O76024 (WFS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Wolframin

Gene names

Name:

WFS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	890 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Participates in the regulation of cellular Ca2+ homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca2+ store. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
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.
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.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.10 Ref.17 Ref.19 Ref.20 Ref.24 Ref.25 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.18 Ref.22 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.23 Ref.24

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Diabetes insipidus Diabetes mellitus Disease mutation Non-syndromic deafness
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER overload response Traceable author statement PubMed 17947299. Source: BHF-UCL ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: BHF-UCL activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome endoplasmic reticulum calcium ion homeostasis Inferred from direct assay Ref.7. Source: BHF-UCL glucose homeostasis Inferred from mutant phenotype Ref.1. Source: BHF-UCL kidney development Inferred from mutant phenotype Ref.1. Source: BHF-UCL negative regulation of neuron apoptotic process Inferred from mutant phenotype Ref.2Ref.1. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of type B pancreatic cell apoptotic process Inferred from electronic annotation. Source: Compara polyubiquitinated misfolded protein transport Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of calcium ion transport Inferred from direct assay Ref.7. Source: BHF-UCL positive regulation of growth Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein ubiquitination Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of proteolysis Inferred from sequence or structural similarity. Source: BHF-UCL protein maturation by protein folding Inferred by curator Ref.7. Source: BHF-UCL protein stabilization Inferred from sequence or structural similarity. Source: BHF-UCL renal water homeostasis Inferred from mutant phenotype Ref.1. Source: BHF-UCL sensory perception of sound Inferred from mutant phenotype PubMed 17492394. Source: BHF-UCL visual perception Inferred from mutant phenotype Ref.2Ref.1. Source: BHF-UCL
Cellular_component	dendrite Inferred from sequence or structural similarity PubMed 11181571. Source: BHF-UCL integral to endoplasmic reticulum membrane Inferred from direct assay PubMed 11181571PubMed 14527944. Source: BHF-UCL
Molecular_function	activating transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL transporter activity Inferred from sequence or structural similarity. Source: BHF-UCL ubiquitin protein ligase binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 890	890	Wolframin		PRO_0000065963
Regions
	Transmembrane	314 – 334	21	Helical; Potential
	Transmembrane	340 – 360	21	Helical; Potential
	Transmembrane	402 – 422	21	Helical; Potential
	Transmembrane	427 – 447	21	Helical; Potential
	Transmembrane	465 – 485	21	Helical; Potential
	Transmembrane	496 – 516	21	Helical; Potential
	Transmembrane	529 – 549	21	Helical; Potential
	Transmembrane	563 – 583	21	Helical; Potential
	Transmembrane	589 – 609	21	Helical; Potential
	Transmembrane	632 – 652	21	Helical; Potential
	Transmembrane	870 – 890	21	Helical; Potential
	Compositional bias	190 – 193	4	Poly-Lys
	Compositional bias	877 – 886	10	Poly-Phe
Amino acid modifications
	Modified residue	32	1	Phosphoserine By similarity
Natural variations
	Natural variant	16	1	P → L. Corresponds to variant rs34653805 [ dbSNP | Ensembl ].		VAR_032791
	Natural variant	58	1	A → V in WFS1. Ref.19		VAR_011305
	Natural variant	107	1	G → R. Ref.15		VAR_032962
	Natural variant	110	1	Y → N in WFS1. Ref.20		VAR_029499
	Natural variant	126	1	A → T in WFS1. Ref.19		VAR_011306
	Natural variant	133	1	A → T in WFS1. Ref.20		VAR_014034
	Natural variant	169	1	E → K in WFS1.		VAR_009109
	Natural variant	193	1	K → Q. Corresponds to variant rs41264699 [ dbSNP | Ensembl ].		VAR_014995
	Natural variant	292	1	P → S in WFS1.		VAR_009110
	Natural variant	296	1	I → S in WFS1.		VAR_009111
	Natural variant	326	1	A → V. Ref.20		VAR_029500
	Natural variant	333	1	V → I. Ref.1 Ref.2 Ref.3 Ref.10 Ref.14 Ref.15 Ref.17 Ref.20 Ref.22 Corresponds to variant rs1801212 [ dbSNP | Ensembl ].		VAR_005840
	Natural variant	350	1	Missing in WFS1. Ref.19		VAR_011307
	Natural variant	354	1	Missing in WFS1. Ref.19		VAR_009112
	Natural variant	414	1	Missing in WFS1. Ref.20		VAR_029501
	Natural variant	415	1	Missing in WFS1; greatly reduces protein expression compared to wild-type. Ref.20 Ref.24		VAR_009113
	Natural variant	437	1	G → R in WFS1.		VAR_009114
	Natural variant	443	1	S → I in WFS1. Ref.17		VAR_011308
	Natural variant	456	1	R → H. Ref.2 Ref.12 Ref.13 Ref.20 Corresponds to variant rs1801208 [ dbSNP | Ensembl ].		VAR_005841
	Natural variant	457	1	R → S in WFS1. Ref.20		VAR_029502
	Natural variant	461 – 463	3	Missing in WFS1.		VAR_014035
	Natural variant	468	1	Missing in WFS1. Ref.20		VAR_029503
	Natural variant	504	1	P → L in WFS1. Ref.2 Ref.19 Ref.20 Corresponds to variant rs28937892 [ dbSNP | Ensembl ].		VAR_005842
	Natural variant	508 – 512	5	Missing in WFS1.		VAR_014036
	Natural variant	540	1	Missing in WFS1. Ref.20		VAR_029504
	Natural variant	558	1	R → C in WFS1. Ref.25		VAR_068343
	Natural variant	559	1	A → T. Ref.11 Corresponds to variant rs55814513 [ dbSNP | Ensembl ].		VAR_010602
	Natural variant	567 – 568	2	Missing in WFS1.		VAR_009115
	Natural variant	576	1	G → S. Ref.12 Ref.13 Corresponds to variant rs1805069 [ dbSNP | Ensembl ].		VAR_010603
	Natural variant	602	1	A → V. Corresponds to variant rs2230720 [ dbSNP | Ensembl ].		VAR_024554
	Natural variant	611	1	R → H. Ref.2 Ref.5 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.20 Ref.22 Corresponds to variant rs734312 [ dbSNP | Ensembl ].		VAR_005843
	Natural variant	629	1	R → W in WFS1. Ref.20		VAR_029505
	Natural variant	634	1	K → T in DFNA6. Ref.18		VAR_032963
	Natural variant	653	1	R → C in a patient with type 2 diabetes. Ref.12		VAR_014037
	Natural variant	669	1	Y → C in WFS1. Ref.1		VAR_014038
	Natural variant	674	1	G → R. Ref.19		VAR_011309
	Natural variant	684	1	A → V in WFSL; greatly reduces protein expression compared to wild-type. Ref.17 Ref.24		VAR_011310
	Natural variant	690	1	C → R in WFS1.		VAR_009116
	Natural variant	695	1	G → V in WFS1. Ref.2 Corresponds to variant rs28937891 [ dbSNP | Ensembl ].		VAR_005844
	Natural variant	699	1	T → M in DFNA6. Ref.14 Corresponds to variant rs28937894 [ dbSNP | Ensembl ].		VAR_032964
	Natural variant	700	1	W → C in WFS1.		VAR_009117
	Natural variant	708	1	R → C. Ref.17		VAR_011311
	Natural variant	716	1	A → T in DFNA6. Ref.14 Ref.15 Corresponds to variant rs28937893 [ dbSNP | Ensembl ].		VAR_032965
	Natural variant	720	1	I → V. Ref.12 Ref.13 Corresponds to variant rs1805070 [ dbSNP | Ensembl ].		VAR_010604
	Natural variant	724	1	P → L in WFS1. Ref.2 Corresponds to variant rs28937890 [ dbSNP | Ensembl ].		VAR_005845
	Natural variant	736	1	G → S in WFS1. Ref.20		VAR_009118
	Natural variant	737	1	E → K. Ref.13 Ref.19		VAR_011312
	Natural variant	779	1	V → M in DFNA6. Ref.14		VAR_032966
	Natural variant	780	1	G → R in WFS1. Ref.19		VAR_011313
	Natural variant	780	1	G → S in WFSL; mildly decreases protein expression compared to wild-type. Ref.24		VAR_068344
	Natural variant	797	1	D → Y in WFSL. Ref.24		VAR_068345
	Natural variant	802	1	I → V. Ref.20		VAR_029506
	Natural variant	818	1	R → C in WFS1. Ref.19 Corresponds to variant rs35932623 [ dbSNP | Ensembl ].		VAR_011314
	Natural variant	829	1	L → P in DFNA6. Ref.14		VAR_032967
	Natural variant	831	1	G → D in DFNA6. Ref.14 Corresponds to variant rs28937895 [ dbSNP | Ensembl ].		VAR_032968
	Natural variant	836	1	K → N in WFSL. Ref.23		VAR_068346
	Natural variant	859	1	R → Q in DFNA6. Ref.22		VAR_068347
	Natural variant	864	1	E → K in WFSL. Ref.21		VAR_032969
	Natural variant	871	1	V → M. Ref.15 Ref.20		VAR_014996
	Natural variant	885	1	P → L in WFS1; mild form.		VAR_009119

Sequences

	Sequence		Length	Mass (Da)
	O76024 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 4D7F27C547004EC6	FASTA	890	100,292
	10 20 30 40 50 60 MDSNTAPLGP SCPQPPPAPQ PQARSRLNAT ASLEQERSER PRAPGPQAGP GPGVRDAAAP 70 80 90 100 110 120 AEPQAQHTRS RERADGTGPT KGDMEIPFEE VLERAKAGDP KAQTEVGKHY LQLAGDTDEE 130 140 150 160 170 180 LNSCTAVDWL VLAAKQGRRE AVKLLRRCLA DRRGITSENE REVRQLSSET DLERAVRKAA 190 200 210 220 230 240 LVMYWKLNPK KKKQVAVAEL LENVGQVNEH DGGAQPGPVP KSLQKQRRML ERLVSSESKN 250 260 270 280 290 300 YIALDDFVEI TKKYAKGVIP SSLFLQDDED DDELAGKSPE DLPLRLKVVK YPLHAIMEIK 310 320 330 340 350 360 EYLIDMASRA GMHWLSTIIP THHINALIFF FIVSNLTIDF FAFFIPLVIF YLSFISMVIC 370 380 390 400 410 420 TLKVFQDSKA WENFRTLTDL LLRFEPNLDV EQAEVNFGWN HLEPYAHFLL SVFFVIFSFP 430 440 450 460 470 480 IASKDCIPCS ELAVITGFFT VTSYLSLSTH AEPYTRRALA TEVTAGLLSL LPSMPLNWPY 490 500 510 520 530 540 LKVLGQTFIT VPVGHLVVLN VSVPCLLYVY LLYLFFRMAQ LRNFKGTYCY LVPYLVCFMW 550 560 570 580 590 600 CELSVVILLE STGLGLLRAS IGYFLFLFAL PILVAGLALV GVLQFARWFT SLELTKIAVT 610 620 630 640 650 660 VAVCSVPLLL RWWTKASFSV VGMVKSLTRS SMVKLILVWL TAIVLFCWFY VYRSEGMKVY 670 680 690 700 710 720 NSTLTWQQYG ALCGPRAWKE TNMARTQILC SHLEGHRVTW TGRFKYVRVT DIDNSAESAI 730 740 750 760 770 780 NMLPFFIGDW MRCLYGEAYP ACSPGNTSTA EEELCRLKLL AKHPCHIKKF DRYKFEITVG 790 800 810 820 830 840 MPFSSGADGS RSREEDDVTK DIVLRASSEF KSVLLSLRQG SLIEFSTILE GRLGSKWPVF 850 860 870 880 890 ELKAISCLNC MAQLSPTRRH VKIEHDWRST VHGAVKFAFD FFFFPFLSAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein." Strom T.M., Hoertnagel K., Hofmann S., Gekeler F., Scharfe C., Rabl W., Gerbitz K.-D., Meitinger T. Hum. Mol. Genet. 7:2021-2028(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS WFS1 461-THR--VAL-463 DEL; ILE-333 AND CYS-669. Tissue: Brain.
[2]	"A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram Syndrome)." Inoue H., Tanizawa Y., Wasson J., Behn P., Kalidas K., Bernal-Mizrachi E., Mueckler M., Marshall H., Donis-Keller H., Crock P., Rogers D., Mikuni M., Kumashiro H., Higashi K., Sobue G., Oka Y., Permutt M.A. Nat. Genet. 20:143-148(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS WFS1 LEU-504; 508-TYR--LEU-512 DEL; VAL-695 AND LEU-724, VARIANTS ILE-333; HIS-456 AND HIS-611. Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-333. Tissue: Amygdala.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT HIS-611.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum." Takei D., Ishihara H., Yamaguchi S., Yamada T., Tamura A., Katagiri H., Maruyama Y., Oka Y. FEBS Lett. 580:5635-5640(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"WFS1/wolframin mutations, Wolfram syndrome, and associated diseases." Khanim F., Kirk J., Latif F., Barrett T.G. Hum. Mutat. 17:357-367(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1." Hardy C., Khanim F., Torres R., Scott-Brown M., Seller A., Poulton J., Collier D., Kirk J., Polymeropoulos M., Latif F., Barrett T. Am. J. Hum. Genet. 65:1279-1290(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS WFS1, VARIANTS ILE-333 AND HIS-611.
[11]	"A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases." Furlong R.A., Ho L.W., Rubinsztein J.S., Michael A., Walsh C., Paykel E.S., Rubinsztein D.C. Neurosci. Lett. 277:123-126(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-559 AND HIS-611.
[12]	"Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese: possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis." Awata T., Inoue K., Kurihara S., Ohkubo T., Inoue I., Abe T., Takino H., Kanazawa Y., Katayama S. Biochem. Biophys. Res. Commun. 268:612-616(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-456; SER-576; HIS-611; CYS-653 AND VAL-720.
[13]	"WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder." Ohtsuki T., Ishiguro H., Yoshikawa T., Arinami T. J. Affect. Disord. 58:11-17(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-456; SER-576; HIS-611; VAL-720 AND LYS-737.
[14]	"Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss." Bespalova I.N., Van Camp G., Bom S.J.H., Brown D.J., Cryns K., DeWan A.T., Erson A.E., Flothmann K., Kunst H.P.M., Kurnool P., Sivakumaran T.A., Cremers C.W.R.J., Leal S.M., Burmeister M., Lesperance M.M. Hum. Mol. Genet. 10:2501-2508(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DFNA6 MET-699; THR-716; MET-779; PRO-829 AND ASP-831, VARIANT ILE-333.
[15]	"Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1." Young T.-L., Ives E., Lynch E., Person R., Snook S., MacLaren L., Cater T., Griffin A., Fernandez B., Lee M.K., King M.-C. Hum. Mol. Genet. 10:2509-2514(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNA6 THR-716, VARIANTS ARG-107; ILE-333; HIS-611 AND MET-871.
[16]	Erratum Young T.L., Ives E., Lynch E., Person R., Snook S., MacLaren L., Cater T., Griffin A., Fernandez B., Lee M.K., King M.C. Hum. Mol. Genet. 10:3111-3111(2001)
[17]	"Identification of novel WFS1 mutations in Italian children with Wolfram syndrome." Tessa A., Carbone I., Matteoli M.C., Bruno C., Patrono C., Patera I.P., De Luca F., Lorini R., Santorelli F.M. Hum. Mutat. 17:348-349(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT WFS1 ILE-443, VARIANTS ILE-333; HIS-611; VAL-684 AND CYS-708.
[18]	"Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family." Komatsu K., Nakamura N., Ghadami M., Matsumoto N., Kishino T., Ohta T., Niikawa N., Yoshiura K. J. Hum. Genet. 47:395-399(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNA6 THR-634.
[19]	"Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees." Gomez-Zaera M., Strom T.M., Rodriguez B., Estivill X., Meitinger T., Nunes V. Mol. Genet. Metab. 72:72-81(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS WFS1 VAL-58; THR-126; PHE-350 DEL; PHE-354 DEL; LEU-504; ARG-780 AND CYS-818, VARIANTS ARG-674 AND LYS-737.
[20]	"Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene." Giuliano F., Bannwarth S., Monnot S., Cano A., Chabrol B., Vialettes B., Delobel B., Paquis-Flucklinger V. Hum. Mutat. 25:99-100(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS WFS1 ASN-110; THR-133; PHE-414 DEL; VAL-415 DEL; SER-457; LEU-468 DEL; LEU-504; TRP-540 DEL; TRP-629 AND SER-736, VARIANTS VAL-326; ILE-333; HIS-456; HIS-611; VAL-802 AND MET-871.
[21]	"Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene." Eiberg H., Hansen L., Kjer B., Hansen T., Pedersen O., Bille M., Rosenberg T., Tranebjaerg L. J. Med. Genet. 43:435-440(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT WFSL LYS-864.
[22]	"Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1." Hildebrand M.S., Sorensen J.L., Jensen M., Kimberling W.J., Smith R.J. Am. J. Med. Genet. A 146:2258-2265(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNA6 GLN-859, VARIANTS ILE-333 AND HIS-611.
[23]	"Autosomal dominant optic neuropathy and sensorineural hearing loss associated with a novel mutation of WFS1." Hogewind B.F., Pennings R.J., Hol F.A., Kunst H.P., Hoefsloot E.H., Cruysberg J.R., Cremers C.W. Mol. Vis. 16:26-35(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT WFSL ASN-836.
[24]	"Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment." Rendtorff N.D., Lodahl M., Boulahbel H., Johansen I.R., Pandya A., Welch K.O., Norris V.W., Arnos K.S., Bitner-Glindzicz M., Emery S.B., Mets M.B., Fagerheim T., Eriksson K., Hansen L., Bruhn H., Moller C., Lindholm S., Ensgaard S., Lesperance M.M., Tranebjaerg L. Am. J. Med. Genet. A 155:1298-1313(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS WFSL VAL-684; SER-780 AND TYR-797, VARIANT WFS1 VAL-415 DEL, CHARACTERIZATION OF VARIANTS WFSL VAL-684 AND SER-780, CHARACTERIZATION OF VARIANT WFS1 VAL-415 DEL.
[25]	"Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease." Lieber D.S., Vafai S.B., Horton L.C., Slate N.G., Liu S., Borowsky M.L., Calvo S.E., Schmahmann J.D., Mootha V.K. BMC Med. Genet. 13:3-3(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT WFS1 CYS-558.
+	Additional computationally mapped references.

Web resources

WFS1 gene mutation and polymorphism database

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y18064 mRNA. Translation: CAA77022.1. AF084481 mRNA. Translation: AAC64943.1. AK312897 mRNA. Translation: BAG35744.1. AC116317 Genomic DNA. No translation available. CH471131 Genomic DNA. Translation: EAW82396.1. CH471131 Genomic DNA. Translation: EAW82397.1. CH471131 Genomic DNA. Translation: EAW82398.1. BC030130 mRNA. Translation: AAH30130.1.
IPI	IPI00008711.
RefSeq	NP_001139325.1. NM_001145853.1. NP_005996.2. NM_006005.3.
UniGene	Hs.518602. Hs.727283.
3D structure databases
ProteinModelPortal	O76024.
SMR	O76024. Positions 86-162.
ModBase	Search...
Protein-protein interaction databases
IntAct	O76024. 2 interactions.
MINT	MINT-1418252.
STRING	9606.ENSP00000226760.
PTM databases
PhosphoSite	O76024.
Proteomic databases
PaxDb	O76024.
PRIDE	O76024.
Protocols and materials databases
DNASU	7466.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000226760; ENSP00000226760; ENSG00000109501. ENST00000503569; ENSP00000423337; ENSG00000109501.
GeneID	7466.
KEGG	hsa:7466.
UCSC	uc003gix.3. human.
Organism-specific databases
CTD	7466.
GeneCards	GC04P006271.
H-InvDB	HIX0004060.
HGNC	HGNC:12762. WFS1.
HPA	HPA029128.
MIM	222300. phenotype. 600965. phenotype. 606201. gene. 614296. phenotype.
neXtProt	NX_O76024.
Orphanet	90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA. 3463. Wolfram syndrome.
PharmGKB	PA37365.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG82472.
HOGENOM	HOG000132944.
HOVERGEN	HBG014957.
InParanoid	O76024.
KO	K14020.
OMA	TIDFFAF.
PhylomeDB	O76024.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	O76024.
Bgee	O76024.
CleanEx	HS_WFS1.
Genevestigator	O76024.
GermOnline	ENSG00000109501. Homo sapiens.
Family and domain databases
InterPro	IPR026208. Wolframin. IPR026209. Wolframin_fam. [Graphical view]
PANTHER	PTHR13098. PTHR13098. 1 hit.
PRINTS	PR02060. WOLFFAMILY. PR02061. WOLFRAMIN.
ProtoNet	Search...
Other
GenomeRNAi	7466.
NextBio	29240.
SOURCE	Search...

Entry information

Entry name

WFS1_HUMAN

Accession

Primary (citable) accession number: O76024
Secondary accession number(s): B2R797 , D3DVT1, Q8N6I3, Q9UNW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.