UniProtKB/SwissProt variant VAR

Variant information

Variant position:

64

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 Leucine (L) to Proline (P) at position 64 (L64P, p.Leu64Pro).

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

Involvement in disease:

Hyperparathyroidism 1 (HRPT1) [MIM:145000]: An autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid hyperplasia, adenomas, and carcinomas. {ECO:0000269|PubMed:12434154, ECO:0000269|PubMed:12960210, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:16487440, ECO:0000269|PubMed:18755853}. 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 HRPT1; does not affect interaction with the Pfa1 complex.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121434264 [ dbSNP | Ensembl ]

Sequence information

Variant position:

64

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

Protein sequence length:

531

The length of the canonical sequence.

Location on the sequence:

GTGKEGQPREYYTLDSILFL L NNVHLSHPVYVRRAATENIP

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                         GTGKEGQPR-EYYTLDSILFLLNNVHLSHPVYVRRAATENIP

Mouse                         GTGKEGQPR-EYYTLDSILFLLNNVHLSHPVYVRRAATENI

Rat                           GTGKEGQPR-EYYTLDSILFLLNNVHLSHPVYVRRAATENI

Chicken                       GTGKEGQPR-EYYTLDSILFLLNNVHLSHPVYVRRAATENI

Caenorhabditis elegans        GKSD------EFYSLESLVVFLKYSHENHGVYVKEAAAAGV

Baker's yeast                 EETEIEIDG-SLVQLRIIVHCWMNKDSSAADYLADCQNKQL

Fission yeast                 PTKFIKLENDSHFSLRSVYFAWLLRDTSIAEYIQQCSELGI

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	2 – 531	Parafibromin
Helix	57 – 65

Literature citations

The parafibromin tumor suppressor protein is part of a human Paf1 complex.
Rozenblatt-Rosen O.; Hughes C.M.; Nannepaga S.J.; Shanmugam K.S.; Copeland T.D.; Guszczynski T.; Resau J.H.; Meyerson M.;
Mol. Cell. Biol. 25:612-620(2005)
Cited for: FUNCTION; INTERACTION WITH PAF1; LEO1 AND POLR2A; INTERACTION WITH SET1-LIKE COMPLEX; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT HRPT1 PRO-64;

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.
Carpten J.D.; Robbins C.M.; Villablanca A.; Forsberg L.; Presciuttini S.; Bailey-Wilson J.; Simonds W.F.; Gillanders E.M.; Kennedy A.M.; Chen J.D.; Agarwal S.K.; Sood R.; Jones M.P.; Moses T.Y.; Haven C.; Petillo D.; Leotlela P.D.; Harding B.; Cameron D.; Pannett A.A.; Hoeoeg A.; Heath H. III; James-Newton L.A.; Robinson B.; Zarbo R.J.; Cavaco B.M.; Wassif W.; Perrier N.D.; Rosen I.B.; Kristoffersson U.; Turnpenny P.D.; Farnebo L.-O.; Besser G.M.; Jackson C.E.; Morreau H.; Trent J.M.; Thakker R.V.; Marx S.J.; Teh B.T.; Larsson C.; Hobbs M.R.;
Nat. Genet. 32:676-680(2002)
Cited for: INVOLVEMENT IN HRPT2; INVOLVEMENT IN HRPT1; VARIANT HRPT1 PRO-64;

HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.
Howell V.M.; Haven C.J.; Kahnoski K.; Khoo S.K.; Petillo D.; Chen J.; Fleuren G.J.; Robinson B.G.; Delbridge L.W.; Philips J.; Nelson A.E.; Krause U.; Hammje K.; Dralle H.; Hoang-Vu C.; Gimm O.; Marsh D.J.; Morreau H.; Teh B.T.;
J. Med. Genet. 40:657-663(2003)
Cited for: VARIANT HRPT1 PRO-64;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q6P1J9: Variant p.Leu64Pro