CUX2

Summary

CUX2 (cut like homeobox 2, HGNC:19347) is a protein-coding gene on chromosome 12q24.11-q24.12, encoding Homeobox protein cut-like 2 (O14529). Transcription factor involved in the control of neuronal proliferation and differentiation in the brain.

This gene encodes a protein which contains three CUT domains and a homeodomain; both domains are DNA-binding motifs. A similar gene, whose gene product possesses different DNA-binding activities, is located on chromosome on chromosome 7. Two pseudogenes of this gene have been identified on chromosomes 10 and 4.

Source: NCBI Gene 23316 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 67 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 72
• Clinical variants (ClinVar): 474 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 41
• MANE Select transcript: NM_015267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19347
Approved symbol	CUX2
Name	cut like homeobox 2
Location	12q24.11-q24.12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0293, CDP2
Ensembl gene	ENSG00000111249
Ensembl biotype	protein_coding
OMIM	610648
Entrez	23316

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000261726, ENST00000397643, ENST00000551604, ENST00000933089, ENST00000933090, ENST00000933091, ENST00000933092

RefSeq mRNA: 2 — MANE Select: NM_015267 NM_001370598, NM_015267

CCDS: CCDS41837

Canonical transcript exons

ENST00000261726 — 22 exons

Exon	Start	End
ENSE00000755136	111298541	111298589
ENSE00000755138	111304210	111304314
ENSE00000755140	111306921	111307112
ENSE00000755142	111307199	111307257
ENSE00000755143	111308285	111308333
ENSE00000755144	111308427	111308526
ENSE00000834831	111310041	111310682
ENSE00000938106	111296473	111296539
ENSE00000998068	111291418	111291552
ENSE00001128994	111034165	111034240
ENSE00001292378	111341780	111342053
ENSE00001293611	111320012	111320775
ENSE00001299235	111295333	111295409
ENSE00001301644	111322421	111322580
ENSE00001309503	111312100	111312201
ENSE00001310756	111338286	111338474
ENSE00001329663	111334441	111334710
ENSE00001803111	111347524	111350554
ENSE00002345097	111214200	111214310
ENSE00002733113	111293446	111293569
ENSE00003627645	111217890	111217937
ENSE00003668854	111263761	111263839

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 94.48.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8538 / max 69.0911, expressed in 218 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128017	0.2494	146
128030	0.2255	44
128016	0.2236	54
128028	0.0694	5
206896	0.0692	36
128029	0.0167	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	94.48	gold quality
buccal mucosa cell	CL:0002336	93.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.29	gold quality
endothelial cell	CL:0000115	90.94	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.28	gold quality
choroid plexus epithelium	UBERON:0003911	90.02	gold quality
primary visual cortex	UBERON:0002436	89.73	gold quality
ganglionic eminence	UBERON:0004023	88.93	gold quality
occipital lobe	UBERON:0002021	88.80	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.64	gold quality
postcentral gyrus	UBERON:0002581	87.57	gold quality
parietal lobe	UBERON:0001872	86.83	gold quality
superior frontal gyrus	UBERON:0002661	86.60	gold quality
orbitofrontal cortex	UBERON:0004167	84.64	gold quality
liver	UBERON:0002107	83.72	gold quality
entorhinal cortex	UBERON:0002728	83.66	gold quality
right lobe of liver	UBERON:0001114	82.37	gold quality
cortical plate	UBERON:0005343	82.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.09	gold quality
frontal pole	UBERON:0002795	80.13	gold quality
right frontal lobe	UBERON:0002810	80.10	gold quality
Brodmann (1909) area 10	UBERON:0013541	79.47	gold quality
frontal cortex	UBERON:0001870	79.29	gold quality
neocortex	UBERON:0001950	78.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.44	gold quality
cerebral cortex	UBERON:0000956	76.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.26	gold quality
prostate gland	UBERON:0002367	76.09	gold quality
seminal vesicle	UBERON:0000998	75.62	gold quality
prefrontal cortex	UBERON:0000451	75.40	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	508.43
E-HCAD-35	yes	455.92
E-ANND-3	yes	4.19
E-MTAB-7381	no	63.97

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
ACTB	Activation
DLG4	Activation
DLL1	Repression
GRIN2B	Activation
NCAM1

JASPAR motifs

Motif	Name	Family
MA0755.1	CUX2	HD-CUT
MA0755.2	CUX2	HD-CUT

JASPAR matrix evidence (PMIDs): PMID:7799919

Upstream regulators (CollecTRI, top): LMX1A

miRNA regulators (miRDB)

145 targeting CUX2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
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-4282	99.99	75.36	6408
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691

Literature-anchored findings (GeneRIF, showing 7)

• results suggest that the persistent expression of CUX2 in postmitotic neurons contributes to the maintenance of genome integrity through its stimulation of oxidative DNA damage repair. (PMID:26221032)
• Significant allelic and genotypic associations were identified between NEURL variant rs6584555 and GJA1 variant rs13216675 and Atrial fibrillation (AF). Significant genotypic association was found between CUX2 SNP rs6490029 and AF (PMID:29459676)
• Patients with CUX2 p.Glu590Lys display a distinctive phenotypic spectrum, which is predominantly generalized epilepsy (PMID:29630738)
• De novo variant c.1768G>A; p.(Glu590Lys) in CUX2 was identifies in a patient with intellectual disability, seizures, and autism spectrum disorder. (PMID:29795476)
• this is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case-control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. (PMID:30720667)
• CUX2, BRAP and ALDH2 are associated with metabolic traits in people with excessive alcohol consumption. (PMID:33093602)
• CUX2/KDM5B/SOX17 Axis Affects the Occurrence and Development of Breast Cancer. (PMID:35881915)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cux2b	ENSDARG00000086345
mus_musculus	Cux2	ENSMUSG00000042589
rattus_norvegicus	Cux2	ENSRNOG00000001259
drosophila_melanogaster	ct	FBGN0004198
caenorhabditis_elegans		WBGENE00000464

Paralogs (1): CUX1 (ENSG00000257923)

Protein

Protein identifiers

Homeobox protein cut-like 2 — O14529 (reviewed: O14529)

Alternative names: Homeobox protein cux-2

All UniProt accessions (2): F5GWR6, O14529

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in the control of neuronal proliferation and differentiation in the brain. Regulates dendrite development and branching, dendritic spine formation, and synaptogenesis in cortical layers II-III. Binds to DNA in a sequence-specific manner.

Subcellular location. Nucleus.

Disease relevance. Developmental and epileptic encephalopathy 67 (DEE67) [MIM:618141] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE67 is an autosomal dominant form characterized by onset of seizures in infancy. Later onset of seizures in childhood may occur in some patients. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CUT homeobox family.

RefSeq proteins (2): NP_001357527, NP_056082* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003350	CUT_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR057476	Cux_N	Domain

Pfam: PF00046, PF02376, PF25398

UniProt features (55 total): compositionally biased region 17, helix 17, region of interest 8, DNA-binding region 4, turn 3, coiled-coil region 2, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1WH6	SOLUTION NMR
1WH8	SOLUTION NMR
1X2L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14529-F1	60.99	0.25

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 (1): 143

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 258 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_SYNAPSE_ASSEMBLY, AAGTCCA_MIR422B_MIR422A, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, AAGCCAT_MIR135A_MIR135B, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), short-term memory (GO:0007614), positive regulation of gene expression (GO:0010628), positive regulation of dendrite morphogenesis (GO:0050775), cognition (GO:0050890), positive regulation of synapse assembly (GO:0051965), positive regulation of dendritic spine morphogenesis (GO:0061003), positive regulation of excitatory postsynaptic potential (GO:2000463), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
regulation of gene expression	2
DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
memory	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
nervous system process	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
positive regulation of neuron projection development	1
positive regulation of dendrite morphogenesis	1
dendritic spine morphogenesis	1
positive regulation of dendritic spine development	1
regulation of dendritic spine morphogenesis	1
positive regulation of signal transduction	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1

Protein interactions and networks

STRING

2002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUX2	PHETA1	Q8N4B1	833
CUX2	SATB2	Q9UPW6	692
CUX2	FEZF2	Q8TBJ5	675
CUX2	RORB	Q92753	668
CUX2	TSPEAR	Q8WU66	649
CUX2	TBR1	Q16650	616
CUX2	BCL11B	Q9C0K0	592
CUX2	ACAD10	Q6JQN1	582
CUX2	EMX1	Q04741	566
CUX2	PAX6	P26367	563
CUX2	SLC4A4	Q9Y6R1	563
CUX2	ABCA13	Q86UQ4	547
CUX2	ATXN2	Q99700	547
CUX2	NAA25	Q14CX7	545
CUX2	ETV1	P50549	537

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CUX2	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
CUX2	KPNA3	psi-mi:“MI:0914”(association)	0.350
NAV3	CUX2	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): HNRNPC (Proximity Label-MS), CUX2 (Affinity Capture-MS), KPNA4 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), CUX1 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), KPNA3 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), TMCO1 (Cross-Linking-MS (XL-MS)), CUX2 (Cross-Linking-MS (XL-MS)), CUX2 (Cross-Linking-MS (XL-MS)), CUX2 (Proximity Label-MS), CUX2 (Proximity Label-MS), CUX2 (Proximity Label-MS), TRMT1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: O08755, O14529, O60422, O95948, P70298, P70512, Q04650, Q19720, Q22811, Q22812, Q6XBJ3, Q8K557, Q8TE12, Q9BL02, Q9JKU8, Q9NJB5, Q9UBC0, P34237, P39880, P39881, P53564, P53565, P70403, Q13948, Q5R8V1, O59795, A1YEY5, A1YFI3, A1YG57, A2T733, A2T7P4, O15499, O35652, P09082, P0CJ85, P0CJ86, P0CJ87, P0CJ88, P0CJ89, P0CJ90

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CUX2	up-regulates	DNA_repair
CUX2	“up-regulates activity”	OGG1	binding
LMX1A	“up-regulates quantity by expression”	CUX2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	297
Likely benign	127
Benign	16

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1296981	NM_015267.4(CUX2):c.2834C>T (p.Thr945Met)	Pathogenic
2500118	NM_015267.4(CUX2):c.560del (p.Lys187fs)	Likely pathogenic
3347746	NM_015267.4(CUX2):c.3265C>T (p.Pro1089Ser)	Likely pathogenic

SpliceAI

5130 predictions. Top by Δscore:

Variant	Effect	Δscore
12:111034238:CAG:C	donor_loss	1.0000
12:111034239:AGGT:A	donor_loss	1.0000
12:111034240:GGT:G	donor_loss	1.0000
12:111034241:G:GC	donor_loss	1.0000
12:111291411:T:TA	acceptor_gain	1.0000
12:111291413:CACA:C	acceptor_loss	1.0000
12:111291414:A:AG	acceptor_gain	1.0000
12:111291414:ACAG:A	acceptor_loss	1.0000
12:111291415:C:G	acceptor_gain	1.0000
12:111291415:CAGA:C	acceptor_loss	1.0000
12:111291416:A:AC	acceptor_loss	1.0000
12:111291416:A:AG	acceptor_gain	1.0000
12:111291417:G:GC	acceptor_gain	1.0000
12:111291417:GA:G	acceptor_gain	1.0000
12:111291417:GAC:G	acceptor_gain	1.0000
12:111291417:GACC:G	acceptor_gain	1.0000
12:111291417:GACCC:G	acceptor_gain	1.0000
12:111291548:CAAAG:C	donor_loss	1.0000
12:111291549:AAAGG:A	donor_loss	1.0000
12:111291550:AAGG:A	donor_loss	1.0000
12:111291551:AGGT:A	donor_loss	1.0000
12:111291553:G:GA	donor_loss	1.0000
12:111291554:T:A	donor_loss	1.0000
12:111293570:G:GG	donor_gain	1.0000
12:111293575:G:GT	donor_gain	1.0000
12:111293580:G:T	donor_gain	1.0000
12:111295331:A:AG	acceptor_gain	1.0000
12:111295331:AG:A	acceptor_gain	1.0000
12:111295332:G:GG	acceptor_gain	1.0000
12:111295332:GG:G	acceptor_gain	1.0000

AlphaMissense

9574 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:111310479:T:C	L566P	1.000
12:111310494:T:A	I571N	1.000
12:111310496:G:A	G572R	1.000
12:111310496:G:C	G572R	1.000
12:111310497:G:A	G572E	1.000
12:111310501:G:C	Q573H	1.000
12:111310501:G:T	Q573H	1.000
12:111310508:T:C	F576L	1.000
12:111310509:T:C	F576S	1.000
12:111310509:T:G	F576C	1.000
12:111310510:T:A	F576L	1.000
12:111310510:T:G	F576L	1.000
12:111310511:G:A	G577R	1.000
12:111310511:G:C	G577R	1.000
12:111310511:G:T	G577W	1.000
12:111310512:G:A	G577E	1.000
12:111310512:G:T	G577V	1.000
12:111310524:T:C	L581P	1.000
12:111310530:T:C	L583P	1.000
12:111310537:G:C	Q585H	1.000
12:111310537:G:T	Q585H	1.000
12:111310538:G:C	G586R	1.000
12:111310538:G:T	G586C	1.000
12:111310539:G:A	G586D	1.000
12:111310545:T:A	V588D	1.000
12:111310547:A:C	S589R	1.000
12:111310549:C:A	S589R	1.000
12:111310549:C:G	S589R	1.000
12:111310551:A:T	E590V	1.000
12:111310557:T:A	L592Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000003475 (12:111224117 A>C,G), RS1000014126 (12:111309599 T>C), RS1000016037 (12:111249913 A>G,T), RS1000047869 (12:111235202 G>A), RS1000054527 (12:111061391 G>T), RS1000059510 (12:111230099 T>G), RS1000074024 (12:111186962 A>G), RS1000079938 (12:111225519 G>C), RS1000082180 (12:111317459 C>G,T), RS1000090476 (12:111147313 G>A), RS1000090914 (12:111103241 C>T), RS1000103916 (12:111273445 C>T), RS1000109812 (12:111061589 G>A,C), RS1000112105 (12:111318227 A>G), RS1000115169 (12:111272476 A>G)

Disease associations

OMIM: gene MIM:610648 | disease phenotypes: MIM:618141, MIM:120970, MIM:180860

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 67	Strong	Autosomal dominant
Lennox-Gastaut syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Moderate	AD

Mondo (8): developmental and epileptic encephalopathy, 67 (MONDO:0029138), hypertrophic cardiomyopathy (MONDO:0005045), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy (MONDO:0100620), cone-rod dystrophy (MONDO:0015993), Silver-Russell syndrome (MONDO:0008394), Lennox-Gastaut syndrome (MONDO:0016532)

Orphanet (5): Rare hypertrophic cardiomyopathy (Orphanet:217569), Cone rod dystrophy (Orphanet:1872), Silver-Russell syndrome (Orphanet:813), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000741	Apathy
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002305	Athetosis
HP:0002321	Vertigo
HP:0002353	EEG abnormality
HP:0002363	Abnormal brainstem morphology
HP:0002376	Developmental regression
HP:0002521	Hypsarrhythmia
HP:0002527	Falls
HP:0003593	Infantile onset
HP:0006813	Focal hemiclonic seizure
HP:0007270	Atypical absence seizure

GWAS associations

72 associations (top):

Study	Trait	p-value
GCST001394_2	Type 1 diabetes	1.000000e-16
GCST001845_3	Coronary heart disease	1.000000e-06
GCST002773_3	Gout	2.000000e-23
GCST003017_10	Colorectal cancer	2.000000e-08
GCST003017_5	Colorectal cancer	2.000000e-08
GCST003924_5	Renal overload gout	8.000000e-17
GCST003925_11	Gout	4.000000e-20
GCST003926_8	Renal underexcretion gout	2.000000e-18
GCST004267_5	Blood osmolality (transformed sodium)	2.000000e-06
GCST004373_18	Atrial fibrillation	7.000000e-06
GCST005048_2	Idiopathic osteonecrosis of the femoral head	3.000000e-12
GCST005329_1	Coffee consumption	2.000000e-16
GCST005439_1	Response to alcohol consumption (flushing response)	2.000000e-14
GCST005441_8	Alcohol consumption (max-drinks)	2.000000e-12
GCST005951_75	Body mass index	2.000000e-11
GCST005978_15	Diastolic blood pressure	3.000000e-39
GCST005979_20	Systolic blood pressure	2.000000e-42
GCST005983_3	Serum uric acid levels	8.000000e-51
GCST005984_61	Glomerular filtration rate	4.000000e-22
GCST005985_54	Creatinine levels	7.000000e-24
GCST005986_39	Blood urea nitrogen levels	1.000000e-25
GCST005992_17	Mean corpuscular hemoglobin concentration	2.000000e-24
GCST005993_7	Mean corpuscular hemoglobin	7.000000e-80
GCST005996_38	Red blood cell count	1.000000e-29
GCST005998_3	Alanine transaminase levels	1.000000e-30
GCST005999_26	Aspartate aminotransferase levels	1.000000e-26
GCST006002_1	Blood sugar levels	1.000000e-10
GCST006004_18	Low density lipoprotein cholesterol levels	3.000000e-20
GCST006005_20	High density lipoprotein cholesterol levels	2.000000e-80
GCST006009_1	Pulse pressure	1.000000e-12

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:1001930	idiopathic osteonecrosis of the femoral head
EFO:0006782	cups of coffee per day measurement
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004761	uric acid measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004468	glucose measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0009282	sodium measurement
EFO:0004329	alcohol drinking
EFO:0006781	coffee consumption measurement
EFO:0010125	viral load
EFO:0004531	urate measurement
EFO:0006525	cigarettes per day measurement
EFO:0004509	hemoglobin measurement
EFO:0007874	gut microbiome measurement
EFO:0004469	HOMA-B
EFO:0004343	waist-hip ratio
EFO:0004338	body weight

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D056730	Silver-Russell Syndrome	C05.660.207.925; C16.131.077.855; C16.131.260.870; C16.320.180.870; C16.320.240.937; C16.320.447.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7958375	Toxicity	3	rifampin	Tuberculosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7958375	CUX2	3	0.00	1	rifampin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Aflatoxin B1	increases methylation, affects expression, decreases methylation	3
Arsenic	affects methylation, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Progesterone	increases expression, decreases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, 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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00004776	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Topiramate for Lennox-Gastaut Syndrome
NCT01146951	PHASE3	COMPLETED	A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
NCT01151540	PHASE3	COMPLETED	A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
NCT01160770	PHASE3	COMPLETED	Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
NCT01405053	PHASE3	COMPLETED	Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
NCT02224560	PHASE3	COMPLETED	Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults