UniProtKB/Swiss-Prot O15553: Variant p.Val726Ala

Pyrin
Gene: MEFV
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Variant information Variant position:

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

LP/P [Disclaimer] 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 Alanine (A) at position 726 (V726A, p.Val726Ala). 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:

Change from medium size and hydrophobic (V) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Variant description:

In ARFMF; common mutation; in Iraqi and Ashkenazi Jews, Druze, Armenians; reduced interaction with CASP1 and ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation when associated in cis with I-680 and V-694; no effect on CASP1 activation; no effect on interaction with 14-3-3 proteins. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28940579 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

PTRLLIKEPPKRVGIFVDYR V GSISFYNVTARSHIYTFASC 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                         PTRLLIKEPPKRVGIFVDYRVGSISFYNVTARSHIYTFASC

Mouse                         PKDYLHPQPAQ----------DTPELHEIHSRNNKRKFKSF

Rat                           PQDYLHPSSAQ----------DTPELHEIHSQNNKRKFKSF

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 – 781	Pyrin
Domain	580 – 775	B30.2/SPRY
Alternative sequence	587 – 781	VPELIGAQAHAVNVILDAETAYPNLIFSDDLKSVRLGNKWERLPDGPQRFDSCIIVLGSPSFLSGRRYWEVEVGDKTAWILGACKTSISRKGNMTLSPENGYWVVIMMKENEYQASSVPPTRLLIKEPPKRVGIFVDYRVGSISFYNVTARSHIYTFASCSFSGPLQPIFSPGTRDGGKNTAPLTICPVGGQGPD -> DHSPQHGLGSWEERDYTQHSMQGPKQGVPCLSLLSGQCNLAPLNANAQDFFPYLIFLRSSGADWRSGTCC. In isoform 3.
Turn	724 – 727

Literature citations
Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever.
Aksentijevich I.; Centola M.; Deng Z.; Sood R.; Balow J.E. Jr.; Wood G.; Zaks N.; Mansfield E.; Chen X.; Eisenberg S.; Vedula A.; Shafran N.; Raben N.; Pras E.; Pras M.; Kastner D.L.; Blake T.; Baxevanis A.D.; Robbins C.; Krizman D.; Collins F.S.; Liu P.P.; Chen X.; Shohat M.; Hamon M.; Kahan T.; Cercek A.; Rotter J.I.; Fischel-Ghodsian N.; Richards N.; Shelton D.A.; Gumucio D.; Yokoyama Y.; Mangelsdorf M.; Orsborn A.; Richards R.I.; Ricke D.O.; Buckingham J.M.; Moyzis R.K.; Deaven L.L.; Doggett N.A.;
Cell 90:797-807(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS ARFMF ILE-680; VAL-694 AND ALA-726; The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production.
Chae J.J.; Wood G.; Masters S.L.; Richard K.; Park G.; Smith B.J.; Kastner D.L.;
Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006)
Cited for: INTERACTION WITH CASP1; CHARACTERIZATION OF VARIANTS ILE-680; VAL-694 AND ALA-726; TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.
Kimura T.; Jain A.; Choi S.W.; Mandell M.A.; Schroder K.; Johansen T.; Deretic V.;
J. Cell Biol. 210:973-989(2015)
Cited for: FUNCTION; INTERACTION WITH ATG16L1; BECN1; GABARAP; GABARAPL1; GABARAPL2; MAP1LC3A; MAP1LC3C; NLRP3; TRIM21 AND ULK1; SUBCELLULAR LOCATION; INDUCTION BY IFNG; DEGRADATION BY AUTOPHAGY; CHARACTERIZATION OF VARIANTS ARFMF ILE-680; VAL-694 AND ALA-726; MUTAGENESIS OF 397-ILE--HIS-404; 470-TYR--GLY-488 AND 523-SER--ASP-530; Pyrin/marenostrin mutations in familial Mediterranean fever.
Booth D.R.; Gillmore J.D.; Booth S.E.; Pepys M.B.; Hawkins P.N.;
QJM 91:603-606(1998)
Cited for: VARIANTS ARFMF ILE-680; ILE-681; ILE-694; VAL-694; MET-694 DEL AND ALA-726; MEFV-Gene analysis in Armenian patients with familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.
Cazeneuve C.; Sarkisian T.; Pecheux C.; Dervichian M.; Nedelec B.; Reinert P.; Ayvazyan A.; Kouyoumdjian J.-C.; Ajrapetyan H.; Delpech M.; Goossens M.; Dode C.; Grateau G.; Amselem S.;
Am. J. Hum. Genet. 65:88-97(1999)
Cited for: VARIANTS ARFMF GLN-148; SER-369; GLN-408; LEU-479; ILE-680; VAL-694; ALA-726 AND HIS-761; Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis.
Shohat M.; Magal N.; Shohat T.; Chen X.; Dagan T.; Mimouni A.; Danon Y.; Lotan R.; Ogur G.; Sirin A.; Schlezinger M.; Halpern G.J.; Schwabe A.; Kastner D.; Rotter J.I.; Fischel-Ghodsian N.;
Eur. J. Hum. Genet. 7:287-292(1999)
Cited for: VARIANTS ARFMF ILE-680; ILE-694; VAL-694 AND ALA-726; MEFV mutations in Turkish patients suffering from familial Mediterranean fever.
Akar N.; Misiroglu M.; Yalcinkaya F.; Akar E.; Cakar N.; Tumer N.; Akcakus M.; Tastan H.; Matzner Y.;
Hum. Mutat. 15:118-119(2000)
Cited for: VARIANTS ARFMF GLN-148; ILE-680; ILE-694; VAL-694; ARG-695; ALA-726 AND HIS-761; Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations.
Medlej-Hashim M.; Serre J.-L.; Corbani S.; Saab O.; Jalkh N.; Delague V.; Chouery E.; Salem N.; Loiselet J.; Lefranc G.; Megarbane A.;
Eur. J. Med. Genet. 48:412-420(2005)
Cited for: VARIANTS ARFMF ARG-108; GLN-148; VAL-148; ASP-167; ILE-177; ILE-267; LYS-474; LEU-479; HIS-653; ILE-680; ILE-694; VAL-694; ARG-695; MET-720; ALA-726; SER-744 AND HIS-761; Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF).
Goulielmos G.N.; Fragouli E.; Aksentijevich I.; Sidiropoulos P.; Boumpas D.T.; Eliopoulos E.;
Biochem. Biophys. Res. Commun. 345:1326-1332(2006)
Cited for: VARIANTS ARFMF SER-632; MET-640; PHE-641; LEU-646; PRO-649; HIS-653; ALA-656; ASN-661; ASN-675; GLU-678; LEU-680; ILE-681; CYS-688; ILE-694; LEU-694; VAL-694; MET-695; ARG-695; ILE-704; SER-705; MET-720; ALA-726; LEU-743; SER-744; SER-758; HIS-761 AND THR-780; VARIANT CYS-702; Frequency of MEFV gene mutations in Hatay province, Mediterranean region of Turkey and report of a novel missense mutation (I247V).
Gunesacar R.; Celik M.M.; Arica V.; Elmacioglu S.; Ozturk O.H.;
Gene 546:195-199(2014)
Cited for: VARIANTS ARFMF PRO-110; GLN-148; TRP-196; LYS-230; VAL-247; LEU-283; ARG-304; ALA-632; ILE-680; ILE-694; VAL-694; ARG-695; ALA-726; SER-744 AND HIS-761; VARIANT GLN-202; Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.
Masters S.L.; Lagou V.; Jeru I.; Baker P.J.; Van Eyck L.; Parry D.A.; Lawless D.; De Nardo D.; Garcia-Perez J.E.; Dagley L.F.; Holley C.L.; Dooley J.; Moghaddas F.; Pasciuto E.; Jeandel P.Y.; Sciot R.; Lyras D.; Webb A.I.; Nicholson S.E.; De Somer L.; van Nieuwenhove E.; Ruuth-Praz J.; Copin B.; Cochet E.; Medlej-Hashim M.; Megarbane A.; Schroder K.; Savic S.; Goris A.; Amselem S.; Wouters C.; Liston A.;
Sci. Transl. Med. 8:332ra45-332ra45(2016)
Cited for: VARIANT PAAND ARG-242; INVOLVEMENT IN PAAND; FUNCTION; PHOSPHORYLATION AT SER-242; INTERACTION WITH YWHAB; YWHAE; YWHAG; YWHAH; YWHAQ AND YWHAZ; CHARACTERIZATION OF VARIANT PAAND ARG-242; CHARACTERIZATION OF VARIANT GLN-202; CHARACTERIZATION OF VARIANTS ARFMF ARG-304; ILE-680; ILE-694 AND ALA-726;

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.