JPH1
protein-codingjunctophilin 1, the group of Junctophilins
Gene 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. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0975808
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0975808
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to JPH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020647.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 7 | 3 | 12 | ||
| missense | 75 | 1 | 4 | 80 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 3 | 79 | 8 | 7 | 98 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065698.1 | 5 | MANE Select | |
| Ensembl | ENSP00000344488.4 | 5 | MANE Select | |
| RefSeq | NP_001304759.1 | 5 | Standard | |
| RefSeq | NP_001349979.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- muscle organ development
- release of sequestered calcium ion into cytosol
- regulation of ryanodine-sensitive calcium-release channel activity
- calcium ion transport into cytosol
Molecular Function
- molecular_function
- structural constituent of muscle
- calcium-release channel activity
Cellular Component
- nucleus
- nucleoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000342232
- Coding exons
- 5
- Length
- 86629
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125748
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.46 | 340 | 425 | 0.800 | 0.0000269 | 4309 |
| Missense (PolyPhen) | 87 | 161.53 | 0.53861 | 1506 | ||
| Synonymous | 0.868 | 169 | 184 | 0.919 | 0.0000140 | 1311 |
| Loss of Function | 3.60 | 4 | 22.4 | 0.179 | 9.57e-7 | 284 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes.;
Recessive Scores
- pRec
- 0.140
Intolerance Scores
- LoFtool
- 0.215
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.789
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |