MGME1 (mitochondrial genome maintenance exonuclease 1)

Gene

• Entrez ID: 92667
• Gene name: Mitochondrial genome maintenance exonuclease 1
• Gene symbol: MGME1
• Synonyms (NCBI Gene): C20orf72, DDK1, MTDPS11, bA504H3.4
• Chromosome: 20
• Chromosome location: 20p11.23
• Summary: The protein encoded by this gene is a nuclear-encoded mitochondrial protein necessary for the maintenance of mitochondrial genome synthesis. The encoded protein is a RecB-type exonuclease and primarily cleaves single-stranded DNA. Defects in this gene hav

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs76599088	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant, intron variant
rs143417446	C>G,T	Conflicting-interpretations-of-pathogenicity, not-provided	Missense variant, coding sequence variant, intron variant
rs587776944	A>G	Pathogenic	Intron variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005230	hsa-let-7b-5p	pSILAC	18668040
MIRT005230	hsa-let-7b-5p	Proteomics;Other	18668040

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004518	Function	Nuclease activity	IEA
GO:0004527	Function	Exonuclease activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	23313956
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006264	Process	Mitochondrial DNA replication	IBA
GO:0006264	Process	Mitochondrial DNA replication	IMP	23313956
GO:0006264	Process	Mitochondrial DNA replication	TAS
GO:0006281	Process	DNA repair	IEA
GO:0006974	Process	DNA damage response	IEA
GO:0008297	Function	Single-stranded DNA exodeoxyribonuclease activity	IBA
GO:0008297	Function	Single-stranded DNA exodeoxyribonuclease activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0017108	Function	5'-flap endonuclease activity	EXP	27220468
GO:0043504	Process	Mitochondrial DNA repair	IEA
GO:0043504	Process	Mitochondrial DNA repair	TAS	23313956
GO:0045145	Function	Single-stranded DNA 5'-3' DNA exonuclease activity	IDA	23313956

Other IDs

• MIM: 615076
• HGNC: 16205
• e!Ensembl: ENSG00000125871

Protein

• UniProt ID: Q9BQP7
• Protein name: Mitochondrial genome maintenance exonuclease 1 (EC 3.1.-.-)
• Protein function: Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endonuclease activity on linear substrates. Necessary for maintenance of p
• PDB: 5ZYT, 5ZYU, 5ZYV, 5ZYW, 8XA9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12705	PDDEXK_1	149 → 343	PD-(D/E)XK nuclease superfamily	Domain

• Sequence:

  MKMKLFQTICRQLRSSKFSVESAALVAFSTSSYSCGRKKKVNPYEEVDQEKYSNLVQSVL
  SSRGVAQTPGSVEEDALLCGPVSKHKLPNQGEDRRVPQNWFPIFNPERSDKPNASDPSVP
  LKIPLQRNVIPSVTRVLQQTMTKQQVFLLERWKQRMILELGEDGFKEYTSNVFLQGKRFH
  EALESILSPQETLKERDENLLKSGYIESVQHILKDVSGVRALESAVQHETLNYIGLLDCV
  AEYQGKLCVIDWKTSEKPKPFIQSTFDNPLQVVAYMGAMNHDTNYSFQVQCGLIVVAYKD
  GSPAHPHFMDAELCSQYWTKWLLRLEEYTEKKKNQNIQKPEYSE

• Sequence length: 344

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Mitochondrial DNA depletion syndrome 11	Pathogenic; Likely pathogenic	rs1555789140, rs587776943, rs587776944	RCV000578900 RCV000033150 RCV000033151	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MGME1-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOTAL OPHTHALMOPLEGIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	40286336	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ataxia	Ataxia	Pubtator	28711739	Associate	★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	30570852	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	28594148	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Dilated	Dilated cardiomyopathy	Pubtator	28594148	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Ataxia	Cerebellar ataxia	Pubtator	28711739	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Ataxia, Early Onset	Cerebellar Ataxia	BEFREE	28711739		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	CLINVAR_DG	28711739		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	28711739	Associate	★☆☆☆☆ Found in Text Mining only
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Electron Transport Chain Deficiencies, Mitochondrial	Mitochondrial Electron Transport Chain Deficiencies	CTD_human_DG	23313956		★☆☆☆☆ Found in Text Mining only
External Ophthalmoplegia	External Ophthalmoplegia	BEFREE	23313956, 30247721		★☆☆☆☆ Found in Text Mining only
External Ophthalmoplegia	External Ophthalmoplegia	CTD_human_DG	23313956		★☆☆☆☆ Found in Text Mining only
Facial paralysis	Facial paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized amyotrophy	Amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	37166417	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lupus Nephritis	Lupus nephritis	Pubtator	31298388	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	23313956, 24985751, 29572490		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	CTD_human_DG	23313956		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	23313956, 27220468, 30247721	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DNA DEPLETION SYNDROME 11	Mitochondrial DNA Deletion Syndrome	UNIPROT_DG	23313956		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MITOCHONDRIAL DNA DEPLETION SYNDROME 11	Mitochondrial DNA Deletion Syndrome	GENOMICS_ENGLAND_DG	23313956		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MITOCHONDRIAL DNA DEPLETION SYNDROME 11	Mitochondrial DNA Deletion Syndrome	ORPHANET_DG	23313956		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MITOCHONDRIAL DNA DEPLETION SYNDROME 11	Mitochondrial DNA Deletion Syndrome	CLINVAR_DG	28711739		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MITOCHONDRIAL DNA DEPLETION SYNDROME 11	Mitochondrial DNA Deletion Syndrome	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial Respiratory Chain Deficiencies	Mitochondrial Respiratory Chain Deficiencies	CTD_human_DG	23313956		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nephrolithiasis	Nephrolithiasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia	Ophthalmoplegia	Pubtator	23313956, 30247721	Associate	★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia Chronic Progressive External	Progressive external ophthalmoplegia	Pubtator	28711739	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	BEFREE	30178828		★☆☆☆☆ Found in Text Mining only
Oxidative Phosphorylation Deficiencies	Oxidative Phosphorylation Deficiency	CTD_human_DG	23313956		★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progeria	Progeria	BEFREE	29572490		★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	CLINVAR_DG	28711739		★☆☆☆☆ Found in Text Mining only
Progressive external ophthalmoplegia-myopathy-emaciation syndrome	Progressive External Ophthalmoplegia-Myopathy-Emaciation Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Proximal amyotrophy	Amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	CTD_human_DG	23313956		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	BEFREE	30247721		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Visceral myopathy familial external ophthalmoplegia	Visceral neuropathy	Pubtator	36311265	Associate	★☆☆☆☆ Found in Text Mining only