POLG DNA polymerase gamma, catalytic subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: POLGprovided by HGNC
Official Full Name: DNA polymerase gamma, catalytic subunitprovided by HGNC
Primary source: HGNC:HGNC:9179
See related: Ensembl:ENSG00000140521 MIM:174763; AllianceGenome:HGNC:9179
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: PEO; MDP1; SCAE; MIRAS; POLG1; POLGA; SANDO; MTDPS4A; MTDPS4B
Summary: Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 14.2), spleen (RPKM 13.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q26.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (89316320..89334824, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (87071147..87089647, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (89859551..89878055, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

POLG1 variants can at most cause MNGIE-like but not classic MNGIE phenotype.
Title: POLG1 variants can at most cause MNGIE-like but not classic MNGIE phenotype.
DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?
Title: DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?
POLG genotype influences degree of mitochondrial dysfunction in iPSC derived neural progenitors, but not the parent iPSC or derived glia.
Title: POLG genotype influences degree of mitochondrial dysfunction in iPSC derived neural progenitors, but not the parent iPSC or derived glia.
Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.
Title: Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.
[Adult-onset sensory neuropathy and ataxia as a clinical manifestation of POLG gene mutations].
Title: [Adult-onset sensory neuropathy and ataxia as a clinical manifestation of POLG gene mutations].
POLG mutation setting off 'FIRES'.
Title: POLG mutation setting off 'FIRES'.
Heterozygous p.Y955C mutation in DNA polymerase gamma leads to alterations in bioenergetics, complex I subunit expression, and mtDNA replication.
Title: Heterozygous p.Y955C mutation in DNA polymerase γ leads to alterations in bioenergetics, complex I subunit expression, and mtDNA replication.
POLG mutations lead to abnormal mitochondrial remodeling during neural differentiation of human pluripotent stem cells via SIRT3/AMPK pathway inhibition.
Title: POLG mutations lead to abnormal mitochondrial remodeling during neural differentiation of human pluripotent stem cells via SIRT3/AMPK pathway inhibition.
Mitochondrial biogenesis gene POLG correlates with outcome in pediatric acute myeloid leukemia.
Title: Mitochondrial biogenesis gene POLG correlates with outcome in pediatric acute myeloid leukemia.
Identification of a POLG Variant in a Family With Arrhythmogenic Cardiomyopathy and Left Ventricular Fibrosis.
Title: Identification of a POLG Variant in a Family With Arrhythmogenic Cardiomyopathy and Left Ventricular Fibrosis.

Submit: New GeneRIF Correction See all GeneRIFs (264)

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
Mitochondrial DNA depletion syndrome 1 MedGen: C4551995 OMIM: 603041 GeneReviews: Mitochondrial Neurogastrointestinal Encephalopathy Disease	Compare labs
Mitochondrial DNA depletion syndrome 4b MedGen: C3150914 OMIM: 613662 GeneReviews: POLG-Related Disorders	Compare labs
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 MedGen: C1834846 OMIM: 157640 GeneReviews: Mitochondrial DNA Deletion Syndromes, POLG-Related Disorders	Compare labs
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 MedGen: C4225153 OMIM: 258450 GeneReviews: POLG-Related Disorders	Compare labs
Progressive sclerosing poliodystrophy MedGen: C0205710 OMIM: 203700 GeneReviews: POLG-Related Disorders, Mitochondrial DNA Maintenance Defects Overview	Compare labs
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis MedGen: C1843851 OMIM: 607459 GeneReviews: POLG-Related Disorders	Compare labs

EBI GWAS Catalog

Description
Common variants in the GDF5-UQCC region are associated with variation in human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_7859-7860:996688105:3 (e-PCR)
- UniSTS:269839

POLG (e-PCR)
- UniSTS:503075

RH77770 (e-PCR)
- UniSTS:58968

RH68306 (e-PCR)
- UniSTS:8311

csnppolg-pcr2-1 (e-PCR)
- UniSTS:243082

csnppolg-pcr23-1 (e-PCR)
- UniSTS:243083

RH93713 (e-PCR)
- UniSTS:89826

G16014 (e-PCR)
- UniSTS:37092

RH67845 (e-PCR)
- UniSTS:28408

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3'-5' exonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables 3'-5' exonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables 5'-deoxyribose-5-phosphate lyase activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA 3'-5' DNA exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables single-stranded DNA 3'-5' DNA exonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in DNA metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in DNA replication proofreading	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication proofreading	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA-templated DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in base-excision repair	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within base-excision repair, gap-filling	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial DNA replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of gamma DNA polymerase complex	IDA Inferred from Direct Assay more info	PubMed
part_of gamma DNA polymerase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial nucleoid	IDA Inferred from Direct Assay more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA polymerase subunit gamma-1

Names: 3'-5' exodeoxyribonuclease; 5'-deoxyribose-phosphate lyase; PolG-alpha; mitochondrial DNA polymerase catalytic subunit; mitochondrial polymerase gamma catalytic subunit; polymerase (DNA directed), gamma; polymerase (DNA) gamma, catalytic subunit

NP_001119603.1

EC 2.7.7.7

NP_002684.1

EC 2.7.7.7

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

NG_008218.2 RefSeqGene

Range

5001..23491

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_765

mRNA and Protein(s)

NM_001126131.2 → NP_001119603.1 DNA polymerase subunit gamma-1

See identical proteins and their annotated locations for NP_001119603.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants encode the same protein.

Source sequence(s)

AC124068, BC050559, X98093

Consensus CDS

CCDS10350.1

UniProtKB/Swiss-Prot

P54098, Q8NFM2, Q92515

UniProtKB/TrEMBL

A8K5G6, E5KNU5, E5KNV8, E5KNW2, E5KNX5

Related

ENSP00000399851.2, ENST00000442287.6

Conserved Domains (3) summary

cd08641
Location:785 → 1203

DNA_pol_gammaA; Pol gammaA is a family A polymerase that is responsible for DNA replication and repair in mitochondria

cl02626
Location:431 → 473

DNA_pol_A; Family A polymerase primarily fills DNA gaps that arise during DNA repair, recombination and replication

cl10012
Location:265 → 297

DnaQ_like_exo; DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily
NM_002693.3 → NP_002684.1 DNA polymerase subunit gamma-1

See identical proteins and their annotated locations for NP_002684.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants encode the same protein.

Source sequence(s)

AC124068, X98093

Consensus CDS

CCDS10350.1

UniProtKB/Swiss-Prot

P54098, Q8NFM2, Q92515

UniProtKB/TrEMBL

A8K5G6, E5KNU5, E5KNV8, E5KNW2, E5KNX5

Related

ENSP00000268124.5, ENST00000268124.11

Conserved Domains (3) summary

cd08641
Location:785 → 1203

DNA_pol_gammaA; Pol gammaA is a family A polymerase that is responsible for DNA replication and repair in mitochondria

cl02626
Location:431 → 473

DNA_pol_A; Family A polymerase primarily fills DNA gaps that arise during DNA repair, recombination and replication

cl10012
Location:265 → 297

DnaQ_like_exo; DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily