MTRF1L

Summary

MTRF1L (mitochondrial translation release factor 1 like, HGNC:21051) is a protein-coding gene on chromosome 6q25.2, encoding Peptide chain release factor 1-like, mitochondrial (Q9UGC7). Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain termination codons UAA and UAG. It is a selective cancer dependency (DepMap: 33.0% of cell lines).

The protein encoded by this gene plays a role in mitochondrial translation termination, and is thought to be a release factor that is involved in the dissociation of the complete protein from the final tRNA, the ribosome, and the cognate mRNA. This protein acts upon UAA and UAG stop codons, but has no in vitro activity against UGA, which encodes tryptophan in human mitochondrion, or, the mitochondrial non-cognate stop codons, AGA and AGG. This protein shares sequence similarity to bacterial release factors. Pseudogenes of this gene are found on chromosomes 4, 8, and 11. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 54516 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 48 total
• Cancer dependency (DepMap): dependent in 33.0% of screened cell lines
• MANE Select transcript: NM_019041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21051
Approved symbol	MTRF1L
Name	mitochondrial translation release factor 1 like
Location	6q25.2
Locus type	gene with protein product
Status	Approved
Aliases	HMRF1L, mtRF1a
Ensembl gene	ENSG00000112031
Ensembl biotype	protein_coding
OMIM	613542
Entrez	54516

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000367230, ENST00000367231, ENST00000367233, ENST00000414771, ENST00000448966, ENST00000461949, ENST00000463251, ENST00000464135, ENST00000482526, ENST00000485283, ENST00000485512, ENST00000936987

RefSeq mRNA: 6 — MANE Select: NM_019041 NM_001114184, NM_001301047, NM_001301870, NM_001301871, NM_001301872, NM_019041

CCDS: CCDS47502, CCDS5243, CCDS75540

Canonical transcript exons

ENST00000367233 — 7 exons

Exon	Start	End
ENSE00000765355	152995136	152995319
ENSE00003500848	152992857	152992974
ENSE00003504063	152994513	152994676
ENSE00003561176	152998550	152998629
ENSE00003594161	152991185	152991321
ENSE00003608999	152987362	152990095
ENSE00003843702	153002427	153002709

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7136 / max 208.2473, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76273	18.3627	1819
76274	0.3509	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	95.54	gold quality
endothelial cell	CL:0000115	95.13	gold quality
kidney epithelium	UBERON:0004819	94.81	gold quality
buccal mucosa cell	CL:0002336	94.75	gold quality
pancreatic ductal cell	CL:0002079	94.44	silver quality
medial globus pallidus	UBERON:0002477	94.34	gold quality
tibialis anterior	UBERON:0001385	94.31	silver quality
deltoid	UBERON:0001476	94.14	gold quality
body of tongue	UBERON:0011876	93.48	gold quality
globus pallidus	UBERON:0001875	93.33	gold quality
tongue	UBERON:0001723	93.04	gold quality
tendon of biceps brachii	UBERON:0008188	92.95	gold quality
pericardium	UBERON:0002407	92.84	gold quality
inferior vagus X ganglion	UBERON:0005363	92.73	gold quality
myocardium	UBERON:0002349	92.70	gold quality
superior surface of tongue	UBERON:0007371	92.26	gold quality
vastus lateralis	UBERON:0001379	92.17	gold quality
heart right ventricle	UBERON:0002080	92.17	gold quality
pons	UBERON:0000988	92.08	gold quality
medulla oblongata	UBERON:0001896	91.94	gold quality
parotid gland	UBERON:0001831	91.88	gold quality
saphenous vein	UBERON:0007318	91.72	gold quality
superior vestibular nucleus	UBERON:0007227	91.67	gold quality
quadriceps femoris	UBERON:0001377	91.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.52	gold quality
upper arm skin	UBERON:0004263	91.26	gold quality
ventral tegmental area	UBERON:0002691	90.96	gold quality
renal medulla	UBERON:0000362	90.95	gold quality
nipple	UBERON:0002030	90.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting MTRF1L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-516B-5P	99.56	66.33	1495

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• mtRF1a is a mitochondrial translation release factor that is capable in vitro and in vivo of terminating translation at UAA/UAG codons. (PMID:17803939)
• Study identified a human mitochondrial release factor candidate, HMRF1L, and demonstrated that HMRF1L is indeed a mitochondrial protein that functions specifically as an RF for the decoding of mitochondrial UAA and UAG termination codons in vitro. (PMID:18429816)
• The methylation of HMRF1L by HMPrmC in human mitochondria is involved in the control of the translation termination process. (PMID:18541145)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtrf1l	ENSDARG00000060005
mus_musculus	Mtrf1l	ENSMUSG00000019774
rattus_norvegicus	Mtrf1l	ENSRNOG00000018773
drosophila_melanogaster	mRF1	FBGN0032486

Paralogs (2): MTRF1 (ENSG00000120662), MRPL58 (ENSG00000167862)

Protein

Protein identifiers

Peptide chain release factor 1-like, mitochondrial — Q9UGC7 (reviewed: Q9UGC7)

Alternative names: Mitochondrial translational release factor 1-like, mtRF1a

All UniProt accessions (3): Q9UGC7, Q5TF45, X6RKB4

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 termination codons UAA and UAG.

Subcellular location. Mitochondrion.

Tissue specificity. Expressed in skeletal muscle (at protein level).

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 (4)

UniProt ID	Names	Canonical?
Q9UGC7-1	1	yes
Q9UGC7-2	2
Q9UGC7-3	3
Q9UGC7-4	4

RefSeq proteins (5): NP_001107656, NP_001287976, NP_001288799, NP_001288800, NP_061914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000352	Pep_chain_release_fac_I	Domain
IPR005139	PCRF	Domain
IPR045853	Pep_chain_release_fac_I_sf	Homologous_superfamily
IPR050057	Prokaryotic/Mito_RF	Family

Pfam: PF00472, PF03462

UniProt features (15 total): sequence variant 4, splice variant 4, transit peptide 1, chain 1, mutagenesis site 1, region of interest 1, coiled-coil region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7NQH	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGC7-F1	83.86	0.55

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): 252

Mutagenesis-validated functional residues (1):

Position	Phenotype
250–251	impaired mitochondrial peptide chain release factor activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5419276	Mitochondrial translation termination

MSigDB gene sets: 122 (showing top): GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATIONAL_TERMINATION, GOBP_TRANSLATION, chr6q25, MORF_ZNF10, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, OCT1_06, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, GCM_NF2, MORF_WNT1, MORF_DCC, GOCC_MITOCHONDRIAL_MATRIX, MARSON_BOUND_BY_FOXP3_STIMULATED

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:

Category	Pathways
Mitochondrial translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
translational termination	2
mitochondrial translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
protein-containing complex disassembly	1
translation termination factor activity	1
translation release factor activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTRF1L	MTIF2	P46199	775
MTRF1L	MRPL58	Q14197	763
MTRF1L	MTRFR	Q9H3J6	722
MTRF1L	MRRF	Q96E11	705
MTRF1L	MTIF3	Q9H2K0	678
MTRF1L	HEMK1	Q9Y5R4	673
MTRF1L	NDUFAF5	Q5TEU4	651
MTRF1L	GFM2	Q969S9	642
MTRF1L	GFM1	Q96RP9	577
MTRF1L	LYRM1	O43325	564
MTRF1L	NDUFAF7	Q7L592	536
MTRF1L	TACO1	Q9BSH4	527
MTRF1L	MRPL20	Q9BYC9	522
MTRF1L	RMND1	Q9NWS8	513
MTRF1L	MRPL49	Q13405	512

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MTRF1L	PDIA6	psi-mi:“MI:0915”(physical association)	0.400
MTRF1L	PDS5B	psi-mi:“MI:0915”(physical association)	0.400
MTRF1L	TTC4	psi-mi:“MI:0915”(physical association)	0.400
MTRF1L	CHI3L1	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
MGST3	VWA8	psi-mi:“MI:2364”(proximity)	0.270
PDK1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
TRMT61B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (257): CHI3L1 (Affinity Capture-MS), HEMK1 (Affinity Capture-MS), MECR (Co-fractionation), PRPSAP2 (Co-fractionation), HEMK1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), ACAD9 (Affinity Capture-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (Proximity Label-MS), MTRF1L (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: A1B0G1, A1BJT9, A1VAK8, A3DIL4, A3PJZ6, A4VPB9, A4WRK0, A4XJN1, A4XR61, A5GIR6, A5V9C3, A5VYG5, A6VC61, A8GXI1, A8LLU7, A9HJ50, A9IMM3, A9W1A4, B0JYC5, B0KNE4, B1GZI5, B1I6L2, B1JEP6, B1M766, B1XJH8, B1Z914, B3CL87, B3QCF6, B4U955, B5YDB2, B5ZRR4, B6JA06, B7K205, B7L246, B8DLL6, B8E003, B8EI32, B8FZ76, B8J4R4, B9KIV2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

675 predictions. Top by Δscore:

Variant	Effect	Δscore
6:152991179:TTTTA:T	donor_loss	1.0000
6:152991180:TTTAC:T	donor_loss	1.0000
6:152991181:TTA:T	donor_loss	1.0000
6:152991182:TACC:T	donor_loss	1.0000
6:152991183:ACC:A	donor_loss	1.0000
6:152991184:CC:C	donor_loss	1.0000
6:152991320:ACCTG:A	acceptor_loss	1.0000
6:152992853:ACAC:A	donor_loss	1.0000
6:152992854:CACC:C	donor_loss	1.0000
6:152992855:A:T	donor_loss	1.0000
6:152992856:C:CA	donor_loss	1.0000
6:152992970:TTAAT:T	acceptor_gain	1.0000
6:152992971:TAAT:T	acceptor_gain	1.0000
6:152992972:AAT:A	acceptor_gain	1.0000
6:152992973:AT:A	acceptor_gain	1.0000
6:152992973:ATC:A	acceptor_loss	1.0000
6:152992974:TCTAT:T	acceptor_loss	1.0000
6:152992975:C:CC	acceptor_gain	1.0000
6:152992977:A:AC	acceptor_gain	1.0000
6:152992977:A:C	acceptor_gain	1.0000
6:152994507:CCTTA:C	donor_loss	1.0000
6:152994508:CTTAC:C	donor_loss	1.0000
6:152994509:TTAC:T	donor_loss	1.0000
6:152994510:TAC:T	donor_loss	1.0000
6:152994674:CACC:C	acceptor_loss	1.0000
6:152994674:CACCT:C	acceptor_gain	1.0000
6:152994676:CCT:C	acceptor_gain	1.0000
6:152994677:CTTGA:C	acceptor_loss	1.0000
6:152994678:T:C	acceptor_gain	1.0000
6:152994678:T:TC	acceptor_gain	1.0000

AlphaMissense

2470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:152992880:A:T	V261D	0.998
6:152994549:G:C	S217R	0.998
6:152994549:G:T	S217R	0.998
6:152994551:T:G	S217R	0.998
6:152992877:C:G	R262P	0.997
6:152990040:C:G	R333P	0.995
6:152992885:A:C	S259R	0.995
6:152992885:A:T	S259R	0.995
6:152992887:T:G	S259R	0.995
6:152990063:T:A	R325S	0.994
6:152990063:T:G	R325S	0.994
6:152990064:C:G	R325T	0.994
6:152990037:A:T	V334D	0.993
6:152990024:T:A	R338S	0.991
6:152990024:T:G	R338S	0.991
6:152991267:G:T	A287D	0.991
6:152991280:T:C	N283D	0.991
6:152992874:A:T	I263K	0.991
6:152992884:C:G	A260P	0.991
6:152992906:C:A	Q252H	0.991
6:152992906:C:G	Q252H	0.991
6:152990059:A:C	Y327D	0.990
6:152991255:A:G	L291S	0.990
6:152990029:G:C	H337D	0.989
6:152994661:G:T	A180E	0.989
6:152992883:G:T	A260D	0.988
6:152994602:G:C	H200D	0.988
6:152995235:C:G	A142P	0.988
6:152990065:T:C	R325G	0.987
6:152994588:T:A	R204S	0.987

dbSNP variants (sampled 300 via entrez): RS1000141447 (6:153000167 G>C,T), RS1000618169 (6:153000483 T>C), RS1000954770 (6:153001678 C>T), RS1001546377 (6:152998755 C>T), RS1001547859 (6:152994670 A>C), RS1001926119 (6:152994398 A>T), RS1002376676 (6:152998055 G>A), RS1002867557 (6:152994571 T>C), RS1002876892 (6:152991740 G>A), RS1002931898 (6:152986986 A>T), RS1003088452 (6:152994357 T>G), RS1003248672 (6:152993507 C>T), RS1003373480 (6:152987311 G>A), RS1003406960 (6:152999674 T>C), RS1003464859 (6:153001290 G>A)

Disease associations

OMIM: gene MIM:613542 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001942_11	Prostate cancer	4.000000e-18
GCST005951_154	Body mass index	1.000000e-09
GCST007565_84	Morning person	3.000000e-27
GCST007576_424	Chronotype	3.000000e-27
GCST009259_3	Amygdala volume	9.000000e-06
GCST90002398_414	Neutrophil count	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs766127	Efficacy	3	antidepressants	Major Depressive Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs766127	MTRF1L	3	0.00	1	antidepressants
rs3192723	MTRF1L	3	0.00	1	methadone

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beauvericin	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrimidin-2-one beta-ribofuranoside	increases expression	1
trichostatin A	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
enniatins	affects cotreatment, decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
Vincristine	decreases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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