EIF4A2

eukaryotic translation initiation factor 4A2, the group of DEAD-box helicases|MicroRNA protein coding host genes|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 3:186783205-186789897

Previous symbols: [ "EIF4F" ]

Links

ENSG00000156976 ∙ NCBI:1974 ∙ OMIM:601102 ∙ HGNC:3284 ∙ Uniprot:Q14240 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with hypotonia and speech delay, with or without seizures (Limited), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia and speech delay, with or without seizures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	36528028

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF4A2 gene.

• Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures (1 variants)
• not provided (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF4A2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense	1	1	7			9
nonsense			1			1
start loss			2			2
frameshift			5			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1	1		3
splice region				1	2	3
non coding				1		1
Total	1	2	16	3	1

Variants in EIF4A2

This is a list of pathogenic ClinVar variants found in the EIF4A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-186783602-TTTCGGATCATGTCTGGTGGC-T		EIF4A2-related disorder	Uncertain significance (Aug 25, 2022)
3-186783603-T-C		EIF4A2-related disorder	Likely benign (Aug 09, 2019)
3-186783611-A-T			Uncertain significance (May 14, 2023)
3-186783615-C-G		Neurodevelopmental disorder	Likely pathogenic (-)
3-186783634-T-C		EIF4A2-related disorder	Likely benign (Apr 25, 2019)
3-186784592-TTGA-T		Neurodevelopmental disorder	Likely pathogenic (-)
3-186784614-GTC-G		Neurodevelopmental disorder	Likely pathogenic (Feb 02, 2023)
3-186784669-CAG-C		Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures	Pathogenic (Jun 10, 2024)
3-186784952-C-CT		EIF4A2-related disorder	Likely benign (Sep 23, 2020)
3-186785009-A-C			Uncertain significance (Nov 17, 2023)
3-186785047-G-T		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
3-186785048-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
3-186785875-G-A			Uncertain significance (Feb 01, 2024)
3-186785902-C-T			Uncertain significance (Jan 19, 2022)
3-186785934-G-T			Uncertain significance (Dec 18, 2023)
3-186785957-T-A		EIF4A2-related disorder	Likely benign (Sep 18, 2024)
3-186785991-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
3-186785998-T-C		Inborn genetic diseases	Uncertain significance (Jun 13, 2023)
3-186786015-G-T		Neurodevelopmental disorder	Likely pathogenic (-)
3-186786046-AC-A		EIF4A2-related disorder	Uncertain significance (Dec 18, 2023)
3-186786052-G-T		Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures	Likely pathogenic (Dec 19, 2023)
3-186786157-C-T		EIF4A2-related disorder	Benign (Dec 16, 2019)
3-186786263-C-CAAGT			Uncertain significance (Jan 16, 2024)
3-186786515-C-A		Neurodevelopmental disorder	Likely pathogenic (-)
3-186786520-A-G		Neurodevelopmental disorder	Pathogenic (Jan 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF4A2	protein_coding	protein_coding	ENST00000323963	11	6696

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00165	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.90	60	224	0.268	0.0000113	2704
Missense in Polyphen		6	73.67	0.081444		967
Synonymous	-2.41	100	73.7	1.36	0.00000358	755
Loss of Function	4.26	1	23.1	0.0433	0.00000116	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.
• Pathway: RNA transport - Homo sapiens (human);Translation Factors;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Cytokine Signaling in Immune system;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Metabolism of RNA;Immune System;insulin Mam;eukaryotic protein translation;Ribosomal scanning and start codon recognition;L13a-mediated translational silencing of Ceruloplasmin expression;GTP hydrolysis and joining of the 60S ribosomal subunit;Cap-dependent Translation Initiation;Deadenylation of mRNA;Deadenylation-dependent mRNA decay;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;insulin (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.183
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.981
• hipred: Y
• hipred_score: 0.783
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif4a2

Gene ontology

• Biological process: translational initiation;regulation of translational initiation;viral process;negative regulation of RNA-directed 5'-3' RNA polymerase activity;cellular response to leukemia inhibitory factor
• Cellular component: cytosol;eukaryotic translation initiation factor 4F complex;perinuclear region of cytoplasm
• Molecular function: RNA binding;translation initiation factor activity;ATP-dependent RNA helicase activity;helicase activity;protein binding;ATP binding;ATPase activity