WFS1
MCID: WLF013
MIFTS: 60

Wolfram Syndrome 1 (WFS1)

Categories: Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Wolfram Syndrome 1

MalaCards integrated aliases for Wolfram Syndrome 1:

Name: Wolfram Syndrome 1 57 12 72 29 6 15
Didmoad 57 12 72
Wfs1 57 12 72
Wfs 57 72
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness; Didmoad 57
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness Syndrome 72
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness 57
Diabetes Mellitus and Insipidus with Optic Atrophy and Deafness 12
Syndrome, Wolfram, Type 1 39
Wolfram Syndrome 70

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
wolfram syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Wolfram Syndrome 1

OMIM® : 57 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) (Updated 05-Apr-2021)

MalaCards based summary : Wolfram Syndrome 1, also known as didmoad, is related to wolfram-like syndrome, autosomal dominant and polyneuropathy due to drug, 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 Prion disease. The drugs Acetylcysteine and Metformin have been mentioned in the context of this disorder. Affiliated tissues include brain, hypothalamus and cortex, and related phenotypes are intellectual disability and ptosis

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 : 72 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.

Related Diseases for Wolfram Syndrome 1

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 189)
# Related Disease Score Top Affiliating Genes
1 wolfram-like syndrome, autosomal dominant 32.5 WFS1 HERC2
2 polyneuropathy due to drug 31.3 WFS1 COMT
3 permanent neonatal diabetes mellitus 31.1 WFS1 TCF7L2 KCNJ11
4 diabetes insipidus 30.6 WFS1 CRH CISD2 AVP
5 deafness, autosomal dominant 6 30.2 WFS1 CISD2
6 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 30.1 XBP1 WFS1 KCNJ11 HSPA5 DNAJC3 ATF6
7 mood disorder 30.0 WFS1 TH CRH COMT
8 type 2 diabetes mellitus 29.9 WFS1 TCF7L2 KCNJ11 IGF2BP2 HHEX DNAJC3
9 maturity-onset diabetes of the young 29.6 WFS1 TH TCF7L2 KCNJ11 IGF2BP2 HHEX
10 bipolar disorder 29.3 XBP1 WFS1 TH CRH COMT
11 diabetes mellitus 27.4 WFS1 TH TCF7L2 KCNJ11 IGF2BP2 HSPA5
12 wolfram syndrome 26.4 XBP1 WFS1 TH TCF7L2 SYVN1 PSMA5
13 cataract 41 11.2
14 cataract 11.1
15 insulinoma 11.1
16 neuropathy 11.1
17 type 1 diabetes mellitus 11.0
18 autosomal dominant nonsyndromic deafness 11.0
19 hydronephrosis 11.0
20 nonsyndromic hearing loss 11.0
21 waterhouse-friderichsen syndrome 10.9
22 leber plus disease 10.9
23 autosomal dominant wolfram syndrome 10.9
24 optic nerve disease 10.8
25 peripheral nervous system disease 10.8
26 wolf-hirschhorn syndrome 10.8
27 leber hereditary optic neuropathy, modifier of 10.8
28 optic atrophy 4 10.8
29 optic atrophy 5 10.8
30 nonsyndromic deafness 10.8
31 chromosome 4p deletion 10.8
32 maternal uniparental disomy 10.8
33 maternal uniparental disomy of chromosome 4 10.8
34 diabetes insipidus, neurohypophyseal 10.8
35 maturity-onset diabetes of the young, type 2 10.8
36 laryngomalacia 10.8
37 waardenburg syndrome, type 1 10.8
38 dandy-walker syndrome 10.8
39 deafness, autosomal dominant 9 10.8
40 type 1 diabetes mellitus 15 10.8
41 deafness, autosomal recessive 18a 10.8
42 optic atrophy 7 with or without auditory neuropathy 10.8
43 deafness, autosomal dominant 54 10.8
44 optic atrophy 8 10.8
45 usher syndrome 10.8
46 diaphragmatic eventration 10.8
47 auditory system disease 10.8
48 inner ear disease 10.8
49 cranial nerve disease 10.8
50 night blindness 10.8

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



Diseases related to Wolfram Syndrome 1

Symptoms & Phenotypes for Wolfram Syndrome 1

Human phenotypes related to Wolfram Syndrome 1:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 ptosis 31 HP:0000508
3 nystagmus 31 HP:0000639
4 ataxia 31 HP:0001251
5 dysarthria 31 HP:0001260
6 tremor 31 HP:0001337
7 dysphagia 31 HP:0002015
8 diabetes mellitus 31 HP:0000819
9 hypothyroidism 31 HP:0000821
10 behavioral abnormality 31 HP:0000708
11 sensorineural hearing impairment 31 HP:0000407
12 optic atrophy 31 HP:0000648
13 growth delay 31 HP:0001510
14 thrombocytopenia 31 HP:0001873
15 diabetes insipidus 31 HP:0000873
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®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
dysarthria
tremor
dysphagia
more
Endocrine Features:
diabetes mellitus
hypothyroidism
diabetes insipidus

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:
ptosis
nystagmus
optic atrophy
pigmentary retinopathy

Genitourinary Kidneys:
hydronephrosis

Genitourinary Ureters:
hydroureter

Genitourinary Bladder:
neurogenic bladder

Growth Other:
growth retardation

Clinical features from OMIM®:

222300 (Updated 05-Apr-2021)

UMLS symptoms related to Wolfram Syndrome 1:


seizures; ataxia; tremor

MGI Mouse Phenotypes related to Wolfram Syndrome 1:

46 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.34 AVP CDC123 CDKAL1 CISD2 COMT CRH
2 homeostasis/metabolism MP:0005376 10.33 ATF6 AVP CDC123 CDKAL1 CISD2 COMT
3 growth/size/body region MP:0005378 10.28 ATF6 CDKAL1 CISD2 CRH DNAJC3 HERC2
4 endocrine/exocrine gland MP:0005379 10.27 ATF6 CDKAL1 CISD2 COMT CRH DNAJC3
5 cellular MP:0005384 10.22 ATF6 CDKAL1 CISD2 CRH HERC2 HHEX
6 adipose tissue MP:0005375 10.16 CDKAL1 CISD2 CRH DNAJC3 HERC2 IGF2BP2
7 mortality/aging MP:0010768 10.13 ATF6 AVP CDC123 CISD2 DNAJC3 HERC2
8 integument MP:0010771 10.11 CDC123 CDKAL1 CISD2 CRH HSPA5 IGF2BP2
9 nervous system MP:0003631 9.93 AVP CISD2 COMT CRH DNAJC3 HERC2
10 liver/biliary system MP:0005370 9.92 ATF6 CDKAL1 CRH HHEX IGF2BP2 TCF7L2
11 renal/urinary system MP:0005367 9.56 AVP CISD2 COMT CRH DNAJC3 HSPA5
12 respiratory system MP:0005388 9.23 AVP CISD2 COMT CRH HHEX HSPA5

Drugs & Therapeutics for Wolfram Syndrome 1

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
Metformin Approved Phase 2, Phase 3 657-24-9 4091 14219
3
Iron Approved Phase 2, Phase 3 7439-89-6 23925 29936
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5 Antidotes Phase 2, Phase 3
6 Chelating Agents Phase 2, Phase 3
7 Respiratory System Agents Phase 2, Phase 3
8 Protective Agents Phase 2, Phase 3
9 Hormone Antagonists Phase 2, Phase 3
10 Incretins Phase 2, Phase 3
11 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
12 Hormones Phase 2, Phase 3
13 Sitagliptin Phosphate Phase 2, Phase 3
14 Expectorants Phase 2, Phase 3
15 Iron Chelating Agents Phase 2, Phase 3
16 Antioxidants Phase 2, Phase 3
17
protease inhibitors Phase 2, Phase 3
18 Hypoglycemic Agents Phase 2, Phase 3
19 Antiviral Agents Phase 2, Phase 3
20 HIV Protease Inhibitors Phase 2, Phase 3
21 Anti-Infective Agents Phase 2, Phase 3
22 N-monoacetylcystine Phase 2, Phase 3
23
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
24
Dantrolene Approved, Investigational Phase 1, Phase 2 7261-97-4 2952 6914273
25 Psychotropic Drugs Phase 2
26 Neurotransmitter Agents Phase 2
27 Anticonvulsants Phase 2
28
Exenatide Approved, Investigational 141758-74-9 15991534
29 Glucagon-Like Peptide 1
30 Anti-Obesity Agents
31 insulin
32 Insulin, Globin Zinc
33 Arginine Vasopressin
34 Immunoglobulins
35 Antibodies
36 Autoantibodies

Interventional clinical trials:


# 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 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
3 A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Active, not recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
4 GLP Analogs for Diabetes in Wolfram Syndrome Patients Unknown status NCT01302327 Exenatide
5 Tracking Neurodegeneration in Early Wolfram Syndrome Completed NCT02455414
6 International Tracking Neurodegeneration in Early Wolfram Syndrome Recruiting NCT03951298
7 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
8 Accurate Diagnosis of Diabetes for Appropriate Management Recruiting NCT03988764

Search NIH Clinical Center for Wolfram Syndrome 1

Genetic Tests for Wolfram Syndrome 1

Genetic tests related to Wolfram Syndrome 1:

# Genetic test Affiliating Genes
1 Wolfram Syndrome 1 29 WFS1

Anatomical Context for Wolfram Syndrome 1

MalaCards organs/tissues related to Wolfram Syndrome 1:

40
Brain, Hypothalamus, Cortex, Heart, Kidney, Pancreatic Islet, Bone

Publications for Wolfram Syndrome 1

Articles related to Wolfram Syndrome 1:

(show top 50) (show all 500)
# 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 57 6
21538838 2011
2
WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. 57 6 61
18806274 2008
3
Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. 61 57 6
10521293 1999
4
A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). 6 57 61
9771706 1998
5
Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. 57 6
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. 57 6
9817917 1998
7
Lamination of the Outer Plexiform Layer in Optic Atrophy Caused by Dominant WFS1 Mutations. 61 6
26875006 2016
8
Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms in WFS1. 61 6
26435059 2015
9
Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. 6 61
25211237 2014
10
Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. 61 57
23429432 2013
11
Phenotypic characteristics of early Wolfram syndrome. 61 6
23981289 2013
12
Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility. 61 57
22781099 2013
13
Wolfram syndrome: new mutations, different phenotype. 61 6
22238590 2012
14
Neurologic features and genotype-phenotype correlation in Wolfram syndrome. 57 61
21446023 2011
15
Congenital cataracts in two siblings with Wolfram syndrome. 6 61
21067485 2010
16
Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. 61 6
19042979 2009
17
Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. 6 61
18040659 2008
18
Common variants in WFS1 confer risk of type 2 diabetes. 6 61
17603484 2007
19
Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. 57 61
17568405 2007
20
Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. 61 57
16151413 2005
21
Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. 61 6
15151504 2004
22
Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. 57 61
15070927 2004
23
Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. 61 6
12754709 2003
24
WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. 57 61
11317350 2001
25
Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. 61 6
11295831 2001
26
Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. 61 6
11161832 2001
27
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
28
Selective cognitive and psychiatric manifestations in Wolfram Syndrome. 6
26025012 2015
29
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. 57
10739754 2000
30
The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2. 57
9814487 1998
31
Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family. 6
9856492 1998
32
Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. 57
9491819 1998
33
Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. 57
9399900 1997
34
Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity. 57
8808601 1996
35
A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome. 57
8601620 1996
36
Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. 57
8602754 1996
37
Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. 57
7987399 1994
38
Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). 57
8383698 1993
39
Wolfram syndrome: evidence of a diffuse neurodegenerative disease by magnetic resonance imaging. 57
1603350 1992
40
Psychiatric disorders in 36 families with Wolfram syndrome. 57
2035720 1991
41
Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD syndrome). A clinical study in two Sudanese families. 57
1872184 1991
42
Psychiatric findings in Wolfram syndrome homozygotes. 57
1975860 1990
43
Treatment of DIDMOAD syndrome with thiamine. 57
2809920 1989
44
Thiamine-responsive anemia in DIDMOAD syndrome. 57
2537896 1989
45
Documented vasopressin deficiency in a child with Wolfram syndrome. 57
3746539 1986
46
Wolfram (DIDMOAD) syndrome: a complex long-term problem in management. 57
3086928 1986
47
A variant of the "DIDMOAD" syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). 57
3081288 1986
48
HLA type and islet cell antibody status in family with (diabetes insipidus and mellitus, optic atrophy, and deafness) DIDMOAD syndrome. 57
6134087 1983
49
Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. 3 cases of 'DIDMOAD' syndrome. 57
931428 1977
50
Diabetes mellitus, diabetes insipidus, and optic atrophy. An autosomal recessive syndrome? 57
881709 1977

Variations for Wolfram Syndrome 1

ClinVar genetic disease variations for Wolfram Syndrome 1:

6 (show top 50) (show all 68)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WFS1 WFS1, 2-BP DEL, 2812TC Deletion Pathogenic 4507 GRCh37:
GRCh38:
2 WFS1 WFS1, 15-BP DEL, NT1685 Deletion Pathogenic 4508 GRCh37:
GRCh38:
3 WFS1 NM_006005.3(WFS1):c.2171C>T (p.Pro724Leu) SNV Pathogenic 4509 rs28937890 GRCh37: 4:6303693-6303693
GRCh38: 4:6301966-6301966
4 WFS1 NM_006005.3(WFS1):c.2084G>T (p.Gly695Val) SNV Pathogenic 4510 rs28937891 GRCh37: 4:6303606-6303606
GRCh38: 4:6301879-6301879
5 WFS1 NM_006005.3(WFS1):c.1944G>A (p.Trp648Ter) SNV Pathogenic 4511 rs104893879 GRCh37: 4:6303466-6303466
GRCh38: 4:6301739-6301739
6 WFS1 NM_006005.3(WFS1):c.1511C>T (p.Pro504Leu) SNV Pathogenic 4512 rs28937892 GRCh37: 4:6303033-6303033
GRCh38: 4:6301306-6301306
7 WFS1 WFS1, 7-BP INS, NT1610 Insertion Pathogenic 4513 GRCh37:
GRCh38:
8 WFS1 NM_006005.3(WFS1):c.1385_1393del (p.Glu462_Thr464del) Deletion Pathogenic 4514 rs1578609780 GRCh37: 4:6302902-6302910
GRCh38: 4:6301175-6301183
9 WFS1 NM_006005.3(WFS1):c.460+1G>A SNV Pathogenic 4515 rs1191510461 GRCh37: 4:6290859-6290859
GRCh38: 4:6289132-6289132
10 WFS1 NM_006005.3(WFS1):c.676C>T (p.Gln226Ter) SNV Pathogenic 4516 rs104893880 GRCh37: 4:6293688-6293688
GRCh38: 4:6291961-6291961
11 WFS1 NM_006005.3(WFS1):c.2455C>T (p.Gln819Ter) SNV Pathogenic 4517 rs104893881 GRCh37: 4:6303977-6303977
GRCh38: 4:6302250-6302250
12 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs) Duplication Pathogenic 4519 rs1362648752 GRCh37: 4:6290805-6290806
GRCh38: 4:6289078-6289079
13 WFS1 WFS1, 16-BP DEL, NT1362 Deletion Pathogenic 4525 GRCh37:
GRCh38:
14 WFS1 NM_006005.3(WFS1):c.2119G>T (p.Val707Phe) SNV Pathogenic 30552 rs71524377 GRCh37: 4:6303641-6303641
GRCh38: 4:6301914-6301914
15 WFS1 WFS1, 8-BP DEL, NT2106 Deletion Pathogenic 30553 GRCh37:
GRCh38:
16 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val) SNV Pathogenic 30556 rs387906930 GRCh37: 4:6303573-6303573
GRCh38: 4:6301846-6301846
17 WFS1 V415del Deletion Pathogenic 30557 GRCh37:
GRCh38:
18 WFS1 WFS1, 4-BP DEL, 1387CTCT Deletion Pathogenic 30558 GRCh37:
GRCh38:
19 WFS1 NM_006005.3(WFS1):c.124C>T (p.Arg42Ter) SNV Pathogenic 189251 rs71530923 GRCh37: 4:6279306-6279306
GRCh38: 4:6277579-6277579
20 WFS1 NM_006005.3(WFS1):c.873C>G (p.Tyr291Ter) SNV Pathogenic 212616 rs777580652 GRCh37: 4:6302395-6302395
GRCh38: 4:6300668-6300668
21 WFS1 NM_006005.3(WFS1):c.2369C>A (p.Ser790Ter) SNV Pathogenic 212614 rs369107336 GRCh37: 4:6303891-6303891
GRCh38: 4:6302164-6302164
22 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs) Duplication Pathogenic 4519 rs1362648752 GRCh37: 4:6290805-6290806
GRCh38: 4:6289078-6289079
23 WFS1 NM_006005.3(WFS1):c.439del (p.Arg147fs) Deletion Pathogenic 620589 rs1560408865 GRCh37: 4:6290836-6290836
GRCh38: 4:6289109-6289109
24 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val) SNV Pathogenic 30556 rs387906930 GRCh37: 4:6303573-6303573
GRCh38: 4:6301846-6301846
25 WFS1 NM_006005.3(WFS1):c.2224dup (p.Cys742fs) Duplication Pathogenic 807719 rs1578612324 GRCh37: 4:6303745-6303746
GRCh38: 4:6302018-6302019
26 WFS1 NM_006005.3(WFS1):c.2638_2643del (p.Asp880_Phe881del) Deletion Pathogenic 807720 rs1272826809 GRCh37: 4:6304156-6304161
GRCh38: 4:6302429-6302434
27 WFS1 NM_006005.3(WFS1):c.1620G>A (p.Trp540Ter) SNV Pathogenic 929945 GRCh37: 4:6303142-6303142
GRCh38: 4:6301415-6301415
28 WFS1 NM_006005.3(WFS1):c.1949_1950del (p.Tyr650fs) Deletion Pathogenic 929946 GRCh37: 4:6303470-6303471
GRCh38: 4:6301743-6301744
29 WFS1 NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs) Deletion Pathogenic 209207 rs797045076 GRCh37: 4:6304168-6304171
GRCh38: 4:6302441-6302444
30 WFS1 NM_006005.3(WFS1):c.1829del (p.Leu610fs) Deletion Pathogenic 802051 rs1578611240 GRCh37: 4:6303350-6303350
GRCh38: 4:6301623-6301623
31 WFS1 NM_006005.3(WFS1):c.2007T>G (p.Tyr669Ter) SNV Pathogenic 802052 rs1443751733 GRCh37: 4:6303529-6303529
GRCh38: 4:6301802-6301802
32 WFS1 NM_006005.3(WFS1):c.2663C>A (p.Ser888Ter) SNV Pathogenic 1031591 GRCh37: 4:6304185-6304185
GRCh38: 4:6302458-6302458
33 WFS1 NM_006005.3(WFS1):c.1610G>A (p.Cys537Tyr) SNV Likely pathogenic 215390 rs199910987 GRCh37: 4:6303132-6303132
GRCh38: 4:6301405-6301405
34 WFS1 NM_006005.3(WFS1):c.320G>A (p.Gly107Glu) SNV Likely pathogenic 982858 GRCh37: 4:6290718-6290718
GRCh38: 4:6288991-6288991
35 WFS1 NM_006005.3(WFS1):c.578dup (p.Gln194fs) Duplication Likely pathogenic 996897 GRCh37: 4:6293039-6293040
GRCh38: 4:6291312-6291313
36 WFS1 NM_006005.3(WFS1):c.568_570AAG[3] (p.Lys193del) Microsatellite Likely pathogenic 623222 rs752461187 GRCh37: 4:6293031-6293033
GRCh38: 4:6291304-6291306
37 WFS1 NM_006005.3(WFS1):c.1237_1239TTC[1] (p.Phe414del) Microsatellite Likely pathogenic 212611 rs797046112 GRCh37: 4:6302757-6302759
GRCh38: 4:6301030-6301032
38 WFS1 NM_006005.3(WFS1):c.1692_1697CCTCTT[1] (p.565_566LF[1]) Microsatellite Likely pathogenic 212612 rs797046113 GRCh37: 4:6303211-6303216
GRCh38: 4:6301484-6301489
39 WFS1 NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys) SNV Likely pathogenic 198835 rs199946797 GRCh37: 4:6303194-6303194
GRCh38: 4:6301467-6301467
40 WFS1 NM_006005.3(WFS1):c.2654C>T (p.Pro885Leu) SNV Likely pathogenic 437297 rs372855769 GRCh37: 4:6304176-6304176
GRCh38: 4:6302449-6302449
41 WFS1 NM_006005.3(WFS1):c.2263T>C (p.Cys755Arg) SNV Likely pathogenic 209206 rs797045075 GRCh37: 4:6303785-6303785
GRCh38: 4:6302058-6302058
42 WFS1 NM_006005.3(WFS1):c.2209G>A (p.Glu737Lys) SNV Conflicting interpretations of pathogenicity 143132 rs147834269 GRCh37: 4:6303731-6303731
GRCh38: 4:6302004-6302004
43 WFS1 NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys) SNV Uncertain significance 178597 rs201064551 GRCh37: 4:6303479-6303479
GRCh38: 4:6301752-6301752
44 WFS1 NM_006005.3(WFS1):c.535G>A (p.Ala179Thr) SNV Uncertain significance 229647 rs776685250 GRCh37: 4:6292998-6292998
GRCh38: 4:6291271-6291271
45 WFS1 NM_006005.3(WFS1):c.716A>G (p.Lys239Arg) SNV Uncertain significance 166574 rs727503747 GRCh37: 4:6296771-6296771
GRCh38: 4:6295044-6295044
46 WFS1 NM_006005.3(WFS1):c.728C>T (p.Ala243Val) SNV Uncertain significance 215381 rs147147660 GRCh37: 4:6296783-6296783
GRCh38: 4:6295056-6295056
47 WFS1 NM_006005.3(WFS1):c.817G>A (p.Glu273Lys) SNV Uncertain significance 215382 rs142428158 GRCh37: 4:6296872-6296872
GRCh38: 4:6295145-6295145
48 WFS1 NM_006005.3(WFS1):c.1079G>A (p.Cys360Tyr) SNV Uncertain significance 374398 rs147157374 GRCh37: 4:6302601-6302601
GRCh38: 4:6300874-6300874
49 WFS1 NM_006005.3(WFS1):c.1124G>A (p.Arg375His) SNV Uncertain significance 504709 rs142671083 GRCh37: 4:6302646-6302646
GRCh38: 4:6300919-6300919
50 WFS1 NM_006005.3(WFS1):c.1396G>A (p.Gly466Ser) SNV Uncertain significance 166589 rs727503750 GRCh37: 4:6302918-6302918
GRCh38: 4:6301191-6301191

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

72 (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

Expression for Wolfram Syndrome 1

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

Pathways for Wolfram Syndrome 1

GO Terms for Wolfram Syndrome 1

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.17 XBP1 TH SYVN1 PSMA5 IGF2BP2 HSPA5
2 cytosol GO:0005829 10.15 XBP1 TH PSMA5 KCNJ11 IGF2BP2 HSPA5
3 endoplasmic reticulum GO:0005783 9.81 XBP1 WFS1 SYVN1 KCNJ11 HSPA5 DNAJC3
4 endoplasmic reticulum membrane GO:0005789 9.8 XBP1 WFS1 SYVN1 HSPA5 CISD2 CDKAL1
5 integral component of endoplasmic reticulum membrane GO:0030176 9.35 XBP1 WFS1 SYVN1 HSPA5 ATF6
6 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 25)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.98 XBP1 HSPA5 DNAJC3 CRYAA AVP
2 response to drug GO:0042493 9.89 TH KCNJ11 CRH COMT
3 visual perception GO:0007601 9.8 WFS1 TH CRYAA ATF6
4 response to ethanol GO:0045471 9.79 TH CRH AVP
5 ubiquitin-dependent ERAD pathway GO:0030433 9.72 WFS1 SYVN1 HSPA5
6 response to unfolded protein GO:0006986 9.69 XBP1 DNAJC3 ATF6
7 response to endoplasmic reticulum stress GO:0034976 9.67 XBP1 WFS1 HSPA5 DNAJC3
8 cellular response to glucose stimulus GO:0071333 9.65 XBP1 TH KCNJ11
9 protein refolding GO:0042026 9.62 HSPA5 CRYAA
10 response to corticosterone GO:0051412 9.61 TH CRH
11 response to pain GO:0048265 9.61 CRH COMT
12 proteolysis involved in cellular protein catabolic process GO:0051603 9.61 PSMA5 HSPA5 DNAJC3
13 multicellular organism aging GO:0010259 9.6 TH CISD2
14 protein folding in endoplasmic reticulum GO:0034975 9.58 HSPA5 DNAJC3
15 synaptic transmission, dopaminergic GO:0001963 9.57 TH CRH
16 ER overload response GO:0006983 9.56 WFS1 HSPA5
17 cellular response to nicotine GO:0071316 9.54 TH KCNJ11
18 cellular response to manganese ion GO:0071287 9.52 TH HSPA5
19 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.5 XBP1 WFS1 SYVN1
20 negative regulation of type B pancreatic cell apoptotic process GO:2000675 9.46 WFS1 TCF7L2
21 endoplasmic reticulum unfolded protein response GO:0030968 9.46 XBP1 WFS1 HSPA5 ATF6
22 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990440 9.43 XBP1 HSPA5 ATF6
23 response to ether GO:0045472 9.4 TH CRH
24 ATF6-mediated unfolded protein response GO:0036500 9.13 XBP1 HSPA5 ATF6
25 IRE1-mediated unfolded protein response GO:0036498 9.02 XBP1 WFS1 SYVN1 HSPA5 DNAJC3

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 10.13 XBP1 WFS1 TH TCF7L2 SYVN1 PSMA5
2 unfolded protein binding GO:0051082 9.5 SYVN1 HSPA5 CRYAA
3 chaperone binding GO:0051087 9.43 SYVN1 HSPA5 DNAJC3
4 transcription regulatory region sequence-specific DNA binding GO:0000976 9.26 XBP1 TCF7L2 HHEX ATF6
5 ubiquitin protein ligase binding GO:0031625 9.02 XBP1 WFS1 HSPA5 HERC2 ATF6

Sources for Wolfram Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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