EIF3F

eukaryotic translation initiation factor 3 subunit F, the group of Eukaryotic translation initiation factor 3|JAMM/MPN+ metallopeptidase family

Basic information

Region (hg38): 11:7970250-8001862

Previous symbols: [ "EIF3S5" ]

Links

ENSG00000175390 ∙ NCBI:8665 ∙ OMIM:603914 ∙ HGNC:3275 ∙ Uniprot:O00303 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 67 (Moderate), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 67 (Limited), mode of inheritance: Unknown
• syndromic intellectual disability (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder 67	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	Neurologic	30409806

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF3F gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF3F 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				11	2	13
missense		1	22	3	4	30
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	1	23	14	8

Variants in EIF3F

This is a list of pathogenic ClinVar variants found in the EIF3F region.

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

Position	Type	Phenotype	Significance	ClinVar
11-7987362-C-G			Uncertain significance (Jun 01, 2023)
11-7987362-C-T		EIF3F-related disorder	Likely benign (Sep 13, 2022)
11-7987371-C-T		Inborn genetic diseases	Likely benign (Dec 06, 2021)
11-7987373-A-G		EIF3F-related disorder	Likely benign (Aug 01, 2023)
11-7987375-T-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
11-7987387-C-T		EIF3F-related disorder	Benign (Sep 26, 2019)
11-7987399-C-T		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
11-7987401-C-G			Uncertain significance (Feb 01, 2024)
11-7987402-C-A			Uncertain significance (Jul 01, 2023)
11-7987407-C-T		EIF3F-related disorder	Likely benign (Feb 07, 2023)
11-7987468-C-T		EIF3F-related disorder	Benign (Oct 28, 2019)
11-7987481-A-C			Likely benign (Jul 01, 2023)
11-7987486-C-T		EIF3F-related disorder	Benign (Jun 17, 2019)
11-7987492-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
11-7987504-C-G		Inborn genetic diseases	Uncertain significance (May 04, 2021)
11-7987556-T-A			Likely benign (Sep 01, 2023)
11-7987577-C-A		EIF3F-related disorder	Likely benign (May 20, 2019)
11-7987578-GC-TG			Uncertain significance (Apr 07, 2023)
11-7987579-C-G		EIF3F-related disorder	Benign (Sep 19, 2019)
11-7987585-C-T		EIF3F-related disorder	Conflicting classifications of pathogenicity (Jul 01, 2023)
11-7987594-C-G		Inborn genetic diseases	Uncertain significance (May 15, 2023)
11-7987615-G-A		Intellectual disability	Uncertain significance (Mar 10, 2020)
11-7987628-C-G		EIF3F-related disorder	Likely benign (Dec 27, 2023)
11-7987653-T-A		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
11-7987694-C-T		EIF3F-related disorder	Benign (Oct 18, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF3F	protein_coding	protein_coding	ENST00000533626	8	31612

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.970	0.0296	125747	0	1	125748	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.108	212	208	1.02	0.0000109	2268
Missense in Polyphen		31	48.671	0.63692		632
Synonymous	-2.24	113	86.5	1.31	0.00000503	768
Loss of Function	3.39	1	15.3	0.0654	7.38e-7	181

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)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre- initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF- 3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03005, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.
• Pathway: RNA transport - Homo sapiens (human);Translation Factors;Formation of the ternary complex, and subsequently, the 43S complex;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Formation of a pool of free 40S subunits;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 (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.435
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.204
• hipred: Y
• hipred_score: 0.783
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.806

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif3f

Zebrafish Information Network

• Gene name: eif3f
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: formation of cytoplasmic translation initiation complex;translational initiation;protein deubiquitination;IRES-dependent viral translational initiation
• Cellular component: cytosol;eukaryotic translation initiation factor 3 complex;membrane;eukaryotic 43S preinitiation complex;eukaryotic 48S preinitiation complex;eukaryotic translation initiation factor 3 complex, eIF3m
• Molecular function: translation initiation factor activity;thiol-dependent ubiquitin-specific protease activity;protein binding;translation initiation factor binding