RHBDF1

Summary

RHBDF1 (rhomboid 5 homolog 1, HGNC:20561) is a protein-coding gene on chromosome 16p13.3, encoding Inactive rhomboid protein 1 (Q96CC6). Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation.

Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane.

Source: NCBI Gene 64285 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 177 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_022450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20561
Approved symbol	RHBDF1
Name	rhomboid 5 homolog 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	EGFR-RS, FLJ2235, Dist1, iRhom1
Ensembl gene	ENSG00000007384
Ensembl biotype	protein_coding
OMIM	614403
Entrez	64285

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 27 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay

ENST00000262316, ENST00000417043, ENST00000419764, ENST00000428730, ENST00000448893, ENST00000450643, ENST00000472390, ENST00000482904, ENST00000486045, ENST00000487201, ENST00000493647, ENST00000886898, ENST00000886899, ENST00000886900, ENST00000886901, ENST00000886902, ENST00000886903, ENST00000886904, ENST00000917250, ENST00000917251, ENST00000917252, ENST00000917253, ENST00000944433, ENST00000944434, ENST00000944435, ENST00000944436, ENST00000944437, ENST00000944438, ENST00000944439, ENST00000944440, ENST00000944441, ENST00000944442, ENST00000944443, ENST00000944444

RefSeq mRNA: 1 — MANE Select: NM_022450 NM_022450

CCDS: CCDS32344

Canonical transcript exons

ENST00000262316 — 18 exons

Exon	Start	End
ENSE00001530514	72513	72631
ENSE00001671010	64699	64829
ENSE00001947408	58059	58759
ENSE00002268228	64899	65039
ENSE00003347967	63587	63800
ENSE00003470255	61120	61281
ENSE00003481793	62973	63182
ENSE00003494468	60439	60539
ENSE00003508586	59419	59494
ENSE00003553428	58974	59127
ENSE00003562519	62538	62695
ENSE00003568795	59732	59826
ENSE00003574304	60216	60279
ENSE00003578704	62775	62897
ENSE00003610255	59249	59349
ENSE00003616048	61585	61696
ENSE00003626305	61385	61459
ENSE00003646450	61798	62052

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8581 / max 50.7950, expressed in 1520 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155694	5.9803	1501
155693	0.8778	615

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	98.83	gold quality
popliteal artery	UBERON:0002250	98.19	gold quality
tibial artery	UBERON:0007610	98.19	gold quality
aorta	UBERON:0000947	97.87	gold quality
ascending aorta	UBERON:0001496	97.73	gold quality
thoracic aorta	UBERON:0001515	97.66	gold quality
right coronary artery	UBERON:0001625	97.64	gold quality
lower esophagus mucosa	UBERON:0035834	97.46	gold quality
left coronary artery	UBERON:0001626	97.41	gold quality
endocervix	UBERON:0000458	97.28	gold quality
descending thoracic aorta	UBERON:0002345	97.28	gold quality
right lung	UBERON:0002167	97.26	gold quality
mucosa of stomach	UBERON:0001199	97.18	gold quality
sural nerve	UBERON:0015488	97.10	gold quality
ectocervix	UBERON:0012249	97.00	gold quality
coronary artery	UBERON:0001621	96.92	gold quality
apex of heart	UBERON:0002098	96.67	gold quality
right ovary	UBERON:0002118	96.53	gold quality
left ovary	UBERON:0002119	96.25	gold quality
stromal cell of endometrium	CL:0002255	96.22	gold quality
skin of leg	UBERON:0001511	95.73	gold quality
upper lobe of left lung	UBERON:0008952	95.61	gold quality
left uterine tube	UBERON:0001303	95.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.39	gold quality
body of uterus	UBERON:0009853	95.32	gold quality
lower esophagus	UBERON:0013473	95.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.28	gold quality
skin of abdomen	UBERON:0001416	95.22	gold quality
minor salivary gland	UBERON:0001830	95.05	gold quality
upper lobe of lung	UBERON:0008948	94.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting RHBDF1, 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-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-4435	95.90	65.47	1201
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 14)

• RHBDF1 is a seven-transmembrane protein with a long N-terminal cytoplasmic extension that comprises half of the polypeptide sequence, and is found in the endoplasmic reticulum and Golgi, but not on the cell surface (PMID:15965977)
• RHBDF1 has a pivotal role in sustaining growth signals in epithelial cancer cells and thus may serve as a therapeutic target for treating epithelial cancers. (PMID:18524845)
• RHBDF1 is critically involved in a G protein-coupled receptors ligand-stimulated process leading to the activation of latent epidermal growth factor receptor ligands (PMID:18832597)
• RHBDF1 is a critical component of a molecular switch that regulates HIF1alpha stability in cancer cells in hypoxia. (PMID:24648344)
• The expression of iRhom1 was increased by endoplasmic reticulum (ER) stressors, such as thapsigargin and tunicamycin, leading to the enhancement of proteasome activity, especially in ER-containing microsomes. (PMID:26109405)
• results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity (PMID:26535007)
• that the regulatory effects of RHBDF1 on epithelial-to-mesenchymal transition and on cell proliferation are partially attributable to the Wnt/beta-catenin signalling pathway (PMID:29654741)
• findings indicate that perturbations of apicobasal polarity by high levels of RHBDF1 is a significant attribute in the development of breast neoplasia. (PMID:29727209)
• RHBDF1 is an indispensable component of the protein trafficking machinery involved in GPCR-mediated EGFR transactivation, and is an attractive therapeutic target for cancer. (PMID:30279141)
• Results revealed that cervical cancer (CC) tissues had higher levels of iRhom1 than adjacent normal tissues. Its increased expression was significantly associated with tumor stage, size, and parametrium invasion as well as poor outcomes. Knockdown of iRhom1 in HeLa cells inhibited cell growth, disrupted the cell cycle, and promoted apoptosis. (PMID:31661139)
• RHBDF1 promotes AP-1-activated endothelial-mesenchymal transition in tumor fibrotic stroma formation. (PMID:34276048)
• Attenuation of Excess TNF-alpha Release in Crohn’s Disease by Silencing of iRHOMs 1/2 and the Restoration of TGF-beta Mediated Immunosuppression Through Modulation of TACE Trafficking. (PMID:35585977)
• Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation. (PMID:35595096)
• RHBDF1 deficiency suppresses melanoma glycolysis and enhances efficacy of immunotherapy by facilitating glucose-6-phosphate isomerase degradation via TRIM32. (PMID:37979663)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhbdf1b	ENSDARG00000017367
danio_rerio	rhbdf1a	ENSDARG00000036541
mus_musculus	Rhbdf1	ENSMUSG00000020282
rattus_norvegicus	Rhbdf1	ENSRNOG00000020594
drosophila_melanogaster	rho-5	FBGN0041723
caenorhabditis_elegans		WBGENE00004402
caenorhabditis_elegans		WBGENE00004403

Paralogs (5): RHBDL1 (ENSG00000103269), RHBDF2 (ENSG00000129667), RHBDL3 (ENSG00000141314), RHBDL2 (ENSG00000158315), PARL (ENSG00000175193)

Protein

Protein identifiers

Inactive rhomboid protein 1 — Q96CC6 (reviewed: Q96CC6)

Alternative names: Epidermal growth factor receptor-related protein, Rhomboid 5 homolog 1, Rhomboid family member 1, p100hRho

All UniProt accessions (6): Q96CC6, A0A1B0GXG1, B8ZZ07, F8WBS4, F8WCF7, H0Y6L9

UniProt curated annotations — full annotation on UniProt →

Function. Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.

Subunit / interactions. Homodimer, or homooligomer. Interacts with TGFA and HBEGF. Interacts with EGF; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD). Interacts (via cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to mutual protein stabilization. Interacts with ADAM17/TACE.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Highly expressed in cerebellum, cerebrum, heart, skeletal muscle, placenta, pancreatic islet and testis. Detected at lower levels in colon, kidney, small intestine and lung.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the peptidase S54 family.

RefSeq proteins (1): NP_071895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022241	iRhom1_2_N	Domain
IPR022764	Peptidase_S54_rhomboid_dom	Domain
IPR035952	Rhomboid-like_sf	Homologous_superfamily
IPR051512	Inactive_Rhomboid	Family

Pfam: PF01694, PF12595

UniProt features (30 total): topological domain 8, transmembrane region 7, modified residue 5, sequence conflict 4, mutagenesis site 3, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9XY4	ELECTRON MICROSCOPY	3.12
9Q7Y	ELECTRON MICROSCOPY	3.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CC6-F1	68.69	0.36

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): 76, 176, 180, 183, 390

Glycosylation sites (1): 583

Mutagenesis-validated functional residues (3):

Position	Phenotype
131	no effect.
381	no effect.
583	loss of n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 192 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, AP1_Q4_01, GOBP_REGULATION_OF_CATABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_ERBB_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_SECRETION, GOBP_SECRETION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5

GO Biological Process (7): cell population proliferation (GO:0008283), protein transport (GO:0015031), cell migration (GO:0016477), regulation of epidermal growth factor receptor signaling pathway (GO:0042058), regulation of protein secretion (GO:0050708), negative regulation of protein secretion (GO:0050709), regulation of proteasomal protein catabolic process (GO:0061136)

GO Molecular Function (3): growth factor binding (GO:0019838), serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein secretion	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell motility	1
epidermal growth factor receptor signaling pathway	1
regulation of ERBB signaling pathway	1
regulation of protein transport	1
regulation of secretion by cell	1
regulation of protein secretion	1
negative regulation of protein transport	1
negative regulation of secretion by cell	1
proteasomal protein catabolic process	1
regulation of protein catabolic process	1
protein binding	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHBDF1	ADAM17	P78536	753
RHBDF1	TGFA	P01135	706
RHBDF1	RHBDD2	Q6NTF9	667
RHBDF1	NPRL3	Q12980	667
RHBDF1	SNRNP25	Q9BV90	626
RHBDF1	RHBDL1	O75783	621
RHBDF1	EGF	P01133	581
RHBDF1	FRMD8	Q9BZ67	575
RHBDF1	MPG	P29372	567
RHBDF1	PARL	Q9H300	555
RHBDF1	RHBDD1	Q8TEB9	541
RHBDF1	A0A1W2PP11	A0A1W2PP11	538
RHBDF1	UBAC2	Q8NBM4	505
RHBDF1	RHBDD3	Q9Y3P4	490
RHBDF1	AREG	P15514	463

IntAct

19 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
RHBDF1	LHX3	psi-mi:“MI:0915”(physical association)	0.560
CSGALNACT2	TPST1	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
Egf	RHBDF1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
ADGRG5	SLC33A1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TMED5	DGAT1	psi-mi:“MI:0914”(association)	0.350
RHBDF1	LHX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): RHBDF1 (Affinity Capture-RNA), RHBDF1 (Affinity Capture-MS), RHBDF1 (Affinity Capture-Western), RHBDF1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-Western), HIF1A (Affinity Capture-Western), RHBDF1 (Affinity Capture-Western), RHBDF1 (Affinity Capture-MS), RHBDF1 (Proximity Label-MS), LHX3 (Two-hybrid), RHBDF1 (Affinity Capture-MS), RHBDF1 (Affinity Capture-MS), RHBDF1 (Affinity Capture-MS), RHBDF1 (Negative Genetic), RHBDF1 (Affinity Capture-RNA)

ESM2 similar proteins: A0JPA1, A4GG66, A4GVD1, A4IG66, A7YWH9, A9L8T6, B0VX73, B1MT31, F1NVK6, G5EBQ8, P18861, P28228, P28229, P36383, P91682, Q00M95, Q0IHQ3, Q0P5V9, Q11186, Q16625, Q28269, Q2HJ66, Q3UZP0, Q499S9, Q5BKX6, Q5RFS5, Q5YLM1, Q61146, Q62847, Q66IE4, Q6GMF8, Q6NZH5, Q6P6T5, Q6PIX5, Q6PJF5, Q6PYT3, Q6R4A8, Q6WQJ1, Q7TMB7, Q7ZXS7

Diamond homologs: A0JPA1, A7YWH9, A9L8T6, B0VX73, B1MT31, C8VCL5, F4JBM4, O82756, P54493, Q00M95, Q0WQX7, Q499S9, Q695T8, Q695U0, Q6GMF8, Q6GV23, Q6IUY1, Q6PIX5, Q6PJF5, Q76NQ1, Q80WQ6, Q8VZ48, Q96CC6, Q9CAN1, Q9NX52, Q9SSR0, A2AGA4, F4I8K2, P46116, P96617, Q9LYP1, F4ICF4, A1AGU7, A7MGE5, A7ZSV4, A8A5N2, A9MMA7, B1IP42, B1LI84, B1X769

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	7
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3223 predictions. Top by Δscore:

Variant	Effect	Δscore
16:58758:ACCTG:A	acceptor_loss	1.0000
16:58759:CCTGG:C	acceptor_loss	1.0000
16:58760:CTGGG:C	acceptor_loss	1.0000
16:58969:CTTA:C	donor_loss	1.0000
16:58970:TTACC:T	donor_loss	1.0000
16:58971:TACC:T	donor_loss	1.0000
16:58972:A:AC	donor_gain	1.0000
16:58972:AC:A	donor_gain	1.0000
16:58973:C:CA	donor_loss	1.0000
16:58973:C:CC	donor_gain	1.0000
16:58973:CC:C	donor_gain	1.0000
16:58973:CCT:C	donor_gain	1.0000
16:59091:CAT:C	acceptor_gain	1.0000
16:59094:C:CC	acceptor_gain	1.0000
16:59101:C:CT	acceptor_gain	1.0000
16:59112:C:CT	acceptor_gain	1.0000
16:59113:A:T	acceptor_gain	1.0000
16:59416:TA:T	donor_loss	1.0000
16:59417:ACC:A	donor_loss	1.0000
16:59418:C:CG	donor_loss	1.0000
16:59492:CAC:C	acceptor_gain	1.0000
16:59495:CTAG:C	acceptor_loss	1.0000
16:59496:T:A	acceptor_loss	1.0000
16:59727:CGTA:C	donor_loss	1.0000
16:59728:GTA:G	donor_loss	1.0000
16:59729:TA:T	donor_loss	1.0000
16:59730:A:AG	donor_loss	1.0000
16:59730:ACCTG:A	donor_gain	1.0000
16:59731:CCTG:C	donor_gain	1.0000
16:59731:CCTGC:C	donor_gain	1.0000

AlphaMissense

5600 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:58584:C:T	G775E	1.000
16:59249:C:T	G665E	1.000
16:59250:C:A	G665W	1.000
16:59326:A:C	C639W	1.000
16:59327:C:T	C639Y	1.000
16:59341:G:C	C634W	1.000
16:59342:C:T	C634Y	1.000
16:59467:A:C	C615W	1.000
16:59468:C:A	C615F	1.000
16:59468:C:G	C615S	1.000
16:59468:C:T	C615Y	1.000
16:59469:A:T	C615S	1.000
16:59492:C:G	C607S	1.000
16:59492:C:T	C607Y	1.000
16:59493:A:G	C607R	1.000
16:59493:A:T	C607S	1.000
16:59749:G:C	C600W	1.000
16:59750:C:G	C600S	1.000
16:59750:C:T	C600Y	1.000
16:59751:A:G	C600R	1.000
16:59751:A:T	C600S	1.000
16:59752:G:C	C599W	1.000
16:59753:C:T	C599Y	1.000
16:59754:A:G	C599R	1.000
16:59756:G:T	P598H	1.000
16:59759:C:G	R597P	1.000
16:59822:C:G	C576S	1.000
16:59823:A:T	C576S	1.000
16:60219:C:A	W573C	1.000
16:60219:C:G	W573C	1.000

dbSNP variants (sampled 300 via entrez): RS1000068724 (16:69592 G>A,T), RS1000087335 (16:75536 G>A,C), RS1000463847 (16:62871 A>C,G), RS1000610570 (16:68565 C>A,G), RS1000641964 (16:68382 G>A), RS1000773386 (16:64065 G>A,C), RS1000785673 (16:59878 C>G), RS1000936788 (16:73548 C>G,T), RS1001126730 (16:74328 G>C), RS1001137453 (16:69470 C>T), RS1001188372 (16:69290 G>A,C), RS1001300076 (16:60332 C>A,T), RS1001416244 (16:74927 T>C), RS1001551731 (16:59616 T>C), RS1002109547 (16:64436 G>A)

Disease associations

OMIM: gene MIM:614403 | disease phenotypes: MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Moderate	Autosomal recessive

Mondo (2): Wolff-Parkinson-White syndrome (MONDO:0008685), dilated cardiomyopathy (MONDO:0005021)

Orphanet (1): NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001716	Wolff-Parkinson-White syndrome

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005549_11	Alzheimer’s disease (late onset)	2.000000e-06
GCST005931_13	Glioma	3.000000e-06
GCST005933_3	Non-glioblastoma glioma	3.000000e-06
GCST005951_12	Body mass index	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Estradiol	decreases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Resveratrol	decreases expression, affects cotreatment	2
Arsenic	decreases expression, increases abundance, increases methylation, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
bafilomycin A	increases expression, increases reaction	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
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8UL	Ubigene HCT 116 RHBDF1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy