UniProtKB/Swiss-Prot O76024: Variant p.Val333Ile

Wolframin
Gene: WFS1
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Variant information Variant position:

333 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Valine (V) to Isoleucine (I) at position 333 (V333I, p.Val333Ile). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
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. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs1801212 [ dbSNP | Ensembl ]

Sequence information Variant position:

333 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

890 The length of the canonical sequence.
Location on the sequence:

HWLSTIIPTHHINALIFFFI V SNLTIDFFAFFIPLVIFYLS The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         HWLSTIIPTHHINALIFFFIVSNLTIDFFA--FFIPLVIFYLS

Mouse                         HWLSTIVPTHHINALIFFFIISNLTIDFFA--FFIPLVVFY

Drosophila                    --IPNVIPLSVRCSVL-------VAISWWSSRHMLPLVSYY

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 890	Wolframin
Transmembrane	314 – 334	Helical

Literature citations
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)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS WFS1 461-THR--VAL-463 DEL; ILE-333 AND CYS-669; 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)
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; 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)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT ILE-333; 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)
Cited for: VARIANTS WFS1; VARIANTS ILE-333 AND HIS-611; 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)
Cited for: VARIANTS DFNA6 MET-699; THR-716; MET-779; PRO-829 AND ASP-831; VARIANT ILE-333; 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)
Cited for: VARIANT DFNA6 THR-716; VARIANTS ARG-107; ILE-333; HIS-611 AND MET-871; 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)
Cited for: VARIANT WFS1 ILE-443; VARIANTS ILE-333; HIS-611; VAL-684 AND CYS-708; 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)
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; 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)
Cited for: VARIANT DFNA6 GLN-859; VARIANTS ILE-333 AND HIS-611;

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