JPH3

Summary

JPH3 (junctophilin 3, HGNC:14203) is a protein-coding gene on chromosome 16q24.2, encoding Junctophilin-3 (Q8WXH2). 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. 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.

Source: NCBI Gene 57338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Huntington disease-like 2 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 275 total — 1 pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_020655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14203
Approved symbol	JPH3
Name	junctophilin 3
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	JP-3, CAGL237, HDL2, JP3
Ensembl gene	ENSG00000154118
Ensembl biotype	protein_coding
OMIM	605268
Entrez	57338

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000284262, ENST00000301008, ENST00000537256, ENST00000563609

RefSeq mRNA: 3 — MANE Select: NM_020655 NM_001271604, NM_001271605, NM_020655

CCDS: CCDS10962

Canonical transcript exons

ENST00000284262 — 5 exons

Exon	Start	End
ENSE00001121348	87696580	87698156
ENSE00001850352	87602508	87603528
ENSE00003509655	87684142	87684266
ENSE00003570038	87644258	87645035
ENSE00003581966	87689646	87690526

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 96.52.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7062 / max 99.2824, expressed in 442 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155485	1.1294	372
155486	0.9228	223
155487	0.3799	130
155484	0.2304	107
155488	0.0436	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	96.52	gold quality
postcentral gyrus	UBERON:0002581	96.17	gold quality
parietal lobe	UBERON:0001872	95.97	gold quality
anterior cingulate cortex	UBERON:0009835	95.97	gold quality
cingulate cortex	UBERON:0003027	95.78	gold quality
sural nerve	UBERON:0015488	95.62	gold quality
entorhinal cortex	UBERON:0002728	95.59	gold quality
superior frontal gyrus	UBERON:0002661	95.45	gold quality
nucleus accumbens	UBERON:0001882	95.40	gold quality
amygdala	UBERON:0001876	95.35	gold quality
temporal lobe	UBERON:0001871	95.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.04	gold quality
frontal cortex	UBERON:0001870	94.87	gold quality
prefrontal cortex	UBERON:0000451	94.84	gold quality
neocortex	UBERON:0001950	94.72	gold quality
Ammon’s horn	UBERON:0001954	94.62	gold quality
cerebral cortex	UBERON:0000956	94.19	gold quality
caudate nucleus	UBERON:0001873	93.94	gold quality
primary visual cortex	UBERON:0002436	93.93	gold quality
telencephalon	UBERON:0001893	93.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.50	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.28	gold quality
putamen	UBERON:0001874	93.17	gold quality
cerebellar hemisphere	UBERON:0002245	93.17	gold quality
cerebellar cortex	UBERON:0002129	93.16	gold quality
cerebellar vermis	UBERON:0004720	93.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.81	gold quality
cerebellum	UBERON:0002037	92.45	gold quality
occipital lobe	UBERON:0002021	92.39	gold quality
forebrain	UBERON:0001890	92.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting JPH3, 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-532-3P	99.34	65.76	1195
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4676-5P	97.54	65.29	715
HSA-MIR-575	97.54	65.18	718
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 14)

• CAG/CTG repeat expansions at the Huntington’s disease (HD)-like 2 locus have been identified in the gene encoding junctophilin-3 in an HD patient who carried an allele with 50 uninterrupted repeats. (PMID:11914418)
• This report on a South African family that presented with progressive dementia and a movement disorder affecting numerous family members. Genotyping of the JPH3 CTG repeat revealed pathogenic expansions in three affected individuals. (PMID:17708569)
• 244 Patients with the diagnosis of Huntington’s Disease and without mutation of the IT15 gene revealed one case of SCA17 but did not disclose the presence of two other diseases with a similar clinical manifestation: DRPLA and HDL2. (PMID:18651325)
• HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. (PMID:18816802)
• Data revealed that six polymorphisms of F10, PITRM1, PCSK2, JPH3, MYO7B, and AKAP12 were related (P<0.05) to the prevalence of chronic kidney disease. (PMID:19724895)
• This study reveled the an antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington’s disease-like 2 mice. (PMID:21555070)
• 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. (PMID:22367996)
• JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. (PMID:22447335)
• 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. (PMID:26079385)
• The expression of JPH isoforms was examined in human and mouse pancreatic tissues, and JPH3 expression was found in both the beta cells. (PMID:27336719)
• This study identified that abnormal CTG expansions in JPH3 in patient with Huntington Disease. (PMID:27400454)
• 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. (PMID:28656064)
• Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence. (PMID:35089322)
• Both Heterozygous and Homozygous Loss-of-Function JPH3 Variants Are Associated with a Paroxysmal Movement Disorder. (PMID:36273396)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	jph3b	ENSDARG00000102204
mus_musculus	Jph3	ENSMUSG00000025318
rattus_norvegicus	Jph3	ENSRNOG00000018784
drosophila_melanogaster	jp	FBGN0032129
caenorhabditis_elegans	jph-1	WBGENE00002179

Paralogs (3): JPH4 (ENSG00000092051), JPH1 (ENSG00000104369), JPH2 (ENSG00000149596)

Protein

Protein identifiers

Junctophilin-3 — Q8WXH2 (reviewed: Q8WXH2)

Alternative names: Junctophilin type 3, Trinucleotide repeat-containing gene 22 protein

All UniProt accessions (1): Q8WXH2

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. JPH3 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.

Tissue specificity. Specifically expressed in brain.

Disease relevance. 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. 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.

Polymorphism. Isoform 2 length of the poly-Ala region is variable (6 to 27 CTG/CAG triplets) in the normal population and may be expanded (41 to 58 CTG/CAG triplets) in patients suffering from Huntington disease-like type 2.

Similarity. Belongs to the junctophilin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WXH2-1	1	yes
Q8WXH2-2	2

RefSeq proteins (1): NP_065706* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003409	MORN	Repeat
IPR017191	Junctophilin	Family

Pfam: PF02493

UniProt features (34 total): repeat 8, modified residue 8, region of interest 4, compositionally biased region 4, sequence variant 3, splice variant 2, 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-Q8WXH2-F1	61.52	0.32

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 (8): 440, 451, 457, 471, 475, 506, 703, 710

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): learning (GO:0007612), memory (GO:0007613), 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), exploration behavior (GO:0035640), locomotion (GO:0040011), regulation of synaptic plasticity (GO:0048167), regulation of neuronal synaptic plasticity (GO:0048168), neuromuscular process controlling balance (GO:0050885), calcium ion transport into cytosol (GO:0060402)

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

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), junctional sarcoplasmic reticulum membrane (GO:0014701), membrane (GO:0016020), junctional membrane complex (GO:0030314), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
learning or memory	2
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
behavior	1
biological_process	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
regulation of synaptic plasticity	1
musculoskeletal movement	1
neuromuscular process	1
positive regulation of cytosolic calcium ion concentration	1
calcium ion transmembrane import into cytosol	1
binding	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
cellular anatomical structure	1
sarcoplasm	1
protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JPH3	VPS13A	Q96RL7	827
JPH3	CACNA1S	Q13698	762
JPH3	SYPL2	Q5VXT5	730
JPH3	RYR1	P21817	710
JPH3	ASPH	Q12797	705
JPH3	TRDN	Q13061	701
JPH3	MBNL1	Q9NR56	672
JPH3	HTT	P42858	623
JPH3	CACNA1C	Q13936	600
JPH3	ATXN3	P54252	595
JPH3	ATN1	P54259	595
JPH3	PRNP	P04156	584
JPH3	CASQ1	P31415	550
JPH3	DLL1	O00548	547
JPH3	CACNA1D	Q01668	545

IntAct

674 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	JPH3	psi-mi:“MI:0915”(physical association)	0.560
AP2B1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ALDH1A1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
BIRC2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1B2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
BAK1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
BGN	JPH3	psi-mi:“MI:0915”(physical association)	0.560
MRPL49	JPH3	psi-mi:“MI:0915”(physical association)	0.560
CALM1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
CD1C	JPH3	psi-mi:“MI:0915”(physical association)	0.560
CKMT1A	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ERCC8	JPH3	psi-mi:“MI:0915”(physical association)	0.560
CTNNB1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DDIT3	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DES	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DRG2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DVL3	JPH3	psi-mi:“MI:0915”(physical association)	0.560
EPHB2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
EXTL2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
FANCG	JPH3	psi-mi:“MI:0915”(physical association)	0.560
FYN	JPH3	psi-mi:“MI:0915”(physical association)	0.560
GFAP	JPH3	psi-mi:“MI:0915”(physical association)	0.560
GJA5	JPH3	psi-mi:“MI:0915”(physical association)	0.560
GRB10	JPH3	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	JPH3	psi-mi:“MI:0915”(physical association)	0.560
JPH3	HNRNPU	psi-mi:“MI:0915”(physical association)	0.560
IKBKB	JPH3	psi-mi:“MI:0915”(physical association)	0.560
KRT19	JPH3	psi-mi:“MI:0915”(physical association)	0.560
SMAD3	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DKFZP586N0721	JPH3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (56): JPH3 (Affinity Capture-MS), KRTAP10-8 (Two-hybrid), JPH3 (Reconstituted Complex), JPH3 (Proximity Label-MS), JPH3 (Proximity Label-MS), JPH3 (Proximity Label-MS), JPH3 (Proximity Label-MS), JPH3 (Two-hybrid), JPH3 (Two-hybrid), JPH3 (Two-hybrid), JPH3 (Proximity Label-MS), MPRIP (Affinity Capture-MS), SVIL (Affinity Capture-MS), TRIP12 (Affinity Capture-MS), RAI14 (Affinity Capture-MS)

ESM2 similar proteins: A2A7Q9, F1LXF1, O08873, O14795, O35274, O46606, P11274, P12755, P22681, P22682, P49797, P50636, Q08B84, Q0VGY8, Q1L8L6, Q2VJ60, Q3UR85, Q3YEC7, Q4KUS2, Q60698, Q62768, Q69ZT9, Q6PAJ1, Q6R891, Q6T4P5, Q6ZMZ0, Q6ZWB6, Q7TMB0, Q7TPB0, Q80U28, Q86YJ5, Q8HXH0, Q8NEL9, Q8TEK3, Q8WXG6, Q8WXH2, Q92622, Q92625, Q96SB3, Q9CXG9

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 182 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.

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing, via transesterification reactions	5	18.8×	3e-03
protein ubiquitination	18	4.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	189
Likely benign	43
Benign	26

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
5119	NM_001271604.4(JPH3):c.431CWG[41_?]	Pathogenic

SpliceAI

2173 predictions. Top by Δscore:

Variant	Effect	Δscore
16:87684263:AACGG:A	donor_loss	1.0000
16:87684264:ACGGT:A	donor_loss	1.0000
16:87684265:CGGTG:C	donor_loss	1.0000
16:87684266:GGT:G	donor_loss	1.0000
16:87684267:G:C	donor_loss	1.0000
16:87684268:T:A	donor_loss	1.0000
16:87603525:GGAG:G	donor_gain	0.9900
16:87603526:GAG:G	donor_gain	0.9900
16:87603526:GAGG:G	donor_gain	0.9900
16:87603530:T:G	donor_loss	0.9900
16:87637743:G:T	donor_gain	0.9900
16:87637744:A:T	donor_gain	0.9900
16:87637812:G:GA	donor_gain	0.9900
16:87638563:GGT:G	donor_gain	0.9900
16:87644256:A:AG	acceptor_gain	0.9900
16:87644256:AG:A	acceptor_gain	0.9900
16:87644256:AGGG:A	acceptor_loss	0.9900
16:87644257:G:GG	acceptor_gain	0.9900
16:87644257:GG:G	acceptor_gain	0.9900
16:87645016:GC:G	donor_gain	0.9900
16:87645031:TCCAG:T	donor_loss	0.9900
16:87645032:CCAGG:C	donor_loss	0.9900
16:87645033:CAGG:C	donor_loss	0.9900
16:87645034:AG:A	donor_loss	0.9900
16:87645035:GGTAG:G	donor_loss	0.9900
16:87645036:GTAGG:G	donor_loss	0.9900
16:87645037:T:A	donor_loss	0.9900
16:87654928:A:AG	donor_gain	0.9900
16:87656292:A:T	donor_gain	0.9900
16:87662105:AC:A	acceptor_gain	0.9900

AlphaMissense

4868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:87603165:T:C	F7L	1.000
16:87603167:T:A	F7L	1.000
16:87603167:T:G	F7L	1.000
16:87603171:T:C	F9L	1.000
16:87603173:T:A	F9L	1.000
16:87603173:T:G	F9L	1.000
16:87603196:G:A	G17E	1.000
16:87603201:T:A	W19R	1.000
16:87603201:T:C	W19R	1.000
16:87603203:G:C	W19C	1.000
16:87603203:G:T	W19C	1.000
16:87603261:T:G	Y39D	1.000
16:87603273:T:A	W43R	1.000
16:87603273:T:C	W43R	1.000
16:87603285:T:C	F47L	1.000
16:87603287:C:A	F47L	1.000
16:87603287:C:G	F47L	1.000
16:87603297:G:C	G51R	1.000
16:87603309:T:A	W55R	1.000
16:87603309:T:C	W55R	1.000
16:87603333:G:C	G63R	1.000
16:87603339:T:A	W65R	1.000
16:87603339:T:C	W65R	1.000
16:87603341:G:C	W65C	1.000
16:87603341:G:T	W65C	1.000
16:87603354:C:A	R70S	1.000
16:87603399:G:C	G85R	1.000
16:87603405:T:A	W87R	1.000
16:87603405:T:C	W87R	1.000
16:87603432:G:T	G96W	1.000

dbSNP variants (sampled 300 via entrez): RS1000001462 (16:87691319 G>A), RS1000033381 (16:87616463 G>A), RS1000047395 (16:87612278 C>T), RS1000049169 (16:87657089 A>T), RS1000049223 (16:87678897 T>A,C), RS1000101857 (16:87604624 G>C), RS1000154264 (16:87604739 T>C), RS1000156900 (16:87670203 G>A), RS1000169852 (16:87628961 C>A,G), RS1000218323 (16:87648157 T>C), RS1000235097 (16:87659925 G>A), RS1000240559 (16:87692456 C>T), RS1000242707 (16:87619784 C>A,T), RS1000248378 (16:87601497 C>T), RS1000253114 (16:87674109 T>G)

Disease associations

OMIM: gene MIM:605268 | disease phenotypes: MIM:606438

GenCC curated gene-disease

Disease	Classification	Inheritance
Huntington disease-like 2	Definitive	Autosomal dominant
neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (2): Huntington disease-like 2 (MONDO:0011671), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Huntington disease-like 2 (Orphanet:98934)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000726	Dementia
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000746	Delusion
HP:0000751	Personality changes
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001824	Weight loss
HP:0002060	Abnormal cerebral morphology
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002072	Chorea
HP:0002120	Cerebral cortical atrophy
HP:0002340	Caudate atrophy
HP:0002345	Action tremor
HP:0002354	Memory impairment
HP:0002476	Primitive reflex
HP:0003596	Middle age onset
HP:0004302	Functional motor deficit
HP:0004305	Involuntary movements
HP:0007123	Subcortical dementia
HP:0010994	Abnormal corpus striatum morphology

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002593_20	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-06
GCST002593_47	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-06
GCST003262_257	Post bronchodilator FEV1	4.000000e-06
GCST003815_110	Late-onset Alzheimer’s disease	3.000000e-06
GCST003986_12	Migraine	2.000000e-09
GCST004020_1	Small vessel stroke	3.000000e-09
GCST004025_14	Systemic juvenile idiopathic arthritis	2.000000e-06
GCST005588_9	Idiopathic dilated cardiomyopathy	8.000000e-06
GCST006310_7	Post bronchodilator FEV1/FVC ratio in smoking	3.000000e-06
GCST008163_223	Height	3.000000e-07
GCST010002_117	Refractive error	6.000000e-09
GCST012490_64	Femur bone mineral density x serum urate levels interaction	4.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0004314	forced expiratory volume
EFO:1001870	late-onset Alzheimers disease
EFO:1001504	small vessel stroke
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0004713	FEV/FVC ratio
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C564708	Huntington Disease-Like 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
cypermethrin	increases expression	1
tobacco tar	increases expression, decreases reaction	1
benzo(e)pyrene	affects methylation	1
diallyl disulfide	decreases reaction, increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
CGP 52608	increases reaction, affects binding	1
enniatins	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	affects methylation	1
Niclosamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice