JPH2

junctophilin 2, the group of Junctophilins

Basic information

Region (hg38): 20:44106590-44187188

Links

ENSG00000149596 ∙ NCBI:57158 ∙ OMIM:605267 ∙ HGNC:14202 ∙ Uniprot:Q9BR39 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 17 (Moderate), mode of inheritance: AD
• hypertrophic cardiomyopathy 17 (Strong), mode of inheritance: AD
• cardiomyopathy, dilated, 2E (Limited), mode of inheritance: Unknown
• dilated cardiomyopathy (Moderate), mode of inheritance: Semidominant
• hypertrophic cardiomyopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic 17; Cardiomyopathy, dilated, 2E	AD/AR	Cardiovascular	In both hypertrophic and dilated forms of cardiomyopathy, surveillance and medical management, may reduce morbidity; Cardiac transplant has been described in Dilated cardiomyopathy	Cardiovascular	17476457; 17509612; 22515980; 30384889; 31227780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JPH2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JPH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	234	6	243
missense		1	440	9	2	452
nonsense			7			7
start loss						0
frameshift			10			10
inframe indel			16			16
splice donor/acceptor (+/-2bp)			1			1
splice region			7	5	2	14
non coding			2	50	27	79
Total	0	1	479	293	35

Variants in JPH2

This is a list of pathogenic ClinVar variants found in the JPH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-44113260-C-T			Benign (Nov 12, 2019)
20-44113503-T-A		Cardiomyopathy, dilated, 2E;Hypertrophic cardiomyopathy 17	Uncertain significance (Aug 20, 2021)
20-44113618-T-G			Benign (Jun 25, 2020)
20-44114513-G-A			Benign (Jun 19, 2018)
20-44114523-G-A			Likely benign (Jun 19, 2018)
20-44114565-AGT-A			Benign (Aug 18, 2019)
20-44114565-AGTGT-A			Benign (Aug 15, 2019)
20-44114565-AGTGTGT-A			Benign (Aug 15, 2019)
20-44114565-AGTGTGTGT-A			Benign (Aug 06, 2019)
20-44114565-AGTGTGTGTGTGTGTGTGT-A			Benign (Aug 10, 2019)
20-44114565-A-AGT			Benign (Aug 15, 2019)
20-44114607-T-C			Likely benign (Aug 13, 2019)
20-44114609-T-C			Benign (Aug 08, 2019)
20-44114609-T-TGC			Likely benign (Aug 20, 2019)
20-44114609-T-TGCGC			Likely benign (Aug 21, 2019)
20-44114658-G-A			Likely benign (Jun 18, 2018)
20-44114767-G-A		not specified	Likely benign (Dec 20, 2016)
20-44114793-C-T			Likely benign (Sep 07, 2018)
20-44114802-C-A		Hypertrophic cardiomyopathy	Likely benign (Jan 07, 2023)
20-44114802-CAG-C		Cardiovascular phenotype	Uncertain significance (Oct 22, 2020)
20-44114809-T-A		Cardiovascular phenotype	Uncertain significance (Aug 27, 2022)
20-44114810-G-C		Hypertrophic cardiomyopathy	Uncertain significance (Mar 15, 2023)
20-44114813-C-T		Cardiovascular phenotype	Uncertain significance (Dec 14, 2022)
20-44114813-CA-TG		Cardiovascular phenotype • Hypertrophic cardiomyopathy • Cardiomyopathy, dilated, 2E	Uncertain significance (Aug 13, 2024)
20-44114814-A-G		not specified • Cardiovascular phenotype • Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 17	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JPH2	protein_coding	protein_coding	ENST00000372980	5	75884

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000452	0.992	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	328	443	0.740	0.0000333	4311
Missense in Polyphen		124	201.92	0.61412		1892
Synonymous	2.20	172	213	0.808	0.0000181	1496
Loss of Function	2.36	11	23.3	0.472	0.00000116	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000625	0.000601
European (Non-Finnish)	0.0000667	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH2 is necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release. Contributes to the construction of skeletal muscle triad junctions. {ECO:0000269|PubMed:20095964}.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 17 (CMH17) [MIM:613873]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:17509612, ECO:0000269|PubMed:24001019}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.144

Haploinsufficiency Scores

• pHI: 0.164
• hipred: Y
• hipred_score: 0.594
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Jph2
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype

Gene ontology

• Biological process: release of sequestered calcium ion into cytosol;regulation of cardiac muscle tissue development;calcium ion homeostasis;regulation of ryanodine-sensitive calcium-release channel activity;positive regulation of ryanodine-sensitive calcium-release channel activity;calcium ion transport into cytosol
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;junctional sarcoplasmic reticulum membrane;integral component of membrane;sarcoplasmic reticulum;Z disc;junctional membrane complex
• Molecular function: phosphatidylserine binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-5-phosphate binding;calcium-release channel activity;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-4-phosphate binding;phosphatidic acid binding;phosphatidylinositol-3,5-bisphosphate binding