MTRFR (mitochondrial translation release factor in rescue)

Gene

• Entrez ID: 91574
• Gene name: Mitochondrial translation release factor in rescue
• Gene symbol: MTRFR
• Synonyms (NCBI Gene): C12orf65, COXPD7, SPG55, mtRF-R
• Chromosome: 12
• Chromosome location: 12q24.31
• Summary: This nuclear gene encodes a mitochondrial matrix protein that appears to contribute to peptide chain termination in the mitochondrial translation machinery. Two different 1 bp deletions (resulting in the same premature stop codon)result in decreased mitoc

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140411575	C>T	Conflicting-interpretations-of-pathogenicity, benign	Synonymous variant, coding sequence variant
rs147328685	A>G	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs397514539	C>T	Pathogenic	Stop gained, coding sequence variant
rs398122365	C>T	Pathogenic	Stop gained, coding sequence variant
rs398122972	G>-	Pathogenic	Stop gained, coding sequence variant
rs576462794	A>-	Pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, frameshift variant
rs587776508	T>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant
rs587777667	AACAA>-	Pathogenic	Coding sequence variant, frameshift variant
rs587777668	T>A	Pathogenic	Splice donor variant
rs863223926	->ATCC	Pathogenic	Frameshift variant, coding sequence variant
rs1064793074	T>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1439433665	AAAAGAGCAAAGGAAA>-,AAAAGAGCAAAGGAAAAAAAGAGCAAAGGAAA	Likely-pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IDA	33243891
GO:0003723	Function	RNA binding	IEA
GO:0003747	Function	Translation release factor activity	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 31396629, 33243891, 33961781
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	20186120, 20598281
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	NAS	20186120
GO:0005759	Component	Mitochondrial matrix	TAS	33878294
GO:0006412	Process	Translation	IEA
GO:0006415	Process	Translational termination	IEA
GO:0016149	Function	Translation release factor activity, codon specific	IDA	33878294
GO:0043023	Function	Ribosomal large subunit binding	IDA	33243891
GO:0072344	Process	Rescue of stalled ribosome	IDA	33243891

Other IDs

• MIM: 613541
• HGNC: 26784
• e!Ensembl: ENSG00000130921

Protein

• UniProt ID: Q9H3J6
• Protein name: Mitochondrial translation release factor in rescue
• Protein function: Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation (PubMed:33243891). As heterodimer with MTRES1, ejects the unfinished nascent chain and peptidyl transfe
• PDB: 7A5H
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00472	RF-1	48 → 164	RF-1 domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in all areas of the brain tested. {ECO:0000269|PubMed:24198383}.
• Sequence:

  MSTVGLFHFPTPLTRICPAPWGLRLWEKLTLLSPGIAVTPVQMAGKKDYPALLSLDENEL
  EEQFVKGHGPGGQATNKTSNCVVLKHIPSGIVVKCHQTRSVDQNRKLARKILQEKVDVFY
  NGENSPVHKEKREAAKKKQERKKRAKETLEKKKLLKELWESSKKVH

• Sequence length: 166

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
Abnormal brain morphology	Likely pathogenic; Pathogenic	rs587776508	RCV000454329	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Combined oxidative phosphorylation defect type 7	Likely pathogenic; Pathogenic	rs587776508, rs576462794, rs2138800520, rs1380513950, rs863223926, rs1460180114, rs2547597991, rs397514539, rs2048143498, rs2048187051, rs398122972	RCV000000070 RCV000000071 RCV002239179 RCV002510357 RCV000694009 RCV003779433 RCV003815681 RCV002228073 RCV001065062 RCV001035224 RCV005624320	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epileptic encephalopathy	Likely pathogenic; Pathogenic	rs587776508	RCV001003606	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary motor and sensory neuropathy with optic atrophy	Likely pathogenic	rs2138792385	RCV001353165	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia 55	Likely pathogenic; Pathogenic	rs587776508, rs587777667, rs587777668, rs863223926, rs397514539, rs398122365, rs398122972, rs2048145654	RCV000679867 RCV000133580 RCV000133581 RCV002500608 RCV000032782 RCV000074452 RCV000076925 RCV001263155	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MTRFR-related disorder	Likely pathogenic	rs2547600304	RCV003391542	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spastic paraplegia	Likely pathogenic; Pathogenic	rs576462794, rs2138800520, rs863223926, rs1460180114, rs2547597991, rs397514539, rs2048143498, rs2048187051	RCV001382822 RCV002239179 RCV000694009 RCV003779433 RCV003815681 RCV002228073 RCV001065062 RCV001035224	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE SPASTIC PARAPLEGIA TYPE 55	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Combined oxidative phosphorylation deficiency	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 7	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary spastic paraplegia	Uncertain significance; Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL ENCEPHALOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic atrophy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	33482886	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive spastic paraplegia type 55	Spastic Paraplegia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	24424123	Associate	★☆☆☆☆ Found in Text Mining only
Combined oxidative phosphorylation defect type 7	Combined Oxidative Phosphorylation Deficiency	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 7	Combined Oxidative Phosphorylation Deficiency	GENOMICS_ENGLAND_DG	20598281, 24424123, 27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 7	Combined Oxidative Phosphorylation Deficiency	CLINVAR_DG	20598281, 24284555, 27858754		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 7	Combined Oxidative Phosphorylation Deficiency	ORPHANET_DG	20598281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 7	Combined Oxidative Phosphorylation Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Motor And Sensory Neuropathy VI	Hereditary motor and sensory neuropathies	Pubtator	24198383	Associate	★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	24080142		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	24424123	Associate	★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	20598281	Associate	★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	BEFREE	24284555, 25995486		★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	22821833		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	24198383	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	CTD_human_DG	20598281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	20598281, 24424123	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Movement Disorders	Movement Disorders	BEFREE	26187298		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	23188110		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia	Ophthalmoplegia	Pubtator	20598281	Associate	★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic atrophy	Pubtator	20598281, 24198383, 24424123	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Optic Atrophy	Optic Atrophy	BEFREE	23188110, 24198383, 24284555, 24424123, 26187298		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Optic Atrophy	Optic Atrophy	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Paralytic Ileus	Paralytic Ileus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paraparesis Spastic	Paraparesis	Pubtator	24424123	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	24424123		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	24424123, 26556829	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	24424123		★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASDB_DG	23974872		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	23974872		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia	Spastic Paraplegia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spastic Paraplegia	Spastic Paraplegia	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE	Spastic Paraplegia	CLINVAR_DG	20598281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE	Spastic Paraplegia	BEFREE	23188110		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE	Spastic Paraplegia	ORPHANET_DG	23188110		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE	Spastic Paraplegia	GENOMICS_ENGLAND_DG	24424123, 27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	26556829	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	BEFREE	24080142		★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only