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MTIF3

gene
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Also known as IF-3mtIF3(mt)

Summary

MTIF3 (mitochondrial translational initiation factor 3, HGNC:29788) is a protein-coding gene on chromosome 13q12.2, encoding Translation initiation factor IF-3, mitochondrial (Q9H2K0). IF-3 binds to the 28S ribosomal subunit and shifts the equilibrium between 55S ribosomes and their 39S and 28S subunits in favor of the free subunits, thus enhancing the availability of 28S subunits on which protein synthesis initiation begins.

This gene encodes a translation initiation factor that is involved in mitochondrial protein synthesis. Polymorphism in this gene is associated with the onset of Parkinson’s disease. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.

Source: NCBI Gene 219402 — RefSeq curated summary.

At a glance

  • GWAS associations: 13
  • Clinical variants (ClinVar): 32 total
  • MANE Select transcript: NM_152912

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29788
Approved symbolMTIF3
Namemitochondrial translational initiation factor 3
Location13q12.2
Locus typegene with protein product
StatusApproved
AliasesIF-3mt, IF3(mt)
Ensembl geneENSG00000122033
Ensembl biotypeprotein_coding
OMIM619554
Entrez219402

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 60 protein_coding, 9 protein_coding_CDS_not_defined

ENST00000381116, ENST00000381120, ENST00000405591, ENST00000460973, ENST00000461838, ENST00000464753, ENST00000471771, ENST00000483903, ENST00000484342, ENST00000485650, ENST00000485959, ENST00000493719, ENST00000884652, ENST00000884653, ENST00000884654, ENST00000884655, ENST00000884656, ENST00000884657, ENST00000884658, ENST00000884659, ENST00000884660, ENST00000884661, ENST00000884662, ENST00000920841, ENST00000920842, ENST00000920843, ENST00000920844, ENST00000920845, ENST00000920846, ENST00000920847, ENST00000920848, ENST00000920849, ENST00000920850, ENST00000920851, ENST00000966039, ENST00000966040, ENST00000966041, ENST00000966042, ENST00000966043, ENST00000966044, ENST00000966045, ENST00000966046, ENST00000966047, ENST00000966048, ENST00000966049, ENST00000966050, ENST00000966051, ENST00000966052, ENST00000966053, ENST00000966054, ENST00000966055, ENST00000966056, ENST00000966057, ENST00000966058, ENST00000966059, ENST00000966060, ENST00000966061, ENST00000966062, ENST00000966063, ENST00000966064, ENST00000966065, ENST00000966066, ENST00000966067, ENST00000966068, ENST00000966069, ENST00000966070, ENST00000966071, ENST00000966072, ENST00000966073

RefSeq mRNA: 4 — MANE Select: NM_152912 NM_001166261, NM_001166262, NM_001166263, NM_152912

CCDS: CCDS9322

Canonical transcript exons

ENST00000381120 — 5 exons

ExonStartEnd
ENSE000014875582745050927450564
ENSE000014875692743564327435893
ENSE000014875852744508827445156
ENSE000036645142743998927440449
ENSE000036722232743711627437273

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5682 / max 398.8763, expressed in 1805 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
13649421.59851785
13649114.85511776
1364930.6970379
1364880.2601122
1364900.103532
1364890.054122

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
apex of heartUBERON:000209898.16gold quality
right atrium auricular regionUBERON:000663198.03gold quality
heart left ventricleUBERON:000208497.83gold quality
cardiac atriumUBERON:000208197.78gold quality
cardiac ventricleUBERON:000208297.74gold quality
right testisUBERON:000453497.66gold quality
left testisUBERON:000453397.61gold quality
body of pancreasUBERON:000115097.37gold quality
heartUBERON:000094897.36gold quality
calcaneal tendonUBERON:000370197.20gold quality
testisUBERON:000047397.06gold quality
rectumUBERON:000105296.94gold quality
gastrocnemiusUBERON:000138896.94gold quality
right adrenal gland cortexUBERON:003582796.94gold quality
muscle of legUBERON:000138396.89gold quality
C1 segment of cervical spinal cordUBERON:000646996.86gold quality
hindlimb stylopod muscleUBERON:000425296.83gold quality
right adrenal glandUBERON:000123396.81gold quality
gall bladderUBERON:000211096.79gold quality
left ventricle myocardiumUBERON:000656696.78gold quality
adenohypophysisUBERON:000219696.77gold quality
metanephros cortexUBERON:001053396.68gold quality
tendonUBERON:000004396.63gold quality
left adrenal glandUBERON:000123496.57gold quality
left adrenal gland cortexUBERON:003582596.53gold quality
subcutaneous adipose tissueUBERON:000219096.50gold quality
muscle layer of sigmoid colonUBERON:003580596.39gold quality
pancreasUBERON:000126496.36gold quality
pituitary glandUBERON:000000796.35gold quality
adrenal cortexUBERON:000123596.33gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes9.56

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

  • the c.798C>T polymorphism of the MTIF3 gene showed allelic association with Parkinson’s disease (PMID:17267121)
  • Changes in function or expression of MTIF3 indicates mitochondrial dysfunction and contributes to the risk of Parkinson’s disease. (PMID:20887776)
  • genetic association studies in cohorts of prediabetic patients at multiple sites: Data suggest that an SNP in MTIF3 (rs1885988) is associated with greater weight loss following lifestyle intervention in overweight/obese subjects with prediabetes. (PMID:26253612)
  • single nucleotide polymorphisms rs4771122 of MTIF3 was the variant most significantly associated with long-term weight loss after surgery. (PMID:26337695)
  • This is dedicated to the mitochondrial translation initiation factor 3 (IF3mt), which plays a key role in the protein synthesis in mitochondria. Involvement of IF3mt in human health and disease is discussed. (PMID:31694510)
  • Initiation Factor 3 is Dispensable For Mitochondrial Translation in Cultured Human Cells. (PMID:32346061)
  • Identification of a weight loss-associated causal eQTL in MTIF3 and the effects of MTIF3 deficiency on human adipocyte function. (PMID:36876906)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriomtif3ENSDARG00000039649
mus_musculusMtif3ENSMUSG00000016510
rattus_norvegicusMtif3ENSRNOG00000070811

Protein

Protein identifiers

Translation initiation factor IF-3, mitochondrial — Q9H2K0 (reviewed: Q9H2K0)

All UniProt accessions (1): Q9H2K0

UniProt curated annotations — full annotation on UniProt →

Function. IF-3 binds to the 28S ribosomal subunit and shifts the equilibrium between 55S ribosomes and their 39S and 28S subunits in favor of the free subunits, thus enhancing the availability of 28S subunits on which protein synthesis initiation begins.

Subcellular location. Mitochondrion.

Similarity. Belongs to the IF-3 family.

RefSeq proteins (4): NP_001159733, NP_001159734, NP_001159735, NP_690876* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001288Translation_initiation_fac_3Family
IPR019814Translation_initiation_fac_3_NDomain
IPR036787T_IF-3_N_sfHomologous_superfamily
IPR036788T_IF-3_C_sfHomologous_superfamily

Pfam: PF05198

UniProt features (21 total): strand 9, helix 5, turn 2, sequence variant 2, transit peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDBMethodResolution (Å)
7P2EELECTRON MICROSCOPY2.4
6RW4ELECTRON MICROSCOPY2.97
9HFMELECTRON MICROSCOPY3
8QRMELECTRON MICROSCOPY3.05
6RW5ELECTRON MICROSCOPY3.14
9HFNELECTRON MICROSCOPY3.3
6NEQELECTRON MICROSCOPY3.32
6NF8ELECTRON MICROSCOPY3.48

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H2K0-F179.190.56

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-5368286Mitochondrial translation initiation

MSigDB gene sets: 84 (showing top): GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATIONAL_INITIATION, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, WANG_LMO4_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOMF_TRANSLATION_FACTOR_ACTIVITY_RNA_BINDING, GOBP_ORGANELLE_DISASSEMBLY, NUYTTEN_EZH2_TARGETS_DN, GOMF_RIBOSOMAL_SMALL_SUBUNIT_BINDING, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GOMF_RIBOSOME_BINDING, GOBP_RIBOSOME_DISASSEMBLY, GOBP_MITOCHONDRIAL_GENE_EXPRESSION, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN

GO Biological Process (4): ribosome disassembly (GO:0032790), mitochondrial translational initiation (GO:0070124), translation (GO:0006412), translational initiation (GO:0006413)

GO Molecular Function (5): translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), ribosome binding (GO:0043022), ribosomal small subunit binding (GO:0043024), protein binding (GO:0005515)

GO Cellular Component (1): mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Mitochondrial translation1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
translational initiation3
translation2
translation factor activity2
organelle disassembly1
mitochondrion1
mitochondrial translation1
peptidyltransferase activity1
translational elongation1
translational termination1
macromolecule biosynthetic process1
protein metabolic process1
protein biosynthetic process1
formation of translation initiation ternary complex1
metabolic process1
RNA binding1
ribonucleoprotein complex binding1
ribosome binding1
binding1
cytoplasm1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MTIF3MTIF2P46199860
MTIF3MTRF1LQ9UGC7678
MTIF3GTF3AQ92664669
MTIF3TMEM160Q9NX00650
MTIF3MRRFQ96E11636
MTIF3MTRF1O75570630
MTIF3TACO1Q9BSH4619
MTIF3GFM2Q969S9619
MTIF3ATP5IF1Q9UII2614
MTIF3QPCTLQ9NXS2603
MTIF3TNNI3KQ59H18596
MTIF3V9GXZ4V9GXZ4596
MTIF3ZNF608Q9ULD9594
MTIF3LINGO2Q7L985584
MTIF3SEC16BQ96JE7583
MTIF3NUDT3O95989583

IntAct

246 interactions, top by confidence:

ABTypeScore
SIAH1MTIF3psi-mi:“MI:0915”(physical association)0.560
MTIF3SIAH1psi-mi:“MI:0915”(physical association)0.560
NAT8MTIF3psi-mi:“MI:0915”(physical association)0.560
STRIT1MTIF3psi-mi:“MI:0915”(physical association)0.560
PLP1MTIF3psi-mi:“MI:0915”(physical association)0.560
UNC50MTIF3psi-mi:“MI:0915”(physical association)0.560
ITGB2MTIF3psi-mi:“MI:0915”(physical association)0.560
BMP10MTIF3psi-mi:“MI:0915”(physical association)0.560
MTIF3psi-mi:“MI:0915”(physical association)0.560
CD47MTIF3psi-mi:“MI:0915”(physical association)0.560
LHFPL5MTIF3psi-mi:“MI:0915”(physical association)0.560
SELENOKMTIF3psi-mi:“MI:0915”(physical association)0.560
ZNF202MTIF3psi-mi:“MI:0915”(physical association)0.560
CYBC1MTIF3psi-mi:“MI:0915”(physical association)0.560
TMEM254MTIF3psi-mi:“MI:0915”(physical association)0.560
ZDHHC15MTIF3psi-mi:“MI:0915”(physical association)0.560
SERTM1MTIF3psi-mi:“MI:0915”(physical association)0.560
PLNMTIF3psi-mi:“MI:0915”(physical association)0.560
TMEM128MTIF3psi-mi:“MI:0915”(physical association)0.560
TMEM218MTIF3psi-mi:“MI:0915”(physical association)0.560
CXCL9MTIF3psi-mi:“MI:0915”(physical association)0.560
CDIPTMTIF3psi-mi:“MI:0915”(physical association)0.560
CABP7MTIF3psi-mi:“MI:0915”(physical association)0.560
TMEM42MTIF3psi-mi:“MI:0915”(physical association)0.560
TMED8MTIF3psi-mi:“MI:0915”(physical association)0.560
APODMTIF3psi-mi:“MI:0915”(physical association)0.560
MGST3MTIF3psi-mi:“MI:0915”(physical association)0.560

BioGRID (296): MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Biochemical Activity), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid), MTIF3 (Two-hybrid)

ESM2 similar proteins: A0JMA8, A4IHS0, B5DF07, D3ZRC4, D6WMX4, E7EXT2, F7AEX0, F7BJB9, O15091, O93530, Q09287, Q14149, Q1L987, Q24558, Q28C44, Q2KI45, Q2TBE0, Q32NQ8, Q3MHI8, Q3UFY8, Q4KLI2, Q4R366, Q5RDI0, Q5U245, Q5U2R4, Q5VZ89, Q5XTS1, Q66JD1, Q66JJ4, Q6DDV1, Q6GLI9, Q7JUX9, Q7L0Y3, Q7Z401, Q86VD1, Q8C1Z8, Q8JZY4, Q8K1N1, Q8N6Q8, Q8TBZ6

Diamond homologs: A2C586, Q32KZ1, Q3B0M2, Q46IH3, Q9CZD5, Q9H2K0, Q5NL80, Q8XJ67

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance22
Likely benign5
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

960 predictions. Top by Δscore:

VariantEffectΔscore
13:27437279:T:Cacceptor_gain1.0000
13:27437279:T:TCacceptor_gain1.0000
13:27445154:CAG:Cacceptor_gain1.0000
13:27445157:C:CCacceptor_gain1.0000
13:27435890:CCTC:Cacceptor_gain0.9900
13:27435891:CTCC:Cacceptor_gain0.9900
13:27435892:TCC:Tacceptor_loss0.9900
13:27435892:TCCT:Tacceptor_gain0.9900
13:27435893:CCTAA:Cacceptor_loss0.9900
13:27435894:C:CAacceptor_loss0.9900
13:27435894:C:CCacceptor_gain0.9900
13:27437110:ACTT:Adonor_loss0.9900
13:27437111:CTTA:Cdonor_loss0.9900
13:27437112:TTAC:Tdonor_loss0.9900
13:27437114:A:Cdonor_loss0.9900
13:27437115:C:CGdonor_loss0.9900
13:27437274:C:CCacceptor_gain0.9900
13:27445082:TCCTA:Tdonor_loss0.9900
13:27445083:CCTA:Cdonor_loss0.9900
13:27445084:CTACC:Cdonor_loss0.9900
13:27445085:TA:Tdonor_loss0.9900
13:27445086:A:Tdonor_loss0.9900
13:27445087:C:CAdonor_loss0.9900
13:27445152:GACAG:Gacceptor_gain0.9900
13:27445160:A:Cacceptor_gain0.9900
13:27445165:C:CTacceptor_gain0.9900
13:27449749:A:ACdonor_gain0.9900
13:27449750:T:Cdonor_gain0.9900
13:27435891:CTC:Cacceptor_gain0.9800
13:27437271:GTCCT:Gacceptor_loss0.9800

AlphaMissense

1841 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
13:27437168:A:TV189D0.987
13:27437209:C:AK175N0.983
13:27437209:C:GK175N0.983
13:27440099:A:TV117D0.976
13:27437190:A:GW182R0.974
13:27437190:A:TW182R0.974
13:27437257:C:AK159N0.972
13:27437257:C:GK159N0.972
13:27440063:T:GQ129P0.972
13:27440108:A:GL114P0.968
13:27440102:A:TL116Q0.967
13:27437188:C:AW182C0.966
13:27437188:C:GW182C0.966
13:27440067:A:CY128D0.964
13:27440060:A:TL130H0.963
13:27435850:G:TA221D0.961
13:27437162:A:CI191S0.958
13:27440135:A:TV105E0.958
13:27437162:A:GI191T0.951
13:27435800:A:GC238R0.949
13:27440060:A:GL130P0.949
13:27437221:A:CD171E0.948
13:27437221:A:TD171E0.948
13:27440066:T:GY128S0.947
13:27440126:A:GL108P0.947
13:27437222:T:CD171G0.946
13:27437252:A:GL161P0.946
13:27440183:A:GL89S0.946
13:27440105:C:GR115P0.945
13:27440030:C:GR140P0.944

dbSNP variants (sampled 300 via entrez): RS1000056002 (13:27447810 A>C,G), RS1000208911 (13:27442115 G>A,T), RS1000284566 (13:27452378 T>C), RS1000311151 (13:27436687 A>G,T), RS1000348610 (13:27451739 C>G,T), RS1000365430 (13:27436833 G>C), RS1000452425 (13:27451536 C>T), RS1000517173 (13:27440526 G>C,T), RS1000543056 (13:27441869 G>A), RS1000646836 (13:27437716 T>C), RS1000795406 (13:27440806 C>A,T), RS1001329111 (13:27442446 G>C), RS1001382445 (13:27442686 C>G), RS1001625057 (13:27447911 G>A,C,T), RS1001627662 (13:27445138 C>T)

Disease associations

OMIM: gene MIM:619554 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

StudyTraitp-value
GCST000830_34Body mass index9.000000e-10
GCST002783_14Body mass index2.000000e-07
GCST002783_459Body mass index9.000000e-11
GCST002783_494Body mass index2.000000e-10
GCST003542_166Night sleep phenotypes5.000000e-06
GCST004495_55BMI (adjusted for smoking behaviour)8.000000e-07
GCST004497_12Body mass index (joint analysis main effects and smoking interaction)2.000000e-07
GCST004679_4Psychosis proneness (hypomanic personality scale and perceptual aberration scale)7.000000e-07
GCST004904_169Body mass index2.000000e-10
GCST007647_6Estimated glomerular filtration rate change in renal transplantation (recipient effect)1.000000e-06
GCST010988_462Adult body size8.000000e-13
GCST012282_8BMI x environmental factors (excluding physical activity) interaction3.000000e-06
GCST012283_5BMI x environmental factors (including physical activity) interaction4.000000e-06

EFO canonical traits (11, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0004318smoking behavior
EFO:0008337psychosis predisposition measurement
EFO:0005199renal transplant outcome measurement
EFO:0006527smoking status measurement
EFO:0009374energy intake measurement
EFO:0009695household income
EFO:0010810protein intake measurement
EFO:0010811carbohydrate intake measurement
EFO:0011015educational attainment
EFO:0008002physical activity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

ChemicalActions (top 5)PubMed papers
Cisplatinaffects expression, affects cotreatment, increases expression2
dicrotophosdecreases expression1
sodium arsenitedecreases expression1
isobutyl alcoholaffects cotreatment, decreases expression, increases abundance1
beta-methylcholineaffects expression1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
jinfukangaffects cotreatment, increases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Temozolomideincreases expression1
Decitabineaffects expression1
Sunitinibdecreases expression1
Acetaminophenincreases expression1
Benzo(a)pyrenedecreases methylation1
Dimethyl Sulfoxideincreases expression1
Doxorubicindecreases expression1
Estradioldecreases expression1
Gasolinedecreases expression, increases abundance, affects cotreatment1
Hydrogen Peroxideaffects cotreatment, decreases expression1
Leadaffects splicing1
Methotrexateincreases expression1
Polycyclic Aromatic Hydrocarbonsaffects cotreatment, decreases expression, increases abundance1
Quercetindecreases expression1
Theophyllineaffects cotreatment, decreases expression1
Valproic Acidaffects expression1
Josamycindecreases response to substance1
Copper Sulfatedecreases expression1
Particulate Matteraffects cotreatment, decreases expression, increases abundance1

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