UniProtKB/Swiss-Prot Q06124: Variant p.Gln514Glu

Tyrosine-protein phosphatase non-receptor type 11
Gene: PTPN11
Chromosomal location: 12q24.1
Variant information

Variant position:  514
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 Glutamine (Q) to Glutamate (E) at position 514 (Q514E, p.Gln514Glu).
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 polar (Q) to medium size and acidic (E)
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:  LEOPARD syndrome 1 (LPRD1) [MIM:151100]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:12058348, ECO:0000269|PubMed:14961557, ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15389709, ECO:0000269|PubMed:15520399, ECO:0000269|PubMed:15690106, ECO:0000269|PubMed:16679933, ECO:0000269|PubMed:16733669, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:26742426}. 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.

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 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73.
Any additional useful information about the variant.

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



Sequence information

Variant position:  514
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:   VPKTIQMVRSQRSGMVQTEA  Q YRFIYMAVQHYIETLQRRIE
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                         VPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIE

Mouse                         VPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIE

Rat                           VPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIE

Chicken                       VPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIE

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 – 597 Tyrosine-protein phosphatase non-receptor type 11
Domain 247 – 521 Tyrosine-protein phosphatase
Binding site 510 – 510 Substrate
Alternative sequence 465 – 597 Missing. In isoform 3.
Helix 512 – 528


Literature citations

A novel mutation in the PTPN11 gene in a patient with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy.
Takahashi K.; Kogaki S.; Kurotobi S.; Nasuno S.; Ohta M.; Okabe H.; Wada K.; Sakai N.; Taniike M.; Ozono K.;
Eur. J. Pediatr. 164:497-500(2005)
Cited for: VARIANT NS1 GLU-514;

PTPN11 gene mutations: linking the Gln510Glu mutation to the 'LEOPARD syndrome phenotype'.
Digilio M.C.; Sarkozy A.; Pacileo G.; Limongelli G.; Marino B.; Dallapiccola B.;
Eur. J. Pediatr. 165:803-805(2006)
Cited for: VARIANT LPRD1 GLU-514;

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
Noda S.; Takahashi A.; Hayashi T.; Tanuma S.; Hatakeyama M.;
Biochem. Biophys. Res. Commun. 469:1133-1139(2016)
Cited for: VARIANT JMML LYS-76; CHARACTERIZATION OF VARIANT JMML LYS-76; VARIANTS LPRD1 CYS-279; MET-472; PRO-510 AND GLU-514; CHARACTERIZATION OF VARIANTS LPRD1 CYS-279; MET-472; PRO-510 AND GLU-514; FUNCTION; CATALYTIC ACTIVITY; INTERACTION WITH CDC73; SUBCELLULAR LOCATION;

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.