EIF6

eukaryotic translation initiation factor 6, the group of Ribosomal biogenesis factors

Basic information

Region (hg38): 20:35278906-35284985

Previous symbols: [ "EIF3A", "ITGB4BP" ]

Links

ENSG00000242372 ∙ NCBI:3692 ∙ OMIM:602912 ∙ HGNC:6159 ∙ Uniprot:P56537 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Shwachman-Diamond syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF6 gene.

• Inborn genetic diseases (9 variants)
• Exstrophy-epispadias complex (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF6 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						0
missense			10			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	0	0

Variants in EIF6

This is a list of pathogenic ClinVar variants found in the EIF6 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-35279591-T-C		not specified	Uncertain significance (Jan 24, 2024)
20-35279702-C-A		not specified	Uncertain significance (Mar 23, 2022)
20-35279726-T-C		not specified	Uncertain significance (Jun 23, 2023)
20-35279997-T-C		not specified	Uncertain significance (Nov 03, 2023)
20-35280021-T-C		Exstrophy-epispadias complex	Uncertain significance (-)
20-35280058-C-T		not specified	Uncertain significance (Dec 07, 2021)
20-35280117-T-A		not specified	Uncertain significance (Sep 22, 2023)
20-35280684-G-A			Likely benign (Apr 01, 2024)
20-35280724-C-T		not specified	Uncertain significance (Jun 28, 2022)
20-35280752-T-C		not specified	Uncertain significance (Oct 05, 2023)
20-35280769-C-T		not specified	Uncertain significance (Sep 21, 2021)
20-35280791-C-T		not specified	Uncertain significance (Jun 23, 2023)
20-35284212-T-C		not specified	Uncertain significance (Feb 10, 2022)
20-35284388-A-G		not specified	Uncertain significance (Nov 29, 2021)
20-35284435-T-C		not specified	Uncertain significance (Sep 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF6	protein_coding	protein_coding	ENST00000374450	6	6075

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.238	0.756	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	106	145	0.733	0.00000736	1594
Missense in Polyphen		16	38.353	0.41718		427
Synonymous	0.429	53	57.1	0.928	0.00000282	500
Loss of Function	2.35	3	11.7	0.257	5.87e-7	126

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)	0.0000444	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS- dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA- induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity). {ECO:0000255|HAMAP-Rule:MF_03132, ECO:0000269|PubMed:10085284, ECO:0000269|PubMed:14654845, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:21536732}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);Translation Factors;Alpha6Beta4Integrin;eukaryotic protein translation (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.118
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.440
• hipred: Y
• hipred_score: 0.825
• ghis: 0.592

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif6
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: ribosomal subunit export from nucleus;regulation of glycolytic process;translational initiation;response to insulin;gene silencing by miRNA;miRNA mediated inhibition of translation;mature ribosome assembly;ribosomal large subunit biogenesis;regulation of fatty acid biosynthetic process;regulation of megakaryocyte differentiation;positive regulation of translation;assembly of large subunit precursor of preribosome;regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;preribosome, large subunit precursor;extracellular exosome
• Molecular function: translation initiation factor activity;protein binding;ribosome binding;ribosomal large subunit binding