JPH1

Summary

JPH1 (junctophilin 1, HGNC:14201) is a protein-coding gene on chromosome 8q21.11, encoding Junctophilin-1 (Q9HDC5). Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells.

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.

Source: NCBI Gene 56704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myopathy 25 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 107 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 64
• MANE Select transcript: NM_020647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14201
Approved symbol	JPH1
Name	junctophilin 1
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Aliases	JP-1, JP1
Ensembl gene	ENSG00000104369
Ensembl biotype	protein_coding
OMIM	605266
Entrez	56704

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000342232, ENST00000518195, ENST00000519947, ENST00000868437, ENST00000868438, ENST00000868439, ENST00000868440, ENST00000868441, ENST00000868442, ENST00000868443

RefSeq mRNA: 4 — MANE Select: NM_020647 NM_001317830, NM_001363050, NM_001363051, NM_020647

CCDS: CCDS6217

Canonical transcript exons

ENST00000342232 — 6 exons

Exon	Start	End
ENSE00001279798	74320909	74321540
ENSE00001334046	74234700	74237035
ENSE00003636592	74314861	74315620
ENSE00003636700	74237208	74237303
ENSE00003650057	74244529	74245175
ENSE00003651966	74259385	74259503

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.36.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2071 / max 288.0421, expressed in 810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93629	3.1979	732
93630	0.5873	290
93628	0.2035	104
93631	0.1450	69
93626	0.0735	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	99.36	gold quality
vastus lateralis	UBERON:0001379	99.35	gold quality
tibialis anterior	UBERON:0001385	99.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.29	gold quality
deltoid	UBERON:0001476	99.25	gold quality
biceps brachii	UBERON:0001507	99.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.19	gold quality
skeletal muscle tissue	UBERON:0001134	98.89	gold quality
gastrocnemius	UBERON:0001388	97.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.81	gold quality
muscle of leg	UBERON:0001383	96.20	gold quality
body of tongue	UBERON:0011876	96.01	gold quality
muscle tissue	UBERON:0002385	94.05	gold quality
endothelial cell	CL:0000115	91.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.70	gold quality
middle temporal gyrus	UBERON:0002771	90.18	gold quality
tongue	UBERON:0001723	89.02	gold quality
heart right ventricle	UBERON:0002080	88.53	gold quality
tibia	UBERON:0000979	87.36	gold quality
ventricular zone	UBERON:0003053	85.14	gold quality
cerebellum	UBERON:0002037	84.08	gold quality
cerebellar cortex	UBERON:0002129	83.94	gold quality
cerebellar hemisphere	UBERON:0002245	83.94	gold quality
cerebellar vermis	UBERON:0004720	83.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.41	gold quality
primary visual cortex	UBERON:0002436	82.92	gold quality
myocardium	UBERON:0002349	81.95	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.00	gold quality
left ventricle myocardium	UBERON:0006566	80.89	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting JPH1, 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-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-545-3P	99.95	70.74	2783

Literature-anchored findings (GeneRIF, showing 7)

• JP1 and JP2 can facilitate the assembly of DHPR with other proteins of the excitation-contraction coupling machinery (PMID:22020936)
• This study demonstrates that both JP1 and JP2 in skeletal muscle undergo Ca2+-dependent proteolysis by endogenous proteases when the intracellular Ca2+ is raised within the physiological range for a sustained period (PMID:23148318)
• This study suggests that genetic variants of JPH1 may modulate the effect of smoking on carotid plaque burden. (PMID:24954085)
• Results show that JPH1 and GDAP1 share a common pathway and depend on each other; therefore, JPH1 can contribute to the phenotypical consequences of GDAP1 mutations. (PMID:25168384)
• Charcot Marie Tooth 2K patients with early and late onset were analyzed for association of rs139723190 SNP in JPH1 gene responsible for CMT type severe and mild phenotypes. (PMID:30804591)
• Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence. (PMID:35089322)
• Muscle calcium stress cleaves junctophilin1, unleashing a gene regulatory program predicted to correct glucose dysregulation. (PMID:36724092)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	jph1b	ENSDARG00000038826
danio_rerio	jph1a	ENSDARG00000058603
mus_musculus	Jph1	ENSMUSG00000042686
rattus_norvegicus	Jph1	ENSRNOG00000006110
drosophila_melanogaster	jp	FBGN0032129
caenorhabditis_elegans	jph-1	WBGENE00002179

Paralogs (3): JPH4 (ENSG00000092051), JPH2 (ENSG00000149596), JPH3 (ENSG00000154118)

Protein

Protein identifiers

Junctophilin-1 — Q9HDC5 (reviewed: Q9HDC5)

Alternative names: Junctophilin type 1

All UniProt accessions (2): Q9HDC5, E5RHU9

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. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Sarcoplasmic reticulum membrane.

Tissue specificity. Abundantly expressed in skeletal muscle. Very low levels in heart.

Disease relevance. Congenital myopathy 25 (CMYO25) [MIM:620964] A form of congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO25 is an autosomal recessive form characterized by prominent facial, ocular, and bulbar features. The disease is caused by variants affecting the gene represented in this entry.

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 (4): NP_001304759, NP_001349979, NP_001349980, NP_065698* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003409	MORN	Repeat
IPR017191	Junctophilin	Family

Pfam: PF02493

UniProt features (51 total): strand 20, modified residue 9, repeat 7, helix 4, sequence variant 3, region of interest 2, compositionally biased region 2, chain 1, topological domain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7RW4	X-RAY DIFFRACTION	1.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HDC5-F1	66.06	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 157, 216, 220, 448, 452, 461, 465, 469, 475

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 374 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, E2F_Q4, E2F_Q4_01, TAATAAT_MIR126, GOBP_CIRCULATORY_SYSTEM_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, E2F_Q3, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION

GO Biological Process (4): muscle organ development (GO:0007517), 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), calcium ion transport into cytosol (GO:0060402)

GO Molecular Function (2): structural constituent of muscle (GO:0008307), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), junctional sarcoplasmic reticulum membrane (GO:0014701), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), junctional membrane complex (GO:0030314), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), sarcoplasmic reticulum membrane (GO:0033017)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sarcoplasm	2
animal organ development	1
muscle structure development	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
positive regulation of cytosolic calcium ion concentration	1
calcium ion transmembrane import into cytosol	1
structural molecule activity	1
binding	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
sarcoplasmic reticulum membrane	1
endoplasmic reticulum	1
I band	1
protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JPH1	RYR1	P21817	944
JPH1	ASPH	Q12797	821
JPH1	SYPL2	Q5VXT5	787
JPH1	TRDN	Q13061	785
JPH1	CASQ1	P31415	693
JPH1	CACNA1S	Q13698	692
JPH1	STIM1	Q13586	617
JPH1	STAC3	Q96MF2	587
JPH1	CALM1	P02593	565
JPH1	CALML4	Q96GE6	542
JPH1	CALML3	P27482	541
JPH1	CALML5	Q9NZT1	541
JPH1	CALML6	Q8TD86	537
JPH1	RYR2	Q92736	537
JPH1	CACNA1D	Q01668	530
JPH1	CAV3	P56539	530

IntAct

193 interactions, top by confidence:

A	B	Type	Score
IFT70A	IFT56	psi-mi:“MI:0914”(association)	0.790
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
TMEM9B	DNAJC13	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
MEOX2	JPH1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	JPH1	psi-mi:“MI:0915”(physical association)	0.560
SLC16A13	JPH1	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	JPH1	psi-mi:“MI:0915”(physical association)	0.560
EMP1	JPH1	psi-mi:“MI:0915”(physical association)	0.560
TMEM65	JPH1	psi-mi:“MI:0915”(physical association)	0.560
HTATIP2	JPH1	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	JPH1	psi-mi:“MI:0915”(physical association)	0.560
PLP1	JPH1	psi-mi:“MI:0915”(physical association)	0.560
JPH1	NAT8	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	JPH1	psi-mi:“MI:0915”(physical association)	0.560
AQP6	JPH1	psi-mi:“MI:0915”(physical association)	0.560
GPR42	JPH1	psi-mi:“MI:0915”(physical association)	0.560
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
RHEX	NOS1AP	psi-mi:“MI:0914”(association)	0.530
GPR161	USP12	psi-mi:“MI:0914”(association)	0.530

BioGRID (317): JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), JPH1 (Proximity Label-MS), JPH1 (Proximity Label-MS), JPH1 (Proximity Label-MS), JPH1 (Proximity Label-MS), JPH1 (Proximity Label-MS), JPH1 (Affinity Capture-MS), JPH1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPP1, E9PSK7, E9Q5G3, O95628, P18847, P26801, P28574, P29596, P52161, P52162, P52164, P53567, P53568, P61244, P61245, P91664, Q01826, Q02241, Q07016, Q28772, Q2YDP3, Q32KS7, Q3T0B9, Q566M1, Q56A18, Q5HYJ3, Q5RDF5, Q5ZKT9, Q60611, Q60765, Q6DEE7, Q6PBM7, Q6QB00, Q80XP8, Q80YA9, Q80ZQ5, Q86UE8, Q86VZ6, Q8BT14, Q8C0V0

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 213 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
VEGFR2 mediated cell proliferation	5	21.6×	2e-04
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	19.7×	2e-04
SHC1 events in ERBB2 signaling	5	18.0×	3e-04
Signaling by ERBB2 TMD/JMD mutants	5	18.0×	3e-04
Downstream signal transduction	6	17.3×	1e-04
EPHA-mediated growth cone collapse	6	17.3×	1e-04
Signaling by ERBB2 KD Mutants	5	16.0×	4e-04
Signaling by high-kinase activity BRAF mutants	5	12.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	7	16.4×	3e-04
cell surface receptor protein tyrosine kinase signaling pathway	9	8.7×	7e-04
protein autophosphorylation	9	7.3×	1e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	12	5.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	76
Likely benign	8
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3024350	NM_020647.4(JPH1):c.1510del (p.Glu504fs)	Pathogenic
2683802	NM_020647.4(JPH1):c.373del (p.Asp125fs)	Likely pathogenic
2683803	NM_020647.4(JPH1):c.354C>A (p.Tyr118Ter)	Likely pathogenic
2683804	NM_020647.4(JPH1):c.1738del (p.Leu580fs)	Likely pathogenic

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
8:74244523:ACTT:A	donor_loss	1.0000
8:74244524:CTTA:C	donor_gain	1.0000
8:74244526:TA:T	donor_loss	1.0000
8:74244527:A:AC	donor_gain	1.0000
8:74244528:C:CT	donor_gain	1.0000
8:74244528:CT:C	donor_gain	1.0000
8:74244528:CTG:C	donor_gain	1.0000
8:74244528:CTGA:C	donor_gain	1.0000
8:74244528:CTGAA:C	donor_gain	1.0000
8:74245181:C:CT	acceptor_gain	1.0000
8:74259501:GTCC:G	acceptor_loss	1.0000
8:74259502:TC:T	acceptor_gain	1.0000
8:74259503:CC:C	acceptor_gain	1.0000
8:74259503:CCTAC:C	acceptor_loss	1.0000
8:74259504:C:CC	acceptor_gain	1.0000
8:74259504:CTA:C	acceptor_loss	1.0000
8:74259505:T:G	acceptor_loss	1.0000
8:74237202:TCTTA:T	donor_loss	0.9900
8:74237203:CTTA:C	donor_loss	0.9900
8:74237204:TTAC:T	donor_loss	0.9900
8:74237205:TACCT:T	donor_loss	0.9900
8:74237206:A:C	donor_loss	0.9900
8:74237207:C:CA	donor_loss	0.9900
8:74237301:GCCC:G	acceptor_loss	0.9900
8:74237303:CCT:C	acceptor_loss	0.9900
8:74237304:C:CG	acceptor_loss	0.9900
8:74237305:T:G	acceptor_loss	0.9900
8:74244523:A:AC	donor_gain	0.9900
8:74244524:C:CC	donor_gain	0.9900
8:74245174:GC:G	acceptor_gain	0.9900

AlphaMissense

4340 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:74259472:C:G	A391P	1.000
8:74314861:C:A	R380M	1.000
8:74314861:C:G	R380T	1.000
8:74315009:A:C	Y331D	1.000
8:74315014:C:T	G329E	1.000
8:74315015:C:G	G329R	1.000
8:74315015:C:T	G329R	1.000
8:74315050:C:T	G317D	1.000
8:74315056:C:T	G315E	1.000
8:74315061:C:A	R313S	1.000
8:74315061:C:G	R313S	1.000
8:74315062:C:G	R313T	1.000
8:74315076:C:A	W308C	1.000
8:74315076:C:G	W308C	1.000
8:74315077:C:G	W308S	1.000
8:74315078:A:G	W308R	1.000
8:74315078:A:T	W308R	1.000
8:74315083:C:A	G306V	1.000
8:74315083:C:T	G306E	1.000
8:74315084:C:A	G306W	1.000
8:74315084:C:G	G306R	1.000
8:74315084:C:T	G306R	1.000
8:74315090:A:C	Y304D	1.000
8:74315112:G:C	S296R	1.000
8:74315112:G:T	S296R	1.000
8:74315114:T:G	S296R	1.000
8:74315119:C:T	G294D	1.000
8:74315120:C:G	G294R	1.000
8:74315132:G:T	R290S	1.000
8:74315137:T:A	D288V	1.000

dbSNP variants (sampled 300 via entrez): RS1000007194 (8:74268815 G>A), RS1000010107 (8:74317329 G>A,T), RS1000030510 (8:74275435 G>A), RS1000089823 (8:74285506 A>G), RS1000111008 (8:74242284 T>C), RS1000162499 (8:74246702 C>T), RS1000163585 (8:74275585 C>A), RS1000180049 (8:74282173 A>T), RS1000192375 (8:74241950 A>G), RS1000213089 (8:74317110 C>T), RS1000216189 (8:74247160 T>C), RS1000302465 (8:74262798 T>G), RS1000375948 (8:74305213 T>C), RS1000378648 (8:74241454 G>A), RS1000455819 (8:74256981 C>T)

Disease associations

OMIM: gene MIM:605266 | disease phenotypes: MIM:214400, MIM:614052, MIM:607831, MIM:117000, MIM:620964

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myopathy 25	Strong	Autosomal recessive

Mondo (5): Charcot-Marie-Tooth disease type 4A (MONDO:0008961), mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (MONDO:0013546), Charcot-Marie-Tooth disease axonal type 2K (MONDO:0011916), congenital myopathy (MONDO:0019952), congenital myopathy 25 (MONDO:0975808)

Orphanet (5): TMEM70-related mitochondrial encephalo-cardio-myopathy (Orphanet:1194), Charcot-Marie-Tooth disease type 4A (Orphanet:99948), Autosomal recessive Charcot-Marie-Tooth disease with hoarseness (Orphanet:101097), Autosomal dominant Charcot-Marie-Tooth disease type 2K (Orphanet:99944), Congenital myopathy (Orphanet:97245)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000938	Osteopenia
HP:0001171	Split hand
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001349	Facial diplegia
HP:0001488	Bilateral ptosis
HP:0001611	Hypernasal speech
HP:0001762	Talipes equinovarus
HP:0001883	Talipes
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002076	Migraine
HP:0002093	Respiratory insufficiency
HP:0002311	Incoordination
HP:0002460	Distal muscle weakness
HP:0002522	Areflexia of lower limbs
HP:0002650	Scoliosis
HP:0002751	Kyphoscoliosis
HP:0002936	Distal sensory impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002482_3	Carotid plaque burden (smoking interaction)	5.000000e-06
GCST004779_3	Uterine fibroids	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535419	Charcot-Marie-Tooth disease, Type 4A (supp.)
C567528	Encephalocardiomyopathy, Mitochondrial, Neonatal, Due To Atp Synthase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	3
Arsenic	increases abundance, increases expression, affects cotreatment	2
Estradiol	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	increases abundance, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT02020187	Not specified	COMPLETED	Aerobic Training in Patients With Congenital Myopathies
NCT03018184	Not specified	COMPLETED	Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies
NCT04733976	Not specified	COMPLETED	Bullying in Youth With Muscular Dystrophy and Congenital Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05692349	Not specified	UNKNOWN	Magnetic Resonance Imaging and Ultrasonography in Evaluation of Muscle Diseases
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT06833489	Not specified	RECRUITING	Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
NCT07138963	Not specified	RECRUITING	Phenotype - Genotype Correlation in a Sample of Egyptian Patients With Congenital Myopathies and Congenital Muscular Dystrophies
NCT07415837	Not specified	RECRUITING	Evaluation of the Role of miR-1 in the Pathogenesis and as a Biomarker in Muscular Dystrophies and Congenital Myopathies
NCT07502989	Not specified	RECRUITING	Muscle Health Measurements Using Electrical Impedance Myography
NCT07580365	Not specified	NOT_YET_RECRUITING	VirtualPark_Pediatric