UniProtKB/Swiss-Prot P62140: Variant p.Pro49Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 49 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Proline (P) to Arginine (R) at position 49 (P49R, p.Pro49Arg). 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 (P) to large size and basic (R) 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 NSLH2. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs886037952 [ dbSNP | Ensembl ]

Sequence information

Variant position: 49 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 327 The length of the canonical sequence.
Location on the sequence: MTEAEVRGLCIKSREIFLSQ P ILLELEAPLKICGDIHGQYT 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.

Type	Positions	Description
Chain	2 – 327	Serine/threonine-protein phosphatase PP1-beta catalytic subunit
Binding site	63 – 63
Binding site	65 – 65

Literature citations

A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair.
Gripp K.W.; Aldinger K.A.; Bennett J.T.; Baker L.; Tusi J.; Powell-Hamilton N.; Stabley D.; Sol-Church K.; Timms A.E.; Dobyns W.B.;
Am. J. Med. Genet. A 170:2237-2247(2016)
Cited for: INVOLVEMENT IN NSLH2; VARIANTS NSLH2 ARG-49 AND PRO-56; De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease.
Ma L.; Bayram Y.; McLaughlin H.M.; Cho M.T.; Krokosky A.; Turner C.E.; Lindstrom K.; Bupp C.P.; Mayberry K.; Mu W.; Bodurtha J.; Weinstein V.; Zadeh N.; Alcaraz W.; Powis Z.; Shao Y.; Scott D.A.; Lewis A.M.; White J.J.; Jhangiani S.N.; Gulec E.Y.; Lalani S.R.; Lupski J.R.; Retterer K.; Schnur R.E.; Wentzensen I.M.; Bale S.; Chung W.K.;
Hum. Genet. 135:1399-1409(2016)
Cited for: INVOLVEMENT IN NSLH2; VARIANTS NSLH2 ARG-49; ALA-183; VAL-183; TYR-252 AND LYS-274; Further evidence that variants in PPP1CB cause a rasopathy similar to Noonan syndrome with loose anagen hair.
Zambrano R.M.; Marble M.; Chalew S.A.; Lilje C.; Vargas A.; Lacassie Y.;
Am. J. Med. Genet. A 173:565-567(2017)
Cited for: INVOLVEMENT IN NSLH2; VARIANT NSLH2 ARG-49; The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: Broadening the clinical phenotype.
Bertola D.; Yamamoto G.; Buscarilli M.; Jorge A.; Passos-Bueno M.R.; Kim C.;
Am. J. Med. Genet. A 173:824-828(2017)
Cited for: INVOLVEMENT IN NSLH2; VARIANT NSLH2 ARG-49; Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes.
Umeki I.; Niihori T.; Abe T.; Kanno S.I.; Okamoto N.; Mizuno S.; Kurosawa K.; Nagasaki K.; Yoshida M.; Ohashi H.; Inoue S.I.; Matsubara Y.; Fujiwara I.; Kure S.; Aoki Y.;
Hum. Genet. 138:21-35(2019)
Cited for: VARIANT NSLH2 ARG-49; INTERACTION WITH LZTR1;