XBP1
X-box binding protein 1, the group of Basic leucine zipper proteins
Basic information
Region (hg38): 22:28794554-28800597
Previous symbols: [ "XBP2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the XBP1 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 | 1 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 1 | 0 | 0 |
Variants in XBP1
This is a list of pathogenic ClinVar variants found in the XBP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 22-28795581-G-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 22-28795632-T-G | not specified | Uncertain significance (Mar 29, 2022) | ||
| 22-28795660-C-T | not specified | Likely benign (Nov 07, 2023) | ||
| 22-28796046-C-A | Major affective disorder 7 | Uncertain significance (Jul 12, 2018) | ||
| 22-28796056-T-C | not specified | Uncertain significance (Jan 07, 2022) | ||
| 22-28796071-G-A | not specified | Uncertain significance (Dec 28, 2023) | ||
| 22-28796168-C-T | not specified | Uncertain significance (Nov 14, 2023) | ||
| 22-28797070-G-T | Likely benign (May 14, 2018) | |||
| 22-28797139-G-C | not specified | Uncertain significance (Jul 19, 2022) | ||
| 22-28797159-T-C | not specified | Uncertain significance (Jan 24, 2024) | ||
| 22-28797187-C-G | not specified | Uncertain significance (Nov 09, 2021) | ||
| 22-28800335-G-A | not specified | Uncertain significance (Dec 27, 2023) | ||
| 22-28800345-C-G | not specified | Uncertain significance (Aug 02, 2023) | ||
| 22-28800346-T-G | not specified | Uncertain significance (Mar 24, 2023) | ||
| 22-28800353-C-A | not specified | Uncertain significance (Sep 27, 2021) | ||
| 22-28800374-C-T | not specified | Uncertain significance (Jan 04, 2024) | ||
| 22-28800430-G-A | Autosomal dominant polycystic liver disease | Likely benign (Sep 01, 2021) | ||
| 22-28800481-G-A | Autosomal dominant polycystic liver disease | Likely benign (Sep 01, 2021) | ||
| 22-28800510-T-TGCC | Autosomal dominant polycystic liver disease | Likely benign (Sep 01, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| XBP1 | protein_coding | protein_coding | ENST00000216037 | 5 | 6043 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0320 | 0.960 | 125739 | 0 | 7 | 125746 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 94 | 126 | 0.745 | 0.00000648 | 1623 |
| Missense in Polyphen | 25 | 42.196 | 0.59247 | 562 | ||
| Synonymous | 1.29 | 39 | 50.7 | 0.769 | 0.00000260 | 540 |
| Loss of Function | 2.31 | 5 | 14.5 | 0.345 | 8.09e-7 | 145 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000464 | 0.0000462 |
| European (Non-Finnish) | 0.0000356 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000341 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins (PubMed:11460154). Modulates the cellular response to ER stress in a PIK3R-dependent manner (PubMed:20348923). Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (PubMed:8349596). Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions. Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity). {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11460154, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:8349596}.; FUNCTION: Isoform 2: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components to enhance the capacity of productive folding and degradation mechanism, respectively, in order to maintain the homeostasis of the ER under ER stress (PubMed:11779464, PubMed:25239945). Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation (By similarity). Induces phospholipid biosynthesis and ER expansion (PubMed:15466483). Contributes to the VEGF-induced endothelial cell (EC) growth and proliferation in a Akt/GSK-dependent and/or -independent signaling pathway, respectively, leading to beta-catenin nuclear translocation and E2F2 gene expression (PubMed:23529610). Promotes umbilical vein EC apoptosis and atherosclerotisis development in a caspase-dependent signaling pathway, and contributes to VEGF- induced EC proliferation and angiogenesis in adult tissues under ischemic conditions (PubMed:19416856, PubMed:23529610). Involved in the regulation of endostatin-induced autophagy in EC through BECN1 transcriptional activation (PubMed:23184933). Plays a role as an oncogene by promoting tumor progression: stimulates zinc finger protein SNAI1 transcription to induce epithelial-to- mesenchymal (EMT) transition, cell migration and invasion of breast cancer cells (PubMed:25280941). Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation. Plays a role in the survival of both dopaminergic neurons of the substantia nigra pars compacta (SNpc), by maintaining protein homeostasis and of myeloma cells. Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance. Improves also glucose homeostasis in an ER stress- and/or insulin- independent manner through both binding and proteasome-induced degradation of the transcription factor FOXO1, hence resulting in suppression of gluconeogenic genes expression and in a reduction of blood glucose levels. Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner (By similarity). Associates preferentially to the HDAC3 gene promoter region in a disturbed flow-dependent manner (PubMed:25190803). Binds to the BECN1 gene promoter region (PubMed:23184933). Binds to the CDH5/VE-cadherin gene promoter region (PubMed:19416856). Binds to the ER stress response element (ERSE) upon ER stress (PubMed:11779464). Binds to the 5'-CCACG-3' motif in the PPARG promoter (By similarity). {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:15466483, ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25239945, ECO:0000269|PubMed:25280941}.;
- Disease
- DISEASE: Major affective disorder 7 (MAFD7) [MIM:612371]: A major psychiatric disorder that is characterized by severe mood swings, with fluctuation between two abnormal mood states (manic or major depressive episode). Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
- Pathway
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);ATF6 (ATF6-alpha) activates chaperone genes;Photodynamic therapy-induced unfolded protein response;Insulin Signaling;FOXA1 transcription factor network;Validated nuclear estrogen receptor alpha network
(Consensus)
Recessive Scores
- pRec
- 0.567
Intolerance Scores
- loftool
- 0.129
- rvis_EVS
- -0.1
- rvis_percentile_EVS
- 46.2
Haploinsufficiency Scores
- pHI
- 0.462
- hipred
- Y
- hipred_score
- 0.725
- ghis
- 0.509
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.674
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Xbp1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland 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); embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); hematopoietic 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype;
Zebrafish Information Network
- Gene name
- xbp1
- Affected structure
- hatching gland cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- angiogenesis;liver development;endothelial cell proliferation;positive regulation of immunoglobulin production;transcription by RNA polymerase II;ubiquitin-dependent protein catabolic process;fatty acid biosynthetic process;autophagy;immune response;positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response;muscle organ development;positive regulation of cell population proliferation;regulation of autophagy;negative regulation of myotube differentiation;protein transport;positive regulation of cell migration;endoplasmic reticulum unfolded protein response;exocrine pancreas development;protein destabilization;cellular response to nutrient;cellular response to insulin stimulus;cellular triglyceride homeostasis;positive regulation of vascular wound healing;IRE1-mediated unfolded protein response;ATF6-mediated unfolded protein response;cellular response to glucose starvation;cholesterol homeostasis;negative regulation of apoptotic process;positive regulation of MHC class II biosynthetic process;positive regulation of B cell differentiation;positive regulation of T cell differentiation;positive regulation of fat cell differentiation;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;neuron development;positive regulation of immunoglobulin secretion;fatty acid homeostasis;sterol homeostasis;adipose tissue development;epithelial cell maturation involved in salivary gland development;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;cellular response to lipopolysaccharide;cellular response to amino acid stimulus;cellular response to fructose stimulus;cellular response to glucose stimulus;cellular response to interleukin-4;cellular response to peptide hormone stimulus;positive regulation of plasma cell differentiation;positive regulation of endoplasmic reticulum unfolded protein response;negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;positive regulation of lactation;response to insulin-like growth factor stimulus;cellular response to leukemia inhibitory factor;positive regulation of hepatocyte proliferation;positive regulation of interleukin-6 secretion
- Cellular component
- nucleus;nucleoplasm;cytoplasm;endoplasmic reticulum;integral component of endoplasmic reticulum membrane
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;DNA binding;DNA-binding transcription factor activity;protein binding;protein heterodimerization activity