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UniProtKB/Swiss-Prot P08F94: Variant p.Ile2957Thr

Fibrocystin
Gene: PKHD1
Chromosomal location: 6p12.2
Variant information

Variant position:  2957
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Threonine (T) at position 2957 (I2957T, p.Ile2957Thr).
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 (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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

Involvement in disease:  Polycystic kidney disease 4, with or without polycystic liver disease (PKD4) [MIM:263200]: A severe form of polycystic kidney disease affecting the kidneys and, in some cases, the hepatic biliary tract. The clinical spectrum is widely variable, with most cases presenting during infancy. The fetal phenotypic features classically include enlarged and echogenic kidneys, as well as oligohydramnios secondary to a poor urine output. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis. PKD4 inheritance is autosomal recessive. {ECO:0000269|PubMed:11898128, ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281, ECO:0000269|PubMed:16677362, ECO:0000269|PubMed:19914852, ECO:0000269|PubMed:25701400}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PKD4.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  2957
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  4074
The length of the canonical sequence.

Location on the sequence:   VTEDGRHIRLAAEVGLLTRN  I QIQPDVSCRGRLFVGSFRKS
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.

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.

TypePositionsDescription
Chain 24 – 4074 Fibrocystin
Topological domain 24 – 3858 Extracellular


Literature citations

The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.
Ward C.J.; Hogan M.C.; Rossetti S.; Walker D.; Sneddon T.; Wang X.; Kubly V.; Cunningham J.M.; Bacallao R.; Ishibashi M.; Milliner D.S.; Torres V.E.; Harris P.C.;
Nat. Genet. 30:259-269(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS PKD4 MET-36; VAL-222; TRP-1249; ARG-1407; PHE-1664; MET-1741; ARG-1917; GLY-1995; LYS-2331; THR-2957; PHE-3018 AND THR-3553; VARIANTS VAL-25; MET-752; CYS-760; ARG-852; VAL-1262; MET-2938; TYR-3139; ILE-3960 AND ARG-4048;

PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like-plexin-transcription-factor domains and parallel beta-helix 1 repeats.
Onuchic L.F.; Furu L.; Nagasawa Y.; Hou X.; Eggermann T.; Ren Z.; Bergmann C.; Senderek J.; Esquivel E.; Zeltner R.; Rudnik-Schoeneborn S.; Mrug M.; Sweeney W.; Avner E.D.; Zerres K.; Guay-Woodford L.M.; Somlo S.; Germino G.G.;
Am. J. Hum. Genet. 70:1305-1317(2002)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); ALTERNATIVE SPLICING; VARIANTS PKD4 MET-36; VAL-222; LEU-253; HIS-760; SER-1122; TRP-1624 AND THR-2957; VARIANTS VAL-1870 AND TYR-3139;

Spectrum of mutations in the gene for autosomal recessive polycystic kidney disease (ARPKD/PKHD1).
Bergmann C.; Senderek J.; Sedlacek B.; Pegiazoglou I.; Puglia P.; Eggermann T.; Rudnik-Schoeneborn S.; Furu L.; Onuchic L.F.; De Baca M.; Germino G.G.; Guay-Woodford L.; Somlo S.; Moser M.; Buettner R.; Zerres K.;
J. Am. Soc. Nephrol. 14:76-89(2003)
Cited for: VARIANTS PKD4 MET-36; SER-223; LEU-253; SER-473; PRO-496; CYS-656; ASN-703; HIS-760; LEU-805; LYS-997; GLU-1030; SER-1122; SER-1123; TRP-1249; ARG-1407; LEU-1486; TRP-1624; PHE-1664; MET-1741; ARG-1917; GLY-1995; THR-1998; PRO-2134; LYS-2331; TYR-2761; THR-2957; PHE-3018; VAL-3081; VAL-3293; GLY-3471; CYS-3482 AND THR-3553; VARIANTS MET-579; SER-830 AND TYR-3139;

Milder presentation of recessive polycystic kidney disease requires presence of amino acid substitution mutations.
Furu L.; Onuchic L.F.; Gharavi A.; Hou X.; Esquivel E.L.; Nagasawa Y.; Bergmann C.; Senderek J.; Avner E.; Zerres K.; Germino G.G.; Guay-Woodford L.M.; Somlo S.;
J. Am. Soc. Nephrol. 14:2004-2014(2003)
Cited for: VARIANTS PKD4 MET-36; VAL-326; ASN-387 DEL; PRO-899; SER-1123; ILE-1584; ILE-1781; LEU-1789; GLY-1942; ASP-1971; LEU-2032; GLY-2422; PRO-2772; CYS-2863; THR-2957; LEU-2983; GLY-3036; TYR-3124; LEU-3167; ASP-3175; SER-3175; THR-3177; VAL-3293 AND SER-3783; VARIANTS ASP-457; PHE-732; CYS-760; PRO-1150; LEU-1283; PHE-1709; VAL-1870; GLY-2615; ALA-2641; GLY-2861; LYS-2869; TYR-3139; ILE-3143; ASP-3440; LYS-3551; ARG-3899 AND ILE-3960;

A complete mutation screen of PKHD1 in autosomal-recessive polycystic kidney disease (ARPKD) pedigrees.
Rossetti S.; Torra R.; Coto E.; Consugar M.; Kubly V.; Malaga S.; Navarro M.; El-Youssef M.; Torres V.E.; Harris P.C.;
Kidney Int. 64:391-403(2003)
Cited for: VARIANTS PKD4 VAL-17; MET-36; VAL-222; LEU-739; LEU-757; LEU-805; THR-1389; MET-1741; LEU-1833; CYS-1838; ASN-1867; GLY-1942; PHE-2688; THR-2957; THR-3177; ARG-3346; VAL-3468; VAL-3502 AND TYR-3622; VARIANTS CYS-760; SER-830; VAL-1262; PHE-1709; VAL-1870; LYS-2869; TYR-3139; ARG-3505; GLN-3529; ARG-3899; ILE-3960 AND ARG-4048;

PKHD1 mutations in families requesting prenatal diagnosis for autosomal recessive polycystic kidney disease (ARPKD).
Bergmann C.; Senderek J.; Schneider F.; Dornia C.; Kuepper F.; Eggermann T.; Rudnik-Schoeneborn S.; Kirfel J.; Moser M.; Buettner R.; Zerres K.;
Hum. Mutat. 23:487-495(2004)
Cited for: VARIANTS PKD4 MET-36; THR-307; HIS-486; LEU-805; TYR-1472; PHE-2303; THR-2957; GLY-2962; TYR-3124; THR-3177 AND CYS-3482; VARIANTS LYS-2869 AND TYR-3139;

A labor and cost effective next generation sequencing of PKHD1 in autosomal recessive polycystic kidney disease patients.
Tavira B.; Gomez J.; Malaga S.; Santos F.; Fernandez-Aracama J.; Alonso B.; Iglesias S.; Benavides A.; Hernando I.; Plasencia A.; Alvarez V.; Coto E.;
Gene 561:165-169(2015)
Cited for: VARIANTS PKD4 HIS-19; MET-36; LYS-218; VAL-222; TRP-1624; TRP-1624; THR-2957 AND ILE-3289; VARIANTS MET-579; SER-830 AND LYS-2869;

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.