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WFS1
MCID: WLF013
MIFTS: 60

Wolfram Syndrome 1 (WFS1)

Categories: Blood diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Wolfram Syndrome 1

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MalaCards integrated aliases for Wolfram Syndrome 1:

Name: Wolfram Syndrome 1 56 12 73 15
Diabetes Mellitus and Insipidus with Optic Atrophy and Deafness 12 29 6
Didmoad 56 12 73
Wfs1 56 12 73
Wfs 56 73
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness; Didmoad 56
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness Syndrome 73
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness 56
Syndrome, Wolfram, Type 1 39
Wolfram Syndrome 71

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
wolfram syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Eye diseases Ear diseases Endocrine diseases Neuronal diseases Blood diseases
See all MalaCards categories (disease lists)
ICD10: 32


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Summaries for Wolfram Syndrome 1

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OMIM : 56 Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness (DIDMOAD). Additional clinical features may include renal abnormalities, ataxia, dementia or mental retardation, and diverse psychiatric illnesses. The minimal diagnostic criteria for Wolfram syndrome are optic atrophy and diabetes mellitus of juvenile onset. Hearing impairment in Wolfram syndrome is typically progressive and mainly affects the higher frequencies, but a small fraction of affected individuals have congenital deafness (summary by Rendtorff et al., 2011). Autosomal dominant mutations in the WFS1 gene have been found to cause low-frequency nonsyndromic deafness (600965) as well as a Wolfram syndrome-like phenotype (614296) in which affected individuals have hearing impairment with diabetes mellitus and/or optic atrophy. (222300)

MalaCards based summary : Wolfram Syndrome 1, also known as diabetes mellitus and insipidus with optic atrophy and deafness, is related to early-onset nuclear cataract and rare diabetes mellitus type 2, and has symptoms including seizures, ataxia and tremor. An important gene associated with Wolfram Syndrome 1 is WFS1 (Wolframin ER Transmembrane Glycoprotein), and among its related pathways/superpathways are Metabolism of proteins and Parkinson disease. The drugs Acetylcysteine and Iron have been mentioned in the context of this disorder. Affiliated tissues include brain, pancreatic islet and testes, and related phenotypes are intellectual disability and behavioral abnormality

Disease Ontology : 12 An autosomal recessive disease that is characterized by diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders and has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the WFS1 gene on chromosome 4p16.1.

UniProtKB/Swiss-Prot : 73 Wolfram syndrome 1: A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses.

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Related Diseases for Wolfram Syndrome 1

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Diseases in the Wolfram Syndrome family:

Wolfram Syndrome 1 Wolfram Syndrome 2
Wolfram-Like Syndrome, Autosomal Dominant Autosomal Dominant Wolfram Syndrome

Diseases related to Wolfram Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 213)
# Related Disease Score Top Affiliating Genes
1 early-onset nuclear cataract 32.2 WFS1 CRYAA
2 rare diabetes mellitus type 2 31.4 WFS1 KCNJ11 IGF2BP2
3 monogenic diabetes 31.4 WFS1 KCNJ11 INS
4 maturity-onset diabetes of the young, type 2 30.4 WFS1 TCF7L2 KCNJ11 INS
5 neonatal diabetes mellitus 30.1 WFS1 TH TCF7L2 KCNJ11 INS
6 deafness, autosomal dominant 6 30.1 WFS1 CISD2
7 mood disorder 29.9 WFS1 TH CRH COMT
8 diabetes insipidus 29.7 WFS1 INS CRH CISD2 AVP
9 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 29.6 XBP1 WFS1 KCNJ11 INS DNAJC3 ATF6
10 pituitary gland disease 29.5 INS CRH AVP
11 anxiety 29.2 TH INS CRH COMT
12 bipolar disorder 29.0 XBP1 WFS1 TH CRH COMT
13 maturity-onset diabetes of the young 28.6 WFS1 THADA TH TCF7L2 KCNJ11 INS
14 diabetes mellitus, noninsulin-dependent 28.2 XBP1 WFS1 THADA TH TCF7L2 KCNJ11
15 diabetes mellitus 27.4 WFS1 TH TCF7L2 KCNJ11 INS IGF2BP2
16 wolfram syndrome 25.1 XBP1 WFS1 TH TCF7L2 SYVN1 PSMA5
17 wolfram-like syndrome, autosomal dominant 12.2
18 cataract 41 12.1
19 insulinoma 11.6
20 cataract 11.6
21 hydronephrosis 11.6
22 diabetes mellitus, type i 11.5
23 autosomal dominant nonsyndromic deafness 11.5
24 nonsyndromic hearing loss 11.5
25 peripheral nervous system disease 11.4
26 optic nerve disease 11.3
27 wolf-hirschhorn syndrome 11.3
28 leber optic atrophy 11.3
29 optic atrophy 4 11.3
30 optic atrophy 5 11.3
31 nonsyndromic deafness 11.3
32 chromosome 4p deletion 11.3
33 maternal uniparental disomy 11.3
34 maternal uniparental disomy of chromosome 4 11.3
35 autosomal dominant wolfram syndrome 11.2
36 laryngomalacia 11.1
37 dandy-walker syndrome 11.1
38 hereditary ataxia 11.1
39 leber plus disease 11.1
40 diaphragmatic eventration 11.1
41 rare genetic deafness 11.1
42 cleft palate, isolated 11.0
43 diabetes insipidus, neurohypophyseal 11.0
44 duane retraction syndrome 1 11.0
45 waardenburg syndrome, type 1 11.0
46 marden-walker syndrome 11.0
47 night blindness, congenital stationary, type 1a 11.0
48 deafness, autosomal dominant 9 11.0
49 optic atrophy 7 with or without auditory neuropathy 11.0
50 deafness, autosomal dominant 54 11.0

Graphical network of the top 20 diseases related to Wolfram Syndrome 1:



Diseases related to Wolfram Syndrome 1
Sources

Symptoms & Phenotypes for Wolfram Syndrome 1

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Human phenotypes related to Wolfram Syndrome 1:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 behavioral abnormality 31 HP:0000708
3 sensorineural hearing impairment 31 HP:0000407
4 optic atrophy 31 HP:0000648
5 hypothyroidism 31 HP:0000821
6 dysphagia 31 HP:0002015
7 ataxia 31 HP:0001251
8 nystagmus 31 HP:0000639
9 tremor 31 HP:0001337
10 growth delay 31 HP:0001510
11 ptosis 31 HP:0000508
12 thrombocytopenia 31 HP:0001873
13 diabetes insipidus 31 HP:0000873
14 diabetes mellitus 31 HP:0000819
15 dysarthria 31 HP:0001260
16 hydronephrosis 31 HP:0000126
17 testicular atrophy 31 HP:0000029
18 hydroureter 31 HP:0000072
19 cardiomyopathy 31 HP:0001638
20 cerebral atrophy 31 HP:0002059
21 pigmentary retinopathy 31 HP:0000580
22 megaloblastic anemia 31 HP:0001889
23 neurogenic bladder 31 HP:0000011
24 stroke-like episode 31 HP:0002401
25 seizure 31 HP:0001250
26 sideroblastic anemia 31 HP:0001924
27 limited mobility of proximal interphalangeal joint 31 HP:0006217

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
dysphagia
ataxia
tremor
dysarthria
more
Endocrine Features:
hypothyroidism
diabetes insipidus
diabetes mellitus

Genitourinary Internal Genitalia Male:
testicular atrophy

Cardiovascular Heart:
cardiomyopathy

Skeletal Hands:
limited mobility of proximal interphalangeal joint

Head And Neck Ears:
hearing loss, sensorineural

Head And Neck Eyes:
optic atrophy
nystagmus
ptosis
pigmentary retinopathy

Genitourinary Kidneys:
hydronephrosis

Genitourinary Ureters:
hydroureter

Genitourinary Bladder:
neurogenic bladder

Growth Other:
growth retardation

Clinical features from OMIM:

222300

UMLS symptoms related to Wolfram Syndrome 1:


seizures, ataxia, tremor

MGI Mouse Phenotypes related to Wolfram Syndrome 1:

45 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.32 AVP CDC123 CDKAL1 CISD2 COMT CRH
2 homeostasis/metabolism MP:0005376 10.24 ATF6 AVP CDKAL1 CISD2 COMT CRH
3 growth/size/body region MP:0005378 10.22 ATF6 CDKAL1 CISD2 CRH DNAJC3 HSPA5
4 endocrine/exocrine gland MP:0005379 10.21 ATF6 CDKAL1 CISD2 COMT CRH DNAJC3
5 adipose tissue MP:0005375 10.19 CDKAL1 CISD2 CRH DNAJC3 HSPA5 IGF2BP2
6 integument MP:0010771 10.1 CDC123 CDKAL1 CISD2 CRH HSPA5 IGF2BP2
7 digestive/alimentary MP:0005381 10 CISD2 DNAJC3 HSPA5 INS TCF7L2 WFS1
8 mortality/aging MP:0010768 10 ATF6 AVP CDC123 CISD2 DNAJC3 HSPA5
9 liver/biliary system MP:0005370 9.86 ATF6 CDKAL1 CRH IGF2BP2 INS TCF7L2
10 nervous system MP:0003631 9.7 AVP CISD2 COMT CRH DNAJC3 HSPA5
11 renal/urinary system MP:0005367 9.23 AVP CISD2 COMT CRH DNAJC3 HSPA5
Sources

Drugs & Therapeutics for Wolfram Syndrome 1

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Drugs for Wolfram Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 36)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
2
Iron Approved, Experimental Phase 2, Phase 3 15438-31-0, 7439-89-6 27284 23925
3
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5 Hormones Phase 2, Phase 3
6 Hypoglycemic Agents Phase 2, Phase 3
7 Hormone Antagonists Phase 2, Phase 3
8 Incretins Phase 2, Phase 3
9 Respiratory System Agents Phase 2, Phase 3
10 Antidotes Phase 2, Phase 3
11 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
12 Antioxidants Phase 2, Phase 3
13 Chelating Agents Phase 2, Phase 3
14 Anti-Infective Agents Phase 2, Phase 3
15
protease inhibitors Phase 2, Phase 3
16 Antiviral Agents Phase 2, Phase 3
17 Iron Chelating Agents Phase 2, Phase 3
18 HIV Protease Inhibitors Phase 2, Phase 3
19 Sitagliptin Phosphate Phase 2, Phase 3
20 Protective Agents Phase 2, Phase 3
21 Expectorants Phase 2, Phase 3
22 N-monoacetylcystine Phase 2, Phase 3
23
Dantrolene Approved, Investigational Phase 1, Phase 2 7261-97-4 6914273 2952
24
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
25 Psychotropic Drugs Phase 2
26 Anticonvulsants Phase 2
27 Neurotransmitter Agents Phase 2
28
Exenatide Approved, Investigational 141758-74-9 15991534
29 Anti-Obesity Agents
30 Glucagon-Like Peptide 1
31 Arginine Vasopressin
32 Immunoglobulins
33 Antibodies
34 Autoantibodies
35 Insulin, Globin Zinc
36 insulin

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy Unknown status NCT02882477 Phase 2, Phase 3 Deferiprone;Acetylcysteine;Sitagliptin and Metformin
2 A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
3 A Pivotal, International, Randomised, Double-blind, Efficacy and Safety Trial of Sodium Valproate, in Paediatric and Adult Patients With Wolfram Syndrome Recruiting NCT03717909 Phase 2 Sodium Valproate 200Mg E/C Tablet;Sodium Valproate matched placebo
4 GLP Analogs for Diabetes in Wolfram Syndrome Patients Unknown status NCT01302327 Exenatide
5 Tracking Neurodegeneration in Early Wolfram Syndrome Completed NCT02455414
6 Constitution of a Cohort of Families With Monogenic Diabetes to Identify Novel Causes of Non Auto-immune Diabetes Mellitus in Children and Young Adults Completed NCT02634229
7 Evaluation of Genetic, Biochemical and Clinical Determinants of Type 2 Diabetes Progression in Subjects at High Risk Completed NCT00879801
8 International Tracking Neurodegeneration in Early Wolfram Syndrome Recruiting NCT03951298
9 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
10 Accurate Diagnosis of Diabetes for Appropriate Management Recruiting NCT03988764
11 Characterization of β-cell Function and Insulin Sensitivity in Pre-transplant Patients With Cystic Fibrosis Not yet recruiting NCT04379726

Search NIH Clinical Center for Wolfram Syndrome 1

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Genetic Tests for Wolfram Syndrome 1

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Genetic tests related to Wolfram Syndrome 1:

# Genetic test Affiliating Genes
1 Diabetes Mellitus and Insipidus with Optic Atrophy and Deafness 29 WFS1
Sources

Anatomical Context for Wolfram Syndrome 1

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MalaCards organs/tissues related to Wolfram Syndrome 1:

40
Brain, Pancreatic Islet, Testes, Kidney, Hypothalamus, Cortex, Heart
Sources

Publications for Wolfram Syndrome 1

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Articles related to Wolfram Syndrome 1:

(show top 50) (show all 475)
# Title Authors PMID Year
1
Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. 61 56 6
21538838 2011
2
WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. 6 56 61
18806274 2008
3
Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. 56 6 61
10521293 1999
4
A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). 6 56 61
9771706 1998
5
Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. 6 56
11260218 2001
6
Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. 6 56
9817917 1998
7
Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. 61 56
23429432 2013
8
Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility. 56 61
22781099 2013
9
Neurologic features and genotype-phenotype correlation in Wolfram syndrome. 56 61
21446023 2011
10
WFS1 Wolfram Syndrome Spectrum Disorder 61 6
20301750 2009
11
Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. 56 61
17568405 2007
12
Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. 61 56
16151413 2005
13
Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. 61 6
15151504 2004
14
Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. 61 56
15070927 2004
15
Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. 6 61
12754709 2003
16
WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. 61 56
11317350 2001
17
Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. 61 6
11295831 2001
18
Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. 61 6
11161832 2001
19
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. 56
10739754 2000
20
Hereditary Hearing Loss and Deafness Overview 6
20301607 1999
21
The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2. 56
9814487 1998
22
Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. 56
9491819 1998
23
Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. 56
9399900 1997
24
Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity. 56
8808601 1996
25
A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome. 56
8601620 1996
26
Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. 56
8602754 1996
27
Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. 56
7987399 1994
28
Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). 56
8383698 1993
29
Wolfram syndrome: evidence of a diffuse neurodegenerative disease by magnetic resonance imaging. 56
1603350 1992
30
Psychiatric disorders in 36 families with Wolfram syndrome. 56
2035720 1991
31
Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD syndrome). A clinical study in two Sudanese families. 56
1872184 1991
32
Psychiatric findings in Wolfram syndrome homozygotes. 56
1975860 1990
33
Treatment of DIDMOAD syndrome with thiamine. 56
2809920 1989
34
Thiamine-responsive anemia in DIDMOAD syndrome. 56
2537896 1989
35
Documented vasopressin deficiency in a child with Wolfram syndrome. 56
3746539 1986
36
Wolfram (DIDMOAD) syndrome: a complex long-term problem in management. 56
3086928 1986
37
A variant of the "DIDMOAD" syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). 56
3081288 1986
38
HLA type and islet cell antibody status in family with (diabetes insipidus and mellitus, optic atrophy, and deafness) DIDMOAD syndrome. 56
6134087 1983
39
Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. 3 cases of 'DIDMOAD' syndrome. 56
931428 1977
40
Diabetes mellitus, diabetes insipidus, and optic atrophy. An autosomal recessive syndrome? 56
881709 1977
41
Juvenile diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, atonia of the urinary tract and bladder, and other abnormalities (Wolfram syndrome). A review of 88 cases from the literature with personal observations on 3 new patients. 56
270276 1977
42
Juvenile diabetes mellitus, optic atrophy, sensory nerve deafness, and diabetes insipidus--a syndrome. 56
956998 1976
43
Recessive inheritance of diabetes: the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness. 56
948548 1976
44
Familial syndrome of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (didmoad) in childhood. 56
1276119 1976
45
Co-existent diabetes mellitus and diabetes insipidus, a familial disease. 56
1206090 1975
46
[Familial syndrome of diabetes mellitus, primary optic nerve atrophy and inner-ear deafness]. 56
4684648 1973
47
Retinal function in an unique syndrome of optic atrophy, juvenile diabetes mellitus, diabetes insipidus, neurosensory hearing loss, autonomic dysfunction, and hyperalanineuria. 56
5046561 1972
48
Familial incidence of juvenile diabets mellitus, progressive optic atrophy, and neurogenic deafness. 56
5069191 1972
49
Association of juvenile diabetes mellitus, primary optic atrophy and perceptive hearing loss in three sibs, with additional idiopathic diabetes mellitus insipidus in one case. 56
5468975 1970
50
Coexistence of diabetes mellitus and insipidus and optic atrophy in two male siblings. Studies and review of literature. 56
5435652 1970
Sources

Variations for Wolfram Syndrome 1

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ClinVar genetic disease variations for Wolfram Syndrome 1:

6 (show top 50) (show all 53) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WFS1 NM_006005.3(WFS1):c.439del (p.Arg147fs)deletion Pathogenic 620589 rs1560408865 4:6290836-6290836 4:6289109-6289109
2 WFS1 NM_006005.3(WFS1):c.1829del (p.Leu610fs)deletion Pathogenic 802051 4:6303350-6303350 4:6301623-6301623
3 WFS1 NM_006005.3(WFS1):c.2007T>G (p.Tyr669Ter)SNV Pathogenic 802052 4:6303529-6303529 4:6301802-6301802
4 WFS1 NM_006005.3(WFS1):c.2224dup (p.Cys742fs)duplication Pathogenic 807719 4:6303745-6303746 4:6302018-6302019
5 WFS1 NM_006005.3(WFS1):c.2638_2643del (p.Asp880_Phe881del)deletion Pathogenic 807720 4:6304156-6304161 4:6302429-6302434
6 WFS1 WFS1, 2-BP DEL, 2812TCdeletion Pathogenic 4507
7 WFS1 WFS1, 15-BP DEL, NT1685deletion Pathogenic 4508
8 WFS1 NM_006005.3(WFS1):c.2084G>T (p.Gly695Val)SNV Pathogenic 4510 rs28937891 4:6303606-6303606 4:6301879-6301879
9 WFS1 NM_006005.3(WFS1):c.1944G>A (p.Trp648Ter)SNV Pathogenic 4511 rs104893879 4:6303466-6303466 4:6301739-6301739
10 WFS1 NM_006005.3(WFS1):c.1511C>T (p.Pro504Leu)SNV Pathogenic 4512 rs28937892 4:6303033-6303033 4:6301306-6301306
11 WFS1 WFS1, 7-BP INS, NT1610insertion Pathogenic 4513
12 WFS1 NM_006005.3(WFS1):c.1385_1393del (p.Glu462_Thr464del)deletion Pathogenic 4514 4:6302902-6302910 4:6301175-6301183
13 WFS1 NM_006005.3(WFS1):c.460+1G>ASNV Pathogenic 4515 4:6290859-6290859 4:6289132-6289132
14 WFS1 NM_006005.3(WFS1):c.676C>T (p.Gln226Ter)SNV Pathogenic 4516 rs104893880 4:6293688-6293688 4:6291961-6291961
15 WFS1 NM_006005.3(WFS1):c.2455C>T (p.Gln819Ter)SNV Pathogenic 4517 rs104893881 4:6303977-6303977 4:6302250-6302250
16 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs)duplication Pathogenic 4519 rs1362648752 4:6290805-6290806 4:6289078-6289079
17 WFS1 WFS1, 16-BP DEL, NT1362deletion Pathogenic 4525
18 WFS1 NM_006005.3(WFS1):c.2119G>T (p.Val707Phe)SNV Pathogenic 30552 rs71524377 4:6303641-6303641 4:6301914-6301914
19 WFS1 WFS1, 8-BP DEL, NT2106deletion Pathogenic 30553
20 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val)SNV Pathogenic 30556 rs387906930 4:6303573-6303573 4:6301846-6301846
21 WFS1 WFS1, 3-BP DEL, VAL415DELdeletion Pathogenic 30557
22 WFS1 WFS1, 4-BP DEL, 1387CTCTdeletion Pathogenic 30558
23 WFS1 NM_006005.3(WFS1):c.124C>T (p.Arg42Ter)SNV Pathogenic/Likely pathogenic 189251 rs71530923 4:6279306-6279306 4:6277579-6277579
24 WFS1 NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs)deletion Pathogenic/Likely pathogenic 209207 rs797045076 4:6304168-6304171 4:6302441-6302444
25 WFS1 NM_006005.3(WFS1):c.568_570AAG[3] (p.Lys193del)short repeat Likely pathogenic 623222 rs752461187 4:6293031-6293033 4:6291304-6291306
26 WFS1 NM_006005.3(WFS1):c.2263T>C (p.Cys755Arg)SNV Likely pathogenic 209206 rs797045075 4:6303785-6303785 4:6302058-6302058
27 WFS1 NM_006005.3(WFS1):c.1235T>C (p.Val412Ala)SNV Conflicting interpretations of pathogenicity 215387 rs144951440 4:6302757-6302757 4:6301030-6301030
28 WFS1 NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser)SNV Conflicting interpretations of pathogenicity 215389 rs113446173 4:6302893-6302893 4:6301166-6301166
29 WFS1 NM_006005.3(WFS1):c.1610G>A (p.Cys537Tyr)SNV Conflicting interpretations of pathogenicity 215390 rs199910987 4:6303132-6303132 4:6301405-6301405
30 WFS1 NM_006005.3(WFS1):c.683G>A (p.Arg228His)SNV Conflicting interpretations of pathogenicity 198190 rs150771247 4:6293695-6293695 4:6291968-6291968
31 WFS1 NM_006005.3(WFS1):c.2452C>T (p.Arg818Cys)SNV Conflicting interpretations of pathogenicity 130748 rs35932623 4:6303974-6303974 4:6302247-6302247
32 WFS1 NM_006005.3(WFS1):c.1294C>G (p.Leu432Val)SNV Conflicting interpretations of pathogenicity 137913 rs35031397 4:6302816-6302816 4:6301089-6301089
33 WFS1 NM_006005.3(WFS1):c.2209G>A (p.Glu737Lys)SNV Conflicting interpretations of pathogenicity 143132 rs147834269 4:6303731-6303731 4:6302004-6302004
34 WFS1 NM_006005.3(WFS1):c.716A>G (p.Lys239Arg)SNV Uncertain significance 166574 rs727503747 4:6296771-6296771 4:6295044-6295044
35 WFS1 NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys)SNV Uncertain significance 178597 rs201064551 4:6303479-6303479 4:6301752-6301752
36 WFS1 NM_006005.3(WFS1):c.1396G>A (p.Gly466Ser)SNV Uncertain significance 166589 rs727503750 4:6302918-6302918 4:6301191-6301191
37 WFS1 NM_006005.3(WFS1):c.2029G>A (p.Ala677Thr)SNV Uncertain significance 198834 rs757027394 4:6303551-6303551 4:6301824-6301824
38 WFS1 NM_006005.3(WFS1):c.728C>T (p.Ala243Val)SNV Uncertain significance 215381 rs147147660 4:6296783-6296783 4:6295056-6295056
39 WFS1 NM_006005.3(WFS1):c.817G>A (p.Glu273Lys)SNV Uncertain significance 215382 rs142428158 4:6296872-6296872 4:6295145-6295145
40 WFS1 NM_006005.3(WFS1):c.1167T>G (p.Asp389Glu)SNV Uncertain significance 215385 rs201282601 4:6302689-6302689 4:6300962-6300962
41 WFS1 NM_006005.3(WFS1):c.1724C>G (p.Ala575Gly)SNV Uncertain significance 440419 rs71524360 4:6303246-6303246 4:6301519-6301519
42 WFS1 NM_006005.3(WFS1):c.1124G>A (p.Arg375His)SNV Uncertain significance 504709 rs142671083 4:6302646-6302646 4:6300919-6300919
43 WFS1 NM_006005.3(WFS1):c.2171C>T (p.Pro724Leu)SNV Uncertain significance 4509 rs28937890 4:6303693-6303693 4:6301966-6301966
44 WFS1 NM_006005.3(WFS1):c.1633G>A (p.Val545Met)SNV Uncertain significance 215391 rs201993978 4:6303155-6303155 4:6301428-6301428
45 WFS1 NM_006005.3(WFS1):c.535G>A (p.Ala179Thr)SNV Uncertain significance 229647 rs776685250 4:6292998-6292998 4:6291271-6291271
46 WFS1 NM_006005.3(WFS1):c.1079G>A (p.Cys360Tyr)SNV Uncertain significance 374398 rs147157374 4:6302601-6302601 4:6300874-6300874
47 WFS1 NM_006005.3(WFS1):c.2191A>G (p.Met731Val)SNV Uncertain significance 374399 rs144010362 4:6303713-6303713 4:6301986-6301986
48 WFS1 NM_006005.3(WFS1):c.1538A>C (p.Tyr513Ser)SNV Uncertain significance 215412 rs544933961 4:6303060-6303060 4:6301333-6301333
49 WFS1 NM_006005.3(WFS1):c.712+16G>ASNV Benign/Likely benign 215380 rs71524367 4:6293740-6293740 4:6292013-6292013
50 WFS1 NM_006005.3(WFS1):c.482G>A (p.Arg161Gln)SNV Benign/Likely benign 137911 rs115346085 4:6292945-6292945 4:6291218-6291218

UniProtKB/Swiss-Prot genetic disease variations for Wolfram Syndrome 1:

73 (show all 22)
# Symbol AA change Variation ID SNP ID
1 WFS1 p.Pro504Leu VAR_005842 rs28937892
2 WFS1 p.Gly695Val VAR_005844 rs28937891
3 WFS1 p.Pro724Leu VAR_005845 rs28937890
4 WFS1 p.Glu169Lys VAR_009109 rs148953711
5 WFS1 p.Pro292Ser VAR_009110 rs746923441
6 WFS1 p.Ile296Ser VAR_009111
7 WFS1 p.Gly437Arg VAR_009114 rs147974629
8 WFS1 p.Cys690Arg VAR_009116 rs754373473
9 WFS1 p.Trp700Cys VAR_009117
10 WFS1 p.Gly736Ser VAR_009118 rs71532864
11 WFS1 p.Pro885Leu VAR_009119 rs372855769
12 WFS1 p.Ala58Val VAR_011305 rs369671890
13 WFS1 p.Ala126Thr VAR_011306 rs145639028
14 WFS1 p.Ser443Ile VAR_011308
15 WFS1 p.Gly780Arg VAR_011313
16 WFS1 p.Arg818Cys VAR_011314 rs35932623
17 WFS1 p.Ala133Thr VAR_014034 rs372249044
18 WFS1 p.Tyr669Cys VAR_014038 rs140299920
19 WFS1 p.Tyr110Asn VAR_029499
20 WFS1 p.Arg457Ser VAR_029502 rs113446173
21 WFS1 p.Arg629Trp VAR_029505 rs71530910
22 WFS1 p.Arg558Cys VAR_068343 rs199946797

Sources

Expression for Wolfram Syndrome 1

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Search GEO for disease gene expression data for Wolfram Syndrome 1.
Sources

Pathways for Wolfram Syndrome 1

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Pathways related to Wolfram Syndrome 1 according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Metabolism of proteins 65
Show member pathways
 13.51 XBP1 WFS1 TCF7L2 SYVN1 PSMA5 INS
2
Parkinson disease 36
Show member pathways
 12.76 XBP1 TH PSMA5 INS HSPA5 ATF6
3
Aldosterone synthesis and secretion 36
Show member pathways
 12.62 TCF7L2 KCNJ11 INS HSPA5 CRH
4
Glucose / Energy Metabolism 4
12.27 WFS1 INS CISD2 ATF6
5
Unfolded Protein Response (UPR) 65
Show member pathways
 11.99 XBP1 WFS1 SYVN1 HSPA5 DNAJC3 ATF6
6
Translational Control 4
11.84 XBP1 IGF2BP2 HSPA5 DNAJC3
7
Regulation of degradation of deltaF508 CFTR in CF 22
Show member pathways
 11.58 PSMA5 HSPA5 CRYAA
8
Protein processing in endoplasmic reticulum 36
11.39 XBP1 WFS1 SYVN1 HSPA5 DNAJC3 CRYAA
9
Antipsychotics Pathway (Metabolic Side Effects), Pharmacodynamics 60
10.8 TH INS
10
Photodynamic therapy-induced unfolded protein response 1
10.72 XBP1 HSPA5 DNAJC3 ATF6
11
Dopamine metabolism 1
10.51 TH COMT
Sources

GO Terms for Wolfram Syndrome 1

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Cellular components related to Wolfram Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.81 XBP1 WFS1 SYVN1 KCNJ11 HSPA5 DNAJC3
2 endoplasmic reticulum membrane GO:0005789 9.8 XBP1 WFS1 SYVN1 HSPA5 CISD2 CDKAL1
3 endoplasmic reticulum lumen GO:0005788 9.62 WFS1 INS HSPA5 DNAJC3
4 integral component of endoplasmic reticulum membrane GO:0030176 9.35 XBP1 WFS1 SYVN1 HSPA5 ATF6
5 smooth endoplasmic reticulum GO:0005790 8.92 TH SYVN1 HSPA5 DNAJC3

Biological processes related to Wolfram Syndrome 1 according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.98 XBP1 INS CRH CDC123 AVP
2 negative regulation of apoptotic process GO:0043066 9.97 XBP1 HSPA5 DNAJC3 CRYAA AVP
3 response to drug GO:0042493 9.9 TH KCNJ11 CRH COMT
4 glucose homeostasis GO:0042593 9.8 WFS1 TCF7L2 INS
5 response to ethanol GO:0045471 9.78 TH CRH AVP
6 visual perception GO:0007601 9.76 WFS1 TH CRYAA ATF6
7 response to endoplasmic reticulum stress GO:0034976 9.74 WFS1 HSPA5 DNAJC3
8 ubiquitin-dependent ERAD pathway GO:0030433 9.67 WFS1 SYVN1 HSPA5
9 cellular response to glucose stimulus GO:0071333 9.65 XBP1 TH KCNJ11
10 response to pain GO:0048265 9.63 CRH COMT
11 synaptic transmission, dopaminergic GO:0001963 9.62 TH CRH
12 response to corticosterone GO:0051412 9.62 TH CRH
13 multicellular organism aging GO:0010259 9.61 TH CISD2
14 proteolysis involved in cellular protein catabolic process GO:0051603 9.61 PSMA5 HSPA5 DNAJC3
15 fatty acid homeostasis GO:0055089 9.59 XBP1 INS
16 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990440 9.56 HSPA5 ATF6
17 response to unfolded protein GO:0006986 9.56 XBP1 HSPA5 DNAJC3 ATF6
18 protein folding in endoplasmic reticulum GO:0034975 9.55 HSPA5 DNAJC3
19 ER overload response GO:0006983 9.54 WFS1 HSPA5
20 cellular response to nicotine GO:0071316 9.52 TH KCNJ11
21 cellular response to manganese ion GO:0071287 9.51 TH HSPA5
22 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.5 XBP1 WFS1 SYVN1
23 negative regulation of type B pancreatic cell apoptotic process GO:2000675 9.4 WFS1 TCF7L2
24 response to ether GO:0045472 9.37 TH CRH
25 IRE1-mediated unfolded protein response GO:0036498 9.35 XBP1 WFS1 SYVN1 HSPA5 DNAJC3
26 ATF6-mediated unfolded protein response GO:0036500 9.33 XBP1 HSPA5 ATF6
27 endoplasmic reticulum unfolded protein response GO:0030968 9.02 XBP1 WFS1 SYVN1 HSPA5 ATF6

Molecular functions related to Wolfram Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.58 XBP1 WFS1 THADA TH TCF7L2 SYVN1
2 hormone activity GO:0005179 9.33 INS CRH AVP
3 chaperone binding GO:0051087 9.13 SYVN1 HSPA5 DNAJC3
Sources

Sources for Wolfram Syndrome 1

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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