EIF5B

protein-coding

eukaryotic translation initiation factor 5B

Gene summary

Accurate initiation of translation in eukaryotes is complex and requires many factors, some of which are composed of multiple subunits. The process is simpler in prokaryotes which have only three initiation factors (IF1, IF2, IF3). Two of these factors are conserved in eukaryotes: the homolog of IF1 is eIF1A and the homolog of IF2 is eIF5B. This gene encodes eIF5B. Factors eIF1A and eIF5B interact on the ribosome along with other initiation factors and GTP to position the initiation methionine tRNA on the start codon of the mRNA so that translation initiates accurately. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015904.4

Inheritance

—

ClinVar variants

U:136B:8

Top phenotype

Neurodevelopmental delay

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr2:99,337,389-99,401,326

External References & Databases

Ensembl (ENSG00000158417)

Transcript & Mutation Effects

hg38 • Region Span ~63.9 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 EIF5B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 7

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015904.4. 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			2 clinvar		4 clinvar	6
missense			123 clinvar	3 clinvar	1 clinvar	127
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	136	3	5	144

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015904.4	RefSeq	NP_056988.3	24	MANE Select
ENST00000289371.11	Ensembl	ENSP00000289371.5	24	MANE Select
ENST00000856198.1	Ensembl	ENSP00000526257.1	24	Standard
ENST00000856198.2	Ensembl	ENSP00000526257.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Translation Factors
Eukaryotic Translation Initiation
Translation
Metabolism of proteins

Biological Process

translational initiation
regulation of translational initiation

Molecular Function

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

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000289371
Coding exons: 24
Length: 63974
Individuals with no LoFs: 124757
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 124793
p: 0.000144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.62	424	606	0.700	0.0000301	8126
Missense (PolyPhen)		59	172.95	0.34114		2200
Synonymous	-0.259	203	198	1.02	0.00000949	2106
Loss of Function	6.38	9	64.2	0.140	0.00000349	872

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00045	rare
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00018	0.00017	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00015	0.00011	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in translation initiation. Translational GTPase that catalyzes the joining of the 40S and 60S subunits to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon. GTP binding and hydrolysis induces conformational changes in the enzyme that renders it active for productive interactions with the ribosome. The release of the enzyme after formation of the initiation complex is a prerequisite to form elongation-competent ribosomes. {ECO:0000250|UniProtKB:P39730}.;

Recessive Scores

pRec: 0.211

Intolerance Scores

LoFtool: 0.634
RVIS EVS: -0.2
RVIS percentile EVS: 39.21

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.758

Gene Damage Prediction

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