JPH4

Summary

JPH4 (junctophilin 4, HGNC:20156) is a protein-coding gene on chromosome 14q11.2, encoding Junctophilin-4 (Q96JJ6). Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells.

This gene encodes a member of the junctophilin family of transmembrane proteins that are involved in the formation of the junctional membrane complexes between the plasma membrane and the endoplasmic/sarcoplasmic reticulum in excitable cells. The encoded protein contains a conserved N-terminal repeat region called the membrane occupation and recognition nexus sequence that is found in other members of the junctophilin family. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 84502 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001146028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20156
Approved symbol	JPH4
Name	junctophilin 4
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1831, JP4
Ensembl gene	ENSG00000092051
Ensembl biotype	protein_coding
OMIM	619863
Entrez	84502

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000356300, ENST00000397118, ENST00000544177, ENST00000553505, ENST00000927987, ENST00000927988, ENST00000927989, ENST00000927990, ENST00000970525

RefSeq mRNA: 2 — MANE Select: NM_001146028 NM_001146028, NM_032452

CCDS: CCDS9603

Canonical transcript exons

ENST00000356300 — 6 exons

Exon	Start	End
ENSE00000940680	23575685	23576456
ENSE00000940681	23571802	23571920
ENSE00000940682	23570928	23571460
ENSE00001424689	23578180	23578790
ENSE00001527341	23568038	23569717
ENSE00003660716	23577075	23577624

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 98.25.

FANTOM5 (CAGE): breadth broad, TPM avg 15.3704 / max 722.3062, expressed in 424 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142513	10.0213	354
142506	0.8080	98
142512	0.5748	110
142503	0.5195	215
142501	0.4244	137
142511	0.3793	91
142515	0.3657	107
142508	0.3314	79
142516	0.3293	112
142510	0.2713	79

Top tissues by expression

130 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	98.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.12	gold quality
cerebellar hemisphere	UBERON:0002245	97.82	gold quality
cerebellar cortex	UBERON:0002129	97.81	gold quality
cerebellum	UBERON:0002037	97.80	gold quality
right frontal lobe	UBERON:0002810	97.70	gold quality
nucleus accumbens	UBERON:0001882	97.54	gold quality
cortical plate	UBERON:0005343	97.51	gold quality
frontal cortex	UBERON:0001870	97.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.23	gold quality
temporal lobe	UBERON:0001871	97.19	gold quality
amygdala	UBERON:0001876	97.17	gold quality
primary visual cortex	UBERON:0002436	97.16	gold quality
anterior cingulate cortex	UBERON:0009835	97.05	gold quality
prefrontal cortex	UBERON:0000451	97.03	gold quality
cerebral cortex	UBERON:0000956	96.99	gold quality
Ammon’s horn	UBERON:0001954	96.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.88	gold quality
putamen	UBERON:0001874	96.46	gold quality
caudate nucleus	UBERON:0001873	96.43	gold quality
brain	UBERON:0000955	96.00	gold quality
hypothalamus	UBERON:0001898	94.25	gold quality
pituitary gland	UBERON:0000007	93.32	gold quality
adenohypophysis	UBERON:0002196	91.54	gold quality
substantia nigra	UBERON:0002038	88.23	gold quality
body of uterus	UBERON:0009853	86.83	gold quality
myometrium	UBERON:0001296	85.03	gold quality
ganglionic eminence	UBERON:0004023	84.96	gold quality
left uterine tube	UBERON:0001303	84.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.55	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1088.62
E-HCAD-13	yes	20.63
E-MTAB-7316	yes	18.22
E-MTAB-7303	no	80.66
E-ANND-3	no	2.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting JPH4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029

Literature-anchored findings (GeneRIF, showing 2)

• reports the gene structure of human JPH4 (PMID:14559359)
• reviews the structure and function of human junctophilins (PMID:19095005)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Jph4	ENSMUSG00000022208
rattus_norvegicus	Ap1g2	ENSRNOG00000025619
drosophila_melanogaster	jp	FBGN0032129
caenorhabditis_elegans	jph-1	WBGENE00002179

Paralogs (3): JPH1 (ENSG00000104369), JPH2 (ENSG00000149596), JPH3 (ENSG00000154118)

Protein

Protein identifiers

Junctophilin-4 — Q96JJ6 (reviewed: Q96JJ6)

Alternative names: Junctophilin-like 1 protein

All UniProt accessions (2): Q96JJ6, F5H1L9

UniProt curated annotations — full annotation on UniProt →

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. JPH4 is brain-specific and appears to have an active role in certain neurons involved in motor coordination and memory.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Domain organisation. The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids.

Similarity. Belongs to the junctophilin family.

RefSeq proteins (2): NP_001139500, NP_115828 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003409	MORN	Repeat
IPR017191	Junctophilin	Family

Pfam: PF02493

UniProt features (22 total): repeat 8, compositionally biased region 6, region of interest 3, sequence conflict 2, chain 1, topological domain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JJ6-F1	64.48	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (8): regulation of cytokine production (GO:0001817), learning (GO:0007612), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by calcium ion signaling (GO:0010882), regulation of synaptic plasticity (GO:0048167), neuromuscular process controlling balance (GO:0050885), calcium ion transport into cytosol (GO:0060402), regulation of store-operated calcium entry (GO:2001256)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): endoplasmic reticulum membrane (GO:0005789), smooth endoplasmic reticulum (GO:0005790), plasma membrane (GO:0005886), junctional sarcoplasmic reticulum membrane (GO:0014701), junctional membrane complex (GO:0030314), dendritic shaft (GO:0043198), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
learning or memory	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
calcium-mediated signaling	1
regulation of cardiac muscle contraction	1
cardiac muscle contraction	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
musculoskeletal movement	1
neuromuscular process	1
positive regulation of cytosolic calcium ion concentration	1
calcium ion transmembrane import into cytosol	1
store-operated calcium entry	1
regulation of calcium ion transport	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum	1
membrane	1
cell periphery	1
sarcoplasmic reticulum membrane	1
sarcoplasm	1
protein-containing complex	1
dendrite	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JPH4	CACNA1S	Q13698	822
JPH4	ASPH	Q12797	776
JPH4	SYPL2	Q5VXT5	752
JPH4	RYR1	P21817	744
JPH4	TRDN	Q13061	741
JPH4	STIM1	Q13586	727
JPH4	CACNA1C	Q13936	631
JPH4	CASQ1	P31415	577
JPH4	CACNA1D	Q01668	576
JPH4	CALM1	P02593	545
JPH4	CALML4	Q96GE6	527
JPH4	CALML3	P27482	519
JPH4	CALML5	Q9NZT1	519
JPH4	CALML6	Q8TD86	517
JPH4	STIMATE	Q86TL2	506

IntAct

11 interactions, top by confidence:

A	B	Type	Score
JPH4	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
JPH4	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
UBQLN1	JPH4	psi-mi:“MI:0915”(physical association)	0.000
UBQLN2	JPH4	psi-mi:“MI:0915”(physical association)	0.000
corE	JPH4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (113): ARHGAP29 (Affinity Capture-MS), GCC1 (Affinity Capture-MS), RAD18 (Affinity Capture-MS), MYO10 (Affinity Capture-MS), UACA (Affinity Capture-MS), TRIOBP (Affinity Capture-MS), PPP1R12C (Affinity Capture-MS), MPRIP (Affinity Capture-MS), UBE2O (Affinity Capture-MS), ZSWIM8 (Affinity Capture-MS), CCDC14 (Affinity Capture-MS), IFT74 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), PRRC2B (Affinity Capture-MS), IFT22 (Affinity Capture-MS)

ESM2 similar proteins: A2A288, A6NIX2, A6NLJ0, A6QQ91, B7Z1M9, B7ZBB8, B8ZZ34, D3ZZN9, J3QNX5, O02756, O88671, P0C7L8, P0CG09, P0DKB5, P27539, P37318, Q02779, Q2KJ18, Q2M3V2, Q2MJR0, Q3U0S6, Q4G0M1, Q4VYA0, Q5JR98, Q5T442, Q5U651, Q6GL23, Q6NY19, Q6P6N5, Q6UXK2, Q6ZW31, Q7Z4P5, Q86YV0, Q8BLS7, Q8BRJ4, Q8C013, Q8CII9, Q8N144, Q8NCU7, Q96BM1

Diamond homologs: Q2PS20, Q69FB3, Q80WT0, Q8WXH2, Q96JJ6, Q9BR39, Q9ET77, Q9ET78, Q9ET80, Q9GKY7, Q9GKY8, Q9HDC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

74 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

746 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23571919:CC:C	acceptor_gain	0.9900
14:23571920:CC:C	acceptor_gain	0.9900
14:23571921:C:CC	acceptor_gain	0.9900
14:23577076:T:TA	donor_gain	0.9900
14:23571796:CCTCA:C	donor_loss	0.9800
14:23571797:CTCA:C	donor_loss	0.9800
14:23571798:TCACC:T	donor_loss	0.9800
14:23571799:CACC:C	donor_loss	0.9800
14:23571800:A:C	donor_loss	0.9800
14:23571801:C:T	donor_loss	0.9800
14:23571916:CTGCC:C	acceptor_gain	0.9800
14:23571918:GCCCT:G	acceptor_loss	0.9800
14:23571919:CCCTG:C	acceptor_loss	0.9800
14:23571922:T:A	acceptor_loss	0.9800
14:23571923:G:C	acceptor_loss	0.9700
14:23571925:C:CT	acceptor_gain	0.9700
14:23575846:G:A	donor_gain	0.9700
14:23577107:T:TA	donor_gain	0.9700
14:23575725:CGG:C	donor_gain	0.9600
14:23571931:C:CT	acceptor_gain	0.9500
14:23572836:C:A	donor_gain	0.9500
14:23575679:GCCCA:G	donor_loss	0.9500
14:23575680:CCCA:C	donor_loss	0.9500
14:23575683:ACCTG:A	donor_loss	0.9500
14:23575684:CCTG:C	donor_loss	0.9500
14:23576456:CCT:C	acceptor_loss	0.9500
14:23576458:T:C	acceptor_loss	0.9500
14:23576465:G:T	acceptor_gain	0.9500
14:23575767:TA:T	donor_gain	0.9400
14:23575768:AA:A	donor_gain	0.9400

AlphaMissense

3972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23575909:C:A	W309C	1.000
14:23575909:C:G	W309C	1.000
14:23575911:A:G	W309R	1.000
14:23575911:A:T	W309R	1.000
14:23575917:C:A	G307C	1.000
14:23575917:C:G	G307R	1.000
14:23575965:G:T	R291S	1.000
14:23575978:C:A	W286C	1.000
14:23575978:C:G	W286C	1.000
14:23575980:A:G	W286R	1.000
14:23575980:A:T	W286R	1.000
14:23576251:G:C	F195L	1.000
14:23576251:G:T	F195L	1.000
14:23576253:A:G	F195L	1.000
14:23576437:C:A	W133C	1.000
14:23576437:C:G	W133C	1.000
14:23576439:A:G	W133R	1.000
14:23576439:A:T	W133R	1.000
14:23575841:T:C	Y332C	0.999
14:23575841:T:G	Y332S	0.999
14:23575842:A:C	Y332D	0.999
14:23575883:C:T	G318E	0.999
14:23575884:C:A	G318W	0.999
14:23575889:C:A	G316V	0.999
14:23575889:C:T	G316D	0.999
14:23575900:G:C	N312K	0.999
14:23575900:G:T	N312K	0.999
14:23575901:T:A	N312I	0.999
14:23575910:C:G	W309S	0.999
14:23575916:C:A	G307V	0.999

dbSNP variants (sampled 300 via entrez): RS1000130078 (14:23569116 C>A,T), RS1000175614 (14:23569344 G>A), RS1000189645 (14:23572470 G>A), RS1000255769 (14:23569757 A>G,T), RS1000310383 (14:23568726 C>A), RS1000449298 (14:23576704 G>A), RS1000794867 (14:23574131 G>C,T), RS1000858874 (14:23576329 G>A,T), RS1001063730 (14:23574732 T>C), RS1001184676 (14:23574461 C>T), RS1001186641 (14:23570827 G>A,C), RS1001299595 (14:23577732 C>T), RS1001303250 (14:23569495 CAAAG>C), RS1001465066 (14:23577980 G>A), RS1001852651 (14:23578266 C>G)

Disease associations

OMIM: gene MIM:619863 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
licochalcone B	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Niclosamide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.