317665). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).

    Three dimensional structures from OCA and Proteopedia for POLD4 Gene

    Alternative splice isoforms for POLD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for POLD4 Gene

Post-translational modifications for POLD4 Gene

  • Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:17317665, PubMed:16934752, PubMed:23233665, PubMed:23913683). This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)) (PubMed:23233665, PubMed:24022480). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage (PubMed:24022480).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for POLD4 Gene

No data available for DME Specific Peptides for POLD4 Gene

Domains & Families for POLD4 Gene

Gene Families for POLD4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for POLD4 Gene

InterPro:
Blocks:
  • DNA polymerase delta, subunit 4
ProtoNet:

Suggested Antigen Peptide Sequences for POLD4 Gene

GenScript: Design optimal peptide antigens:
  • DNA polymerase delta subunit p12 (DPOD4_HUMAN)
  • Polymerase (DNA-directed), delta 4 (Q6NSD7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HCU8

UniProtKB/Swiss-Prot:

DPOD4_HUMAN :
  • Belongs to the DNA polymerase delta subunit 4 family.
Family:
  • Belongs to the DNA polymerase delta subunit 4 family.
genes like me logo Genes that share domains with POLD4: view

Function for POLD4 Gene

Molecular function for POLD4 Gene

UniProtKB/Swiss-Prot Function:
As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480).
UniProtKB/Swiss-Prot Induction:
In response to DNA damage, genotoxic stress and replication stress, following UV irradiation, ionizing radiation, treatment with methyl methanesulfonate, hydroxyurea, or with aphidicolin, protein expression drops to undetectable levels, due to proteasomal degradation (PubMed:17317665, PubMed:22801543, PubMed:23233665, PubMed:23913683, PubMed:24300032). This down-regulation is ATR-dependent (PubMed:17317665).

Phenotypes From GWAS Catalog for POLD4 Gene

Gene Ontology (GO) - Molecular Function for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003887 contributes_to DNA-directed DNA polymerase activity IBA 21873635
GO:0005515 protein binding IPI 12403614
genes like me logo Genes that share ontologies with POLD4: view
genes like me logo Genes that share phenotypes with POLD4: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for POLD4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for POLD4 Gene

Localization for POLD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for POLD4 Gene

Nucleus. Note=Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation. {ECO:0000269 PubMed:22801543}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for POLD4 gene
Compartment Confidence
nucleus 5
cytosol 1
extracellular 0
mitochondrion 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0042025 host cell nucleus IEA --
GO:0043625 delta DNA polymerase complex IBA 21873635
genes like me logo Genes that share ontologies with POLD4: view

Pathways & Interactions for POLD4 Gene

PathCards logo

SuperPathways for POLD4 Gene

SuperPathway Contained pathways
1 Telomere C-strand (Lagging Strand) Synthesis
.48
2 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
3 Mismatch repair
4 DNA Double-Strand Break Repair
5 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
genes like me logo Genes that share pathways with POLD4: view

Pathways by source for POLD4 Gene

1 GeneGo (Thomson Reuters) pathway for POLD4 Gene
  • Cell cycle Transition and termination of DNA replication
2 Qiagen pathways for POLD4 Gene
  • Cell Cycle Control of Chromosomal Replication
  • DNA Repair Mechanisms

Gene Ontology (GO) - Biological Process for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000723 telomere maintenance TAS --
GO:0000731 DNA synthesis involved in DNA repair IBA 21873635
GO:0006260 DNA replication IEA --
GO:0006261 DNA-dependent DNA replication IBA 21873635
GO:0006281 DNA repair IEA --
genes like me logo Genes that share ontologies with POLD4: view

No data available for SIGNOR curated interactions for POLD4 Gene

Drugs & Compounds for POLD4 Gene

(2) Drugs for POLD4 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clofarabine Approved, Investigational Pharma Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 167
Cytarabine Approved, Experimental, Investigational Pharma 1335

(2) ApexBio Compounds for POLD4 Gene

Compound Action Cas Number
Clofarabine Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 123318-82-1
Cytarabine 147-94-4
genes like me logo Genes that share compounds with POLD4: view

Drug Products

Transcripts for POLD4 Gene

mRNA/cDNA for POLD4 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for POLD4

Alternative Splicing Database (ASD) splice patterns (SP) for POLD4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c · 2d · 2e · 2f ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c · 6d · 6e
SP1: - - - - - - - - - - -
SP2: - - - - - -
SP3: - - - - - - -
SP4: - - - - -
SP5: - - -
SP6: - - - - - - -
SP7: - - -
SP8: - - - - - -
SP9: - - -
SP10: - -
SP11:
SP12: - - -

Relevant External Links for POLD4 Gene

GeneLoc Exon Structure for
POLD4

Expression for POLD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for POLD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for POLD4 Gene

This gene is overexpressed in Breast (31.8) and Plasma (21.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for POLD4 Gene



Protein tissue co-expression partners for POLD4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for POLD4

SOURCE GeneReport for Unigene cluster for POLD4 Gene:

Hs.523829

Evidence on tissue expression from TISSUES for POLD4 Gene

  • Kidney(2.3)
  • Nervous system(2.3)
  • Muscle(2.1)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with POLD4: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for POLD4 Gene

Orthologs for POLD4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for POLD4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia POLD4 30 31
  • 99.69 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia POLD4 30 31
  • 90.03 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia POLD4 30 31
  • 88.16 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Pold4 30 17 31
  • 85.67 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pold4 30
  • 85.36 (n)
Oppossum
(Monodelphis domestica)
Mammalia POLD4 31
  • 39 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii POLD4 31
  • 38 (a)
OneToOne
Species where no ortholog for POLD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for POLD4 Gene

ENSEMBL:
Gene Tree for POLD4 (if available)
TreeFam:
Gene Tree for POLD4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for POLD4: view image

Paralogs for POLD4 Gene

Paralogs for POLD4 Gene

genes like me logo Genes that share paralogs with POLD4: view

Variants for POLD4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for POLD4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs28364240 - p.Arg39Pro
rs34136263 - p.Gly59Arg

Additional dbSNP identifiers (rs#s) for POLD4 Gene

Structural Variations from Database of Genomic Variants (DGV) for POLD4 Gene

Variant ID Type Subtype PubMed ID
nsv367 CNV insertion 18451855
nsv468603 CNV loss 19166990
nsv555253 CNV loss 21841781

Variation tolerance for POLD4 Gene

Residual Variation Intolerance Score: 54.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.39; 8.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for POLD4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
POLD4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for POLD4 Gene

Disorders for POLD4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for POLD4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
bloom syndrome
  • bls
autosomal recessive non-syndromic intellectual disability
  • autosomal recessive mental retardation
- elite association - COSMIC cancer census association via MalaCards
Search POLD4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with POLD4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for POLD4 Gene

Publications for POLD4 Gene

  1. Identification of a fourth subunit of mammalian DNA polymerase delta. (PMID: 10751307) Liu L … Lee MY (The Journal of biological chemistry 2000) 2 3 4
  2. The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression. (PMID: 24300032) Lee MY … Lee EY (Cell cycle (Georgetown, Tex.) 2014) 3 4
  3. A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase δ in response to DNA damage and during the S phase. (PMID: 23913683) Zhang S … Lee MY (The Journal of biological chemistry 2013) 3 4
  4. Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase δ. (PMID: 24035200) Lin SH … Lee MY (DNA repair 2013) 3 4
  5. Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase δ for degradation in response to DNA damage. (PMID: 23233665) Zhang S … Lee MY (The Journal of biological chemistry 2013) 3 4

Products for POLD4 Gene

Sources for POLD4 Gene