CASZ1

Summary

CASZ1 (castor zinc finger 1, HGNC:26002) is a protein-coding gene on chromosome 1p36.22, encoding Zinc finger protein castor homolog 1 (Q86V15). Transcriptional activator.

The protein encoded by this gene is a zinc finger transcription factor. The encoded protein may function as a tumor suppressor, and single nucleotide polymorphisms in this gene are associated with blood pressure variation. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 54897 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• GWAS associations: 82
• Clinical variants (ClinVar): 690 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 99
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001079843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26002
Approved symbol	CASZ1
Name	castor zinc finger 1
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20321, ZNF693, castor, cst, SRG
Ensembl gene	ENSG00000130940
Ensembl biotype	protein_coding
OMIM	609895
Entrez	54897

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000344008, ENST00000377022, ENST00000447850, ENST00000472814, ENST00000478524, ENST00000478728, ENST00000490176, ENST00000492173, ENST00000496432

RefSeq mRNA: 2 — MANE Select: NM_001079843 NM_001079843, NM_017766

CCDS: CCDS120, CCDS41246

Canonical transcript exons

ENST00000377022 — 21 exons

Exon	Start	End
ENSE00000897823	10649070	10649192
ENSE00000897830	10649283	10649437
ENSE00000897837	10650692	10650755
ENSE00000897844	10650941	10651076
ENSE00000897850	10653377	10654218
ENSE00001401205	10760701	10760857
ENSE00001404652	10705492	10705544
ENSE00001472500	10644917	10645088
ENSE00001472502	10646128	10646326
ENSE00001472504	10647801	10648139
ENSE00001615333	10636604	10640059
ENSE00002025796	10796564	10796646
ENSE00002825992	10642859	10643000
ENSE00002885067	10643160	10643311
ENSE00003469264	10658508	10658576
ENSE00003491714	10654419	10654591
ENSE00003499527	10665083	10665571
ENSE00003527639	10655649	10655813
ENSE00003571335	10659702	10660536
ENSE00003613107	10693874	10693912
ENSE00003613254	10656646	10656736

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 95.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6376 / max 316.8337, expressed in 997 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10267	2.3655	734
10271	0.9629	436
10269	0.8340	281
10270	0.8334	331
10265	0.5667	219
10264	0.0429	15
10266	0.0322	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	95.20	gold quality
skin of abdomen	UBERON:0001416	95.13	gold quality
zone of skin	UBERON:0000014	93.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.50	gold quality
pancreatic ductal cell	CL:0002079	92.38	silver quality
buccal mucosa cell	CL:0002336	92.30	gold quality
gastrocnemius	UBERON:0001388	92.08	gold quality
bronchial epithelial cell	CL:0002328	91.45	gold quality
muscle of leg	UBERON:0001383	91.05	gold quality
upper arm skin	UBERON:0004263	90.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.72	gold quality
body of stomach	UBERON:0001161	90.41	gold quality
minor salivary gland	UBERON:0001830	90.01	gold quality
apex of heart	UBERON:0002098	89.78	gold quality
prostate gland	UBERON:0002367	89.62	gold quality
saliva-secreting gland	UBERON:0001044	89.48	gold quality
heart left ventricle	UBERON:0002084	89.33	gold quality
right uterine tube	UBERON:0001302	89.32	gold quality
cardiac ventricle	UBERON:0002082	89.15	gold quality
right lung	UBERON:0002167	88.90	gold quality
mouth mucosa	UBERON:0003729	88.88	gold quality
jejunal mucosa	UBERON:0000399	88.85	gold quality
lower esophagus mucosa	UBERON:0035834	88.77	gold quality
stomach	UBERON:0000945	88.70	gold quality
epithelium of bronchus	UBERON:0002031	88.68	gold quality
muscle organ	UBERON:0001630	88.61	gold quality
parotid gland	UBERON:0001831	88.44	gold quality
bronchus	UBERON:0002185	88.32	gold quality
fundus of stomach	UBERON:0001160	87.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	916.10
E-ANND-3	yes	11.38

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
BRMS1
EGFL7	Activation
KISS1
TP53

JASPAR motifs

Motif	Name	Family
MA2508.1	CASZ1	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

19 targeting CASZ1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-7976	95.75	65.67	1186

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 22)

• CASZ1 is expressed in a number of human tumors and localizes to a chromosomal region frequently lost in tumors of neuroectodermal origin. (PMID:16631614)
• CASZ1 is a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human Neuroblastoma. (PMID:21252912)
• The study indicates that although their mechanisms of regulation may be distinct, both CASZ1b and CASZ1a have largely redundant but critical roles in suppressing tumor cell growth. (PMID:21490919)
• determined that the tumor suppressors CLU, NGFR, and RUNX3 were also directly repressed by EZH2 like CASZ1 in NB cells (PMID:22068036)
• Papillomavirus DNA integration is associated with loss of CASZ1 gene and thus cervical carcinogenesis. (PMID:22262398)
• This study identifies key domains needed for CASZ1b to regulate gene transcription; a link between loss of CASZ1b transcriptional activity and attenuation of CASZ1b-mediated inhibition of neuroblastoma growth and tumorigenicity (PMID:22331471)
• CASZ1 inhibits cell cycle progression in neuroblastoma by restoring retinoblastoma protein activity. (PMID:23892435)
• CASZ1b binds to chromatin and recruits NuRD complexes to orchestrate epigenetic-mediated transcriptional programs (PMID:26296975)
• These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as NB tumorigenesis. (PMID:27270431)
• the current study firstly identifies CASZ1 as a new gene predisposing to congenital heart disease in humans (PMID:27693370)
• The current study reveals CASZ1 as a new gene responsible for human dilated cardiomyopathy (DCM), which provides novel mechanistic insight and potential therapeutic target for CASZ1-associated DCM, implying potential implications in improved prophylactic and therapeutic strategies for DCM, the most common type of primary myocardial disease. (PMID:28099117)
• Collectively, our proteomic, biochemical, genetic, and structural studies suggest that the physical interaction between TBX20 and CASZ1 is required for cardiac homeostasis, and further, that reduction or loss of this critical interaction leads to dilated cardiomyopathy (DCM) (PMID:28945738)
• these data identify Casz1 as a new Th plasticity regulator having important clinical implications for autoimmune inflammation and mucosal immunity. (PMID:29467767)
• only rs11121615 (CASZ1)reached a nominal significance level of P < .05. Results of original GWAS and replication studies were combined by a meta-analysis, and polymorphisms listed above as well as rs111434909 (ANGPT1) and rs4463578 passed a genome-wide significant threshold. (PMID:29660117)
• A variant of the castor zinc finger 1 (CASZ1) gene is differentially associated with the clinical classification of chronic venous disease. (PMID:31570750)
• Epigenome-Wide Association Study for All-Cause Mortality in a Cardiovascular Cohort Identifies Differential Methylation in Castor Zinc Finger 1 (CASZ1). (PMID:31642367)
• CASZ1 up-regulates MYOD signature genes and induces skeletal muscle differentiation in normal myoblasts and Embryonal rhabdomyosarcoma. (PMID:32060262)
• Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation. (PMID:33205602)
• Loss of CASZ1 tumor suppressor linked to oncogenic subversion of neuroblastoma core regulatory circuitry. (PMID:36243768)
• Role of the CASZ1 transcription factor in tissue development and disease. (PMID:38053207)
• CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia. (PMID:38058200)
• CASZ1 Is Essential for Skin Epidermal Terminal Differentiation. (PMID:38458428)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	casz1	ENSDARG00000037030
rattus_norvegicus	Casz1	ENSRNOG00000013474
drosophila_melanogaster	cas	FBGN0004878

Protein

Protein identifiers

Zinc finger protein castor homolog 1 — Q86V15 (reviewed: Q86V15)

Alternative names: Castor-related protein, Putative survival-related protein, Zinc finger protein 693

All UniProt accessions (2): Q86V15, K7EQC6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7.

Subcellular location. Nucleus.

Tissue specificity. Expressed in heart, lung, skeletal muscle, pancreas, testis, small intestine, and stomach, but it is not detectable in the adult brain.

Miscellaneous. Endothelial cells depleted in CASZ1 by siRNAs display dramatic alterations in adhesion, morphology and sprouting; normal behavior can be rescued by restoration of EGFL7 expression. The defects are in part due to diminished RhoA expression and impaired focal adhesion localization.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86V15-1	1, hCASZ11	yes
Q86V15-2	2, hCASZ5

RefSeq proteins (2): NP_001073312, NP_060236 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR040373	CASZ1	Family

UniProt features (54 total): compositionally biased region 14, sequence conflict 12, region of interest 11, zinc finger region 8, modified residue 3, cross-link 2, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V15-F1	53.66	0.01

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 (5): 720, 721, 981, 288, 975

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 402 (showing top): BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, PEREZ_TP63_TARGETS, AACYNNNNTTCCS_UNKNOWN, GOBP_NEUROGENESIS, LHX3_01, NKX61_01, IRF7_01, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, KOYAMA_SEMA3B_TARGETS_UP, OCT1_03, GATA6_01, IRF1_Q6, TCF11_01, GATA1_04

GO Biological Process (4): regulation of neuron differentiation (GO:0045664), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
neuron differentiation	1
regulation of cell differentiation	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASZ1	ZFP1	Q6P2D0	893
CASZ1	EFS	O43281	651
CASZ1	CSE1L	P55060	522
CASZ1	TBX20	Q9UMR3	521
CASZ1	SH2B3	Q9UQQ2	508
CASZ1	SUZ12	Q15022	500
CASZ1	CAMTA1	Q9Y6Y1	498
CASZ1	IL3	P08700	496
CASZ1	FEM1B	Q9UK73	492
CASZ1	RNF2	Q99496	487
CASZ1	IK	Q13123	482
CASZ1	HDAC2	Q92769	459
CASZ1	ATP2B1	P20020	453
CASZ1	TP53INP1	Q96A56	451
CASZ1	DNAAF10	Q96MX6	433

IntAct

21 interactions, top by confidence:

A	B	Type	Score
CASZ1	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
BAG4	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
BCAR3	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
ESR2	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
PALB2	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
CASZ1	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
PTPN1	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
RAF1	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
WT1	CASZ1	psi-mi:“MI:0915”(physical association)	0.370
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SFMBT2	DCD	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (55): CASZ1 (Affinity Capture-MS), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Two-hybrid), CASZ1 (Affinity Capture-MS), CASZ1 (Affinity Capture-RNA), CASZ1 (Affinity Capture-RNA), CASZ1 (Affinity Capture-MS), CASZ1 (Affinity Capture-MS), CASZ1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IYX6, A0A1L8H0H2, A5X7A0, A7XYJ6, E1BE02, F6NSX9, F8VPJ6, O35914, O57415, P37275, P59598, P59759, Q03172, Q13029, Q2KHR2, Q3UH06, Q5EXX3, Q5R7F2, Q5ZIE8, Q5ZLR2, Q62947, Q63755, Q64318, Q6NRM0, Q6ZPY7, Q76L83, Q7LBC6, Q7YR76, Q80VX4, Q86V15, Q8BHZ4, Q8BLG0, Q8BRH4, Q8BX22, Q8BZ32, Q8C0C0, Q8IZQ8, Q8NEZ4, Q8R5I7, Q8VIM5

Diamond homologs: Q7M3M8, Q86V15, Q9CWL2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CASZ1	“up-regulates quantity”	EGFL7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
negative regulation of apoptotic process	6	8.3×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	363
Likely benign	177
Benign	79

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1175188	NM_001079843.3(CASZ1):c.2443_2459del (p.Val815fs)	Pathogenic
2505332	NM_001079843.3(CASZ1):c.559G>A (p.Gly187Ser)	Pathogenic
3773653	NM_001079843.3(CASZ1):c.2440_2443dup (p.Val815fs)	Pathogenic
4087715	NM_001079843.3(CASZ1):c.3027C>A (p.Tyr1009Ter)	Pathogenic
148364	GRCh38/hg38 1p36.22(chr1:10245412-10637093)x1	Likely pathogenic
3067744	NM_001079843.3(CASZ1):c.1968C>G (p.Tyr656Ter)	Likely pathogenic
3910013	NM_001079843.3(CASZ1):c.2583del (p.Ile862fs)	Likely pathogenic
4075648	NM_001079843.3(CASZ1):c.139C>T (p.Arg47Ter)	Likely pathogenic

SpliceAI

5259 predictions. Top by Δscore:

Variant	Effect	Δscore
1:10642854:CTCAC:C	donor_loss	1.0000
1:10642855:TCA:T	donor_loss	1.0000
1:10642856:CAC:C	donor_loss	1.0000
1:10642996:GGGCC:G	acceptor_gain	1.0000
1:10642997:GGCC:G	acceptor_gain	1.0000
1:10642998:GCC:G	acceptor_gain	1.0000
1:10642999:CC:C	acceptor_gain	1.0000
1:10642999:CCC:C	acceptor_gain	1.0000
1:10643000:CC:C	acceptor_gain	1.0000
1:10643001:C:CC	acceptor_gain	1.0000
1:10643001:C:T	acceptor_gain	1.0000
1:10643156:TCA:T	donor_loss	1.0000
1:10643158:ACCTG:A	donor_loss	1.0000
1:10643312:C:CC	acceptor_gain	1.0000
1:10644920:G:C	donor_gain	1.0000
1:10644931:T:TA	donor_gain	1.0000
1:10644932:C:CA	donor_gain	1.0000
1:10645084:CAGTG:C	acceptor_gain	1.0000
1:10645085:AGTG:A	acceptor_gain	1.0000
1:10645085:AGTGC:A	acceptor_loss	1.0000
1:10645086:GTG:G	acceptor_gain	1.0000
1:10645087:TG:T	acceptor_gain	1.0000
1:10645087:TGC:T	acceptor_loss	1.0000
1:10645088:GCT:G	acceptor_loss	1.0000
1:10645089:C:CC	acceptor_gain	1.0000
1:10645089:C:T	acceptor_loss	1.0000
1:10646123:CTGA:C	donor_loss	1.0000
1:10646124:TGA:T	donor_loss	1.0000
1:10646126:ACCT:A	donor_loss	1.0000
1:10646322:GATCG:G	acceptor_gain	1.0000

AlphaMissense

11566 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:10639451:G:C	H1591D	1.000
1:10639471:C:T	G1584D	1.000
1:10639472:C:G	G1584R	1.000
1:10639490:A:G	C1578R	1.000
1:10639503:G:C	C1573W	1.000
1:10639504:C:G	C1573S	1.000
1:10639504:C:T	C1573Y	1.000
1:10639505:A:G	C1573R	1.000
1:10639505:A:T	C1573S	1.000
1:10639509:G:C	F1571L	1.000
1:10639509:G:T	F1571L	1.000
1:10639510:A:G	F1571S	1.000
1:10639511:A:G	F1571L	1.000
1:10639512:G:C	H1570Q	1.000
1:10639512:G:T	H1570Q	1.000
1:10639514:G:C	H1570D	1.000
1:10639578:G:C	F1548L	1.000
1:10639578:G:T	F1548L	1.000
1:10639579:A:G	F1548S	1.000
1:10639580:A:G	F1548L	1.000
1:10639621:C:G	R1534P	1.000
1:10639622:G:T	R1534S	1.000
1:10639625:G:C	H1533D	1.000
1:10639633:A:T	V1530D	1.000
1:10639650:G:C	C1524W	1.000
1:10639652:A:G	C1524R	1.000
1:10639656:G:C	F1522L	1.000
1:10639656:G:T	F1522L	1.000
1:10639658:A:G	F1522L	1.000
1:10639662:G:C	C1520W	1.000

dbSNP variants (sampled 300 via entrez): RS1000005027 (1:10675696 C>A,T), RS1000041809 (1:10645549 C>T), RS1000055969 (1:10671037 G>A), RS1000065042 (1:10772153 G>A), RS1000065352 (1:10727503 C>T), RS1000067905 (1:10644530 C>T), RS1000105471 (1:10638929 C>A), RS1000105816 (1:10726372 C>T), RS1000113153 (1:10729847 G>A,T), RS1000137224 (1:10662772 C>T), RS1000143075 (1:10741623 G>A), RS1000145470 (1:10703412 C>T), RS1000154135 (1:10720592 G>A,C), RS1000167134 (1:10729697 A>G), RS1000176245 (1:10767199 C>CG)

Disease associations

OMIM: gene MIM:609895 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (5): dilated cardiomyopathy (MONDO:0005021), cardiomyopathy (MONDO:0004994), peroxisome biogenesis disorder, complementation group K (MONDO:0800365), autism spectrum disorder (MONDO:0005258), congenital heart disease (MONDO:0005453)

Orphanet (3): Dilated cardiomyopathy (Orphanet:217604), Rare cardiomyopathy (Orphanet:167848), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

82 associations (top):

Study	Trait	p-value
GCST000393_1	Systolic blood pressure	5.000000e-06
GCST001072_1	Blood pressure	7.000000e-07
GCST001074_4	Blood pressure	3.000000e-10
GCST002627_5	Hypertension	2.000000e-09
GCST002630_6	Systolic blood pressure	6.000000e-10
GCST002631_10	Diastolic blood pressure	8.000000e-08
GCST003255_1	Urinary albumin-to-creatinine ratio	9.000000e-06
GCST003475_1	Beard thickness	4.000000e-07
GCST004775_14	Pulse pressure	2.000000e-10
GCST004776_8	Systolic blood pressure	9.000000e-16
GCST004777_44	Diastolic blood pressure	4.000000e-10
GCST005978_4	Diastolic blood pressure	6.000000e-12
GCST005979_5	Systolic blood pressure	7.000000e-18
GCST006009_12	Pulse pressure	5.000000e-09
GCST006010_1	Mean arterial pressure	2.000000e-16
GCST006020_15	Diastolic blood pressure	6.000000e-16
GCST006061_195	Atrial fibrillation	5.000000e-09
GCST006166_15	Diastolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-29
GCST006166_44	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-26
GCST006167_14	Mean arterial pressure x alcohol consumption interaction (2df test)	4.000000e-20
GCST006168_39	Pulse pressure x alcohol consumption interaction (2df test)	9.000000e-17
GCST006168_53	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-20
GCST006169_20	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-11
GCST006170_41	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	7.000000e-14
GCST006170_7	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	9.000000e-13
GCST006172_5	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	5.000000e-14
GCST006187_1	Diastolic blood pressure (cigarette smoking interaction)	7.000000e-42
GCST006188_16	Systolic blood pressure (cigarette smoking interaction)	2.000000e-54
GCST006231_10	Mean arterial pressure	5.000000e-17
GCST006258_42	Diastolic blood pressure	1.000000e-11

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0009927	Antihypertensive use measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:1002006	treatment-resistant hypertension
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	6
trichostatin A	increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Tretinoin	decreases expression	2
bisphenol F	increases methylation	1
dicrotophos	increases expression	1
urushiol	increases expression	1
bisphenol A	affects methylation, decreases methylation, affects cotreatment	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
tobacco tar	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation