UniProtKB/Swiss-Prot Q9BR39: Variant p.Ser165Phe

Junctophilin-2
Gene: JPH2
Chromosomal location: 20q13.12
Variant information

Variant position:  165
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Serine (S) to Phenylalanine (F) at position 165 (S165F, p.Ser165Phe).
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 small size and polar (S) to large size and aromatic (F)
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 CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. Greatly reduced phosphorylation. Increased myotube diameter. Reduced RYR1 activity and EC gain. Disruption of interaction with TRPC3.
Any additional useful information about the variant.



Sequence information

Variant position:  165
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  696
The length of the canonical sequence.

Location on the sequence:   QSVPYGMAVVVRSPLRTSLS  S LRSEHSNGTVAPDSPASPAS
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                         QSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSPASPAS

Mouse                         QSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPD---SPAA

Rat                           QSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPD---SPAA

Rabbit                        QSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSPASPAA

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 – 696 Junctophilin-2
Topological domain 1 – 674 Cytoplasmic
Modified residue 165 – 165 Phosphoserine
Alternative sequence 130 – 696 Missing. In isoform 2.


Literature citations

S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle.
Woo J.S.; Hwang J.H.; Ko J.K.; Weisleder N.; Kim do H.; Ma J.; Lee E.H.;
Biochem. J. 427:125-134(2010)
Cited for: PHOSPHORYLATION AT SER-165; INTERACTION WITH TRPC3; FUNCTION; CHARACTERIZATION OF VARIANT PHE-165;

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans.
Landstrom A.P.; Weisleder N.; Batalden K.B.; Bos J.M.; Tester D.J.; Ommen S.R.; Wehrens X.H.; Claycomb W.C.; Ko J.K.; Hwang M.; Pan Z.; Ma J.; Ackerman M.J.;
J. Mol. Cell. Cardiol. 42:1026-1035(2007)
Cited for: VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165; CHARACTERIZATION OF VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165;

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.