UniProtKB/Swiss-Prot Q96RY7: Variant p.Gly522Glu

Intraflagellar transport protein 140 homolog
Gene: IFT140
Feedback?

Variant information Variant position:

522 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 Glycine (G) to Glutamate (E) at position 522 (G522E, p.Gly522Glu). 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 glycine (G) to medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 SRTD9 and CED5; pathogenic; risk factor for PKD9. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs199826737 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1462 The length of the canonical sequence.
Location on the sequence:

VQVRTWQGTVKQLLLFSETE G NPCFLDICGNFLVVGTDLAH 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                         VQVRTWQGTVKQLLLFSETEGNPCFLDICGNFLVVGTDLAH

Mouse                         LQVRTWQGTVKQLLLFSETEGSPCFLDVCGTFLVAGTDLAH

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 – 1462	Intraflagellar transport protein 140 homolog
Alternative sequence	1 – 806	Missing. In isoform 2.

Literature citations
Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations.
Perrault I.; Saunier S.; Hanein S.; Filhol E.; Bizet A.A.; Collins F.; Salih M.A.; Gerber S.; Delphin N.; Bigot K.; Orssaud C.; Silva E.; Baudouin V.; Oud M.M.; Shannon N.; Le Merrer M.; Roche O.; Pietrement C.; Goumid J.; Baumann C.; Bole-Feysot C.; Nitschke P.; Zahrate M.; Beales P.; Arts H.H.; Munnich A.; Kaplan J.; Antignac C.; Cormier-Daire V.; Rozet J.M.;
Am. J. Hum. Genet. 90:864-870(2012)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANTS SRTD9 ARG-212; MET-233; MET-292; CYS-311; GLU-522; GLN-576 AND LYS-664; CHARACTERIZATION OF VARIANTS SRTD9 ARG-212; CYS-311 AND LYS-664;
Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease.
Schmidts M.; Frank V.; Eisenberger T.; Al Turki S.; Bizet A.A.; Antony D.; Rix S.; Decker C.; Bachmann N.; Bald M.; Vinke T.; Toenshoff B.; Di Donato N.; Neuhann T.; Hartley J.L.; Maher E.R.; Bogdanovic R.; Peco-Antic A.; Mache C.; Hurles M.E.; Joksic I.; Guc-Scekic M.; Dobricic J.; Brankovic-Magic M.; Bolz H.J.; Pazour G.J.; Beales P.L.; Scambler P.J.; Saunier S.; Mitchison H.M.; Bergmann C.;
Hum. Mutat. 34:714-724(2013)
Cited for: SUBCELLULAR LOCATION; VARIANTS HIS-110; THR-161; GLY-243; SER-459; HIS-514; GLY-787 AND ARG-1353; VARIANTS SRTD9 ARG-140; PHE-152; 164-GLU--PRO-1462 DEL; GLY-267; MET-292; GLU-522 AND ARG-1360; CHARACTERIZATION OF VARIANTS SRTD9 MET-292 AND LYS-664;
Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140.
Geoffroy V.; Stoetzel C.; Scheidecker S.; Schaefer E.; Perrault I.; Baer S.; Kroell A.; Delbarre M.; Antin M.; Leuvrey A.S.; Henry C.; Blanche H.; Decker E.; Kloth K.; Klaus G.; Mache C.; Martin-Coignard D.; McGinn S.; Boland A.; Deleuze J.F.; Friant S.; Saunier S.; Rozet J.M.; Bergmann C.; Dollfus H.; Muller J.;
Hum. Mutat. 39:983-992(2018)
Cited for: VARIANTS SRTD9 PHE-152; ARG-212; MET-292; PRO-440; GLU-522 AND LEU-726; VARIANT RP80 ARG-212; INVOLVEMENT IN SRTD9; INVOLVEMENT IN RP80;
Compound heterozygous IFT140 variants in two Polish families with Sensenbrenner syndrome and early onset end-stage renal disease.
Walczak-Sztulpa J.; Posmyk R.; Bukowska-Olech E.M.; Wawrocka A.; Jamsheer A.; Oud M.M.; Schmidts M.; Arts H.H.; Latos-Bielenska A.; Wasilewska A.;
Orphanet J. Rare Dis. 15:36-36(2020)
Cited for: VARIANTS CED5 PRO-109 AND GLU-522; INVOLVEMENT IN CED5;
Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.
Senum S.R.; Li Y.S.M.; Benson K.A.; Joli G.; Olinger E.; Lavu S.; Madsen C.D.; Gregory A.V.; Neatu R.; Kline T.L.; Audrezet M.P.; Outeda P.; Nau C.B.; Meijer E.; Ali H.; Steinman T.I.; Mrug M.; Phelan P.J.; Watnick T.J.; Peters D.J.M.; Ong A.C.M.; Conlon P.J.; Perrone R.D.; Cornec-Le Gall E.; Hogan M.C.; Torres V.E.; Sayer J.A.; Harris P.C.;
Am. J. Hum. Genet. 109:136-156(2022)
Cited for: VARIANTS 164-GLU--PRO-1462 DEL; 347-ARG--PRO-1462 DEL; 383-GLN--PRO-1462 DEL; 416-GLN--PRO-1462 DEL; 459-TRP--PRO-1462 DEL; GLU-522; 550-ARG--PRO-1462 DEL; 653-TRP--PRO-1462 DEL; 760-ARG--PRO-1462 DEL; 834-ARG--PRO-1462 DEL; 848-ARG--ALA-853 DEL; 970-GLU--ALA-973 DEL AND 1072-ARG--PRO-1462 DEL; INVOLVEMENT IN PKD9;
Fetal ciliopathies: a retrospective observational single-center study.
Simonini C.; Floeck A.; Strizek B.; Mueller A.; Gembruch U.; Geipel A.;
Arch. Gynecol. Obstet. 306:71-83(2022)
Cited for: VARIANTS SRTD9 PHE-152; GLU-522 AND 1037-GLN--PRO-1462 DEL;
Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies.
Sharova M.; Markova T.; Sumina M.; Petukhova M.; Bulakh M.; Ryzhkova O.; Nagornova T.; Ionova S.; Marakhonov A.; Dadali E.; Kutsev S.;
Genes (Basel) 14:0-0(2023)
Cited for: VARIANT SRTD9 GLU-522; INVOLVEMENT IN CED5; INVOLVEMENT IN SRTD9;

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.