MTIF2

protein-coding

mitochondrial translational initiation factor 2

Gene summary

During the initiation of protein biosynthesis, initiation factor-2 (IF-2) promotes the binding of the initiator tRNA to the small subunit of the ribosome in a GTP-dependent manner. Prokaryotic IF-2 is a single polypeptide, while eukaryotic cytoplasmic IF-2 (eIF-2) is a trimeric protein. Bovine liver mitochondria contain IF-2(mt), an 85-kD monomeric protein that is equivalent to prokaryotic IF-2. The predicted 727-amino acid human protein contains a 29-amino acid presequence. Human IF-2(mt) shares 32 to 38% amino acid sequence identity with yeast IF-2(mt) and several prokaryotic IF-2s, with the greatest degree of conservation in the G domains of the proteins. [provided by RefSeq, Mar 2016]

MANE transcript

NM_002453.3

Inheritance

—

ClinVar variants

P:2U:110B:8

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr2:55,236,595-55,269,347

External References & Databases

Ensembl (ENSG00000085760)

Transcript & Mutation Effects

hg38 • Region Span ~32.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTIF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 107

Inborn genetic diseasesTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002453.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense	1 clinvar		104 clinvar	7 clinvar		112
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	0	110	8	0	120

Highest pathogenic variant AF is 0.00000273627

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 124 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002453.3	RefSeq	NP_002444.2	13	MANE Select
ENST00000263629.9	Ensembl	ENSP00000263629.4	13	MANE Select
NM_001005369.1	RefSeq	NP_001005369.1	13	Standard
NM_001321001.1	RefSeq	NP_001307930.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitochondrial translation initiation
Translation
Metabolism of proteins
Mitochondrial translation
TNFalpha

Biological Process

regulation of translational initiation
ribosome disassembly
mitochondrial translational initiation

Molecular Function

RNA binding
translation initiation factor activity
GTPase activity
GTP binding
translation factor activity, RNA binding

Cellular Component

nucleoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394600
Coding exons: 13
Length: 32753
Individuals with no LoFs: 125641
Homozygous LoFs: 0
Heterozygous LoFs: 106
Defined: 125747
p: 0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.302	389	373	1.04	0.0000182	4732
Missense (PolyPhen)		112	126.94	0.8823		1642
Synonymous	-0.779	139	128	1.09	0.00000617	1387
Loss of Function	2.34	21	36.2	0.581	0.00000178	474

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00083	0.00082	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00052	0.00049	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex.;

Recessive Scores

pRec: 0.197

Intolerance Scores

LoFtool: 0.976
RVIS EVS: -0.89
RVIS percentile EVS: 10.46

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.728

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium