MTRES1

Summary

MTRES1 (mitochondrial transcription rescue factor 1, HGNC:17971) is a protein-coding gene on chromosome 6q21, encoding Mitochondrial transcription rescue factor 1 (Q9P0P8). Mitochondrial RNA-binding protein involved in mitochondrial transcription regulation.

Enables ribosomal large subunit binding activity and tRNA binding activity. Involved in regulation of mitochondrial transcription and rescue of stalled ribosome. Located in mitochondrial matrix.

Source: NCBI Gene 51250 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_016487

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17971
Approved symbol	MTRES1
Name	mitochondrial transcription rescue factor 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	HSPC230, PRED31
Ensembl gene	ENSG00000130349
Ensembl biotype	protein_coding
OMIM	618583
Entrez	51250

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000311381, ENST00000405204, ENST00000489790, ENST00000625458, ENST00000878887, ENST00000878888, ENST00000878889, ENST00000878890, ENST00000878891, ENST00000878892, ENST00000878893, ENST00000878894, ENST00000878895, ENST00000878896, ENST00000878897, ENST00000878898, ENST00000878899, ENST00000913923, ENST00000913924, ENST00000959607, ENST00000959608, ENST00000959609, ENST00000959610

RefSeq mRNA: 3 — MANE Select: NM_016487 NM_001142468, NM_001142470, NM_016487

CCDS: CCDS5058, CCDS78167

Canonical transcript exons

ENST00000311381 — 4 exons

Exon	Start	End
ENSE00000895024	107044260	107044332
ENSE00001018089	107028199	107028271
ENSE00001904229	107051057	107051586
ENSE00003593673	107039749	107040230

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8292 / max 71.7681, expressed in 1754 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69150	7.2671	1742
69151	0.5620	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.35	gold quality
tendon of biceps brachii	UBERON:0008188	94.59	gold quality
secondary oocyte	CL:0000655	94.42	gold quality
mucosa of transverse colon	UBERON:0004991	92.95	gold quality
oviduct epithelium	UBERON:0004804	92.33	gold quality
biceps brachii	UBERON:0001507	92.21	gold quality
vastus lateralis	UBERON:0001379	92.01	gold quality
right adrenal gland	UBERON:0001233	91.70	gold quality
right adrenal gland cortex	UBERON:0035827	91.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.37	gold quality
quadriceps femoris	UBERON:0001377	91.23	gold quality
medial globus pallidus	UBERON:0002477	91.15	gold quality
skeletal muscle tissue	UBERON:0001134	91.00	gold quality
left adrenal gland	UBERON:0001234	90.97	gold quality
apex of heart	UBERON:0002098	90.87	gold quality
kidney epithelium	UBERON:0004819	90.87	gold quality
left adrenal gland cortex	UBERON:0035825	90.37	gold quality
adrenal cortex	UBERON:0001235	90.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.28	gold quality
muscle of leg	UBERON:0001383	90.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.20	gold quality
adrenal gland	UBERON:0002369	90.16	gold quality
heart left ventricle	UBERON:0002084	90.12	gold quality
gastrocnemius	UBERON:0001388	90.06	gold quality
cardiac ventricle	UBERON:0002082	90.00	gold quality
deltoid	UBERON:0001476	89.90	gold quality
muscle tissue	UBERON:0002385	89.90	gold quality
globus pallidus	UBERON:0001875	89.48	gold quality
rectum	UBERON:0001052	89.32	gold quality
tendon	UBERON:0000043	89.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.98
E-GEOD-111727	no	142.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting MTRES1, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-4769-5P	95.37	66.09	570

Literature-anchored findings (GeneRIF, showing 2)

• Data show that mitochondrial transcription rescue factor 1 (MTRES1) is elevated in cells under stress and that this upregulation of MTRES1 prevents mitochondrial transcript loss under perturbed mitochondrial gene expression. (PMID:31226201)
• Although mitoribosome stability is not affected in C6orf203-depleted cells, mitoribosome profiling analysis revealed a global disruption of the association of mt-mRNAs with the mitoribosome, suggesting that C6orf203 may be required for the proper maturation and functioning of the mitoribosome. (PMID:31396629)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtres1	ENSDARG00000077614
mus_musculus	Mtres1	ENSMUSG00000019797
rattus_norvegicus	Mtres1	ENSRNOG00000047118
drosophila_melanogaster	CG4884	FBGN0039565
caenorhabditis_elegans	C47B2.9	WBGENE00008134

Protein

Protein identifiers

Mitochondrial transcription rescue factor 1 — Q9P0P8 (reviewed: Q9P0P8)

All UniProt accessions (2): Q9P0P8, A0A0D9SEI0

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial RNA-binding protein involved in mitochondrial transcription regulation. Functions as a protective factor to maintain proper mitochondrial RNA level during stress. Acts at the transcription level and its protective function depends on its RNA binding ability. Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation. As heterodimer with MTRF, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue.

Subunit / interactions. Monomer. Interacts with POLRMT. Interacts (via S4 domain) with MTRFR (via C-terminus). Associates with mitoribosomal S39 large subunit, peptidyl tRNA and nascent chain.

Subcellular location. Mitochondrion matrix.

Induction. Up-regulated upon depletion of mitochondrial nucleic acids.

RefSeq proteins (3): NP_001135940, NP_001135942, NP_057571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR057896	MTRES1_C	Domain

Pfam: PF25818

UniProt features (12 total): mutagenesis site 5, modified residue 2, transit peptide 1, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7A5H	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0P8-F1	67.10	0.35

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 (2): 106, 116

Mutagenesis-validated functional residues (5):

Position	Phenotype
156	decreased rna-binding; when associated with a-143; a-145: a-149 and a-158. does not rescue diminished mitochondrial tran
158	decreased rna-binding; when associated with a-143; a-145: a-149 and a-156. does not rescue diminished mitochondrial tran
143	decreased rna-binding; when associated with a-145; a-149: a-156 and a-158. does not rescue diminished mitochondrial tran
145	decreased rna-binding; when associated with a-143; a-149: a-156 and a-158. does not rescue diminished mitochondrial tran
149	decreased rna-binding; when associated with a-143; a-145: a-156 and a-158. does not rescue diminished mitochondrial tran

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9937383	Mitochondrial ribosome-associated quality control

MSigDB gene sets: 87 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, TGACCTY_ERR1_Q2, GOBP_TRANSLATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, TSENG_IRS1_TARGETS_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, GOBP_TRANSLATIONAL_ELONGATION, TGACCTTG_SF1_Q6, GOBP_ORGANELLE_DISASSEMBLY, GOCC_MITOCHONDRIAL_MATRIX, GOMF_TRNA_BINDING, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GOMF_RIBOSOME_BINDING, HORIUCHI_WTAP_TARGETS_UP, GOBP_MITOCHONDRIAL_TRANSCRIPTION

GO Biological Process (2): rescue of stalled cytosolic ribosome (GO:0072344), regulation of mitochondrial transcription (GO:1903108)

GO Molecular Function (4): tRNA binding (GO:0000049), RNA binding (GO:0003723), ribosomal large subunit binding (GO:0043023), protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

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
cytoplasmic translational elongation	1
ribosome disassembly	1
regulation of DNA-templated transcription	1
mitochondrial transcription	1
regulation of mitochondrial gene expression	1
RNA binding	1
nucleic acid binding	1
ribosome binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTRES1	MTRFR	Q9H3J6	747
MTRES1	MALSU1	Q96EH3	579
MTRES1	TFAM	Q00059	559
MTRES1	CEBPZOS	A8MTT3	522
MTRES1	RTN4IP1	Q8WWV3	498
MTRES1	TEFM	Q96QE5	476
MTRES1	QRSL1	Q9H0R6	470
MTRES1	RUSF1	Q96GQ5	447
MTRES1	MTRF1L	Q9UGC7	434
MTRES1	SLIRP	Q9GZT3	433
MTRES1	POLRMT	O00411	416
MTRES1	PRDM1	O75626	404
MTRES1	GTPBP10	A4D1E9	396
MTRES1	MRPL58	Q14197	395
MTRES1	MRM3	Q9HC36	394

IntAct

18 interactions, top by confidence:

A	B	Type	Score
RCC1L	NME6	psi-mi:“MI:0914”(association)	0.720
MTRES1	CPNE7	psi-mi:“MI:0915”(physical association)	0.400
COPS5	MTRES1	psi-mi:“MI:0915”(physical association)	0.370
CFTR	MTRES1	psi-mi:“MI:0915”(physical association)	0.370
MTRES1	UQCRH	psi-mi:“MI:0914”(association)	0.350
MTRES1	MRPL33	psi-mi:“MI:0914”(association)	0.350
MTRES1	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
MRPL58		psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
STRAP	MTRES1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (321): C6orf203 (Affinity Capture-MS), C6orf203 (Affinity Capture-MS), SLC30A9 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL9 (Affinity Capture-MS), MRPL40 (Affinity Capture-MS), MRPL33 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), MRPL22 (Affinity Capture-MS), MRPL13 (Affinity Capture-MS), MRPL16 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), MRPL46 (Affinity Capture-MS), MRPL35 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS)

ESM2 similar proteins: A2BHB7, A8PJJ2, A9P2J1, B0W041, B0WGN4, B0WV73, B0XHW8, B3MN22, B4GX14, B4HXA6, B4KEN8, B4M8L8, B4MVR2, B4P3Q9, B4Q572, B5DF07, B5DFW7, B5DK05, B7PZ18, B9INH0, B9RRX2, C3XVM1, C5DHL6, D3ZY68, D7STK2, E1FU46, E2RK33, E3MIE2, E3WSB5, F4JV80, O15091, O43716, P14629, P53260, Q16Q94, Q2KIF1, Q3ZBC2, Q4R366, Q4RSW7, Q5M8Z2

Diamond homologs: Q9CQF4, Q9P0P8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

805 predictions. Top by Δscore:

Variant	Effect	Δscore
6:107040007:A:G	acceptor_gain	1.0000
6:107044259:GCAAA:G	acceptor_gain	1.0000
6:107051048:A:AG	acceptor_gain	1.0000
6:107051049:A:G	acceptor_gain	1.0000
6:107051050:T:G	acceptor_gain	1.0000
6:107051052:TTCA:T	acceptor_loss	1.0000
6:107051053:TCAG:T	acceptor_loss	1.0000
6:107051054:CAG:C	acceptor_loss	1.0000
6:107051055:A:AG	acceptor_gain	1.0000
6:107051055:AGGT:A	acceptor_gain	1.0000
6:107051056:G:GA	acceptor_gain	1.0000
6:107051056:GGT:G	acceptor_gain	1.0000
6:107051056:GGTG:G	acceptor_gain	1.0000
6:107051056:GGTGA:G	acceptor_gain	1.0000
6:107028270:AGG:A	donor_loss	0.9900
6:107028273:T:G	donor_loss	0.9900
6:107043790:GTTT:G	donor_gain	0.9900
6:107043791:TTTT:T	donor_gain	0.9900
6:107044258:A:AG	acceptor_gain	0.9900
6:107044259:G:GG	acceptor_gain	0.9900
6:107044259:GC:G	acceptor_gain	0.9900
6:107044259:GCA:G	acceptor_gain	0.9900
6:107044259:GCAA:G	acceptor_gain	0.9900
6:107044328:GAACG:G	donor_gain	0.9900
6:107051055:AG:A	acceptor_gain	0.9900
6:107051056:GG:G	acceptor_gain	0.9900
6:107028272:G:GG	donor_gain	0.9800
6:107028551:G:GT	donor_gain	0.9800
6:107039908:T:G	donor_gain	0.9800
6:107040006:A:AG	acceptor_gain	0.9800

AlphaMissense

1565 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:107044320:G:C	K177N	0.995
6:107044320:G:T	K177N	0.995
6:107044323:A:C	K178N	0.995
6:107044323:A:T	K178N	0.995
6:107051195:T:A	W228R	0.995
6:107051195:T:C	W228R	0.995
6:107051127:G:C	R205P	0.994
6:107044321:A:G	K178E	0.993
6:107051190:G:C	R226P	0.993
6:107040176:T:A	V139D	0.992
6:107044276:T:C	F163L	0.992
6:107044278:C:A	F163L	0.992
6:107044278:C:G	F163L	0.992
6:107040200:T:A	V147D	0.991
6:107044301:A:T	N171I	0.991
6:107044322:A:T	K178I	0.991
6:107044324:A:C	S179R	0.991
6:107044326:C:A	S179R	0.991
6:107044326:C:G	S179R	0.991
6:107044277:T:C	F163S	0.990
6:107040212:G:A	G151E	0.989
6:107044318:A:G	K177E	0.989
6:107051193:G:C	R227P	0.989
6:107044273:G:C	A162P	0.988
6:107051076:T:C	L188S	0.988
6:107040211:G:T	G151W	0.987
6:107044292:T:A	L168H	0.987
6:107044298:T:C	L170P	0.987
6:107044313:T:C	L175S	0.987
6:107051082:T:C	L190P	0.987

dbSNP variants (sampled 300 via entrez): RS1000083621 (6:107050275 G>A), RS1000193914 (6:107043079 C>A,G), RS1000332643 (6:107038106 T>C), RS1000660957 (6:107032509 G>A,C), RS1001033002 (6:107048422 G>A,C), RS1001086795 (6:107048256 T>C), RS1001334747 (6:107036782 G>A), RS1001602274 (6:107041663 A>C,T), RS1002063346 (6:107030876 C>G,T), RS1002296670 (6:107040903 A>C), RS1002339066 (6:107035449 C>T), RS1002451526 (6:107035214 A>G), RS1002662825 (6:107029598 C>G,T), RS1003134594 (6:107039790 C>T), RS1003145485 (6:107044952 G>A,C)

Disease associations

OMIM: gene MIM:618583 | 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):

Study	Trait	p-value
GCST003427_49	Alzheimer disease and age of onset	5.000000e-07
GCST010204_34	Low density lipoprotein cholesterol levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	7
trichostatin A	affects expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Doxorubicin	increases expression	1
Pantothenic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SG33	HAP1 C6orf203 (-) 1	Cancer cell line	Male
CVCL_SG34	HAP1 C6orf203 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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