EIF2D

protein-coding

eukaryotic translation initiation factor 2D

Gene summary

This gene encodes a translation initiation factor involved in the recruitment and delivery of aminoacyl-tRNAs to the P-site of the eukaryotic ribosome in a GTP-independent manner. This gene was previously referred to as ligatin, but is now known to localize to the cytoplasm and localize and function with translation factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

MANE transcript

NM_006893.3

Inheritance

—

ClinVar variants

U:81B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:206,571,292-206,612,465

External References & Databases

Ensembl (ENSG00000143486)

Transcript & Mutation Effects

hg38 • Region Span ~41.2 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 EIF2D variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006893.3. 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			4 clinvar	2 clinvar		6
missense			72 clinvar	2 clinvar		74
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	81	4	0	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006893.3	RefSeq	NP_008824.2	15	MANE Select
ENST00000271764.7	Ensembl	ENSP00000271764.2	15	MANE Select
NM_001201478.2	RefSeq	NP_001188407.1	13	Standard
ENST00000367114.7	Ensembl	ENSP00000356081.3	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

formation of translation preinitiation complex
intracellular protein transport
ribosome disassembly
IRES-dependent viral translational initiation

Molecular Function

translation initiation factor activity
signaling receptor activity

Cellular Component

cytoplasm
cytosol
nuclear body
cytosolic small ribosomal subunit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000271764
Coding exons: 15
Length: 41285
Individuals with no LoFs: 125689
Homozygous LoFs: 0
Heterozygous LoFs: 59
Defined: 125748
p: 0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.54	241	318	0.757	0.0000162	3802
Missense (PolyPhen)		51	97.233	0.52451		1263
Synonymous	1.32	108	127	0.850	0.00000685	1153
Loss of Function	2.53	20	36.5	0.548	0.00000204	387

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00053	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P- site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. {ECO:0000269|PubMed:20566627, ECO:0000269|PubMed:20713520}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

RVIS EVS: -0.4
RVIS percentile EVS: 26.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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