MTPAP Gene

Name	mitochondrial poly(A) polymerase
Description	The protein encoded by this gene is a member of the DNA polymerase type-B-like family. This enzyme synthesizes the 3' poly(A) tail of mitochondrial transcripts and plays a role in replication-dependent histone mRNA degradation.[provided by RefSeq, Jan 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMitochondrial poly(A) polymerase (MTPAP) is a nuclear‐encoded enzyme that localizes to the mitochondrial compartment where it catalyzes the polyadenylation of mitochondrial mRNAs. This post‐transcriptional modification, demonstrated by RNA interference experiments that result in markedly shortened poly(A) tails, is essential for proper mitochondrial gene expression even though, in some cases, reduced polyadenylation does not immediately affect transcript stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies have revealed that MTPAP possesses a catalytic core comprised of palm and fingers domains resembling those of canonical poly(A) polymerases, along with a novel N‐terminal RL domain. Dimerization, facilitated by a β‐arm insertion, is a prerequisite for its catalytic activity. Moreover, missense mutations such as p.N478D significantly compromise polymerase activity, producing only short oligo(A) extensions and leading to defective polyadenylation that disrupts mitochondrial translation and oxidative phosphorylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in mRNA stabilization and translation, MTPAP is also involved in specific RNA processing events. For example, it is responsible for the targeted addition of a 3′-terminal adenosine to truncated mitochondrial tRNA(Tyr), a necessary step for subsequent CCA addition and tRNA maturation. This precise RNA editing activity illustrates the enzyme’s versatile role in maintaining mitochondrial RNA integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond RNA maturation, alterations in MTPAP function have been linked to human diseases and cellular stress responses. Mutations in MTPAP are associated with severe clinical phenotypes such as spastic ataxia with optic atrophy and learning difficulties, and studies in patient cells have also revealed that compromised MTPAP activity leads to increased reactive oxygen species, delayed DNA repair, and radiosensitivity. In addition, genetic analyses have implicated MTPAP (sometimes referred to as PAPD1) in metabolic phenotypes related to obesity. Furthermore, recent findings indicate that MTPAP interacts via its SKICH domain with autophagic receptors like NDP52, thereby enhancing mitophagy and promoting the clearance of damaged mitochondria."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rafal Tomecki, Aleksandra Dmochowska, Kamil Gewartowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel human nuclear-encoded mitochondrial poly(A) polymerase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkh923"}], "href": "https://doi.org/10.1093/nar/gkh923"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15547249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15547249"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "William C Wilson, Hue-Tran Hornig-Do, Francesco Bruni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu352"}], "href": "https://doi.org/10.1093/hmg/ddu352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25008111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25008111"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yun Bai, Sandeep K Srivastava, Jeong Ho Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for dimerization and activity of human PAPD1, a noncanonical poly(A) polymerase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2011.01.013"}], "href": "https://doi.org/10.1016/j.molcel.2011.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21292163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21292163"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mario Fiedler, Walter Rossmanith, Elmar Wahle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial poly(A) polymerase is involved in tRNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkv891"}], "href": "https://doi.org/10.1093/nar/gkv891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26354863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26354863"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qianjun Xiao, Xiao-Lin Wu, Jennifer J Michal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel nuclear-encoded mitochondrial poly(A) polymerase PAPD1 is a potential candidate gene for the extreme obesity related phenotypes in mammals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.2.171"}], "href": "https://doi.org/10.7150/ijbs.2.171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16810331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16810331"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "N T Martin, K Nakamura, U Paila, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous mutation of MTPAP causes cellular radiosensitivity and persistent DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.99"}], "href": "https://doi.org/10.1038/cddis.2014.99"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24651433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24651433"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Norihiko Furuya, Soichiro Kakuta, Katsuhiko Sumiyoshi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDP52 interacts with mitochondrial RNA poly(A) polymerase to promote mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201846363"}], "href": "https://doi.org/10.15252/embr.201846363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30309841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30309841"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lien Van Eyck, Francesco Bruni, Anne Ronan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic Mutations in MTPAP Associated with a Lethal Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0039-3400979"}], "href": "https://doi.org/10.1055/s-0039-3400979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31779033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31779033"}]}]}]}
Synonyms	PAPD1, SPAX4, TENT6
Proteins	PAPD1_HUMAN
NCBI Gene ID	55149
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MTPAP has 5,587 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 121 datasets.

Click the + buttons to view associations for MTPAP from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MTPAP Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MTPAP gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MTPAP gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of MTPAP gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MTPAP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of MTPAP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MTPAP gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MTPAP gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MTPAP gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MTPAP gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of MTPAP gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MTPAP gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MTPAP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MTPAP protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MTPAP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MTPAP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MTPAP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MTPAP gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MTPAP gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MTPAP protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MTPAP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MTPAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MTPAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MTPAP protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing MTPAP protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MTPAP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MTPAP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MTPAP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MTPAP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MTPAP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MTPAP protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving MTPAP gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MTPAP gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MTPAP gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MTPAP gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MTPAP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MTPAP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MTPAP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MTPAP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MTPAP gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MTPAP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.