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UniProtKB/Swiss-Prot P10644: Variant p.Tyr175Cys

cAMP-dependent protein kinase type I-alpha regulatory subunit
Gene: PRKAR1A
Chromosomal location: 17q23-q24
Variant information

Variant position:  175
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 Tyrosine (Y) to Cysteine (C) at position 175 (Y175C, p.Tyr175Cys).
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 large size and aromatic (Y) to medium size and polar (C)
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:  Acrodysostosis 1, with or without hormone resistance (ACRDYS1) [MIM:101800]: A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities. {ECO:0000269|PubMed:21651393, ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:22723333, ECO:0000269|PubMed:23043190, ECO:0000269|PubMed:23425300, ECO:0000269|PubMed:26405036}. 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 ACRDYS1; reduces PKA activity; decreases cAMP binding.
Any additional useful information about the variant.



Sequence information

Variant position:  175
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  381
The length of the canonical sequence.

Location on the sequence:   SVSFIAGETVIQQGDEGDNF  Y VIDQGETDVYVNNEWATSVG
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                         SVSFIAGETVIQQGDEGDNFYVIDQGETDVYVNNEWATSVG

Mouse                         PVSFIAGETVIQQGDEGDNFYVIDQGEMDVYVNNEWATSVG

Rat                           PVSFIAGETVIQQGDEGDNFYVIDQGEMDVYVNNEWATSVG

Pig                           PVSFIAGETVIQQGDEGDNFYVIDQGEMDVYVNNEWATSVG

Bovine                        PVSFIAGETVIQQGDEGDNFYVIDQGEMDVYVNNEWATSVG

Chicken                       PVTYIAGETVIQQGDEGDNFYVVDQGEMDVYVNNEWATSVG

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 1 – 381 cAMP-dependent protein kinase type I-alpha regulatory subunit
Nucleotide binding 137 – 254 cAMP 1


Literature citations

Functional characterization of PRKAR1A mutations reveals a unique molecular mechanism causing acrodysostosis but multiple mechanisms causing carney complex.
Rhayem Y.; Le Stunff C.; Abdel Khalek W.; Auzan C.; Bertherat J.; Linglart A.; Couvineau A.; Silve C.; Clauser E.;
J. Biol. Chem. 290:27816-27828(2015)
Cited for: VARIANT ACRDYS1 CYS-175; CHARACTERIZATION OF VARIANTS ACRDYS1 CYS-175; THR-213; ARG-285; GLU-289; VAL-328 AND LEU-335; CHARACTERIZATION OF VARIANTS CNC1 ASP-213 AND TRP-289; FUNCTION;

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.