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UniProtKB/Swiss-Prot P62140: Variant p.Pro49Arg

Serine/threonine-protein phosphatase PP1-beta catalytic subunit
Gene: PPP1CB
Variant information

Variant position:  49
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 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

Involvement in disease:  Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2) [MIM:617506]: A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair. {ECO:0000269|PubMed:27264673, ECO:0000269|PubMed:27681385, ECO:0000269|PubMed:27868344, ECO:0000269|PubMed:28211982, ECO:0000269|PubMed:30368668}. 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 NSLH2.
Any additional useful information about the variant.

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



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.

TypePositionsDescription
Chain 2 – 327 Serine/threonine-protein phosphatase PP1-beta catalytic subunit
Metal binding 63 – 63 Manganese 1
Metal binding 65 – 65 Manganese 1


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;

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.