GFM2 (GTP dependent ribosome recycling factor mitochondrial 2)

Gene

• Entrez ID: 84340
• Gene name: GTP dependent ribosome recycling factor mitochondrial 2
• Gene symbol: GFM2
• Synonyms (NCBI Gene): EF-G2mt, EFG2, MRRF2, MST027, MSTP027, RRF, RRF2, RRF2mt, hEFG2, mEF-G 2
• Chromosome: 5
• Chromosome location: 5q13.3
• Summary: Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-o

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140077535	A>T	Pathogenic, uncertain-significance	Non coding transcript variant, missense variant, coding sequence variant, genic downstream transcript variant
rs746538436	T>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs751852874	AGTAAAGAGAAAAA>-	Likely-pathogenic	Intron variant
rs761283105	C>T	Pathogenic, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs773010798	->A	Likely-pathogenic	Splice donor variant, intron variant
rs869320703	T>C	Pathogenic	Intron variant
rs869320704	C>T	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs1554042187	T>G	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019732	hsa-miR-375	Microarray	20215506
MIRT032195	hsa-let-7b-5p	Proteomics	18668040
MIRT1016729	hsa-miR-216b	CLIP-seq
MIRT1016730	hsa-miR-25	CLIP-seq
MIRT1016731	hsa-miR-32	CLIP-seq
MIRT1016732	hsa-miR-363	CLIP-seq
MIRT1016733	hsa-miR-367	CLIP-seq
MIRT1016734	hsa-miR-526b	CLIP-seq
MIRT1016735	hsa-miR-891b	CLIP-seq
MIRT1016736	hsa-miR-92a	CLIP-seq
MIRT1016737	hsa-miR-92b	CLIP-seq
MIRT2000941	hsa-miR-3168	CLIP-seq
MIRT1016729	hsa-miR-216b	CLIP-seq
MIRT1016730	hsa-miR-25	CLIP-seq
MIRT1016731	hsa-miR-32	CLIP-seq
MIRT1016732	hsa-miR-363	CLIP-seq
MIRT1016733	hsa-miR-367	CLIP-seq
MIRT1016734	hsa-miR-526b	CLIP-seq
MIRT1016735	hsa-miR-891b	CLIP-seq
MIRT1016736	hsa-miR-92a	CLIP-seq
MIRT1016737	hsa-miR-92b	CLIP-seq
MIRT2538441	hsa-miR-101	CLIP-seq
MIRT2538442	hsa-miR-2116	CLIP-seq
MIRT2538443	hsa-miR-3140-5p	CLIP-seq
MIRT2538444	hsa-miR-323b-3p	CLIP-seq
MIRT2538445	hsa-miR-3646	CLIP-seq
MIRT2538446	hsa-miR-3647-3p	CLIP-seq
MIRT2538447	hsa-miR-3662	CLIP-seq
MIRT2538448	hsa-miR-3907	CLIP-seq
MIRT2538449	hsa-miR-3942-5p	CLIP-seq
MIRT2538450	hsa-miR-4268	CLIP-seq
MIRT2538451	hsa-miR-4273	CLIP-seq
MIRT2538452	hsa-miR-4422	CLIP-seq
MIRT2538453	hsa-miR-4448	CLIP-seq
MIRT2538454	hsa-miR-4677-5p	CLIP-seq
MIRT2538455	hsa-miR-4680-3p	CLIP-seq
MIRT2538456	hsa-miR-4703-5p	CLIP-seq
MIRT2538457	hsa-miR-4724-5p	CLIP-seq
MIRT2538458	hsa-miR-4768-5p	CLIP-seq
MIRT2538459	hsa-miR-494	CLIP-seq
MIRT2538460	hsa-miR-548c-3p	CLIP-seq
MIRT2538461	hsa-miR-550b	CLIP-seq
MIRT2538462	hsa-miR-562	CLIP-seq
MIRT2538441	hsa-miR-101	CLIP-seq
MIRT2538442	hsa-miR-2116	CLIP-seq
MIRT2681508	hsa-miR-3119	CLIP-seq
MIRT2538443	hsa-miR-3140-5p	CLIP-seq
MIRT2681509	hsa-miR-3182	CLIP-seq
MIRT2538444	hsa-miR-323b-3p	CLIP-seq
MIRT2681510	hsa-miR-330-3p	CLIP-seq
MIRT2538445	hsa-miR-3646	CLIP-seq
MIRT2538446	hsa-miR-3647-3p	CLIP-seq
MIRT2538447	hsa-miR-3662	CLIP-seq
MIRT2681511	hsa-miR-376a	CLIP-seq
MIRT2681512	hsa-miR-376b	CLIP-seq
MIRT2538448	hsa-miR-3907	CLIP-seq
MIRT2538449	hsa-miR-3942-5p	CLIP-seq
MIRT2681513	hsa-miR-410	CLIP-seq
MIRT2681514	hsa-miR-4252	CLIP-seq
MIRT2538450	hsa-miR-4268	CLIP-seq
MIRT2538451	hsa-miR-4273	CLIP-seq
MIRT2538452	hsa-miR-4422	CLIP-seq
MIRT2538453	hsa-miR-4448	CLIP-seq
MIRT2681515	hsa-miR-4493	CLIP-seq
MIRT2681516	hsa-miR-4528	CLIP-seq
MIRT2538454	hsa-miR-4677-5p	CLIP-seq
MIRT2538455	hsa-miR-4680-3p	CLIP-seq
MIRT2538456	hsa-miR-4703-5p	CLIP-seq
MIRT2681517	hsa-miR-4720-3p	CLIP-seq
MIRT2538457	hsa-miR-4724-5p	CLIP-seq
MIRT2538459	hsa-miR-494	CLIP-seq
MIRT2538460	hsa-miR-548c-3p	CLIP-seq
MIRT2538461	hsa-miR-550b	CLIP-seq
MIRT2538462	hsa-miR-562	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003746	Function	Translation elongation factor activity	IDA	19716793
GO:0003924	Function	GTPase activity	EXP	19716793
GO:0003924	Function	GTPase activity	IBA
GO:0003924	Function	GTPase activity	IDA	19716793
GO:0003924	Function	GTPase activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956
GO:0005525	Function	GTP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS	33878294
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006412	Process	Translation	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0032543	Process	Mitochondrial translation	IBA
GO:0032543	Process	Mitochondrial translation	IDA	19716793
GO:0032543	Process	Mitochondrial translation	IEA
GO:0032790	Process	Ribosome disassembly	IBA
GO:0032790	Process	Ribosome disassembly	IDA	19716793, 33878294
GO:0032790	Process	Ribosome disassembly	IEA
GO:0070125	Process	Mitochondrial translational elongation	IDA	19716793
GO:0070126	Process	Mitochondrial translational termination	TAS

Other IDs

• MIM: 606544
• HGNC: 29682
• e!Ensembl: ENSG00000164347

Protein

• UniProt ID: Q969S9
• Protein name: Ribosome-releasing factor 2, mitochondrial (RRF2mt) (EC 3.6.5.-) (Elongation factor G 2, mitochondrial) (EF-G2mt) (mEF-G 2) (Elongation factor G2) (hEFG2)
• Protein function: Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis (PubMed:19716793, PubMed:33878294). Acts in collaboration with MRRF (PubMed:19716793, PubMed:33878294). P
• PDB: 7L20, 7NSH
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00009	GTP_EFTU	68 → 351	Elongation factor Tu GTP binding domain	Domain
  PF03144	GTP_EFTU_D2	381 → 448	Elongation factor Tu domain 2	Domain
  PF14492	EFG_III	485 → 559	Elongation Factor G, domain III	Domain
  PF03764	EFG_IV	560 → 682	Elongation factor G, domain IV	Domain
  PF00679	EFG_C	684 → 771	Elongation factor G C-terminus	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11735030}.
• Sequence:

  MLTNLRIFAMSHQTIPSVYINNICCYKIRASLKRLKPHVPLGRNCSSLPGLIGNDIKSLH
  SIINPPIAKIRNIGIMAHIDAGKTTTTERILYYSGYTRSLGDVDDGDTVTDFMAQERERG
  ITIQSAAVTFDWKGYRVNLIDTPGHVDFTLEVERCLRVLDGAVAVFDASAGVEAQTLTVW
  RQADKHNIPRICFLNKMDKTGASFKYAVESIREKLKAKPLLLQLPIGEAKTFKGVVDVVM
  KEKLLWNCNSNDGKDFERKPLLEMNDPELLKETTEARNALIEQVADLDDEFADLVLEEFS
  ENFDLLPAEKLQTAIHRVTLAQTAVPVLCGSALKNKGIQPLLDAVTMYLPSPEERNYEFL
  QWYKDDLCALAFKVLHDKQRGPLVFMRIYSGTIKPQLAIHNINGNCTERISRLLLPFADQ
  HVEIPSLTAGNIALTVGLKHTATGDTIVSSKSSALAAARRAEREGEKKHRQNNEAERLLL
  AGVEIPEPVFFCTIEPPSLSKQPDLEHALKCLQREDPSLKVRLDPDSGQTVLCGMGELHI
  EIIHDRIKREYGLETYLGPLQVAYRETILNSVRATDTLDRTLGDKRHLVTVEVEARPIET
  SSVMPVIEFEYAESINEGLLKVSQEAIENGIHSACLQGPLLGSPIQDVAITLHSLTIHPG
  TSTTMISACVSRCVQKALKKADKQVLEPLMNLEVTVARDYLSPVLADLAQRRGNIQEIQT
  RQDNKVVIGFVPLAEIMGYSTVLRTLTSGSATFALELSTYQAMNPQDQNTLLNRRSGLT

• Sequence length: 779

Pathways

Reactome:

Mitochondrial translation termination

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
Combined oxidative phosphorylation deficiency 39	Likely pathogenic; Pathogenic	rs1240552971, rs869320703, rs869320704, rs1744128996, rs764127754, rs746538436, rs1554042187	RCV005603717 RCV000210856 RCV000210855 RCV003153048 RCV004547206 RCV000767876 RCV000767877	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GFM2-related disorder	Likely pathogenic	rs1370043372	RCV003405780	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial disease	Pathogenic	rs746538436, rs1554042187	RCV000515499 RCV000515475	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 39	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Germ cell tumor of testis	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SANDHOFF DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma of the head and neck	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthrogryposis	Arthrogryposis multiplex congenita	BEFREE	26016410		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	GENOMICS_ENGLAND_DG	26016410		★☆☆☆☆ Found in Text Mining only
Combined oxidative phosphorylation defect type 39	Combined Oxidative Phosphorylation Deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	BEFREE	18504129, 8064325		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29075935	Associate	★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	22700954	Associate	★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	BEFREE	26016410		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	36675121	Associate	★☆☆☆☆ Found in Text Mining only
LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome Due To Mitochondrial Complex II Deficiency	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex III Deficiency	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex IV Deficiency	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex V Deficiency	Leigh Syndrome	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
MELAS Syndrome	MELAS Syndrome	BEFREE	18753147		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	22700954	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	29075935		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	CLINVAR_DG	29075935		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29075935	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathy	Myopathy	BEFREE	11382203		★☆☆☆☆ Found in Text Mining only
Necrotizing encephalopathy, infantile subacute, of Leigh	Necrotizing encephalomyelopathy	CLINGEN_DG	19716793, 22700954, 26016410, 29075935		★☆☆☆☆ Found in Text Mining only
Trifunctional Protein Deficiency With Myopathy And Neuropathy	Mitochondrial trifunctional protein deficiency	BEFREE	20425236		★☆☆☆☆ Found in Text Mining only