RRAD

Summary

RRAD (RRAD, Ras related glycolysis inhibitor and calcium channel regulator, HGNC:10446) is a protein-coding gene on chromosome 16q22.1, encoding GTP-binding protein RAD (P55042). May regulate basal voltage-dependent L-type Ca(2+) currents and be required for beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force.

Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be involved in small GTPase-mediated signal transduction. Predicted to be located in T-tubule. Predicted to be active in plasma membrane. Implicated in type 2 diabetes mellitus. Biomarker of congestive heart failure.

Source: NCBI Gene 6236 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brugada syndrome (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_004165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10446
Approved symbol	RRAD
Name	RRAD, Ras related glycolysis inhibitor and calcium channel regulator
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	REM3, RAD
Ensembl gene	ENSG00000166592
Ensembl biotype	protein_coding
OMIM	179503
Entrez	6236

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 retained_intron

ENST00000299759, ENST00000566577, ENST00000567791, ENST00000568915, ENST00000889788, ENST00000889790, ENST00000889793, ENST00000889795, ENST00000957037, ENST00000957038, ENST00000957039, ENST00000957040, ENST00000957041, ENST00000957042, ENST00000957043, ENST00000957044, ENST00000957045

RefSeq mRNA: 2 — MANE Select: NM_004165 NM_001128850, NM_004165

CCDS: CCDS10824

Canonical transcript exons

ENST00000299759 — 5 exons

Exon	Start	End
ENSE00001104552	66924810	66925194
ENSE00001104559	66923846	66923919
ENSE00001104564	66923516	66923720
ENSE00001931509	66921685	66922353
ENSE00001943321	66925409	66925535

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9538 / max 2502.2990, expressed in 988 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157728	16.9538	988

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	98.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.63	gold quality
heart right ventricle	UBERON:0002080	98.47	gold quality
apex of heart	UBERON:0002098	98.46	gold quality
gastrocnemius	UBERON:0001388	98.44	gold quality
bronchial epithelial cell	CL:0002328	98.40	gold quality
epithelium of bronchus	UBERON:0002031	98.06	gold quality
right atrium auricular region	UBERON:0006631	98.00	gold quality
triceps brachii	UBERON:0001509	97.87	gold quality
cardiac atrium	UBERON:0002081	97.72	gold quality
lower esophagus mucosa	UBERON:0035834	97.59	gold quality
muscle of leg	UBERON:0001383	97.44	gold quality
bronchus	UBERON:0002185	97.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.27	gold quality
heart left ventricle	UBERON:0002084	97.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.21	gold quality
cardiac ventricle	UBERON:0002082	97.11	gold quality
muscle organ	UBERON:0001630	96.84	gold quality
skeletal muscle organ	UBERON:0014892	96.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.64	gold quality
gluteal muscle	UBERON:0002000	96.54	gold quality
heart	UBERON:0000948	96.09	gold quality
tibial artery	UBERON:0007610	95.98	gold quality
popliteal artery	UBERON:0002250	95.97	gold quality
diaphragm	UBERON:0001103	95.62	silver quality
skeletal muscle tissue	UBERON:0001134	95.60	gold quality
myocardium	UBERON:0002349	95.35	gold quality
vastus lateralis	UBERON:0001379	95.24	gold quality
biceps brachii	UBERON:0001507	95.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	1013.40
E-CURD-114	yes	62.73
E-GEOD-135922	yes	25.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, EGR2, MYF5, MYOD1, TP53

miRNA regulators (miRDB)

21 targeting RRAD, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-591	96.29	68.16	611
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579

Literature-anchored findings (GeneRIF, showing 24)

• crystallization and preliminary crystallographic analysis of human Rad GTPase (PMID:16511212)
• Crystal structure of the GTPase domain of human Rad in the GDP-bound form at 1.8 A resolution. (PMID:16866878)
• Methylation and gene silencing of the Ras-related GTPase gene is associated with lung and breast cancers (PMID:17195088)
• Evidence from Rad transgenic mice suggests that the Rad-associated signaling pathway may play a role in arrhythmogenesis in diverse cardiac diseases. (PMID:17525370)
• occurrence of an unusual TG 3’ splice site in intron 1 (PMID:17672918)
• Rad is a novel mediator that inhibits cardiac hypertrophy through the CaMKII pathway (PMID:18056528)
• the implication of oxidative stress in modulating Rad expression, in association with the initiation and progression of amyotrophic lateral sclerosis muscle atrophy (PMID:20079427)
• It is proposed for the first time that Rad may promote carcinogenesis at least in part by inhibiting GCIP-mediated tumor suppression. (PMID:20460530)
• results indicate that RRAD might act as a functional tumor suppressor and its epigenetic inactivation may play an important role in NPC development (PMID:22487779)
• Rad over expression could be a molecular target to improve bortezomib sensitivity in human leukemia and lymphoma. (PMID:22658652)
• Mouse Rad Q65P (the murine equivalent of human Rad Q66P) inhibits L-type currents conducted by CaV1.2 or CaV1.3 channels as potently as wild-type Rad (>95% inhibition of both channels). (PMID:23973784)
• RRAD hypermethylation is associated with esophageal squamous cell carcinoma. (PMID:24222170)
• Rad suppresses the NF-Kappa-B mediated transcription and downstream gene activation. Rad can directly bind to RelA/p65 and suppress the interaction of RelA/p65 with the NF-kappa-B response DNA element. (PMID:24632303)
• Ras(V12)-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer (PMID:24648519)
• RRAD expression is frequently decreased in lung cancer. Ectopic expression of RRAD greatly reduces glycolysis whereas knockdown of RRAD promotes glycolysis in lung cancer cells. (PMID:25114038)
• RRAD promotes EGFR-mediated STAT3 activation and induces temozolomide resistance of malignant glioblastoma. (PMID:25313011)
• Data show that Ras-related associated with diabetes protein (RRAD) directly binds to the p65 subunit of the NF-kappa B (NF-kappaB)complex and inhibits the nuclear translocation of p65, which in turn negatively regulates the NF-kappaB signaling (PMID:25893381)
• Brg1 inhibits proliferation and migration of human aortic smooth muscle cells by directly up-regulating RRAD in aortic dissection. (PMID:26344687)
• our study revealed that RRAD expression was decreased in Hepatocellular carcinoma (HCC) tumor tissues and predicted poor clinical outcome for HCC patients and played an important role in regulating aerobic glycolysis and cell invasion and metastasis and may represent potential targets for improving the treatment of HCC (PMID:26546438)
• this study established RRAD to be a biomarker as well as a novel negative regulator of cellular senescence. (PMID:30391675)
• RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome. (PMID:31114854)
• RRAD expression in gastric and colorectal cancer with peritoneal carcinomatosis. (PMID:31857616)
• Reconstitution of beta-adrenergic regulation of CaV1.2: Rad-dependent and Rad-independent protein kinase A mechanisms. (PMID:34001616)
• Friend or Foe: Regulation, Downstream Effectors of RRAD in Cancer. (PMID:36979412)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrad	ENSDARG00000052011
mus_musculus	Rrad	ENSMUSG00000031880
rattus_norvegicus	Rrad	ENSRNOG00000011901

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

GTP-binding protein RAD — P55042 (reviewed: P55042)

Alternative names: RAD1, Ras associated with diabetes

All UniProt accessions (3): P55042, J3KRG9, J3KSM6

UniProt curated annotations — full annotation on UniProt →

Function. May regulate basal voltage-dependent L-type Ca(2+) currents and be required for beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force. May play an important role in cardiac antiarrhythmia via the strong suppression of voltage-gated L-type Ca(2+) currents. Regulates voltage-dependent L-type calcium channel subunit alpha-1C trafficking to the cell membrane. Inhibits cardiac hypertrophy through the calmodulin-dependent kinase II (CaMKII) pathway. Inhibits phosphorylation and activation of CAMK2D.

Subunit / interactions. Interacts with calmodulin preferentially in the inactive, GDP-bound form. Binds CAMKII which is capable of phosphorylating RAD in vitro. Interacts with CAMK2D. Interacts with CACNB2; interaction may be involved in beta-adrenergic regulation of heart rate and contractile force. Interaction with CACNB2 regulates the trafficking of CACNA1C to the cell membrane.

Subcellular location. Cell membrane.

Tissue specificity. Most abundantly expressed in the heart. Also found in the skeletal muscle and lung. Lesser amounts in placenta and kidney. Also detected in adipose tissue. Overexpressed in muscle of type II diabetic humans.

Induction. Down-regulated in failing hearts.

Similarity. Belongs to the small GTPase superfamily. RGK family.

RefSeq proteins (2): NP_001122322, NP_004156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR017358	RGK	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR051641	RGK_GTP-binding_reg	Family

Pfam: PF00071

UniProt features (23 total): helix 7, strand 6, region of interest 2, compositionally biased region 2, binding site 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3Q72	X-RAY DIFFRACTION	1.66
2DPX	X-RAY DIFFRACTION	1.8
2GJS	X-RAY DIFFRACTION	1.9
3Q7Q	X-RAY DIFFRACTION	2.3
3Q7P	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55042-F1	74.12	0.43

Functional residue map

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

Ligand- & substrate-binding residues (2): 98–105; 203–206

Post-translational modifications (2): 24, 26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription

MSigDB gene sets: 240 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, MYOGENIN_Q6, YAGI_AML_WITH_INV_16_TRANSLOCATION, chr16q22, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, AREB6_01, RIZKI_TUMOR_INVASIVENESS_3D_DN, GGGTGGRR_PAX4_03, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, YOKOE_CANCER_TESTIS_ANTIGENS, MARTINEZ_RB1_TARGETS_UP, GERY_CEBP_TARGETS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (2): small GTPase-mediated signal transduction (GO:0007264), negative regulation of high voltage-gated calcium channel activity (GO:1901842)

GO Molecular Function (6): GTPase activity (GO:0003924), calcium channel regulator activity (GO:0005246), calmodulin binding (GO:0005516), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular signaling cassette	1
high voltage-gated calcium channel activity	1
negative regulation of voltage-gated calcium channel activity	1
ribonucleoside triphosphate phosphatase activity	1
calcium channel activity	1
ion channel regulator activity	1
protein binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2437 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRAD	LPL	P06858	568
RRAD	TP53	P04637	514
RRAD	ERCC6	Q03468	484
RRAD	CALM1	P02593	478
RRAD	CALML4	Q96GE6	472
RRAD	CALML6	Q8TD86	460
RRAD	CALML3	P27482	460
RRAD	CALML5	Q9NZT1	460
RRAD	CD8A	P01732	446
RRAD	EEA1	Q15075	445
RRAD	SYN3	O14994	434
RRAD	RADIL	Q96JH8	433
RRAD	NHLRC1	Q6VVB1	429
RRAD	MDM2	Q00987	415
RRAD	IFNG	P01579	411
RRAD	CD209	Q9NNX6	411

IntAct

12 interactions, top by confidence:

A	B	Type	Score
RRAD	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.600
CCNDBP1	RRAD	psi-mi:“MI:0403”(colocalization)	0.600
RRAD	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
RRAD	SDC2	psi-mi:“MI:0915”(physical association)	0.400
RRAD	MMP14	psi-mi:“MI:0915”(physical association)	0.370
TP53	SUPT5H	psi-mi:“MI:0914”(association)	0.350
RNF216	RRAD	psi-mi:“MI:0914”(association)	0.350
CCDC141	RRAD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): RRAD (Affinity Capture-Western), EGFR (Reconstituted Complex), STAT3 (Reconstituted Complex), EEA1 (Reconstituted Complex), RRAD (Affinity Capture-MS), RRAD (Reconstituted Complex), CCNDBP1 (Two-hybrid), RRAD (Affinity Capture-Western), CCNDBP1 (Reconstituted Complex), RRAD (Co-localization), RRAD (Affinity Capture-Western), RRAD (Reconstituted Complex), RRAD (Biochemical Activity), CCDC141 (Two-hybrid), TPM2 (Reconstituted Complex)

ESM2 similar proteins: A1A4I4, A1A5B6, A1DZY4, A4D2P6, A5D7J5, O35141, O35929, O62683, O75628, O88667, O88910, O88954, P04629, P0C7J6, P35739, P55040, P55041, P55042, P55043, P70268, Q13368, Q16512, Q3MII6, Q3UFB7, Q5E9J3, Q5EBH1, Q5R541, Q60806, Q63433, Q6IMA7, Q6IMB1, Q6P5Z2, Q7L0Q8, Q864R5, Q8IYK8, Q8K045, Q8R4L0, Q8VEL9, Q8VHP8, Q8WWW0

Diamond homologs: A1DZY4, A5A6J7, A6NIZ1, A8NU18, C4YKT4, D3Z8L7, G4MZY8, G4N1S3, O35929, O42785, O75628, O88667, O93856, P01119, P03967, P08645, P08647, P0CQ42, P0CQ43, P0CY32, P10114, P10301, P10833, P11233, P11234, P13856, P15064, P18613, P22124, P22126, P22278, P22279, P22280, P28775, P32252, P32253, P32254, P34726, P34729, P36860

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	RRAD	phosphorylation
PRKCB	unknown	RRAD	phosphorylation
PRKACA	unknown	RRAD	phosphorylation
CAMK2G	unknown	RRAD	phosphorylation
CSNK2A1	unknown	RRAD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

587 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66922349:GCCCT:G	acceptor_gain	1.0000
16:66922350:CCCT:C	acceptor_gain	1.0000
16:66922350:CCCTC:C	acceptor_gain	1.0000
16:66922351:CCTC:C	acceptor_gain	1.0000
16:66922352:CT:C	acceptor_gain	1.0000
16:66922354:C:CA	acceptor_loss	1.0000
16:66922354:C:CC	acceptor_gain	1.0000
16:66922355:T:A	acceptor_loss	1.0000
16:66922356:G:C	acceptor_gain	1.0000
16:66922356:G:GC	acceptor_gain	1.0000
16:66922358:G:C	acceptor_gain	1.0000
16:66922380:C:CT	acceptor_gain	1.0000
16:66922381:A:T	acceptor_gain	1.0000
16:66923510:A:AC	donor_gain	1.0000
16:66923511:C:CC	donor_gain	1.0000
16:66923512:TCAC:T	donor_loss	1.0000
16:66923513:CA:C	donor_loss	1.0000
16:66923514:A:AC	donor_gain	1.0000
16:66923514:AC:A	donor_gain	1.0000
16:66923514:ACCAT:A	donor_gain	1.0000
16:66923515:C:CC	donor_gain	1.0000
16:66923515:CC:C	donor_gain	1.0000
16:66923515:CCATC:C	donor_gain	1.0000
16:66923654:C:CC	acceptor_gain	1.0000
16:66923721:C:CC	acceptor_gain	1.0000
16:66923841:CCTAC:C	donor_loss	1.0000
16:66923843:TAC:T	donor_loss	1.0000
16:66923844:AC:A	donor_loss	1.0000
16:66923845:C:CT	donor_loss	1.0000
16:66923845:CCTG:C	donor_gain	1.0000

AlphaMissense

1980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66923527:A:T	V213D	1.000
16:66923545:A:G	L207P	1.000
16:66923548:T:C	D206G	1.000
16:66923553:C:A	K204N	1.000
16:66923553:C:G	K204N	1.000
16:66923555:T:C	K204E	1.000
16:66923556:G:C	N203K	1.000
16:66923556:G:T	N203K	1.000
16:66923560:C:T	G202D	1.000
16:66923566:A:G	L200P	1.000
16:66923566:A:T	L200H	1.000
16:66923569:A:T	I199N	1.000
16:66923657:A:G	S170P	1.000
16:66923660:A:C	Y169D	1.000
16:66922245:A:G	L253P	0.999
16:66922248:C:G	R252P	0.999
16:66922257:C:G	R249P	0.999
16:66922267:C:G	G246R	0.999
16:66922272:A:G	F244S	0.999
16:66922306:A:G	S233P	0.999
16:66922308:G:T	T232K	0.999
16:66922316:G:C	F229L	0.999
16:66922316:G:T	F229L	0.999
16:66922317:A:G	F229S	0.999
16:66922318:A:G	F229L	0.999
16:66922319:C:A	K228N	0.999
16:66922319:C:G	K228N	0.999
16:66922322:G:C	C227W	0.999
16:66922323:C:T	C227Y	0.999
16:66922324:A:G	C227R	0.999

dbSNP variants (sampled 300 via entrez): RS1000102227 (16:66925130 C>A,G,T), RS1001046979 (16:66925280 G>A,C), RS1001060859 (16:66925086 C>G,T), RS1001097382 (16:66925574 C>A), RS1001121002 (16:66924659 C>G), RS1001601046 (16:66925592 C>G), RS1001653220 (16:66925266 C>G,T), RS1002603941 (16:66927202 A>C,G), RS1002963820 (16:66921205 C>A), RS1003453997 (16:66923184 T>C), RS1004057965 (16:66924114 C>G), RS1005059662 (16:66923085 T>C), RS1005471195 (16:66925878 G>A,C), RS1006806653 (16:66925666 C>G,T), RS1006965744 (16:66925369 A>C,G)

Disease associations

OMIM: gene MIM:179503 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Brugada syndrome	Limited	Autosomal dominant

Mondo (1): Brugada syndrome (MONDO:0015263)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020029_568	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, increases mutagenesis	11
Aflatoxin B1	increases expression, affects expression	6
Formaldehyde	increases expression	4
Cadmium Chloride	increases expression, decreases expression, increases abundance	4
Cadmium	increases abundance, increases expression	3
Silicon Dioxide	increases expression	3
lasiocarpine	increases expression	2
methyleugenol	increases expression	2
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	increases abundance, increases expression	2
Cisplatin	increases expression, affects cotreatment	2
Copper	affects binding, decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Lipopolysaccharides	increases expression, affects expression, affects response to substance	2
N-Nitrosopyrrolidine	increases expression	2
Smoke	increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	increases expression	1
senecionine	increases expression	1
senkirkine	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
heliotrine	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT02014961	Not specified	UNKNOWN	Worm Study: Modifier Genes in Sudden Cardiac Death
NCT02052765	Not specified	COMPLETED	AnalyST & Brugada Syndrome - Feasibility Study
NCT02302274	Not specified	COMPLETED	Diagnostic Value and Safety of Flecainide Infusion Test in Brugada Syndrome
NCT02344277	Not specified	COMPLETED	Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02641431	Not specified	COMPLETED	Epicardial Ablation in Brugada Syndrome
NCT02704416	Not specified	COMPLETED	Ablation in Brugada Syndrome for the Prevention of VF
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03435393	Not specified	UNKNOWN	Ripple Mapping for Epicardial Mapping of Brugada Syndrome
NCT03485508	Not specified	UNKNOWN	The Brugada Syndrome: a Follow-up Study
NCT03491475	Not specified	UNKNOWN	Echocardiography During Ajmaline Test
NCT03524079	Not specified	COMPLETED	Right Ventricle Morphology and Hemodynamics in BrS
NCT03764592	Not specified	COMPLETED	VF Mapping in Brugada and Early Repolarization Syndromes
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT03992677	Not specified	COMPLETED	Feasibility of Improving Risk Stratification in Brugada Syndrome
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04232787	Not specified	UNKNOWN	Southeast Asian Brugada Syndrome Cohort
NCT04257994	Not specified	RECRUITING	Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
NCT04420078	Not specified	COMPLETED	Brugada Ablation of VF Substrate Ongoing MultiCenter Registry
NCT04580992	Not specified	UNKNOWN	Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04808193	Not specified	UNKNOWN	European Perioperative Brugada Survey
NCT05048602	Not specified	UNKNOWN	Drug-induced Brugada Syndrome Research Database
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05283759	Not specified	RECRUITING	UZ Brussel HRMC Registry of Brugada Syndrome
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05643209	Not specified	RECRUITING	Brugada Syndrome Substrate Characterization and Ablation
NCT05685134	Not specified	COMPLETED	Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome
NCT06376552	Not specified	COMPLETED	Artificial Intelligence for the Prioritization of Genetic Background in Brugada Syndrome
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06567639	Not specified	COMPLETED	High Density Mapping in Brugada Syndrome
NCT06647927	Not specified	RECRUITING	GenLab: Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis
NCT06653504	Not specified	COMPLETED	The Conus Brugada Syndrome Study