EIF4A3

eukaryotic translation initiation factor 4A3, the group of SSU processome|DEAD-box helicases|Spliceosomal Bact complex|Spliceosomal P complex|Exon junction complex

Basic information

Region (hg38): 17:80134369-80147151

Previous symbols: [ "DDX48" ]

Links

ENSG00000141543 ∙ NCBI:9775 ∙ OMIM:608546 ∙ HGNC:18683 ∙ Uniprot:P38919 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Richieri Costa-Pereira syndrome (Definitive), mode of inheritance: AR
• Richieri Costa-Pereira syndrome (Moderate), mode of inheritance: AR
• Richieri Costa-Pereira syndrome (Strong), mode of inheritance: AR
• Richieri Costa-Pereira syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Richieri-Costa-Pereira Syndrome	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; Musculoskeletal	24360810
The genetic cause involves a noncoding expansion

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF4A3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF4A3 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				7	3	10
missense			10			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1		1
Total	0	0	10	8	3

Variants in EIF4A3

This is a list of pathogenic ClinVar variants found in the EIF4A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-80136071-G-A			Likely benign (May 01, 2023)
17-80136093-G-T			Uncertain significance (Aug 23, 2022)
17-80136257-G-A		EIF4A3-related disorder	Likely benign (Jan 01, 2023)
17-80136345-G-C			Likely benign (Apr 04, 2018)
17-80137395-G-A		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
17-80137423-G-A			Uncertain significance (Aug 11, 2017)
17-80137466-G-A			Likely benign (Oct 01, 2024)
17-80138142-C-T			Benign (Dec 31, 2019)
17-80138151-G-A		EIF4A3-related disorder	Likely benign (May 23, 2019)
17-80138199-G-A		EIF4A3-related disorder	Likely benign (Apr 05, 2019)
17-80138200-T-C		Richieri Costa-Pereira syndrome	Pathogenic (Jan 02, 2014)
17-80139036-C-T		Inborn genetic diseases	Uncertain significance (May 08, 2023)
17-80139040-T-C		Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
17-80139167-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 25, 2021)
17-80139701-A-C		EIF4A3-related disorder	Likely benign (Feb 14, 2020)
17-80139742-G-A		Inborn genetic diseases	Uncertain significance (Apr 29, 2024)
17-80140083-T-C		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
17-80141839-G-A			Benign (Dec 31, 2019)
17-80144218-G-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2024)
17-80146799-C-T			Uncertain significance (Apr 12, 2019)
17-80146830-G-A			Likely benign (Dec 31, 2019)
17-80146848-G-T			Likely benign (May 08, 2018)
17-80146872-G-A			Benign (Dec 31, 2019)
17-80146888-T-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
17-80146924-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF4A3	protein_coding	protein_coding	ENST00000269349	12	11970

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000153	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.02	74	255	0.291	0.0000146	2698
Missense in Polyphen		20	113.12	0.17681		1178
Synonymous	-0.814	106	95.9	1.11	0.00000578	782
Loss of Function	4.64	0	25.0	0.00	0.00000131	270

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	0.00	0.00
European (Non-Finnish)	0.00	0.00
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 (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP- bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly (PubMed:22203037). Involved in craniofacial development (PubMed:24360810). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15034551, ECO:0000269|PubMed:16170325, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:24360810, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Spliceosome - Homo sapiens (human);Gene expression (Transcription);Cytokine Signaling in Immune system;RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;Immune System;mRNA Splicing - Major Pathway;Nonsense-Mediated Decay (NMD);Transport of Mature mRNA derived from an Intron-Containing Transcript;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Deadenylation of mRNA;Deadenylation-dependent mRNA decay;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.203

Intolerance Scores

• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.186
• hipred: Y
• hipred_score: 0.802
• ghis: 0.614

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif4a3

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;mRNA splicing, via spliceosome;rRNA processing;RNA export from nucleus;mRNA export from nucleus;associative learning;response to organic cyclic compound;negative regulation of translation;mRNA 3'-end processing;exploration behavior;positive regulation of translation;embryonic cranial skeleton morphogenesis;cellular response to selenite ion;negative regulation of excitatory postsynaptic potential;regulation of translation at postsynapse, modulating synaptic transmission;negative regulation of selenocysteine incorporation;negative regulation of selenocysteine insertion sequence binding;cellular response to brain-derived neurotrophic factor stimulus
• Cellular component: nucleoplasm;cytoplasm;cytosol;membrane;nuclear speck;dendrite;exon-exon junction complex;neuronal cell body;catalytic step 2 spliceosome;glutamatergic synapse;postsynaptic cytosol
• Molecular function: RNA binding;mRNA binding;ATP-dependent RNA helicase activity;protein binding;ATP binding;poly(A) binding;selenocysteine insertion sequence binding;RNA stem-loop binding;ribonucleoprotein complex binding;translation regulator activity