ERN1

endoplasmic reticulum to nucleus signaling 1, the group of Endoribonucleases

Basic information

Region (hg38): 17:64039080-64130819

Links

ENSG00000178607 ∙ NCBI:2081 ∙ OMIM:604033 ∙ HGNC:3449 ∙ Uniprot:O75460 ∙ 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 ERN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERN1 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				2	1	3
missense			43	3	1	47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	43	5	2

Variants in ERN1

This is a list of pathogenic ClinVar variants found in the ERN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-64044010-G-T		not specified	Uncertain significance (Oct 25, 2023)
17-64044134-C-T		not specified	Uncertain significance (Oct 04, 2022)
17-64044143-C-T		not specified	Uncertain significance (Oct 03, 2022)
17-64044167-G-A		not specified	Uncertain significance (Feb 28, 2023)
17-64044176-C-T		not specified	Uncertain significance (Nov 15, 2023)
17-64044184-T-C		not specified	Uncertain significance (Apr 25, 2022)
17-64044871-T-C		not specified	Uncertain significance (Dec 15, 2022)
17-64045389-G-A		not specified	Uncertain significance (Feb 13, 2024)
17-64045445-C-T		not specified	Uncertain significance (Oct 06, 2023)
17-64047885-G-C		not specified	Uncertain significance (Feb 12, 2024)
17-64047911-C-T		not specified	Uncertain significance (Nov 17, 2022)
17-64047941-C-A		not specified	Uncertain significance (Jan 04, 2022)
17-64049098-G-A			Benign (Dec 13, 2017)
17-64049157-C-T		not specified	Uncertain significance (Jan 24, 2023)
17-64049169-C-T		not specified	Uncertain significance (Nov 30, 2022)
17-64049178-C-A		not specified	Uncertain significance (Jun 24, 2022)
17-64052782-G-C		not specified	Uncertain significance (Aug 14, 2023)
17-64053368-C-T		not specified	Uncertain significance (Sep 29, 2023)
17-64054748-T-C		not specified	Uncertain significance (Jan 08, 2024)
17-64054814-C-G		not specified	Uncertain significance (Aug 09, 2021)
17-64055677-C-T		not specified	Likely benign (Aug 16, 2022)
17-64055695-G-A		not specified	Likely benign (Jan 04, 2024)
17-64055698-G-C			Benign (Dec 13, 2017)
17-64055743-T-G		not specified	Uncertain significance (Aug 13, 2021)
17-64055764-G-A		not specified	Uncertain significance (Dec 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERN1	protein_coding	protein_coding	ENST00000433197	22	91678

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.00973	124647	0	11	124658	0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	413	565	0.732	0.0000339	6326
Missense in Polyphen		98	184.63	0.53078		2124
Synonymous	0.254	236	241	0.979	0.0000161	1925
Loss of Function	5.44	8	49.2	0.163	0.00000268	574

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000587	0.0000587
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000754	0.0000619
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11779464, PubMed:11175748, PubMed:12637535, PubMed:9637683, PubMed:21317875). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity (PubMed:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:24508390, PubMed:21317875). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:24508390, PubMed:21317875). {ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:21317875, ECO:0000269|PubMed:9637683, ECO:0000305|PubMed:24508390}.
• Pathway: Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Apoptosis - Homo sapiens (human);Alzheimers Disease;Corticotropin-releasing hormone signaling pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Photodynamic therapy-induced unfolded protein response;VEGFA-VEGFR2 Signaling Pathway;IRE1alpha activates chaperones;Unfolded Protein Response (UPR);Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.311

Intolerance Scores

• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.63

Haploinsufficiency Scores

• pHI: 0.179
• hipred: Y
• hipred_score: 0.694
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ern1
• Phenotype: digestive/alimentary phenotype; immune system phenotype; embryo phenotype; liver/biliary system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: endothelial cell proliferation;mRNA cleavage;mRNA catabolic process;protein phosphorylation;cell cycle arrest;activation of JUN kinase activity;regulation of macroautophagy;endoplasmic reticulum unfolded protein response;positive regulation of RNA splicing;cellular response to unfolded protein;response to endoplasmic reticulum stress;cellular response to vascular endothelial growth factor stimulus;peptidyl-serine autophosphorylation;IRE1-mediated unfolded protein response;protein autophosphorylation;mRNA splicing, via endonucleolytic cleavage and ligation;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;cellular response to glucose stimulus;RNA phosphodiester bond hydrolysis, endonucleolytic;mRNA cleavage involved in mRNA processing;positive regulation of endoplasmic reticulum unfolded protein response;insulin metabolic process;positive regulation of vascular smooth muscle cell proliferation;peptidyl-serine trans-autophosphorylation
• Cellular component: nuclear inner membrane;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane;Ire1 complex;AIP1-IRE1 complex;IRE1-TRAF2-ASK1 complex;IRE1-RACK1-PP2A complex
• Molecular function: magnesium ion binding;endoribonuclease activity;protein kinase activity;protein serine/threonine kinase activity;platelet-derived growth factor receptor binding;protein binding;ATP binding;enzyme binding;Hsp70 protein binding;identical protein binding;protein homodimerization activity;ADP binding;unfolded protein binding;Hsp90 protein binding