JPH3

junctophilin 3, the group of Junctophilins

Basic information

Region (hg38): 16:87601835-87698156

Previous symbols: [ "TNRC22" ]

Links

ENSG00000154118 ∙ NCBI:57338 ∙ OMIM:605268 ∙ HGNC:14203 ∙ Uniprot:Q8WXH2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Huntington disease-like 2 (Definitive), mode of inheritance: AD
• Huntington disease-like 2 (Strong), mode of inheritance: AD
• Huntington disease-like 2 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Huntington disease-like 2	AD	General	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	Neurologic	11694876; 11761463; 11914418; 11940688; 12805114; 14557581; 18816802; 19735092; 22367996; 22971727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JPH3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JPH3 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				28	22	50
missense			76	12	2	90
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				1	1	2
Total	0	0	78	41	25

Variants in JPH3

This is a list of pathogenic ClinVar variants found in the JPH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-87603150-T-A		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
16-87603180-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2024)
16-87603238-C-T		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
16-87603250-G-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
16-87603266-C-A			Likely benign (Mar 02, 2018)
16-87603294-C-G		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
16-87603300-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
16-87603363-A-G		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
16-87603413-C-T			Likely benign (Aug 02, 2018)
16-87603455-C-T		JPH3-related disorder	Likely benign (Feb 20, 2019)
16-87603457-G-A			Uncertain significance (Oct 12, 2022)
16-87603475-C-T		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
16-87603525-G-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2023)
16-87604163-C-T		JPH3-related disorder	Likely benign (Apr 30, 2021)
16-87644271-C-A			Likely benign (May 24, 2018)
16-87644280-C-T			Benign (Dec 31, 2019)
16-87644281-G-A			Benign/Likely benign (Jul 01, 2022)
16-87644301-C-T		JPH3-related disorder	Likely benign (Jan 10, 2023)
16-87644302-G-T		Inborn genetic diseases	Uncertain significance (Nov 16, 2021)
16-87644309-G-A		not specified	Uncertain significance (Jan 31, 2024)
16-87644335-G-A		Inborn genetic diseases	Uncertain significance (Jan 31, 2022)
16-87644335-G-C		JPH3-related disorder	Likely benign (Dec 20, 2022)
16-87644377-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
16-87644382-C-T			Benign (Jul 01, 2022)
16-87644399-C-T		Inborn genetic diseases • not specified	Uncertain significance (Oct 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JPH3	protein_coding	protein_coding	ENST00000284262	5	96322

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00145	111669	0	1	111670	0.00000448

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.318	511	491	1.04	0.0000360	4745
Missense in Polyphen		118	151.96	0.77654		1345
Synonymous	-5.09	324	227	1.43	0.0000178	1526
Loss of Function	4.29	1	23.4	0.0427	0.00000101	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000101	0.0000101
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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. JPH3 is brain- specific and appears to have an active role in certain neurons involved in motor coordination and memory.
• Disease: DISEASE: Huntington disease-like 2 (HDL2) [MIM:606438]: Huntington disease (HD) is a neurodegenerative disorder resulting primarily from the loss of medium spiny projection neurons in the striatum, especially in the caudate nucleus, and, to a lesser extent, atrophy of mesencephalic and cortical structures. The typical clinical picture of HD combines familial adult onset chorea and subcortical dementia that usually begin during the fourth decade of life. {ECO:0000269|PubMed:11914418, ECO:0000269|PubMed:14557581}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.264

Intolerance Scores

• rvis_EVS: -1.23
• rvis_percentile_EVS: 5.54

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.685
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Jph3
• Phenotype: growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); reproductive system phenotype

Gene ontology

• Biological process: learning;memory;exploration behavior;locomotion;regulation of synaptic plasticity;regulation of neuronal synaptic plasticity;neuromuscular process controlling balance;release of sequestered calcium ion into cytosol;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;junctional membrane complex
• Molecular function: molecular_function;calcium-release channel activity