WFS1

Summary

WFS1 (wolframin ER transmembrane glycoprotein, HGNC:12762) is a protein-coding gene on chromosome 4p16.1, encoding Wolframin (O76024). Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store.

This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 7466 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wolfram-like syndrome (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 2,133 total — 101 pathogenic, 76 likely-pathogenic
• Phenotypes (HPO): 90
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12762
Approved symbol	WFS1
Name	wolframin ER transmembrane glycoprotein
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	DIDMOAD, WFS
Ensembl gene	ENSG00000109501
Ensembl biotype	protein_coding
OMIM	606201
Entrez	7466

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 26 protein_coding, 3 retained_intron

ENST00000226760, ENST00000503569, ENST00000506362, ENST00000506588, ENST00000507765, ENST00000513395, ENST00000673642, ENST00000673991, ENST00000674051, ENST00000682059, ENST00000682275, ENST00000683395, ENST00000684054, ENST00000684087, ENST00000684700, ENST00000852027, ENST00000852028, ENST00000852029, ENST00000852030, ENST00000938520, ENST00000938521, ENST00000956579, ENST00000956580, ENST00000956581, ENST00000956582, ENST00000956583, ENST00000956584, ENST00000956585, ENST00000956586

RefSeq mRNA: 2 — MANE Select: NM_006005 NM_001145853, NM_006005

CCDS: CCDS3386

Canonical transcript exons

ENST00000226760 — 8 exons

Exon	Start	End
ENSE00000701006	6287093	6287175
ENSE00000701011	6288987	6289131
ENSE00001317848	6269850	6270014
ENSE00003467547	6277451	6277687
ENSE00003474648	6300657	6303265
ENSE00003635899	6295041	6295189
ENSE00003648875	6291197	6291367
ENSE00003689853	6291917	6291997

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.1630 / max 316.3252, expressed in 1683 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46769	17.3988	1653
46770	14.5813	1590
46772	0.1025	32
46771	0.0803	20

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right ovary	UBERON:0002118	96.91	gold quality
left ovary	UBERON:0002119	96.61	gold quality
body of uterus	UBERON:0009853	96.48	gold quality
nucleus accumbens	UBERON:0001882	96.44	gold quality
stromal cell of endometrium	CL:0002255	96.29	gold quality
popliteal artery	UBERON:0002250	95.95	gold quality
tibial artery	UBERON:0007610	95.95	gold quality
aorta	UBERON:0000947	95.79	gold quality
ascending aorta	UBERON:0001496	95.71	gold quality
thoracic aorta	UBERON:0001515	95.66	gold quality
right lung	UBERON:0002167	95.50	gold quality
mucosa of stomach	UBERON:0001199	95.49	gold quality
left uterine tube	UBERON:0001303	95.36	gold quality
ovary	UBERON:0000992	95.32	gold quality
right coronary artery	UBERON:0001625	95.24	gold quality
apex of heart	UBERON:0002098	94.89	gold quality
endocervix	UBERON:0000458	94.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.60	gold quality
adenohypophysis	UBERON:0002196	94.51	gold quality
descending thoracic aorta	UBERON:0002345	94.51	gold quality
pituitary gland	UBERON:0000007	94.43	gold quality
left lobe of thyroid gland	UBERON:0001120	94.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.26	gold quality
right lobe of thyroid gland	UBERON:0001119	94.24	gold quality
lower esophagus	UBERON:0013473	94.18	gold quality
coronary artery	UBERON:0001621	94.17	gold quality
left coronary artery	UBERON:0001626	94.11	gold quality
heart left ventricle	UBERON:0002084	94.09	gold quality
cardiac ventricle	UBERON:0002082	93.81	gold quality
caudate nucleus	UBERON:0001873	93.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	16.19
E-CURD-46	yes	9.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
DNAJC3	Repression
HSPA5	Repression

Upstream regulators (CollecTRI, top): ATF6, ESR1, XBP1

miRNA regulators (miRDB)

43 targeting WFS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-361-3P	99.19	66.45	1381

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Five different heterozygous missense mutations (T699M, A716T, V779M, L829P, G831D) in the WFS1 gene found in six low frequency sensorineural hearing loss (LFSNHL) families. (PMID:11709537)
• The causal relationship between WFS1 missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. (PMID:11709538)
• Did not find evidence of an increased incidence of WFS carriers in the suicide panel and concluded that WFS1 carrier status is not a significant contributor to suicide in the general population. (PMID:11920861)
• Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations. (PMID:12073007)
• Four new polymorphisms associated with Wolfram syndrome. Not all patients have full syndrome. (PMID:12107816)
• WFS1 is not a major susceptibility gene for the development of psychiatric disorders in subjects with Wolfram syndrome. (PMID:12605098)
• In all affected family members analysed, we detected a missense mutation in WFS1 (K705N) and therefore confirm the finding that the majority of mutations responsible for LFSNHI are missense mutations which localise to the C-terminal domain of the protein. (PMID:12650912)
• found a significantly higher frequency of the 611R/611R genotype in suicide completers. Scores of impulsivity and novelty seeking were higher in subjects with the associated genotype, suggesting a role for WFS1 in the pathophysiology of impulsive suicide (PMID:12707947)
• mutational analysis of the WFS1 coding region in 19 Italian Wolfram syndrome patients and 25 relatives, using a DHPLC-based protocol (PMID:12754709)
• This study does not support the involvement of tyrosine hydroxylase, catechol-O-methyl transferase and Wolfram syndrome 1 polymorphisms in mood disorders. (PMID:12782971)
• Here we investigate, for the first time, the molecular mechanisms that cause loss-of-function of wolframin in affected individuals. (PMID:12913071)
• Overview of the spectrum of WFS1 mutations in Wolfram syndrome, nonsyndromic low frequency sensorineural hearing impairment,diabetes mellitus, and psychiatric disease. (PMID:12955714)
• Wolframin has a role in the regulation of intracellular Ca2+ homeostasis (PMID:14527944)
• In this study we analyzed the phenotype of a large Hungarian family with LFSNHI and linkage to DFNA6. The family contains 14 affected persons. (PMID:14968315)
• most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified outside this region in exon 4 in patients with Wolfram syndrome (PMID:15277431)
• These results support the hypothesis that the WFS1 gene is involved in the genetic predisposition for mood disorders. (PMID:15473915)
• The relative risk of psychiatric hospitalization for depression was estimated to be 7.1 (95% CI 1.9-26.6) for carriers of a single wolframin mutation compared to noncarriers. (PMID:15852062)
• Mutations in one single gene, Wolfram syndrome 1 (WFS1), have been reported to account for most familial cases with low-frequency hearing loss. (PMID:15912360)
• A nine nucleotide insertional mutation in two members of a family with Wolfram syndrome. (PMID:16005363)
• This study presents a six-generation family from Hungary with nonsyndromic, post-lingual, bilateral, symmetric, progressive LFSNHI, that discloses positive linkage to the DFNA6 region. (PMID:16043233)
• Molecular analysis of WFS1 in seven families with Wolfram syndrome identified eight different mutations; one was a de novo mutation occurring independently in 2 families, whereas the remaining ones were inherited. (PMID:16151413)
• the pathogenesis of Wolfram syndrome involves chronic ER stress in pancreatic beta-cells caused by the loss of function of WFS1 (PMID:16195229)
• Mutations in WFS1 are one cause of non-syndromic low frequency sensorineural hearing loss. (PMID:16408729)
• Missense mutations within a defined region are associated with dominant low-frequency hearing loss (DFNA6/14/38), while more severe mutations spanning WFS1 are found in Wolfram syndrome patients. (PMID:16550584)
• WFS1 mutations lead to drastically reduced steady-state levels of wolframin. (PMID:16806192)
• WFS1 minimal promoter contains two DNA binding motifs (GC boxes) for the transcription factors Sp1/3/4 and binding of both Sp1 and Sp3 was demonstrated at both motifs in vitro and in vivo. (PMID:16965966)
• WFS1 protein participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the ER Ca(2+) store (PMID:16989814)
• one-third (3 out of 9) autosomal dominant low frequency sensorineural hearing loss(LFSNHL) families had mutations in WFS1, indicating that in non-syndromic hearing loss WFS1 is restrictively & commonly found within autosomal dominant LFSNHL families (PMID:17492394)
• a novel heterozygous missense mutation in exon 8 of WFS1 (i.e., Y669H) which is likely responsible for the low-frequency sensorineural hearing loss (LFSNHL) phenotype in a Taiwanese family was discovered (PMID:17517145)
• Results reported eight novel WFS1 mutations in Wolfram syndrome. (PMID:17568405)
• In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with common type 2 diabetes risk. (PMID:17603484)
• The wolframin His611Arg polymorphism influences medication overuse headache. (PMID:17719176)
• Study identifies an interaction between Wolframin and Na+/K+ ATPase beta1 subunit in transfected Cos7 cells, and between endogenous proteins in placental, neuroblastoma and MIN6 pancreatic beta-cell lines. (PMID:17947299)
• Replication of the previously reported associations between SNPs at this locus and the risk of type 2 diabetes. (PMID:18040659)
• Genome-wide association datase revealed that a strong linkage disequilibrium with the three WFS1 single nucleotide polymorphisms was associated with type 2 diabetes. (PMID:18060660)
• May be a candidate gene for type 2 diabetes. (PMID:18197395)
• a novel heterozygous missense mutation in exon 8 of WFS1 predicting a p.R685P amino acid substitution that is likely to underlie the low frequency sensorineural hearing loss phenotype in the American family (PMID:18518985)
• maternally inherited combination of diabetes mellitus and hearing impairment in three members of a family was found to be associated with autosomal dominant transmission of the E864K mutation of the WFS1 gene (PMID:18544103)
• The WFS1 gene is located on the short arm of chromosome 4 in Wolfram syndrome. (PMID:18566338)
• Type 2 diabetes-associated risk alleles of WFS1 are associated with estimates of a decreased pancreatic beta cell function among middle-aged individuals with abnormal glucose regulation (PMID:18568334)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wfs1a	ENSDARG00000062341
danio_rerio	wfs1b	ENSDARG00000074617
mus_musculus	Wfs1	ENSMUSG00000039474
rattus_norvegicus	Wfs1	ENSRNOG00000005108
drosophila_melanogaster	wfs1	FBGN0039003

Protein

Protein identifiers

Wolframin — O76024 (reviewed: O76024)

All UniProt accessions (10): O76024, A0A0S2Z4V6, A0A669KAX3, A0A669KB26, A0A669KBF0, A0A804HIL0, A0A804HIL2, A0A804HK77, A0A804HKM5, H0Y9G5

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store. Negatively regulates the ER stress response and positively regulates the stability of V-ATPase subunits ATP6V1A and ATP1B1 by preventing their degradation through an unknown proteasome-independent mechanism.

Subunit / interactions. Interacts with ATP6V1A.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasmic vesicle. Secretory vesicle.

Tissue specificity. Highly expressed in heart followed by brain, placenta, lung and pancreas. Weakly expressed in liver, kidney and skeletal muscle. Also expressed in islet and beta-cell insulinoma cell line.

Disease relevance. Wolfram syndrome 1 (WFS1) [MIM:222300] A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 6 (DFNA6) [MIM:600965] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA6 is a low-frequency hearing loss in which frequencies of 2000 Hz and below are predominantly affected. Many patients have tinnitus, but there are otherwise no associated features such as vertigo. Because high-frequency hearing is generally preserved, patients retain excellent understanding of speech, although presbycusis or noise exposure may cause high-frequency loss later in life. DFNA6 worsens over time without progressing to profound deafness. The disease is caused by variants affecting the gene represented in this entry. Wolfram-like syndrome autosomal dominant (WFSL) [MIM:614296] A disease characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges. The disease is caused by variants affecting the gene represented in this entry. Cataract 41 (CTRCT41) [MIM:116400] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Arg-456-His, Arg-611-His and Ile-720-Val polymorphisms are in tight linkage disequilibrium with one another and associated with type 1 diabetes in Japanese.

RefSeq proteins (2): NP_001139325, NP_005996* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR026208	Wolframin	Family
IPR026209	Wolframin_fam	Family
IPR045400	Wolframin_Cys-rich	Domain
IPR045458	Wolframin_Sel1-like_rpt	Repeat
IPR045460	Wolframin_EF-hand	Domain
IPR045461	Wolframin_OB_fold	Domain

Pfam: PF19913, PF19914, PF20023, PF20053

UniProt features (89 total): sequence variant 67, transmembrane region 11, modified residue 4, region of interest 2, glycosylation site 2, chain 1, topological domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76024-F1	73.85	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 1, 30, 32, 157

Glycosylation sites (2): 661, 746

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 454 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_BEHAVIOR, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN

GO Biological Process (35): negative regulation of transcription by RNA polymerase II (GO:0000122), kidney development (GO:0001822), renal water homeostasis (GO:0003091), ER overload response (GO:0006983), visual perception (GO:0007601), sensory perception of sound (GO:0007605), negative regulation of translation (GO:0017148), endoplasmic reticulum unfolded protein response (GO:0030968), pancreas development (GO:0031016), positive regulation of protein ubiquitination (GO:0031398), endoplasmic reticulum calcium ion homeostasis (GO:0032469), response to endoplasmic reticulum stress (GO:0034976), ERAD pathway (GO:0036503), olfactory behavior (GO:0042048), glucose homeostasis (GO:0042593), negative regulation of apoptotic process (GO:0043066), negative regulation of programmed cell death (GO:0043069), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of growth (GO:0045927), protein stabilization (GO:0050821), nervous system process (GO:0050877), positive regulation of protein metabolic process (GO:0051247), positive regulation of calcium ion transport (GO:0051928), calcium ion homeostasis (GO:0055074), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236), negative regulation of response to endoplasmic reticulum stress (GO:1903573), negative regulation of ATF6-mediated unfolded protein response (GO:1903892), positive regulation of ERAD pathway (GO:1904294), negative regulation of type B pancreatic cell apoptotic process (GO:2000675), regulation of gene expression (GO:0010468), negative regulation of macromolecule biosynthetic process (GO:0010558), intracellular signal transduction (GO:0035556), negative regulation of intracellular signal transduction (GO:1902532), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243)

GO Molecular Function (8): calmodulin binding (GO:0005516), ubiquitin protein ligase binding (GO:0031625), calcium-dependent protein binding (GO:0048306), ATPase binding (GO:0051117), proteasome binding (GO:0070628), DNA-binding transcription factor binding (GO:0140297), protein carrier activity (GO:0140597), protein binding (GO:0005515)

GO Cellular Component (9): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), secretory granule (GO:0030141), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), membrane (GO:0016020), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	3
endomembrane system	3
animal organ development	2
endoplasmic reticulum	2
protein binding	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
renal system development	1
renal system process	1
multicellular organismal-level water homeostasis	1
ER-nucleus signaling pathway	1
cellular response to biotic stimulus	1
sensory perception of light stimulus	1
sensory perception of mechanical stimulus	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cellular response to unfolded protein	1
intracellular signal transduction	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
intracellular calcium ion homeostasis	1
cellular response to stress	1
proteasomal protein catabolic process	1
response to chemical	1
chemosensory behavior	1
carbohydrate homeostasis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1

Protein interactions and networks

STRING

1694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFS1	CISD2	Q8N5K1	946
WFS1	ATP1B1	P05026	868
WFS1	GJB2	P29033	745
WFS1	ABCC8	Q09428	733
WFS1	DIAPH1	O60610	730
WFS1	CDKAL1	Q5VV42	729
WFS1	KCNJ11	Q14654	721
WFS1	CISD1	Q9NZ45	700
WFS1	SLC30A8	Q8IWU4	697
WFS1	HHEX	Q03014	695
WFS1	GJB6	O95452	694
WFS1	INS	P01308	694
WFS1	OTOF	Q9HC10	691
WFS1	TMC1	Q8TDI8	690
WFS1	TCF7L2	Q9NQB0	670

IntAct

1561 interactions, top by confidence:

A	B	Type	Score
IL18RAP	WFS1	psi-mi:“MI:0915”(physical association)	0.610
TUSC5	WFS1	psi-mi:“MI:0915”(physical association)	0.560
WFS1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
WFS1	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
WFS1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
PLIN2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
AGA	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ALB	WFS1	psi-mi:“MI:0915”(physical association)	0.560
WFS1	ANXA8	psi-mi:“MI:0915”(physical association)	0.560
ANXA5	WFS1	psi-mi:“MI:0915”(physical association)	0.560
AQP8	WFS1	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1B1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1B2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
KIF1A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CASP1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CHD1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CKMT1A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
COMT	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CSTA	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CYB5A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
COCH	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DNASE1L1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DNMT3A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DXO	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DVL3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
WFS1	ESR1	psi-mi:“MI:0915”(physical association)	0.560
MECOM	WFS1	psi-mi:“MI:0915”(physical association)	0.560
EWSR1	WFS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (154): WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Proximity Label-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS), AKT1 (Affinity Capture-Western), WFS1 (Affinity Capture-RNA), CYBA (Co-fractionation), WFS1 (Co-fractionation)

ESM2 similar proteins: A2BD92, A4FV45, A5D7N3, A7S641, B0BN86, D3Z2R5, F1Q930, O76024, O95870, P17152, P97587, Q0IJ20, Q17QW2, Q1JPD2, Q1JPG0, Q2HJ63, Q3B8H3, Q4QQM5, Q5BK13, Q5BLE2, Q5RAS8, Q5RJQ8, Q5SWK7, Q5SYH2, Q5ZLD4, Q66H44, Q6DC66, Q6DF19, Q6GR21, Q6MG55, Q6NRI4, Q6NUQ4, Q6NWH5, Q6ZQE4, Q7L4E1, Q7SZC5, Q7ZW11, Q7ZWF4, Q7ZYA0, Q810L4

Diamond homologs: O76024, P56695

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WFS1	“up-regulates quantity”	ATP1B1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

2133 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	101
Likely pathogenic	76
Uncertain significance	928
Likely benign	417
Benign	105

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071979	NM_006005.3(WFS1):c.1885C>T (p.Arg629Trp)	Pathogenic
1179030	NM_006005.3(WFS1):c.76C>T (p.Arg26Ter)	Pathogenic
1179097	NM_006005.3(WFS1):c.1956C>G (p.Tyr652Ter)	Pathogenic
1185083	NM_006005.3(WFS1):c.1008_1018del (p.Thr337fs)	Pathogenic
1205588	NM_006005.3(WFS1):c.1549del (p.Arg517fs)	Pathogenic
1264330	NM_006005.3(WFS1):c.1107_1108insA (p.Ala370fs)	Pathogenic
1264332	NM_006005.3(WFS1):c.1961C>G (p.Ser654Ter)	Pathogenic
1297721	NM_006005.3(WFS1):c.862-1G>A	Pathogenic
1298954	NM_006005.3(WFS1):c.940T>C (p.Trp314Arg)	Pathogenic
1332693	NM_006005.3(WFS1):c.1180G>T (p.Glu394Ter)	Pathogenic
1403322	NM_006005.3(WFS1):c.2026_2027insA (p.Arg676fs)	Pathogenic
1453615	NM_006005.3(WFS1):c.2205C>G (p.Tyr735Ter)	Pathogenic
1455530	NM_006005.3(WFS1):c.1558C>T (p.Gln520Ter)	Pathogenic
1456386	NM_006005.3(WFS1):c.2099G>A (p.Trp700Ter)	Pathogenic
1458000	NM_006005.3(WFS1):c.1234_1237del (p.Val412fs)	Pathogenic
1458536	NM_006005.3(WFS1):c.2115G>C (p.Lys705Asn)	Pathogenic
1458745	NM_006005.3(WFS1):c.2005T>C (p.Tyr669His)	Pathogenic
1458816	NM_006005.3(WFS1):c.2050G>A (p.Ala684Thr)	Pathogenic
1458820	NM_006005.3(WFS1):c.2311G>C (p.Asp771His)	Pathogenic
1709531	NM_006005.3(WFS1):c.1112G>A (p.Trp371Ter)	Pathogenic
1926713	NM_006005.3(WFS1):c.316-2A>G	Pathogenic
2018930	NM_006005.3(WFS1):c.1670_1671insA (p.Arg558fs)	Pathogenic
2022219	NM_006005.3(WFS1):c.386_398del (p.Trp129fs)	Pathogenic
2034137	NM_006005.3(WFS1):c.784del (p.Ser262fs)	Pathogenic
2044055	NM_006005.3(WFS1):c.13dup (p.Thr5fs)	Pathogenic
2045539	NM_006005.3(WFS1):c.1530C>G (p.Tyr510Ter)	Pathogenic
212614	NM_006005.3(WFS1):c.2369C>A (p.Ser790Ter)	Pathogenic
212616	NM_006005.3(WFS1):c.873C>G (p.Tyr291Ter)	Pathogenic
215406	NM_006005.3(WFS1):c.1243_1245del (p.Val415del)	Pathogenic
215413	NM_006005.3(WFS1):c.2425G>A (p.Glu809Lys)	Pathogenic

SpliceAI

1625 predictions. Top by Δscore:

Variant	Effect	Δscore
4:6270010:GGCCG:G	donor_gain	1.0000
4:6270011:GCCGG:G	donor_gain	1.0000
4:6270014:GGT:G	donor_loss	1.0000
4:6270015:GTGA:G	donor_loss	1.0000
4:6287089:AAAG:A	acceptor_gain	1.0000
4:6288982:TGCA:T	acceptor_loss	1.0000
4:6288983:GCAG:G	acceptor_loss	1.0000
4:6288985:A:AG	acceptor_gain	1.0000
4:6288985:AG:A	acceptor_gain	1.0000
4:6288985:AGGT:A	acceptor_gain	1.0000
4:6288985:AGGTG:A	acceptor_gain	1.0000
4:6288986:G:A	acceptor_loss	1.0000
4:6288986:G:GA	acceptor_gain	1.0000
4:6288986:GG:G	acceptor_gain	1.0000
4:6288986:GGT:G	acceptor_gain	1.0000
4:6288986:GGTG:G	acceptor_gain	1.0000
4:6288986:GGTGG:G	acceptor_gain	1.0000
4:6289129:GAG:G	donor_gain	1.0000
4:6289130:AG:A	donor_loss	1.0000
4:6289131:GGTG:G	donor_loss	1.0000
4:6289132:GT:G	donor_loss	1.0000
4:6289133:T:A	donor_loss	1.0000
4:6291363:GCACG:G	donor_gain	1.0000
4:6291915:A:AG	acceptor_gain	1.0000
4:6291916:G:GG	acceptor_gain	1.0000
4:6291996:GT:G	donor_gain	1.0000
4:6291998:G:GG	donor_gain	1.0000
4:6295032:A:AG	acceptor_gain	1.0000
4:6295033:T:G	acceptor_gain	1.0000
4:6295033:T:TA	acceptor_gain	1.0000

AlphaMissense

5836 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:6301863:T:C	C690R	1.000
4:6301893:T:A	W700R	1.000
4:6301893:T:C	W700R	1.000
4:6291266:G:C	R177P	0.999
4:6300984:T:C	F397L	0.999
4:6300986:C:A	F397L	0.999
4:6300986:C:G	F397L	0.999
4:6301122:A:C	S443R	0.999
4:6301124:C:A	S443R	0.999
4:6301124:C:G	S443R	0.999
4:6301413:T:A	W540R	0.999
4:6301413:T:C	W540R	0.999
4:6301812:T:A	C673S	0.999
4:6301812:T:C	C673R	0.999
4:6301813:G:A	C673Y	0.999
4:6301813:G:C	C673S	0.999
4:6301814:C:G	C673W	0.999
4:6301829:G:C	W678C	0.999
4:6301829:G:T	W678C	0.999
4:6301863:T:A	C690S	0.999
4:6301864:G:A	C690Y	0.999
4:6301864:G:C	C690S	0.999
4:6301865:C:G	C690W	0.999
4:6301873:T:C	L693P	0.999
4:6301888:T:A	V698D	0.999
4:6301895:G:C	W700C	0.999
4:6301895:G:T	W700C	0.999
4:6302206:T:C	L804P	0.999
4:6302295:G:C	G834R	0.999
4:6302296:G:A	G834D	0.999

dbSNP variants (sampled 300 via entrez): RS1000065443 (4:6275324 T>G), RS1000106660 (4:6303546 G>A,C), RS10001190 (4:6282906 A>G,T), RS1000254218 (4:6290811 G>A,T), RS10002743 (4:6274854 G>A,T), RS1000317779 (4:6295794 C>T), RS1000347496 (4:6295956 G>A), RS1000416808 (4:6275089 C>T), RS1000459176 (4:6294567 T>C), RS10005859 (4:6281706 G>A), RS1000737720 (4:6283098 G>T), RS1000826240 (4:6268554 A>T), RS1000828711 (4:6303381 A>C), RS10008312 (4:6281930 G>A,T), RS1000908701 (4:6278648 C>A,G)

Disease associations

OMIM: gene MIM:606201 | disease phenotypes: MIM:222300, MIM:125853, MIM:116400, MIM:600965, MIM:614296, MIM:108600, MIM:156000, MIM:601371, MIM:609129, MIM:124900

GenCC curated gene-disease

Disease	Classification	Inheritance
Wolfram-like syndrome	Definitive	Autosomal dominant
Wolfram syndrome	Definitive	Autosomal recessive
Wolfram syndrome 1	Strong	Autosomal recessive
cataract 41	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 6	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant
type 2 diabetes mellitus	Limited	Unknown

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Wolfram-like syndrome	Definitive	AD
Wolfram syndrome	Definitive	AR
nonsyndromic genetic hearing loss	Definitive	AD

Mondo (24): Wolfram syndrome 1 (MONDO:0009101), WFS1-related disorder (MONDO:0700293), type 2 diabetes mellitus (MONDO:0005148), cataract 41 (MONDO:0007287), autosomal dominant nonsyndromic hearing loss 6 (MONDO:0010963), Wolfram-like syndrome (MONDO:0013673), spastic ataxia (MONDO:0017845), hearing loss disorder (MONDO:0005365), optic atrophy (MONDO:0003608), monogenic diabetes (MONDO:0015967), optic nerve disorder (MONDO:0002135), Wolfram syndrome (MONDO:0018105), Meniere disease (MONDO:0007972), inherited retinal dystrophy (MONDO:0019118), diabetes mellitus (MONDO:0005015)

Orphanet (16): Wolfram syndrome (Orphanet:3463), Wolfram-like syndrome (Orphanet:411590), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Early onset non-syndromic cataract (Orphanet:91492), Early-onset nuclear cataract (Orphanet:98991), Early-onset partial cataract (Orphanet:98992), Early-onset zonular cataract (Orphanet:98995), Spastic ataxia (Orphanet:316226), Rare genetic diabetes mellitus (Orphanet:183625), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Bilateral perisylvian polymicrogyria (Orphanet:98889), Rare genetic deafness (Orphanet:96210), Rare non-syndromic genetic deafness (Orphanet:87884), Hereditary ataxia (Orphanet:183518), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000026	Male hypogonadism
HP:0000029	Testicular atrophy
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000112	Nephropathy
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000717	Autism
HP:0000726	Dementia
HP:0000729	Autistic behavior
HP:0000738	Hallucinations

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000478_2	Type 2 diabetes	1.000000e-08
GCST000712_10	Type 2 diabetes	3.000000e-08
GCST002352_55	Type 2 diabetes	2.000000e-09
GCST003898_1	Cisplatin-induced ototoxicity	5.000000e-08
GCST004894_156	Type 2 diabetes	8.000000e-15
GCST004894_49	Type 2 diabetes	1.000000e-15
GCST005047_30	Type 2 diabetes	5.000000e-07
GCST005047_45	Type 2 diabetes	2.000000e-15
GCST005047_94	Type 2 diabetes	3.000000e-12
GCST005414_15	Type 2 diabetes	7.000000e-08
GCST006867_31	Type 2 diabetes	6.000000e-34
GCST007515_10	Type 2 diabetes	1.000000e-24
GCST007516_6	Type 2 diabetes (adjusted for BMI)	7.000000e-21
GCST007517_7	Type 2 diabetes	7.000000e-20
GCST007518_11	Type 2 diabetes (adjusted for BMI)	2.000000e-17
GCST007847_118	Type 2 diabetes	2.000000e-08
GCST007923_35	Medication use (drugs used in diabetes)	4.000000e-20
GCST008833_22	Type 2 diabetes	4.000000e-08
GCST009379_155	Type 2 diabetes	5.000000e-06
GCST009379_156	Type 2 diabetes	2.000000e-08
GCST010118_35	Type 2 diabetes	9.000000e-12
GCST011684_1	High density lipoprotein cholesterol levels	7.000000e-08
GCST90026416_1	Mild age-related type 2 diabetes	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006951	ototoxicity
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008209	Lymphedema	C15.604.496
D008575	Meniere Disease	C09.218.568.217.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D058499	Retinal Dystrophies	C11.768.585.658
D014929	Wolfram Syndrome	C09.218.458.341.186.500.750; C10.292.700.225.500.980; C10.574.500.662.980; C10.597.751.418.341.186.500.750; C10.597.751.941.162.625.750; C11.270.564.980; C11.640.451.451.980; C11.966.075.375.750; C12.050.351.968.419.135.875; C12.200.777.419.135.875; C12.950.419.135.875; C16.131.077.299.750; C16.320.290.564.980; C16.320.400.630.980; C18.452.394.750.124.960; C19.246.267.960; C19.700.159.875
C538268	Auditory neuropathy (supp.)
C563333	Cataract, Age-Related Nuclear (supp.)
C563421	Deafness, Autosomal Dominant 6 (supp.)
C531684	Hereditary spinal ataxia (supp.)
C580334	Nonsyndromic Deafness (supp.)
C564815	Spastic Ataxia (supp.)
C565631	Wolfram-Like Syndrome, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066374 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs734312	WFS1		0.00	0
rs62283056	WFS1		0.00	0
rs10010131	WFS1		0.00	0
rs1046320	WFS1		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.58	Kd	2657	nM	CHEMBL5653589
5.58	ED50	2657	nM	CHEMBL5653589
5.57	Kd	2667	nM	CHEMBL3752910
5.57	ED50	2667	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149781: Binding affinity to human WFS1 incubated for 45 mins by Kinobead based pull down assay	kd	2.6575	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149781: Binding affinity to human WFS1 incubated for 45 mins by Kinobead based pull down assay	kd	2.6667	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
Cyclosporine	increases expression	2
beta-Naphthoflavone	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
deoxynivalenol	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652823	Binding	Binding affinity to human WFS1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

16 cell lines: 14 induced pluripotent stem cell, 1 finite cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1D23	GM01610	Finite cell line	Female
CVCL_1D26	GM01795	Transformed cell line	Female
CVCL_A9K5	WS4unedit	Induced pluripotent stem cell	Female
CVCL_A9K6	WS4corr	Induced pluripotent stem cell	Female
CVCL_A9K7	WS4corr-B	Induced pluripotent stem cell	Female
CVCL_A9K8	WS9unedit	Induced pluripotent stem cell	Male
CVCL_A9K9	WS13unedit	Induced pluripotent stem cell	Female
CVCL_A9L0	WS13corr	Induced pluripotent stem cell	Female
CVCL_A9L7	Wolf-2010-11	Induced pluripotent stem cell	Male
CVCL_A9L8	Wolf-2010-5	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

311 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
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