GCN1

GCN1 activator of EIF2AK4, the group of MicroRNA protein coding host genes|TOG domain containing

Basic information

Region (hg38): 12:120127202-120194715

Previous symbols: [ "GCN1L1" ]

Links

ENSG00000089154 ∙ NCBI:10985 ∙ OMIM:605614 ∙ HGNC:4199 ∙ Uniprot:Q92616 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GCN1 gene.

• not_specified (277 variants)
• not_provided (17 variants)
• Fetal_akinesia_deformation_sequence_1 (1 variants)
• Arthrogryposis_multiplex_congenita (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006836.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	5	13
missense			271	7	1	279
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	271	15	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCN1	protein_coding	protein_coding	ENST00000300648	58	67507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.87e-8	124774	0	46	124820	0.000184

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.44	1069	1.56e+3	0.684	0.0000960	17230
Missense in Polyphen		318	581.67	0.5467		6292
Synonymous	-0.503	693	676	1.02	0.0000443	5612
Loss of Function	9.03	18	128	0.140	0.00000667	1481

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000475	0.000409
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000279	0.000232
European (Non-Finnish)	0.000241	0.000238
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a positive activator of the EIF2AK4/GCN2 protein kinase activity in response to amino acid starvation. Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during this process, GCN1 seems to act as a chaperone to facilitate delivery of uncharged tRNAs that enter the A site of ribosomes to the tRNA- binding domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase activity. Participates in the repression of global protein synthesis and in gene-specific mRNA translation activation, such as the transcriptional activator ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. {ECO:0000250|UniProtKB:E9PVA8, ECO:0000250|UniProtKB:P33892}.

Recessive Scores

• pRec: 0.391

Intolerance Scores

• rvis_EVS: -3.77
• rvis_percentile_EVS: 0.24

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.793
• ghis: 0.625

Essentials

• essential_gene_gene_trap: H

Mouse Genome Informatics

• Gene name: Gcn1l1

Gene ontology

• Biological process: translation;regulation of translation;positive regulation of kinase activity;cellular response to amino acid starvation;positive regulation of transcription from RNA polymerase II promoter in response to stress;regulation of protein kinase activity;cellular response to leucine starvation
• Cellular component: cytoplasm;cytosol;ribosome;polysome;membrane
• Molecular function: RNA binding;translation factor activity, RNA binding;protein kinase regulator activity;protein kinase binding;ribosome binding;cadherin binding