UniProtKB/SwissProt variant VAR

Variant information

Variant position:

261

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 Histidine (H) at position 261 (L261H, p.Leu261His).

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 (L) to medium size and polar (H)

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:

Noonan syndrome 1 (NS1) [MIM:163950]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints. {ECO:0000269|PubMed:11704759, ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12529711, ECO:0000269|PubMed:12634870, ECO:0000269|PubMed:12717436, ECO:0000269|PubMed:12739139, ECO:0000269|PubMed:12960218, ECO:0000269|PubMed:15384080, ECO:0000269|PubMed:15889278, ECO:0000269|PubMed:15948193, ECO:0000269|PubMed:19020799, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:28074573}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in PTPN11 account for more than 50% of the cases.

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 NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs765642157 [ dbSNP | Ensembl ]

Sequence information

Variant position:

261

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

Protein sequence length:

597

The length of the canonical sequence.

Location on the sequence:

DKVKQGFWEEFETLQQQECK L LYSRKEGQRQENKNKNRYKN

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                         DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKN

Mouse                         DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKN

Rat                           DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKN

Chicken                       DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKN

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 – 597	Tyrosine-protein phosphatase non-receptor type 11
Domain	247 – 521	Tyrosine-protein phosphatase
Helix	259 – 262

Literature citations

Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.
Pannone L.; Bocchinfuso G.; Flex E.; Rossi C.; Baldassarre G.; Lissewski C.; Pantaleoni F.; Consoli F.; Lepri F.; Magliozzi M.; Anselmi M.; Delle Vigne S.; Sorge G.; Karaer K.; Cuturilo G.; Sartorio A.; Tinschert S.; Accadia M.; Digilio M.C.; Zampino G.; De Luca A.; Cav e H.; Zenker M.; Gelb B.D.; Dallapiccola B.; Stella L.; Ferrero G.B.; Martinelli S.; Tartaglia M.;
Hum. Mutat. 38:451-459(2017)
Cited for: VARIANTS NS1 HIS-261; PHE-261; ARG-262; PHE-262 AND GLN-265; CHARACTERIZATION OF VARIANTS NS1 HIS-261; PHE-261; ARG-262; PHE-262 AND GLN-265; FUNCTION; CATALYTIC ACTIVITY;

UniProtKB/Swiss-Prot Q06124: Variant p.Leu261His