JPH3 junctophilin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: JPH3provided by HGNC
Official Full Name: junctophilin 3provided by HGNC
Primary source: HGNC:HGNC:14203
See related: Ensembl:ENSG00000154118 MIM:605268; AllianceGenome:HGNC:14203
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: JP3; HDL2; JP-3; TNRC22; CAGL237
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. CAG/CTG repeat expansion from normally 6-28 repeats to 40-59 repeats in the 3' UTR of this gene have been associated with Huntington disease-like 2 (HDL2). This gene is a member of the junctophilin gene family. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2016]
Expression: Biased expression in brain (RPKM 10.9), adrenal (RPKM 0.6) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 16q24.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (87601835..87698156)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (93673276..93769801)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (87635441..87731762)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Both Heterozygous and Homozygous Loss-of-Function JPH3 Variants Are Associated with a Paroxysmal Movement Disorder.
Title: Both Heterozygous and Homozygous Loss-of-Function JPH3 Variants Are Associated with a Paroxysmal Movement Disorder.
Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence.
Title: Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence.
Thus, JPH3 was identified as a novel tumor suppressor gene methylated in colorectal and gastric tumors which promotes mitochondrial-mediated apoptosis, also as a potential metastasis and survival biomarker for digestive cancers.
Title: Epigenomic and Functional Characterization of Junctophilin 3 (JPH3) as a Novel Tumor Suppressor Being Frequently Inactivated by Promoter CpG Methylation in Digestive Cancers.
The expression of JPH isoforms was examined in human and mouse pancreatic tissues, and JPH3 expression was found in both the beta cells.
Title: Junctophilin 3 expresses in pancreatic beta cells and is required for glucose-stimulated insulin secretion.
This study identified that abnormal CTG expansions in JPH3 in patient with Huntington Disease.
Title: Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.
The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation.
Title: Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.
JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent.
Title: JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family.
The pathogenic mechanism of Huntington disease-like 2 is multifactorial, involving both a toxic gain of function of JPH3 RNA transcripts and a toxic loss of JPH3 expression in an experimental Huntington disease-like 2 mouse model.
Title: Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.
This study reveled the an antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.
Title: An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Huntington disease-like 2 MedGen: C1847987 OMIM: 606438 GeneReviews: Huntington Disease-Like 2	not available

EBI GWAS Catalog

Description
Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-60765 (e-PCR)
- UniSTS:65301

SHGC-152224 (e-PCR)
- UniSTS:177437

RH66295 (e-PCR)
- UniSTS:66188

SHGC-145946 (e-PCR)
- UniSTS:182963

D16S305 (e-PCR)
- UniSTS:146904

D16S3123 (e-PCR)
- UniSTS:49130

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in calcium ion transport into cytosol	TAS Traceable Author Statement more info	PubMed
involved_in exploration behavior	IEA Inferred from Electronic Annotation more info
involved_in learning	IEA Inferred from Electronic Annotation more info
involved_in locomotion	IEA Inferred from Electronic Annotation more info
involved_in memory	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of ryanodine-sensitive calcium-release channel activity	TAS Traceable Author Statement more info	PubMed
involved_in regulation of synaptic plasticity	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
part_of junctional membrane complex	IBA Inferred from Biological aspect of Ancestor more info
located_in junctional sarcoplasmic reticulum membrane	TAS Traceable Author Statement more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: junctophilin-3

Names: junctophilin type 3; trinucleotide repeat containing 22

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009797.1 RefSeqGene

Range

4616..100264

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001271604.4 → NP_001258533.1 junctophilin-3 isoform 2

See identical proteins and their annotated locations for NP_001258533.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks several exons and includes an alternate 3' terminal exon compared to variant 1. The latter results in a frame-shift and a much shorter isoform (2) with a distinct C-terminus containing a 13 aa polyalanine stretch compared to isoform 1. This variant is described in PMID:11694876.

Source sequence(s)

AB593088, AC092720, BC008690

UniProtKB/TrEMBL

F8W9A3

Conserved Domains (1) summary

pfam02493
Location:107 → 128

MORN; MORN repeat
NM_001271605.3 → NP_001258534.1 junctophilin-3 isoform 3

See identical proteins and their annotated locations for NP_001258534.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks several exons and includes an alternate 3' terminal exon compared to variant 1. The latter results in a frame-shift and a much shorter isoform (3) with a distinct C-terminus compared to isoform 1. This variant is described in PMID:11694876.

Source sequence(s)

AB593088, AC092720, BC008690

UniProtKB/TrEMBL

F8W9A3, Q96HD8

Conserved Domains (1) summary

PLN03185
Location:5 → 132

PLN03185; phosphatidylinositol phosphate kinase; Provisional
NM_020655.4 → NP_065706.2 junctophilin-3 isoform 1

See identical proteins and their annotated locations for NP_065706.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB593088, AC092720, AK295518, AW954561, BC036533, BQ014355

Consensus CDS

CCDS10962.1

UniProtKB/Swiss-Prot

D3DUN2, Q8N471, Q8WXH2, Q9HDC3, Q9HDC4

UniProtKB/TrEMBL

B4DIC1

Related

ENSP00000284262.2, ENST00000284262.3

Conserved Domains (1) summary

pfam02493
Location:311 → 333

MORN; MORN repeat

RNA

NR_073379.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5' terminal exon and is alternately spliced at the 3' end compared to variant 1. The latter renders this variant a candidate for nonsense-mediated mRNA decay (NMD), hence it is represented as non-coding.

Source sequence(s)

AA813196, AK295518, BC036533, BG205692, BQ014355

Related

ENST00000537256.5