JPH2 (junctophilin 2)

Gene

• Entrez ID: 57158
• Gene name: Junctophilin 2
• Gene symbol: JPH2
• Synonyms: CMD2E, CMH17, JP-2, JP2
• Chromosome: 20
• Chromosome location: 20q13.12
• Summary: Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs387906897	A>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs387906898	G>A	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs398124358	G>A,C	Likely-benign, conflicting-interpretations-of-pathogenicity, benign-likely-benign	Genic downstream transcript variant, coding sequence variant, synonymous variant
rs531877510	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity, benign-likely-benign	Genic downstream transcript variant, coding sequence variant, synonymous variant
rs554853074	G>C	Benign, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, missense variant
rs557878787	C>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, missense variant
rs587782951	G>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs754529157	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1600482909	T>G	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT054386	hsa-miR-24-3p	Luciferase reporter assay	22891046
MIRT054386	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT615558	hsa-miR-3180-5p	HITS-CLIP	23824327
MIRT615559	hsa-miR-4309	HITS-CLIP	23824327
MIRT615560	hsa-miR-3198	HITS-CLIP	23824327
MIRT615561	hsa-miR-525-5p	HITS-CLIP	23824327
MIRT615562	hsa-miR-520a-5p	HITS-CLIP	23824327
MIRT615563	hsa-miR-4294	HITS-CLIP	23824327
MIRT615564	hsa-miR-1289	HITS-CLIP	23824327
MIRT615565	hsa-miR-4534	HITS-CLIP	23824327
MIRT615566	hsa-miR-8082	HITS-CLIP	23824327
MIRT615567	hsa-miR-488-5p	HITS-CLIP	23824327
MIRT615568	hsa-miR-6514-5p	HITS-CLIP	23824327
MIRT618936	hsa-miR-6730-3p	HITS-CLIP	23824327
MIRT618936	hsa-miR-6730-3p	HITS-CLIP	19536157
MIRT618937	hsa-miR-1273h-3p	HITS-CLIP	23824327
MIRT618938	hsa-miR-4771	HITS-CLIP	23824327
MIRT618939	hsa-miR-3166	HITS-CLIP	23824327
MIRT618940	hsa-miR-17-3p	HITS-CLIP	23824327
MIRT618940	hsa-miR-17-3p	HITS-CLIP	19536157
MIRT618941	hsa-miR-1205	HITS-CLIP	23824327
MIRT618941	hsa-miR-1205	HITS-CLIP	19536157
MIRT618942	hsa-miR-1184	HITS-CLIP	23824327
MIRT618942	hsa-miR-1184	HITS-CLIP	19536157
MIRT618943	hsa-miR-3158-5p	HITS-CLIP	23824327
MIRT618943	hsa-miR-3158-5p	HITS-CLIP	19536157
MIRT618944	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT618944	hsa-miR-362-3p	HITS-CLIP	19536157
MIRT618945	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT618945	hsa-miR-329-3p	HITS-CLIP	19536157
MIRT618946	hsa-miR-6829-3p	HITS-CLIP	23824327
MIRT618946	hsa-miR-6829-3p	HITS-CLIP	19536157
MIRT618947	hsa-miR-8485	HITS-CLIP	23824327
MIRT618947	hsa-miR-8485	HITS-CLIP	19536157
MIRT618948	hsa-miR-6791-3p	HITS-CLIP	23824327
MIRT618948	hsa-miR-6791-3p	HITS-CLIP	19536157
MIRT618949	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT618949	hsa-miR-6747-3p	HITS-CLIP	19536157
MIRT618950	hsa-miR-5193	HITS-CLIP	23824327
MIRT618950	hsa-miR-5193	HITS-CLIP	19536157
MIRT657072	hsa-miR-3941	HITS-CLIP	23824327
MIRT657073	hsa-miR-603	HITS-CLIP	23824327
MIRT657074	hsa-miR-640	HITS-CLIP	23824327
MIRT657075	hsa-miR-6513-3p	HITS-CLIP	23824327
MIRT657076	hsa-miR-8079	HITS-CLIP	23824327
MIRT657077	hsa-miR-1245a	HITS-CLIP	23824327
MIRT662945	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT662946	hsa-miR-8057	HITS-CLIP	23824327
MIRT662947	hsa-miR-6805-3p	HITS-CLIP	23824327
MIRT662948	hsa-miR-5691	HITS-CLIP	23824327
MIRT662949	hsa-miR-7641	HITS-CLIP	23824327
MIRT662950	hsa-miR-143-5p	HITS-CLIP	23824327
MIRT662951	hsa-miR-6879-3p	HITS-CLIP	23824327
MIRT662952	hsa-miR-5698	HITS-CLIP	23824327
MIRT662953	hsa-miR-4430	HITS-CLIP	23824327
MIRT662954	hsa-miR-3652	HITS-CLIP	23824327
MIRT662955	hsa-miR-4284	HITS-CLIP	23824327
MIRT662956	hsa-miR-122-5p	HITS-CLIP	23824327
MIRT662957	hsa-miR-504-3p	HITS-CLIP	23824327
MIRT662958	hsa-miR-3135b	HITS-CLIP	23824327
MIRT662959	hsa-miR-3194-3p	HITS-CLIP	23824327
MIRT662960	hsa-miR-6499-3p	HITS-CLIP	23824327
MIRT662961	hsa-miR-6773-3p	HITS-CLIP	23824327
MIRT662962	hsa-miR-5693	HITS-CLIP	23824327
MIRT662963	hsa-miR-500b-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001786	Function	Phosphatidylserine binding	IDA	24001019
GO:0003677	Function	DNA binding	IEA
GO:0005515	Function	Protein binding	IPI	20095964
GO:0005546	Function	Phosphatidylinositol-4,5-bisphosphate binding	IDA	24001019
GO:0005547	Function	Phosphatidylinositol-3,4,5-trisphosphate binding	IDA	24001019
GO:0005634	Component	Nucleus	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0007275	Process	Multicellular organism development	IEA
GO:0010314	Function	Phosphatidylinositol-5-phosphate binding	IDA	24001019
GO:0014701	Component	Junctional sarcoplasmic reticulum membrane	TAS	19095005
GO:0016021	Component	Integral component of membrane	IEA
GO:0016529	Component	Sarcoplasmic reticulum	IBA	21873635
GO:0030018	Component	Z disc	IEA
GO:0030314	Component	Junctional membrane complex	IBA	21873635
GO:0032266	Function	Phosphatidylinositol-3-phosphate binding	IDA	24001019
GO:0055024	Process	Regulation of cardiac muscle tissue development	IEA
GO:0055074	Process	Calcium ion homeostasis	IDA	20095964
GO:0060314	Process	Regulation of ryanodine-sensitive calcium-release channel activity	TAS	19095005
GO:0060316	Process	Positive regulation of ryanodine-sensitive calcium-release channel activity	IDA	20095964
GO:0060402	Process	Calcium ion transport into cytosol	TAS	19095005
GO:0070273	Function	Phosphatidylinositol-4-phosphate binding	IDA	24001019
GO:0070300	Function	Phosphatidic acid binding	IDA	24001019
GO:0080025	Function	Phosphatidylinositol-3,5-bisphosphate binding	IDA	24001019

Other IDs

• MIM: 605267
• HGNC: 14202
• e!Ensembl: ENSG00000149596

Protein

• UniProt ID: Q9BR39
• Protein name: Junctophilin-2 (JP-2) (Junctophilin type 2) [Cleaved into: Junctophilin-2 N-terminal fragment (JP2NT)]
• Protein function: [Junctophilin-2]: Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes (PubMed:20095964). Provides a structural foundation for functional cross-talk between the cell surface and intracellular Ca(2+) release channels by maintaining the 12-15 nm gap between the sarcolemma and the sarcoplasmic reticulum membranes in the cardiac dyads (By similarity). Necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release (By similarity). Contributes to the construction of skeletal muscle triad junctions (By similarity). ; [Junctophilin-2 N-terminal fragment]: Transcription repressor required to safeguard against the deleterious effects of cardiac stress. Generated following cleavage of the Junctophilin-2 chain by calpain in response to cardiac stress in cardiomyocytes. Following cleavage and release from the membrane, translocates to the nucleus, binds DNA and represses expression of genes implicated in cell growth and differentiation, hypertrophy, inflammation and fibrosis. Modifies the transcription profile and thereby attenuates pathological remodeling in response to cardiac stress. Probably acts by competing with MEF2 transcription factors and TATA-binding proteins.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02493	MORN	14 → 36	MORN repeat	Repeat
  PF02493	MORN	38 → 59	MORN repeat	Repeat
  PF02493	MORN	60 → 78	MORN repeat	Repeat
  PF02493	MORN	82 → 103	MORN repeat	Repeat
  PF02493	MORN	106 → 128	MORN repeat	Repeat
  PF02493	MORN	129 → 151	MORN repeat	Repeat
  PF02493	MORN	291 → 313	MORN repeat	Repeat
  PF02493	MORN	314 → 336	MORN repeat	Repeat

• Sequence:

  MSGGRFDFDDGGAYCGGWEGGKAHGHGLCTGPKGQGEYSGSWNFGFEVAGVYTWPSGNTF
  EGYWSQGKRHGLGIETKGRWLYKGEWTHGFKGRYGIRQSSSSGAKYEGTWNNGLQDGYGT
  ETYADGGTYQGQFTNGMRHGYGVRQSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSP
  ASPASDGPALPSPAIPRGGFALSLLANAEAAARAPKGGGLFQRGALLGKLRRAESRTSVG
  SQRSRVSFLKSDLSSGASDAASTASLGEAAEGADEAAPFEADIDATTTETYMGEWKNDKR
  SGFGVSERSSGLRYEGEWLDNLRHGYGCTTLPDGHREEGKYRHNVLVKDTKRRMLQLKSN
  KVRQKVEHSVEGAQRAAAIARQKAEIAASRTSHAKAKAEAAEQAALAANQESNIARTLAR
  ELAPDFYQPGPEYQKRRLLQEILENSESLLEPPDRGAGAAGLPQPPRESPQLHERETPRP
  EGGSPSPAGTPPQPKRPRPGVSKDGLLSPGAWNGEPSGEGSRSVTPSEGAGRRSPARPAT
  ERMAIEALQAPPAPSREPEVALYQGYHSYAVRTTPPEPPPFEDQPEPEVSGSESAPSSPA
  TAPLQAPTLRGPEPARETPAKLEPKPIIPKAEPRAKARKTEARGLTKAGAKKKARKEAAL
  AAEAEVEVEEVPNTILICMVILLNIGLAILFVHLLT

• Sequence length: 696

Associated diseases

Disease name	Disease term	References
	Cardiomyopathies
	Cardiomyopathy, Hypertrophic, Familial
	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 17	17509612, 21216834, 21339484, 17476457, 28393127, 26869393, 15541368, 30235249, 30681346, 23973696, 24001019
	Cardiovascular Diseases	30595370
	NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy
	Left Ventricular Hypertrophy