MTG1

Summary

MTG1 (mitochondrial ribosome associated GTPase 1, HGNC:32159) is a protein-coding gene on chromosome 10q26.3, encoding Mitochondrial ribosome-associated GTPase 1 (Q9BT17). Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity. It is a selective cancer dependency (DepMap: 21.0% of cell lines).

Enables GTPase activity. Involved in mitochondrial large ribosomal subunit assembly; regulation of mitochondrial translation; and regulation of respiratory system process. Located in mitochondrial inner membrane; mitochondrial ribosome; and nucleoplasm. Is active in mitochondrial matrix.

Source: NCBI Gene 92170 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 78 total
• Cancer dependency (DepMap): dependent in 21.0% of screened cell lines
• MANE Select transcript: NM_138384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32159
Approved symbol	MTG1
Name	mitochondrial ribosome associated GTPase 1
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000148824
Ensembl biotype	protein_coding
Entrez	92170

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 retained_intron

ENST00000317502, ENST00000432508, ENST00000460848, ENST00000473735, ENST00000477902, ENST00000492266, ENST00000495014, ENST00000498790, ENST00000851826, ENST00000851827, ENST00000923263, ENST00000923264, ENST00000949007, ENST00000949008, ENST00000949009

RefSeq mRNA: 1 — MANE Select: NM_138384 NM_138384

CCDS: CCDS31320

Canonical transcript exons

ENST00000317502 — 11 exons

Exon	Start	End
ENSE00001237415	133420026	133422520
ENSE00001593483	133394157	133394332
ENSE00003668382	133395713	133395777
ENSE00003695691	133399170	133399226
ENSE00003695811	133401529	133401590
ENSE00003696196	133419480	133419592
ENSE00003696577	133396163	133396267
ENSE00003698138	133402692	133402773
ENSE00003699218	133402149	133402245
ENSE00003699810	133398435	133398515
ENSE00003701777	133399529	133399619

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.3999 / max 362.0980, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107799	23.9418	1813
107798	20.8553	1812
107800	0.6027	366

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.64	gold quality
metanephros cortex	UBERON:0010533	94.95	gold quality
right adrenal gland	UBERON:0001233	94.49	gold quality
pancreatic ductal cell	CL:0002079	94.45	silver quality
right adrenal gland cortex	UBERON:0035827	94.36	gold quality
left adrenal gland	UBERON:0001234	93.83	gold quality
right testis	UBERON:0004534	93.65	gold quality
left testis	UBERON:0004533	93.63	gold quality
left adrenal gland cortex	UBERON:0035825	93.63	gold quality
right lobe of thyroid gland	UBERON:0001119	93.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.53	gold quality
cerebellar hemisphere	UBERON:0002245	93.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.35	gold quality
mucosa of transverse colon	UBERON:0004991	93.32	gold quality
cerebellar cortex	UBERON:0002129	93.31	gold quality
body of pancreas	UBERON:0001150	93.15	gold quality
granulocyte	CL:0000094	93.06	gold quality
sural nerve	UBERON:0015488	93.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.88	gold quality
left lobe of thyroid gland	UBERON:0001120	92.83	gold quality
spleen	UBERON:0002106	92.82	gold quality
adrenal cortex	UBERON:0001235	92.59	gold quality
lower esophagus mucosa	UBERON:0035834	92.33	gold quality
adrenal gland	UBERON:0002369	92.14	gold quality
right ovary	UBERON:0002118	92.05	gold quality
minor salivary gland	UBERON:0001830	91.99	gold quality
body of stomach	UBERON:0001161	91.97	gold quality
adenohypophysis	UBERON:0002196	91.94	gold quality
cerebellum	UBERON:0002037	91.81	gold quality
esophagus mucosa	UBERON:0002469	91.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting MTG1, 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-4696	99.48	67.48	1040
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-3169	96.40	67.58	698

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• The results suggested that Mtg1 functions with the large subunit of the mitochondrial ribosome, and are involved in both the translation and assembly of respiratory complexes. (PMID:23396448)
• MTG1 establishes a quality control checkpoint in mitoribosome assembly. In conclusion, MTG1 controls mitochondrial translation by coupling mtLSU assembly with intersubunit bridge formation using the intrinsic GEF activity acquired by the mtSSU through mS27, a unique occurrence in translational systems. (PMID:30085276)
• dampening oxidative stress with N-acetylcysteine (NAC) lowered hypertrophy in MTG1 KO to WT levels. Collectively, our data indicate that MTG1 protects against pressure overload-induced cardiac hypertrophy and dysfunction by preserving mitochondrial function and reducing oxidative stress and downstream TAK1 stress signaling. (PMID:30707992)
• Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion. (PMID:34385605)
• Vulvar angiomyofibroblastoma is molecularly defined by recurrent MTG1-CYP2E1 fusions. (PMID:36177509)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtg1	ENSDARG00000069386
mus_musculus	Mtg1	ENSMUSG00000039018
rattus_norvegicus	Mtg1	ENSRNOG00000018860
drosophila_melanogaster	CG17141	FBGN0039020
caenorhabditis_elegans		WBGENE00022054

Paralogs (6): LSG1 (ENSG00000041802), NOA1 (ENSG00000084092), GNL3L (ENSG00000130119), GNL2 (ENSG00000134697), GNL3 (ENSG00000163938), GNL1 (ENSG00000204590)

Protein

Protein identifiers

Mitochondrial ribosome-associated GTPase 1 — Q9BT17 (reviewed: Q9BT17)

Alternative names: GTP-binding protein 7, Mitochondrial GTPase 1

All UniProt accessions (3): Q9BT17, E7EVK2, U3KQ69

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity. Displays mitochondrial GTPase activity.

Subunit / interactions. Associates with the mitochondrial ribosome large subunit; the association occurs in a GTP-dependent manner.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the TRAFAC class YlqF/YawG GTPase family. MTG1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BT17-1	1	yes
Q9BT17-2	2

RefSeq proteins (1): NP_612393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006073	GTP-bd	Domain
IPR016478	GTPase_MTG1	Family
IPR019991	GTP-bd_ribosome_bgen	Family
IPR023179	GTP-bd_ortho_bundle_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030378	G_CP_dom	Domain

Pfam: PF01926

UniProt features (9 total): binding site 3, splice variant 2, transit peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7O9M	ELECTRON MICROSCOPY	2.6
8QSJ	ELECTRON MICROSCOPY	3
8PK0	ELECTRON MICROSCOPY	3.03
7O9K	ELECTRON MICROSCOPY	3.1
7PD3	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT17-F1	88.13	0.65

Functional residue map

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

Ligand- & substrate-binding residues (3): 83–86; 153–158; 205

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_REGULATION_OF_RESPIRATORY_SYSTEM_PROCESS, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOBP_RIBOSOME_ASSEMBLY, ZHAN_MULTIPLE_MYELOMA_CD1_UP, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RIBOSOMAL_LARGE_SUBUNIT_ASSEMBLY, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, ATGCTGG_MIR338, GOBP_REGULATION_OF_SYSTEM_PROCESS

GO Biological Process (4): regulation of respiratory system process (GO:0044065), regulation of mitochondrial translation (GO:0070129), mitochondrial large ribosomal subunit assembly (GO:1902775), regulation of translation (GO:0006417)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial ribosome (GO:0005761), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
respiratory system process	1
regulation of respiratory gaseous exchange	1
regulation of system process	1
regulation of translation	1
mitochondrial translation	1
regulation of mitochondrial gene expression	1
ribosomal large subunit assembly	1
mitochondrial ribosome assembly	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
organellar ribosome	1
mitochondrial matrix	1

Protein interactions and networks

STRING

2273 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTG1	SPRN	Q5BIV9	966
MTG1	MTG2	Q9H4K7	880
MTG1	MALSU1	Q96EH3	866
MTG1	GTPBP10	A4D1E9	832
MTG1	NOA1	Q8NC60	822
MTG1	MRM1	Q6IN84	814
MTG1	MTERF4	Q7Z6M4	811
MTG1	GTPBP4	Q9BZE4	793
MTG1	NSUN4	Q96CB9	788
MTG1	MRM2	Q9UI43	764
MTG1	DDX28	Q9NUL7	740
MTG1	ERAL1	O75616	734
MTG1	GTPBP8	Q8N3Z3	700
MTG1	GTPBP6	O43824	690
MTG1	MRM3	Q9HC36	611

IntAct

47 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
MTG1	PICK1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	MTG1	psi-mi:“MI:0915”(physical association)	0.560
STX2	MTG1	psi-mi:“MI:0915”(physical association)	0.560
ERICH1	MTG1	psi-mi:“MI:0915”(physical association)	0.560
TRIP13	INTS11	psi-mi:“MI:0914”(association)	0.550
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MTG1	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
ISLR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRPL12		psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
TRIP13	METTL8	psi-mi:“MI:0914”(association)	0.350
CAMK2D	SETD1A	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CAMK2A	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (169): MTG1 (Two-hybrid), MTG1 (Affinity Capture-MS), MTG1 (Reconstituted Complex), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), MTG1 (Reconstituted Complex), MTG1 (Proximity Label-MS)

ESM2 similar proteins: A4D1E9, A5A6N7, A9JTX2, E3TDS3, F4JJJ3, M1BYJ7, O93545, P00336, P00337, P00341, P07195, P13491, P13743, P16125, P31754, P33571, P42120, P42123, P79912, P79913, Q06849, Q17EJ1, Q28HM1, Q32LU1, Q3MHG6, Q4PS77, Q4R5B6, Q5E9B1, Q5U528, Q6DGK2, Q6DHF7, Q6DIS1, Q7T0W5, Q8K013, Q8R2R6, Q98SK9, Q98SL1, Q9BT17, Q9CY28, Q9LID6

Diamond homologs: A2BPL9, A2BV51, A2C0J7, A2SHB1, A3PBA9, A5CDT2, A5CY46, A5IZG5, A7GGA7, A7ZBS1, A8F732, A8FD69, A8G3A3, A8YTQ7, A8YV35, A9BHZ7, A9JTX2, A9KFU3, A9NDV6, B0B8S4, B0BAF3, B0K530, B0K5N4, B0K8H9, B0KBA1, B0KPJ1, B1JDV4, B1L9N6, B1XXK9, B2J1L2, B2USZ4, B3CR58, B3EMI7, B3QZ96, B5Z7J9, B6IZN3, B6J7Q3, B6JM65, B7GGD6, B7IDZ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2345 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133394331:GG:G	donor_gain	1.0000
10:133394332:GG:G	donor_gain	1.0000
10:133395798:G:T	donor_gain	1.0000
10:133395814:G:GT	donor_gain	1.0000
10:133398429:TTTCA:T	acceptor_loss	1.0000
10:133398430:TTCA:T	acceptor_loss	1.0000
10:133398431:TCA:T	acceptor_loss	1.0000
10:133398432:CA:C	acceptor_loss	1.0000
10:133398433:A:AG	acceptor_gain	1.0000
10:133398433:AGA:A	acceptor_loss	1.0000
10:133398433:AGAA:A	acceptor_loss	1.0000
10:133398434:G:GA	acceptor_gain	1.0000
10:133398434:G:T	acceptor_loss	1.0000
10:133398434:GA:G	acceptor_gain	1.0000
10:133398434:GAA:G	acceptor_gain	1.0000
10:133398434:GAAA:G	acceptor_gain	1.0000
10:133398512:GCAG:G	donor_gain	1.0000
10:133398513:CAGG:C	donor_loss	1.0000
10:133398514:AG:A	donor_loss	1.0000
10:133398515:GGTAG:G	donor_loss	1.0000
10:133398517:T:G	donor_loss	1.0000
10:133399616:A:T	donor_gain	1.0000
10:133402144:CACA:C	acceptor_loss	1.0000
10:133402145:A:AG	acceptor_gain	1.0000
10:133402145:ACAG:A	acceptor_gain	1.0000
10:133402145:ACAGG:A	acceptor_loss	1.0000
10:133402146:C:G	acceptor_gain	1.0000
10:133402146:CA:C	acceptor_loss	1.0000
10:133402147:A:AG	acceptor_gain	1.0000
10:133402147:A:AT	acceptor_loss	1.0000

AlphaMissense

2175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133394311:T:C	F31L	0.998
10:133394313:C:A	F31L	0.998
10:133394313:C:G	F31L	0.998
10:133396237:G:C	K84N	0.996
10:133396237:G:T	K84N	0.996
10:133399563:C:A	P152H	0.996
10:133399567:C:A	N153K	0.996
10:133399567:C:G	N153K	0.996
10:133402180:A:C	D202A	0.996
10:133396227:T:A	V81D	0.995
10:133399572:G:A	G155D	0.995
10:133402179:G:C	D202H	0.995
10:133402740:T:C	L240P	0.995
10:133420089:G:C	R310P	0.995
10:133394325:G:A	M35I	0.994
10:133394325:G:C	M35I	0.994
10:133394325:G:T	M35I	0.994
10:133399557:G:A	G150E	0.994
10:133399574:A:C	K156Q	0.994
10:133399575:A:T	K156M	0.994
10:133399584:T:C	L159P	0.994
10:133402180:A:G	D202G	0.994
10:133402180:A:T	D202V	0.994
10:133394308:T:A	W30R	0.993
10:133394308:T:C	W30R	0.993
10:133395769:G:C	D57H	0.993
10:133395770:A:C	D57A	0.993
10:133395770:A:G	D57G	0.993
10:133395770:A:T	D57V	0.993
10:133395773:C:A	A58D	0.993

dbSNP variants (sampled 300 via entrez): RS1000059681 (10:133407142 C>A,T), RS1000126153 (10:133419351 G>A), RS1000245596 (10:133399687 C>T), RS1000275977 (10:133412958 G>C), RS1000496844 (10:133394824 C>A,T), RS1000608285 (10:133412594 G>A), RS1000697932 (10:133395515 A>C,T), RS1000775826 (10:133421134 G>GGTGCTCAGTGGCCCCTC), RS1000870046 (10:133414567 T>C), RS1000959523 (10:133422970 T>C), RS1001076096 (10:133408480 C>A,T), RS1001134602 (10:133402887 C>T), RS1001137335 (10:133395595 T>G), RS1001225381 (10:133394606 C>G,T), RS1001234550 (10:133406620 C>T)

Disease associations

OMIM: gene `` | 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
GCST002463_18	Systemic lupus erythematosus	3.000000e-06
GCST003264_213	Post bronchodilator FEV1/FVC ratio	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	5
Valproic Acid	affects cotreatment, increases expression	4
Cadmium Chloride	decreases expression	2
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cannabidiol	increases expression	1
Carbamazepine	affects expression	1
Coumestrol	increases expression	1
Ethinyl Estradiol	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Naled	affects expression	1
Phthalic Acids	increases methylation	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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