count	source_label	source_id	relationship	target_label	target_id	entity_type	solr_id	publication_id	sentences
4	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:O76024	Protein	68b59a90-4552-11f0-8978-0050569a1f61	10.1016/j.jns.2022.120267	WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.|||Pathophysiology and genotype WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.
4	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P15502	Protein	68b59a90-4552-11f0-8978-0050569a1f61	10.1016/j.jns.2022.120267	Pathophysiology and genotype WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.|||WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.
4		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	5d35bd96-390f-11e8-87fd-001a4a160176	PMC5112157	Wolfram Syndrome is caused by mutations in the gene WFS1, which encodes for a nine-pass transmembrane protein of the endoplasmic reticulum (ER) (Inoue et al., 1998; Strom et al., 1998).
4		UNIPROT:P15502	activates	Wolfram Syndrome	MESH:D014929	Protein	68b59a90-4552-11f0-8978-0050569a1f61	10.1016/j.jns.2022.120267	WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.|||Pathophysiology and genotype WS is classically caused by autosomal recessive mutations in Wolfram syndrome 1 (WFS1) gene, which is located on chromosome 4p16.1.
2	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:O76024	Protein	681c54d6-053b-11f0-8fe6-0050569a1f61	10.1016/j.molmet.2024.101973	For example, the majority of cases of Wolfram syndrome are caused by autosomal recessive mutations in theWolfram syndrome 1(WFS1) gene, which encodes wolframin [84,85].
2	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:Q8N5K1	Protein	0df5a096-3823-11e6-8a17-001a4ae51247	25448035	NAF-1 is involved in disease, the genetic disorder WFS2, and longevity A recessive mutation inCISD2, the gene encoding NAF-1, located on chromosome 4, leads to Wolfram Syndrome 2 (WFS2)[14,21,87].
2	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:Q15025	Protein	0df5a096-3823-11e6-8a17-001a4ae51247	25448035	NAF-1 is involved in disease, the genetic disorder WFS2, and longevity A recessive mutation inCISD2, the gene encoding NAF-1, located on chromosome 4, leads to Wolfram Syndrome 2 (WFS2)[14,21,87].
2		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	22969a3a-381b-11e6-b56c-001a4ae51246	PMC4404183	Similarly, mutation of the wolfram syndrome 1 (wfs1) gene (Inoue et al., 1998; Strom et al., 1998), which has a protective function against ER stress (Fonseca et al., 2010), causes Wolfram syndrome.
2		UNIPROT:O76024	inhibits	Wolfram Syndrome	MESH:D014929	Protein	85a80cb6-ca03-11e5-be63-001a4ae51246	16195229	Therefore, it is likely that Wolfram syndrome is caused by a loss of function of WFS1.
2		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	0df5a096-3823-11e6-8a17-001a4ae51247	25448035	NAF-1 is involved in disease, the genetic disorder WFS2, and longevity A recessive mutation inCISD2, the gene encoding NAF-1, located on chromosome 4, leads to Wolfram Syndrome 2 (WFS2)[14,21,87].
2		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	9d0cd4c4-ae93-11ec-ae7b-0050569a1f61	PMCPMC8348817	Although not as common as WFS1, mutations in WFS2 or CISD2 gene also cause Wolfram Syndrome.
2		UNIPROT:Q9NQB0	inhibits	Wolfram Syndrome	MESH:D014929	Protein	17c73e00-3791-11e6-b56c-001a4ae51246	PMC4853229	Examples of such genetic aberrations include a polymorphism in the transcription factor 7-like 2 (TCF7L2) gene that impairs GLP-1-induced insulin secretion and the genetic variant of the Wolfram syndrome 1 (WFS1) gene that disrupts GLP-1-induced insulin secretion but not IV glucose-induced insulin secretion.
2		UNIPROT:P16615	activates	Wolfram Syndrome	MESH:D014929	Protein	301437fc-bbee-11e5-9b9d-001a4ae51247	10.1016/j.brainres.2006.07.008	Mutations in ATP2A2 (a gene encoding an ATP-driven calcium pump;Sato et al., 2004) and wolframin (a gene encoding a transmembrane protein related to intracellular calcium homeostasis;Osman et al., 2003), the gene products of which are exclusively localized in the ER organelle, cause Darier's cutaneous disease and Wolfram syndrome with juvenile onset nonautoimmune diabetes mellitus and optic atrophy, respectively.
2		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	a23cb4c2-ae94-11ec-ae7b-0050569a1f61	PMCPMC8369721	Among these 26 papers, five patients had wolfram syndrome caused by mutations in the CISD2 gene, while the rest had disease caused by mutations at different nucleotide sites in exons 4, 5 and 8 of the WFS1 gene.|||Wolfram syndrome caused by the CISD2 gene mutation exhibits very different clinical features, characterized by peptic ulcer disease, bleeding tendencies secondary to abnormal platelet aggregation and absence of enuresis.
2		UNIPROT:P55145	activates	Wolfram Syndrome	MESH:D014929	Protein	0e8cd766-ab77-11ee-bde4-0050569a1f61	PMC7438202	Here we show that MANF-based treatment prevents β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome.|||In this study, we show that MANF treatment activates the proliferation of β cells in human islets and prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P03372	Protein	186a0a9c-a4c5-11eb-bc78-001a4a160175	PMCPMC8059287	Mutations in Wolfram syndrome 1 (WFS1) gene may cause dysregulated endoplasmic reticulum (ER)-stress and cell apoptosis, contributing to WS symptoms.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P03971	Protein	5f85e0ae-bc3d-11e5-8abe-001a4ae51246	PMC2739586	Mis-splicing of the mRNA that codifies this protein is causative in the genetic disease Wolfram Syndrome 2 (WFS2).
1	Wolfram Syndrome	MESH:D014929	increases		UNIPROT:P01275	Protein	81888c98-bc46-11e5-8abe-001a4ae51246	PMC3632188	Wolfram syndrome 1 gene (WFS1) has been associated with type 2 diabetes and with impaired insulin secretion during a GLP-1 infusion (62,63), and the variant rs151290 inKCNQ1has been associated with changes in insulin secretion and increased GIP and GLP-1 secretion (64).
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROTPRO:PRO:0000011258	Protein	5999e77a-d1f7-11ee-8b99-0050569a1f61	10.1007/s00125-018-4679-y	Our present goal was to elucidate the therapeutic effects on insulin insufficiency in Wolfram syndrome of activating the glucagon-like peptide-1 (GLP-1) receptor signal.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:O76024	Protein	54f0ef01-f52b-11eb-a759-001a4a160175	PMC7451204	WS is primarily caused by autosomal recessive mutations in the Wolfram syndrome 1 (WFS1) gene (OMIM 222300), which encodes for wolframin (WFS1).
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:O76024	Protein	5d83d9a8-bc08-11e5-9b9d-001a4ae51247	PMC3925691	Morpholino-mediated knockdown of this NET in zebrafish resulted in aberrant development of skeletal muscle and heart57whereasPOPDC2null mutant mice developed stress-induced bradycardia.58Finally, though not yettested for NE targeting, another NET identified only in the muscle NEs, DTNA (dystrobrevin), when mutated results in left ventricular non-compaction—a rare, unclassified cardiomyopathy.59 Not all disease-linked NETs identified in muscle make such clean associations with muscle disease: though only identified in the muscle NEs, mutations in the gene encoding WFS1 cause Wolfram syndrome characterized by optic atrophy, deafness and/or diabetes.60-62However, this is not necessarily inconsistent with the matched tissue hypothesis because the NE proteome of eyes and ears was not determined.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P41235	Protein	91fc2e7c-34f7-11e9-8aa6-001a4a160176	PMC6209016	A similar finding has been observed in the Wolfram syndrome geneWFS1,which causes a MODY-like phenotype in a small number of families [74], but common variation in the gene is also associated with risk of type 2 diabetes.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P41235	Protein	39241e77-f540-11eb-ae41-001a4a160175	29734081	"</ce:para>
                  <ce:para id=""par0080"" view=""all"">A recent example is that mutations in the Wolfram syndrome gene <ce:italic>WFS1</ce:italic> appear to cause MODY occasionally."
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P23760	Protein	64c391fc-f57a-11eb-85e0-001a4a160175	PMC7744320	Most WS patients belong to Wolfram Syndrome type 1 (WS1) caused by mutations in the Wolfram Syndrome 1 (WFS1/Wolframin) gene, while a small fraction of patients belongs to Wolfram Syndrome type 2 (WS2) caused by pathogenic variants in the CDGSH Iron Sulfur Domain 2 (CISD2/WFS2) gene.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:O75030	Protein	64c391fc-f57a-11eb-85e0-001a4a160175	PMC7744320	Most WS patients belong to Wolfram Syndrome type 1 (WS1) caused by mutations in the Wolfram Syndrome 1 (WFS1/Wolframin) gene, while a small fraction of patients belongs to Wolfram Syndrome type 2 (WS2) caused by pathogenic variants in the CDGSH Iron Sulfur Domain 2 (CISD2/WFS2) gene.
1	Wolfram Syndrome	MESH:D014929	activates		UNIPROT:P15502	Protein	54f0ef01-f52b-11eb-a759-001a4a160175	PMC7451204	WS is primarily caused by autosomal recessive mutations in the Wolfram syndrome 1 (WFS1) gene (OMIM 222300), which encodes for wolframin (WFS1).
1	Wolfram Syndrome	MESH:D014929	inhibits		GO:0030073	Phenotype	17c73e00-3791-11e6-b56c-001a4ae51246	PMC4853229	Examples of such genetic aberrations include a polymorphism in the transcription factor 7-like 2 (TCF7L2) gene that impairs GLP-1-induced insulin secretion and the genetic variant of the Wolfram syndrome 1 (WFS1) gene that disrupts GLP-1-induced insulin secretion but not IV glucose-induced insulin secretion.
1	Wolfram Syndrome	MESH:D014929	activates		MESH:D059865	Phenotype	11cf265e-3b48-11e8-9fbf-001a4a160176	PMC5934260	The precise mechanism whereby Wolfram syndrome 1 (WFS1) mutation induces ER stress, followed by β‐cell failure, is not fully understood.
1	Wolfram Syndrome	MESH:D014929	activates		MESH:D000242	Phenotype	07117626-bbfd-11e5-8abe-001a4ae51246	PMC4607427	The Wolfram syndrome 1 (Wfs1) gene encodes an ER-resident protein associated with protein folding, calcium homeostasis, glucose-stimulated cAMP production, and degradation with ATF6α [32,33].
1	Wolfram Syndrome	MESH:D014929	activates		GO:0006915	Phenotype	186a0a9c-a4c5-11eb-bc78-001a4a160175	PMCPMC8059287	Mutations in Wolfram syndrome 1 (WFS1) gene may cause dysregulated endoplasmic reticulum (ER)-stress and cell apoptosis, contributing to WS symptoms.
1	Wolfram Syndrome	MESH:D014929	activates		GO:0006915	Phenotype	921d3622-868b-11ee-add2-0050569a791b	10.1007/s11892-022-01483-y	Treatment for Wolfram syndrome is targeted to reduce endoplasmic reticulum stress and thereby reduce cell apoptosis.
1	Wolfram Syndrome	MESH:D014929	activates		GO:0034976	Phenotype	4a1afe18-c483-11e5-9cc6-001a4ae51246	PMC3311293	Furthermore, Wolfram syndrome 1 (WFS1) is often upregulated by XBP-1 to mitigate the ER stress response in part through downregulation of ATF6 (10,11,17).
1	Wolfram Syndrome	MESH:D014929	activates		MESH:D003920	Phenotype	6ac05246-c9fe-11e5-b88f-001a4ae51247	15056606	"The observation that the first-degree relatives of Wolfram syndrome patients have increased frequencies of diabetes mellitus
                      and certain psychiatric disorders suggests sequence variants of theWFS1gene predispose these individuals to such conditions (2,8)."
1	Wolfram Syndrome	MESH:D014929	activates		IP:IPR005071	ProteinFamily	795da570-eda2-11e5-872c-001a4ae51246	PMC5010532	Wolfram syndrome is caused by mutations in the WFS1 gene encoding an ER-resident membrane glycoprotein which regulates cellular calcium homeostasis (Inoue et al., 1998, Lu et al., 2014).
1		UNIPROT:P03372	activates	Wolfram Syndrome	MESH:D014929	Protein	4eca1a9a-bc3e-11e5-8d2d-001a4ae51247	PMC2991281	This hypothesis received further support from the study of other monogenic diabetes, where a role of ER stress of the β cell may also be implicated, including Wolfram syndrome (WFS), caused by mutations in the ER Ca2+ channel geneWFS1[27], and neonatal diabetes caused by structural mutations in the insulin gene itself [28].
1		UNIPROT:P03372	activates	Wolfram Syndrome	MESH:D014929	Protein	12f998ec-5c24-11e7-b441-001a4ae51247	PMC5373507	So close is this relationship, in fact, that a recent PLOS Biology paper shows that mutations in an ER protein (wolframin) probably cause a human neurological disease (Wolfram syndrome) via their effects on mitochondrial dynamics [6].
1		UNIPROT:P43220	activates	Wolfram Syndrome	MESH:D014929	Protein	5999e77a-d1f7-11ee-8b99-0050569a1f61	10.1007/s00125-018-4679-y	Based on our finding that Ex-4 mitigated cellular stress while improving function inWfs1-deficient beta cells, we suggest that GLP-1 receptor agonist therapy may provide a means of attenuating or even slowing the progression of diabetes and neuronal degeneration in individuals with Wolfram syndrome.
1		MESH:D034381	inhibits	Wolfram Syndrome	MESH:D014929	Phenotype	d28d7364-c986-11ee-b346-0050569a791b	PMC11446251	Neurogenic weakness, ataxia, and retinitis pigmentosa (NARP), diabetes insipidus, diabetes mellitus, optic atrophy, Wolfram syndrome, and Pearson syndrome are all caused by a large spectrum of mtDNA mutations and hearing loss is not always but is frequently a symptom in individuals with these disorders (Kokotas et al., 2007).
1		UNIPROT:O43312	activates	Wolfram Syndrome	MESH:D014929	Protein	f30e9de2-8e4f-11ee-ae93-0050569a1f61	10.1007/s00439-021-02332-w	Genetic variants presumably associated with syndromic forms of hearing loss Pathogenic variants in theWFS1gene can lead to Wolfram syndrome 1 (MIM 222300), Wolfram-like syndrome autosomal dominant (MIM 614296) as well as to non-syndromic deafness autosomal dominant 6/14/38 (MIM 600965).
1		UNIPROT:P01308	inhibits	Wolfram Syndrome	MESH:D014929	Protein	27eaa310-bc50-11e5-9b9d-001a4ae51247	PMC3931392	In addition to insulin therapy, this molecule—or compounds with similar activity—may be useful in preventing or delaying β-cell dysfunction in Wolfram syndrome and possibly other forms of diabetes.
1		MESH:D003550	inhibits	Wolfram Syndrome	MESH:D014929	Phenotype	e56ba79f-abd7-11eb-8ca4-001a4a160176	PMCPMC8073975	Interestingly, CISD1 (CDGSH iron sulfur domain 1) also associated with LCT; CISD1 is a mitochondrial protein reduced in cystic fibrosis, the deficiency of which may cause Wolfram syndrome with neurodegeneration [34].
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	c52f9158-ae93-11ec-a61d-0050569a1f61	PMCPMC8872384	Wolfram syndrome 1, a rare autosomal recessive neurodegenerative disease, is caused by mutations in the WFS1 gene.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	ed90736c-ab74-11ee-a19b-0050569a791b	10.1007/s13410-020-00797-5	Pathogenic variants are WFS1 that cause Wolfram syndrome.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	ccda20c0-bbd9-11e5-9b9d-001a4ae51247	PMC3728556	Introduction Wolfram syndrome (WS, MIM222300), caused by mutations in the WFS1 gene, is an autosomal recessive disorder most frequently characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	af3506d4-bc1a-11e5-8abe-001a4ae51246	PMC3776697	Researchers have identified more than 100 WFS1 mutations that cause Wolfram syndrome.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	b885cf08-5c13-11e7-9833-001a4ae51246	PMC5423914	Wolframin (WFS1) is a transmembrane ER resident protein encoded by the WFS1 gene that in a mutant form causes Wolfram syndrome 1 (WS1), an autosomal recessive degenerative disease characterized by insulin-dependent diabetes mellitus, optic atrophy, deafness and various neurological symptoms (Hofmann et al.,2003).
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	20cfce18-bbd6-11e5-956b-001a4ae51247	PMC2891295	Mutations in WFS1 that cause autosomal recessive Wolfram syndrome also cause diabetes and sensorineural hearing impairment at low frequencies (Cryns et al., 2003).
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	149d9913-f587-11eb-93a7-001a4a160176	30266217	"</ce:para>
                                    </ce:list-item>
                                 </ce:list>
                              </ce:para>
                           </ce:sections>
                        </ce:textbox-body>
                     </ce:textbox>
                  </ce:display>
               </ce:para>
               <ce:section id=""s0010"" role=""introduction"" view=""all"">
                  <ce:section-title id=""st0070"">Introduction</ce:section-title>
                  <ce:para id=""p0030"" view=""all"">Mutations in the Wolframin1 (Wfs1) gene cause the autosomal recessive disorder Wolfram syndrome (WS)."
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	4eca1a9a-bc3e-11e5-8d2d-001a4ae51247	PMC2991281	Wolfram syndrome (WFS), a monogenic diabetes, is caused by mutations in the WFS1 gene, another important ER gene.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	99036456-bc14-11e5-9b9d-001a4ae51247	10.1016/j.mito.2013.07.105	Although long thought to be a disease of mitochondrial dysfunction, Wolfram Syndrome is caused by mutations in either wolframin or Miner1, both of which are endoplasmic reticular (ER) proteins.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	b225a848-bbdf-11e5-9b9d-001a4ae51247	10.1016/S0304-3940(02)00110-6	Mutations in the wolframin gene cause a severe disorder called the Wolfram syndrome (Diabetes insipidus, diabetes mellitus, optic atrophy and deafness—DIDMOAD).
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	12f998ec-5c24-11e7-b441-001a4ae51247	PMC5373507	So close is this relationship, in fact, that a recent PLOS Biology paper shows that mutations in an ER protein (wolframin) probably cause a human neurological disease (Wolfram syndrome) via their effects on mitochondrial dynamics [6].
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	795da570-eda2-11e5-872c-001a4ae51246	PMC5010532	Wolfram syndrome is caused by mutations in the WFS1 gene encoding an ER-resident membrane glycoprotein which regulates cellular calcium homeostasis (Inoue et al., 1998, Lu et al., 2014).
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	1019da86-bbdc-11e5-9b9d-001a4ae51247	PMC3872449	Mutations in the WFS1 gene, encoding an 890 amino-acid transmembranous glycoprotein, wolframin, which is predominantly localized in the endoplasmic reticulum, can be responsible for nonsyndromic autosomal dominant low-frequency hearing loss (DFNA6/14/38) or cause Wolfram syndrome, which is characterized by diabetes insipidus, juvenile-onset diabetes mellitus, progressive optic atrophy, and sensorineural hearing loss.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	ce6565c0-ae95-11ec-ae7b-0050569a1f61	PMCPMC8455689	Wolfram syndrome is caused by mutations in the WFS1 gene.
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	65c817e6-bc3a-11e5-8abe-001a4ae51246	PMC4422421	The Wolfram syndrome is caused by mutations of the protein Wolframin, essential for the regulation of intracellular calcium homeostasis, the cell cycle progression and the retrieval of homeostasis under conditions such as ER stress [10-12].
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	40b9ac86-ae95-11ec-8b2e-0050569a1f61	PMCPMC8526738	Other examples are Wolfram syndrome, caused by mutations in WFS1 presenting with early-onset ataxia, cognitive deficits, and hearing loss, thus also including clinical hallmarks of the phenotype associated with DNAJC3 mutations (Khanim et al., 2001) and Wollcot-Rallison syndrome, an autosomal recessive disorder caused by mutations in eukaryotic translation initiation factor 2-alpha kinase 3 (E2AK3), characterized by insulin-dependent diabetes, growth retardation, and intellectual disability (Delepine et al., 2000).
1		UNIPROT:O76024	activates	Wolfram Syndrome	MESH:D014929	Protein	a2fbe2d2-bc44-11e5-8d2d-001a4ae51247	PMC3804895	Introduction Wolfram syndrome (WS), a rare autosomal recessive disorder, is caused by a mutation in the gene encoding wolframin (Inoue et al., 1998) on the short arm of chromosome 4 (4p16.1) (Polymeropoulos et al., 1994; Swift and Swift, 2000).
1		UNIPROT:Q96AT9	activates	Wolfram Syndrome	MESH:D014929	Protein	78db857e-bbd7-11e5-956b-001a4ae51247	PMC2788494	Abnormal RPE function could cause photoreceptor dysfunction in Wolfram syndrome.
1		UNIPROT:P17861	activates	Wolfram Syndrome	MESH:D014929	Protein	4a1afe18-c483-11e5-9cc6-001a4ae51246	PMC3311293	Furthermore, Wolfram syndrome 1 (WFS1) is often upregulated by XBP-1 to mitigate the ER stress response in part through downregulation of ATF6 (10,11,17).
1		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	a132c544-3404-11e8-8636-001a4a160175	22520736	Miner1, another endoplasmic reticulum protein is causative in Wolfram syndrome 2[79]and WFS1 negatively regulates a key transcription factor involved in ER stress signalling[80].
1		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	e829a7ac-ae93-11ec-ae7b-0050569a1f61	PMCPMC8724568	Wolfram syndrome 2 is caused by mutations in the CISD2 gene (Rigoli and Di Bella, 2012; Mozzillo et al., 2014).
1		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	65c817e6-bc3a-11e5-8abe-001a4ae51246	PMC4422421	Type 2 Wolfram syndrome, caused by mutations of the CISD2 gene on the chromosome 4q22, has been diagnosed in three large Jordanian families.
1		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	99036456-bc14-11e5-9b9d-001a4ae51247	10.1016/j.mito.2013.07.105	Although long thought to be a disease of mitochondrial dysfunction, Wolfram Syndrome is caused by mutations in either wolframin or Miner1, both of which are endoplasmic reticular (ER) proteins.
1		UNIPROT:Q8N5K1	activates	Wolfram Syndrome	MESH:D014929	Protein	6fef4734-5c85-11e7-b441-001a4ae51247	PMC4833486	Recently, Wolfram syndrome 2 has been described and is caused by mutation in the CISD2 gene on chromosome 4q22-q24, which encodes the protein ERIS (endoplasmic reticulum [ER] intermembrane small protein) (7).
1		MESH:D007239	activates	Wolfram Syndrome	MESH:D014929	Phenotype	619a1ec8-bc4c-11e5-8abe-001a4ae51246	PMC3120194	We also observed in individual patients that febrile infections and general anesthesia may induce acute neurologic deterioration in Wolfram syndrome, indicating that these conditions may constitute an additional source of ER stress enhancement.
1		GO:0006915	activates	Wolfram Syndrome	MESH:D014929	Phenotype	560bd5d0-c8e8-11e5-a1fd-001a4ae51246	17947299	"Pancreatic β-cells are some of the most susceptible cells to ER stress, and ER stress-mediated apoptosis
                      causes diabetes in Wolfram syndrome (14)."
1		GO:0006915	activates	Wolfram Syndrome	MESH:D014929	Phenotype	9a708d02-5c2f-11e7-bcb7-001a4ae51246	PMC5343917	Diabetes mellitus, central diabetes insipidus, and Wolfram syndrome are caused by ER stress-mediated apoptosis.
1		FPLX:Na:K:ATPase	activates	Wolfram Syndrome	MESH:D014929	ProteinFamily	560bd5d0-c8e8-11e5-a1fd-001a4ae51246	17947299	Decreases in Na+/K+ATPase expression may thus contribute to changes in β-cell mass and function in Wolfram syndrome.
1		UNIPROT:P15502	activates	Wolfram Syndrome	MESH:D014929	Protein	54f0ef01-f52b-11eb-a759-001a4a160175	PMC7451204	WS is primarily caused by autosomal recessive mutations in the Wolfram syndrome 1 (WFS1) gene (OMIM 222300), which encodes for wolframin (WFS1).
1		MESH:D008279	activates	Wolfram Syndrome	MESH:D014929	Phenotype	2ec62518-ca5d-11e5-9088-001a4ae51247	12913071	"Atrophy and death of specific cell systems, involving both
                      the neuronal network and the endocrinum, appear to be the morphological hallmarks: (i) post-mortem and MRI studies showed
                      atrophy and cell damage of various brain regions, explaining the severe course and complexity of the syndrome (3,4); and (ii) non-autoimmune diabetes mellitus, the first and one of the essential clinical features in Wolfram syndrome, is
                      caused by selective damage of pancreatic β-cells (5,6)."
1		UNIPROT:Q15025	activates	Wolfram Syndrome	MESH:D014929	Protein	13a3c16a-c46c-11e5-85e4-001a4ae51246	PMC3986192	Missplicing of NAF-1 causes Wolfram syndrome 2 (6).
1		CHEBI:9925	inhibits	Wolfram Syndrome	MESH:D014929	Chemical	e829a7ac-ae93-11ec-ae7b-0050569a1f61	PMCPMC8724568	A recent study showed that sodium valproate also reduces ER stress and cell apoptosis in Wolfram syndrome 1 models caused by dominant WFS1 mutations (Batjargal et al., 2020).
1		MESH:D001284	activates	Wolfram Syndrome	MESH:D014929	Phenotype	2ec62518-ca5d-11e5-9088-001a4ae51247	12913071	"Atrophy and death of specific cell systems, involving both
                      the neuronal network and the endocrinum, appear to be the morphological hallmarks: (i) post-mortem and MRI studies showed
                      atrophy and cell damage of various brain regions, explaining the severe course and complexity of the syndrome (3,4); and (ii) non-autoimmune diabetes mellitus, the first and one of the essential clinical features in Wolfram syndrome, is
                      caused by selective damage of pancreatic β-cells (5,6)."