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MTRF1

gene
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Also known as RF1MTTRF1MGC47721

Summary

MTRF1 (mitochondrial translation release factor 1, HGNC:7469) is a protein-coding gene on chromosome 13q14.11, encoding Peptide chain release factor 1, mitochondrial (O75570). Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain non-canonical stop codons AGG and AGA.

The protein encoded by this gene was determined by in silico methods to be a mitochondrial protein with similarity to the peptide chain release factors (RFs) discovered in bacteria and yeast. The peptide chain release factors direct the termination of translation in response to the peptide chain termination codons. Initially thought to have a role in the termination of mitochondria protein synthesis, a recent publication found no mitochondrial translation release functionality. Multiple alternatively spliced transcript variants have been suggested by mRNA and EST data; however, their full-length natures are not clear.

Source: NCBI Gene 9617 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 58 total
  • MANE Select transcript: NM_004294

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7469
Approved symbolMTRF1
Namemitochondrial translation release factor 1
Location13q14.11
Locus typegene with protein product
StatusApproved
AliasesRF1, MTTRF1, MGC47721
Ensembl geneENSG00000120662
Ensembl biotypeprotein_coding
OMIM604601
Entrez9617

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 74 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000239852, ENST00000379477, ENST00000379480, ENST00000430347, ENST00000452359, ENST00000473492, ENST00000480434, ENST00000492827, ENST00000497679, ENST00000498245, ENST00000897168, ENST00000897169, ENST00000897170, ENST00000897171, ENST00000897172, ENST00000897173, ENST00000897174, ENST00000897175, ENST00000897176, ENST00000897177, ENST00000897178, ENST00000897179, ENST00000897180, ENST00000897181, ENST00000897182, ENST00000897183, ENST00000897184, ENST00000897185, ENST00000897186, ENST00000897187, ENST00000897188, ENST00000897189, ENST00000897190, ENST00000897191, ENST00000897192, ENST00000897193, ENST00000897194, ENST00000897195, ENST00000897196, ENST00000897197, ENST00000897198, ENST00000897199, ENST00000897200, ENST00000897201, ENST00000897202, ENST00000934026, ENST00000934027, ENST00000934028, ENST00000934029, ENST00000934030, ENST00000934031, ENST00000934032, ENST00000934033, ENST00000934034, ENST00000934035, ENST00000934036, ENST00000934037, ENST00000948280, ENST00000948281, ENST00000948282, ENST00000948283, ENST00000948284, ENST00000948285, ENST00000948286, ENST00000948287, ENST00000948288, ENST00000948289, ENST00000948290, ENST00000948291, ENST00000948292, ENST00000948293, ENST00000948294, ENST00000948295, ENST00000948296, ENST00000948297, ENST00000948298, ENST00000948299, ENST00000948300, ENST00000948301

RefSeq mRNA: 4 — MANE Select: NM_004294 NM_001354073, NM_001354074, NM_001354076, NM_004294

CCDS: CCDS9378

Canonical transcript exons

ENST00000379480 — 10 exons

ExonStartEnd
ENSE000008172084122643241226568
ENSE000008172094123389041234007
ENSE000012890864125264541252752
ENSE000017379674121636941217228
ENSE000034568984124026141240433
ENSE000035571164122325641223354
ENSE000035846714125294941253030
ENSE000036787684125452941254620
ENSE000037337184126049341260915
ENSE000038499664126348541263576

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 90.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8568 / max 94.3440, expressed in 1718 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1369607.21741690
1369610.6394373

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
body of pancreasUBERON:000115090.90gold quality
lower esophagus mucosaUBERON:003583487.91gold quality
rectumUBERON:000105287.73gold quality
adrenal tissueUBERON:001830387.64gold quality
right adrenal glandUBERON:000123387.18gold quality
right adrenal gland cortexUBERON:003582787.09gold quality
gall bladderUBERON:000211086.39gold quality
left adrenal glandUBERON:000123486.11gold quality
small intestine Peyer’s patchUBERON:000345486.08gold quality
granulocyteCL:000009486.03gold quality
pancreasUBERON:000126486.02gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047385.94gold quality
left adrenal gland cortexUBERON:003582585.77gold quality
body of stomachUBERON:000116185.65gold quality
metanephros cortexUBERON:001053385.45gold quality
gastrocnemiusUBERON:000138885.17gold quality
lymph nodeUBERON:000002985.08gold quality
adrenal glandUBERON:000236985.07gold quality
adrenal cortexUBERON:000123584.95gold quality
spleenUBERON:000210684.95gold quality
right testisUBERON:000453484.89gold quality
muscle of legUBERON:000138384.79gold quality
left testisUBERON:000453384.69gold quality
monocyteCL:000057684.60gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099184.57gold quality
small intestineUBERON:000210884.38gold quality
hindlimb stylopod muscleUBERON:000425284.33gold quality
mononuclear cellCL:000084284.28gold quality
right lobe of liverUBERON:000111484.14gold quality
testisUBERON:000047384.08gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no4.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting MTRF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-5692A100.0074.406850
HSA-MIR-511-3P99.9968.851467
HSA-MIR-569699.9872.364487
HSA-MIR-485-3P99.9870.681585
HSA-MIR-539-3P99.9870.741616
HSA-MIR-9-3P99.9670.882068
HSA-MIR-391099.9571.132227
HSA-MIR-144-3P99.9473.982698
HSA-MIR-4760-3P99.9370.502385
HSA-MIR-6809-3P99.9171.453814
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-579-3P99.8671.663628
HSA-MIR-664B-3P99.8471.653590
HSA-MIR-430799.8270.453374
HSA-MIR-205299.7969.372031
HSA-MIR-320A-3P99.7769.732107
HSA-MIR-320B99.7769.732107
HSA-MIR-320C99.7769.732107
HSA-MIR-320D99.7769.732107
HSA-MIR-442999.7769.622111
HSA-MIR-472999.6972.184233
HSA-MIR-7152-5P99.6069.332094
HSA-MIR-3120-3P99.5470.282669
HSA-MIR-1212399.5271.792990
HSA-MIR-302B-5P99.5069.491857
HSA-MIR-302D-5P99.5069.341863
HSA-MIR-330-3P99.4169.952521
HSA-MIR-391199.3866.951087
HSA-MIR-130A-5P99.3370.262623

Literature-anchored findings (GeneRIF, showing 4)

  • Purified mtRF1 did not induce translation termination in vitro nor did mtRF1 restore mitochondrial translation machinery in mutated S. cerevisiae in vivo. A different mtRF, mtRF1a, was found. (PMID:17803939)
  • Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control. (PMID:36302763)
  • Human mitochondria require mtRF1 for translation termination at non-canonical stop codons. (PMID:36596788)
  • Molecular basis of translation termination at noncanonical stop codons in human mitochondria. (PMID:37141370)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriomtrf1ENSDARG00000033579
mus_musculusMtrf1ENSMUSG00000022022
rattus_norvegicusMtrf1ENSRNOG00000047106
drosophila_melanogastermRF1FBGN0032486

Paralogs (2): MTRF1L (ENSG00000112031), MRPL58 (ENSG00000167862)

Protein

Protein identifiers

Peptide chain release factor 1, mitochondrial — O75570 (reviewed: O75570)

All UniProt accessions (5): A0A087WZ41, A0A087X1S1, O75570, Q8N6Z2, X6RFD4

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain non-canonical stop codons AGG and AGA. Non-canonical termination codons AGG and AGA are found at the end of MT-CO1/COX1 and MT-ND6/ND6 open reading frames, respectively. Recognizes non-canonical stop codons via a network of interactions between the codon, MTRF1 and the ribosomal RNA (rRNA): in contrast to other translation release factors, which identify the codon in the A-site via direct interactions of amino acid side chains with the bases, MTRF1 repositions the first 2 bases of the stop codon to use an intricate network of interactions that includes residues of the release factor, the rRNA of the small ribosomal subunit, as well as neighboring bases of the mRNA.

Subcellular location. Mitochondrion.

Post-translational modifications. Methylation of glutamine in the GGQ triplet by HEMK1 is conserved from bacteria to mammals.

Domain organisation. The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis.

Similarity. Belongs to the prokaryotic/mitochondrial release factor family.

Isoforms (2)

UniProt IDNamesCanonical?
O75570-11yes
O75570-22

RefSeq proteins (4): NP_001341002, NP_001341003, NP_001341005, NP_004285* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000352Pep_chain_release_fac_IDomain
IPR005139PCRFDomain
IPR045853Pep_chain_release_fac_I_sfHomologous_superfamily
IPR050057Prokaryotic/Mito_RFFamily

Pfam: PF00472, PF03462

UniProt features (19 total): sequence conflict 8, sequence variant 3, splice variant 2, transit peptide 1, chain 1, mutagenesis site 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDBMethodResolution (Å)
8OITELECTRON MICROSCOPY2.9
8OISELECTRON MICROSCOPY3
8OIRELECTRON MICROSCOPY3.1
8OIQELECTRON MICROSCOPY3.5
8OINELECTRON MICROSCOPY3.6
8OIPELECTRON MICROSCOPY3.6

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O75570-F180.030.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 313

Mutagenesis-validated functional residues (1):

PositionPhenotype
311–312impaired mitochondrial peptide chain release factor activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-5419276Mitochondrial translation termination

MSigDB gene sets: 74 (showing top): GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATIONAL_TERMINATION, GOBP_TRANSLATION, MARTIN_NFKB_TARGETS_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, chr13q14, GOCC_MITOCHONDRIAL_MATRIX, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, STEIN_ESRRA_TARGETS_UP, GOBP_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_MITOCHONDRIAL_GENE_EXPRESSION, GOMF_TRANSLATION_TERMINATION_FACTOR_ACTIVITY, PRC2_SUZ12_UP.V1_UP, REACTOME_MITOCHONDRIAL_TRANSLATION, DCA_UP.V1_DN

GO Biological Process (3): mitochondrial translational termination (GO:0070126), translation (GO:0006412), translational termination (GO:0006415)

GO Molecular Function (2): translation release factor activity (GO:0003747), translation release factor activity, codon specific (GO:0016149)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Mitochondrial translation1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
mitochondrion2
translational termination2
mitochondrial translation1
peptidyltransferase activity1
translational initiation1
translational elongation1
macromolecule biosynthetic process1
protein metabolic process1
protein biosynthetic process1
translation1
protein-containing complex disassembly1
translation termination factor activity1
translation release factor activity1
cytoplasm1
intracellular membrane-bounded organelle1
intracellular organelle lumen1
intracellular anatomical structure1
cellular anatomical structure1

Protein interactions and networks

STRING

1972 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MTRF1MRPL58Q14197732
MTRF1HEMK1Q9Y5R4725
MTRF1MTIF2P46199724
MTRF1MRRFQ96E11706
MTRF1GFM2Q969S9664
MTRF1MTIF3Q9H2K0630
MTRF1MRPS11P82912569
MTRF1VWA8A3KMH1564
MTRF1WBP4O75554540
MTRF1HEMK2Q9Y5N5530
MTRF1TUFMP49411510
MTRF1MRPS31Q92665507
MTRF1GFM1Q96RP9492
MTRF1LAMTOR5O43504468
MTRF1MRPL35Q9NZE8467

IntAct

6 interactions, top by confidence:

ABTypeScore
MTRF1KRT8psi-mi:“MI:0915”(physical association)0.400
MYCpsi-mi:“MI:0914”(association)0.350
MTRF1MEIS1psi-mi:“MI:0914”(association)0.350
CLPPNDUFA4psi-mi:“MI:2364”(proximity)0.270
VWA8psi-mi:“MI:2364”(proximity)0.270

BioGRID (250): MTRF1 (Affinity Capture-RNA), MTRF1 (Synthetic Lethality), KRT8 (Proximity Label-MS), MTRF1 (Proximity Label-MS), MTRF1 (Proximity Label-MS), MTRF1 (Proximity Label-MS), MTRF1 (Proximity Label-MS), AARS2 (Proximity Label-MS), ABCB7 (Proximity Label-MS), ACAD9 (Proximity Label-MS), ACAT1 (Proximity Label-MS), ACOT1 (Proximity Label-MS), ACOT2 (Proximity Label-MS), AFG3L2 (Proximity Label-MS), AK4 (Proximity Label-MS)

ESM2 similar proteins: A1AX02, A2RVR7, A5CCS8, A5IED7, A6SXF4, A9IMM3, B0B9D0, B0BB09, B2ITM5, B3CQD1, B7K205, B9KIV2, F4I532, O44568, O75570, O84026, P30775, P41767, P59456, P75420, Q09691, Q110D7, Q1LTH5, Q2GDG2, Q2GE03, Q2GGM5, Q2GKS8, Q2KI15, Q3KMZ9, Q3MF91, Q3MHI7, Q3YS23, Q47WT4, Q492V8, Q4V7E5, Q5FGZ2, Q5HB80, Q5L6U9, Q5PAH2, Q68WK7

Diamond homologs: A0Q312, A0Q844, A1U367, A3DIL4, A4IWC1, A4JB50, A4XR61, A5CCS8, A5HY35, A5IED7, A5V9C3, A5VYG5, A6Q162, A6W1C2, A7FQG2, A7G9P2, A7HTY3, A7NE96, A8GXI1, A8H7A5, A8MJX9, A9KGY3, A9N9K2, B0KNE4, B0S2B6, B0TX37, B1GZI5, B1IE21, B1JEP6, B1KDU3, B1KSR1, B2A3J0, B2SFF6, B2UL99, B3CQD1, B4RSV6, B4U955, B5YDB2, B5YIQ7, B6J390

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

58 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance43
Likely benign1
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2459 predictions. Top by Δscore:

VariantEffectΔscore
13:41226426:TCTTA:Tdonor_loss1.0000
13:41226427:CTTAC:Cdonor_loss1.0000
13:41226428:TTA:Tdonor_loss1.0000
13:41226429:TACC:Tdonor_loss1.0000
13:41226430:A:Cdonor_loss1.0000
13:41226431:C:CAdonor_loss1.0000
13:41226431:CCTG:Cdonor_gain1.0000
13:41226569:C:CCacceptor_gain1.0000
13:41233885:CTTA:Cdonor_loss1.0000
13:41233886:TTACC:Tdonor_loss1.0000
13:41233887:TACC:Tdonor_loss1.0000
13:41233888:A:ACdonor_gain1.0000
13:41233889:C:CCdonor_gain1.0000
13:41234006:ACCT:Aacceptor_loss1.0000
13:41234007:CCTA:Cacceptor_loss1.0000
13:41234008:C:CGacceptor_loss1.0000
13:41234009:T:Gacceptor_loss1.0000
13:41240297:T:Adonor_gain1.0000
13:41252749:TCAC:Tacceptor_gain1.0000
13:41252749:TCACC:Tacceptor_loss1.0000
13:41252750:CAC:Cacceptor_gain1.0000
13:41252750:CACC:Cacceptor_gain1.0000
13:41252751:AC:Aacceptor_gain1.0000
13:41252751:ACC:Aacceptor_loss1.0000
13:41252752:CC:Cacceptor_gain1.0000
13:41252752:CCTAA:Cacceptor_loss1.0000
13:41252753:C:CAacceptor_loss1.0000
13:41252753:C:CCacceptor_gain1.0000
13:41252754:T:Aacceptor_loss1.0000
13:41252945:TGA:Tdonor_loss1.0000

AlphaMissense

2945 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
13:41240355:C:GR259P0.998
13:41240286:A:TV282D0.997
13:41240346:C:GR262P0.997
13:41223296:A:TV395D0.996
13:41240280:A:TV284D0.996
13:41240298:C:TG278E0.996
13:41252733:A:CF203L0.996
13:41252733:A:TF203L0.996
13:41252735:A:GF203L0.996
13:41252742:G:CC200W0.996
13:41223323:C:GR386P0.995
13:41233913:A:TV322D0.995
13:41240305:G:CH276D0.995
13:41240348:C:AQ261H0.995
13:41240348:C:GQ261H0.995
13:41240359:G:CH258D0.995
13:41240299:C:GG278R0.994
13:41240299:C:TG278R0.994
13:41240310:C:GR274P0.994
13:41240311:G:TR274S0.994
13:41240352:A:TV260D0.994
13:41240418:G:TA238E0.994
13:41223318:A:CY388D0.993
13:41233918:A:CS320R0.993
13:41233918:A:TS320R0.993
13:41233920:T:GS320R0.993
13:41240419:C:GA238P0.993
13:41252743:C:TC200Y0.993
13:41223283:C:AR399S0.992
13:41223283:C:GR399S0.992

dbSNP variants (sampled 300 via entrez): RS1000042901 (13:41247541 C>A), RS1000045505 (13:41284807 C>G,T), RS1000099158 (13:41290652 C>T), RS1000171773 (13:41267994 A>G), RS1000222514 (13:41268352 CTT>C), RS1000265989 (13:41254449 T>C,G), RS1000299452 (13:41310368 G>A), RS1000328771 (13:41297493 A>C,G), RS1000342238 (13:41230287 G>A), RS1000379154 (13:41277498 G>C), RS1000382995 (13:41297214 T>C), RS1000406671 (13:41273440 C>T), RS1000426237 (13:41237285 A>G), RS1000482539 (13:41279177 A>G), RS1000483390 (13:41304189 C>T)

Disease associations

OMIM: gene MIM:604601 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST010916_19Proportion of activated microglia (inferior temporal cortex)7.000000e-06
GCST90013442_21Keratoconus6.000000e-35

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression2
dicrotophosdecreases expression1
sodium arseniteincreases abundance, increases expression1
butyraldehydedecreases expression1
pentanaldecreases expression1
monomethylarsonous acidincreases expression1
(+)-JQ1 compounddecreases expression1
Vorinostatincreases expression1
Acetaminophendecreases expression1
Arsenicincreases expression, increases abundance1
Atrazineincreases expression1
Benzo(a)pyreneaffects methylation1
Doxorubicindecreases expression1
Mercurydecreases expression1
Methyl Methanesulfonateincreases expression1
Tunicamycinincreases expression1
Thapsigarginincreases expression1
Copper Sulfatedecreases expression1
Acrylamideincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot