RAPH1

Summary

RAPH1 (Ras association (RalGDS/AF-6) and pleckstrin homology domains 1, HGNC:14436) is a protein-coding gene on chromosome 2q33.2, encoding Ras-associated and pleckstrin homology domains-containing protein 1 (Q70E73). Mediator of localized membrane signals.

This gene encodes a protein that belongs to the Mig10/Rap1-interacting adaptor molecule/Lamellipodin family of adapter proteins, which function in cell migration. Members of this family contain pleckstrin-homology domains, Ras-association domains, and proline-rich C-termini. The protein encoded by this gene regulates actin dynamics through interaction with Ena/Vasodilator proteins as well as direct binding to filamentous actin to regulate actin network assembly. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 65059 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 188 total
• MANE Select transcript: NM_213589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14436
Approved symbol	RAPH1
Name	Ras association (RalGDS/AF-6) and pleckstrin homology domains 1
Location	2q33.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1681
Ensembl gene	ENSG00000173166
Ensembl biotype	protein_coding
OMIM	609035
Entrez	65059

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000308091, ENST00000319170, ENST00000374493, ENST00000418114, ENST00000419464, ENST00000420371, ENST00000423104, ENST00000428637, ENST00000439222, ENST00000453034, ENST00000457812, ENST00000465669, ENST00000630330, ENST00000854570, ENST00000854571

RefSeq mRNA: 3 — MANE Select: NM_213589 NM_001329728, NM_203365, NM_213589

CCDS: CCDS2359, CCDS2360

Canonical transcript exons

ENST00000319170 — 14 exons

Exon	Start	End
ENSE00001199342	203447959	203448079
ENSE00001199349	203448738	203448836
ENSE00001199353	203454430	203454540
ENSE00001199357	203455437	203455580
ENSE00001199362	203457530	203457595
ENSE00001199364	203459907	203460028
ENSE00001199366	203461249	203461408
ENSE00001199371	203461848	203461925
ENSE00001199377	203489584	203490089
ENSE00001199380	203491214	203491319
ENSE00001259426	203433682	203441413
ENSE00001344391	203444868	203445010
ENSE00001811028	203535111	203535301
ENSE00003759252	203495234	203495353

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 101.6497 / max 10113.3698, expressed in 1697 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33312	82.6351	608
33311	9.6274	1600
33314	7.1668	1588
33315	0.6945	416
33310	0.5733	323
33313	0.5107	293
33308	0.2144	75
33316	0.1684	73
33307	0.0591	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	99.55	gold quality
tibia	UBERON:0000979	99.35	gold quality
pancreatic ductal cell	CL:0002079	99.05	gold quality
endothelial cell	CL:0000115	98.80	gold quality
synovial joint	UBERON:0002217	98.49	gold quality
layer of synovial tissue	UBERON:0007616	98.25	gold quality
visceral pleura	UBERON:0002401	97.76	gold quality
upper arm skin	UBERON:0004263	96.95	gold quality
cartilage tissue	UBERON:0002418	96.94	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.73	gold quality
parietal pleura	UBERON:0002400	96.66	gold quality
lower lobe of lung	UBERON:0008949	96.51	gold quality
epithelium of mammary gland	UBERON:0003244	96.27	gold quality
mammary duct	UBERON:0001765	96.24	gold quality
tendon of biceps brachii	UBERON:0008188	96.15	gold quality
sural nerve	UBERON:0015488	96.12	gold quality
skin of hip	UBERON:0001554	96.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.94	gold quality
jejunal mucosa	UBERON:0000399	95.92	gold quality
dorsal root ganglion	UBERON:0000044	95.74	gold quality
gingival epithelium	UBERON:0001949	95.35	gold quality
jejunum	UBERON:0002115	95.03	gold quality
penis	UBERON:0000989	94.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.82	gold quality
substantia nigra pars compacta	UBERON:0001965	94.81	gold quality
saphenous vein	UBERON:0007318	94.44	gold quality
gingiva	UBERON:0001828	94.38	gold quality
oral cavity	UBERON:0000167	94.25	gold quality
germinal epithelium of ovary	UBERON:0001304	94.12	gold quality
trigeminal ganglion	UBERON:0001675	93.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	12.98
E-MTAB-6678	yes	8.91
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 16)

• RMO1 is expressed and deleted in osteosarcoma (PMID:15609301)
• proline-rich peptides organize the 4 subunits of BChE into a 340 kDa tetramer, by interacting with the C-terminal BChE tetramerization domain (PMID:18076380)
• Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. (PMID:19000833)
• Data show that profilin1 negatively regulates lamellipodin targeting to the leading edge; profilin1 depletion increases lamellipodin concentration at the lamellipodial tip (where it binds Ena/VASP), and this mediates the hypermotility. (PMID:21115820)
• Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. (PMID:22194892)
• results of this study suggested that that PI(3,4)P2, Lpd, and Ena/VASP are involved in the process movement of multipolar migrating cells. (PMID:22915108)
• The crystal structure of Lpd cc-RA-PH presents a molecular model of Lpd enhances actin polymerization by oligomerization via two intermolecular contact sites. (PMID:23483482)
• The results suggest that although the RAPH1 gene was deleted or amplified in all samples, the Lpd does not seem to play a major role in tumorigenesis of mammary carcinomas. (PMID:24057252)
• this study suggests a novel mechanism in which Lpd mediates EGFR endocytosis via Mena downstream of endophilin. (PMID:24076656)
• These data indicate a possible role for Lpd in the actin-based movement and the cell-to-cell spread of L. monocytogenes. (PMID:26169271)
• The authors propose that Lpd delivers Ena/VASP proteins to growing barbed ends and increases their actin polymerase activity by tethering them to actin filaments. (PMID:26295568)
• Disruption of the RIAM/lamellipodin-integrin-talin complex markedly impairs cell migration. (PMID:26419705)
• these studies demonstrate an insight into how the Lpd-PH domain regulates cellular signals in a PI(3,4)P2 dependent manner. (PMID:26726010)
• The human RAPH1 gene is the CHE2 locus. (PMID:27346732)
• High RAPH1 expression is correlated with aggressive breast cancer phenotypes and provides independent prognostic value in invasive breast cancer. (PMID:30056565)
• Nuclear isoform of RAPH1 interacts with FOXQ1 to promote aggressiveness and radioresistance in breast cancer. (PMID:38062011)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	raph1a	ENSDARG00000006301
danio_rerio	raph1b	ENSDARG00000061732
mus_musculus	Raph1	ENSMUSG00000026014
rattus_norvegicus	Raph1	ENSRNOG00000014722
drosophila_melanogaster	pico	FBGN0261811
caenorhabditis_elegans		WBGENE00003243

Paralogs (4): APBB1IP (ENSG00000077420), GRB10 (ENSG00000106070), GRB14 (ENSG00000115290), GRB7 (ENSG00000141738)

Protein

Protein identifiers

Ras-associated and pleckstrin homology domains-containing protein 1 — Q70E73 (reviewed: Q70E73)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein, Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein, Lamellipodin, Proline-rich EVH1 ligand 2, Protein RMO1

All UniProt accessions (5): Q70E73, C9J0R8, C9J164, C9JLG4, C9K0J5

UniProt curated annotations — full annotation on UniProt →

Function. Mediator of localized membrane signals. Implicated in the regulation of lamellipodial dynamics. Negatively regulates cell adhesion.

Subunit / interactions. Interacts with EVL and VASP and targets them to the leading edge. Interacts (via Ras associating and PH domains) with RAC1.

Subcellular location. Cell membrane. Cell projection. Lamellipodium. Filopodium. Cytoplasm. Cytoskeleton.

Tissue specificity. Isoform RMO1-RAPH1 is ubiquitously expressed with highest levels in brain, heart, ovary and developing embryo. Isoform RMO1 is widely expressed with highest levels in liver. Low expression in B-cells.

Induction. Reduced expression in metastatic osteosarcomas compared to primary osteosarcoma tumors. Down-regulated in both breast (43% of tissue samples) and ovarian (25% of tissue samples) cancers.

Similarity. Belongs to the MRL family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q70E73-10	RMO1-RAPH1, Lamellipodin, RAPH1	yes
Q70E73-2	RMO1
Q70E73-3	RMO1a
Q70E73-4	RMO1b
Q70E73-5	RMO1c
Q70E73-6	RMO1ab, Lamellipodin-S, Lpd-S
Q70E73-7	RMO1ac
Q70E73-8	RMO1bc
Q70E73-9	RMO1abc

RefSeq proteins (3): NP_001316657, NP_976241, NP_998754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039664	GRB/APBB1IP	Family
IPR039665	PH_APBB1IP	Domain

Pfam: PF00169, PF21989

UniProt features (89 total): modified residue 22, compositionally biased region 20, strand 15, helix 13, region of interest 7, splice variant 6, domain 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4GN1	X-RAY DIFFRACTION	2.4
4GMV	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70E73-F1	57.27	0.20

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 (22): 1, 5, 17, 54, 150, 192, 203, 205, 426, 456, 610, 827, 830, 845, 853, 894, 965, 974, 996, 1012 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, CREL_01, GCM_MAP4K4, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_GROWTH, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, TACAATC_MIR508, RODRIGUES_NTN1_TARGETS_DN, BILD_HRAS_ONCOGENIC_SIGNATURE, GTGCCTT_MIR506, IRF7_01, CATTTCA_MIR203, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_DEVELOPMENTAL_CELL_GROWTH

GO Biological Process (2): signal transduction (GO:0007165), axon extension (GO:0048675)

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

GO Cellular Component (10): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), nuclear body (GO:0016604), lamellipodium (GO:0030027), filopodium (GO:0030175), cytoplasm (GO:0005737), membrane (GO:0016020), cell leading edge (GO:0031252), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
axonogenesis	1
neuron projection extension	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
nucleoplasm	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin-based cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAPH1	VASP	P50552	997
RAPH1	TLN1	Q9Y490	866
RAPH1	PFN4	Q8NHR9	850
RAPH1	PFN3	P60673	849
RAPH1	INPPL1	O15357	832
RAPH1	PFN1	P07737	826
RAPH1	TLN2	Q9Y4G6	769
RAPH1	ABI1	Q8IZP0	763
RAPH1	FLNB	O75369	710
RAPH1	TRIP10	Q15642	694
RAPH1	FNBP1	Q96RU3	666
RAPH1	AKT1	P31749	637
RAPH1	RAP1A	P10113	624
RAPH1	ZYX	Q15942	612
RAPH1	ENAH	Q8N8S7	586

IntAct

58 interactions, top by confidence:

A	B	Type	Score
SH3GL2	RAPH1	psi-mi:“MI:0915”(physical association)	0.720
RAPH1	SH3GL2	psi-mi:“MI:0407”(direct interaction)	0.720
RAPH1	SH3GL2	psi-mi:“MI:0403”(colocalization)	0.720
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
RAPH1	SH3GL3	psi-mi:“MI:0407”(direct interaction)	0.630
Sh3gl1	RAPH1	psi-mi:“MI:0915”(physical association)	0.630
SH3GL3	RAPH1	psi-mi:“MI:0915”(physical association)	0.630
Sh3gl1	RAPH1	psi-mi:“MI:0403”(colocalization)	0.630
SH3GL3	RAPH1	psi-mi:“MI:0403”(colocalization)	0.630
Sh3gl1	RAPH1	psi-mi:“MI:0407”(direct interaction)	0.630
RAPH1	Sh3gl1	psi-mi:“MI:0407”(direct interaction)	0.630
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NCK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
Tln1	RAPH1	psi-mi:“MI:0915”(physical association)	0.400
RAPH1	SH3GL3	psi-mi:“MI:0915”(physical association)	0.400
RAPH1	SH3GL1	psi-mi:“MI:0915”(physical association)	0.400
RAPH1	MATR3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (83): RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Biochemical Activity), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Proximity Label-MS), RAPH1 (Proximity Label-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-MS), RAPH1 (Affinity Capture-RNA), ENAH (Affinity Capture-Western), VASP (Reconstituted Complex)

ESM2 similar proteins: A0A088MLT8, A0A0G2K0D3, A2AQ19, B3KU38, D3ZTQ1, E1BTG2, E6ZGB4, E9PSK7, O35274, O60271, O75151, O75376, P12755, P22682, P29536, P49140, Q08DA0, Q13191, Q3B7T9, Q3TTA7, Q3UHZ5, Q3USH5, Q3YEC7, Q4KKX4, Q58A65, Q5SFM8, Q5U3K5, Q60698, Q60974, Q62415, Q640N2, Q6P5Q4, Q6R891, Q70E73, Q80XA6, Q86YP4, Q8BVA4, Q8CHY6, Q8K4S7, Q8R3Y5

Diamond homologs: A0A8I3NFE2, A6QLK6, B5KFD7, D7PF45, F1N9Y5, O15357, O60880, O88900, P0CE43, P29349, P41242, P41243, P42679, P42686, P43403, P43404, P53356, P97573, Q03160, Q13322, Q13588, Q14449, Q14451, Q1RMW5, Q24708, Q5ICW4, Q5ZL23, Q60760, Q6DCV1, Q6P549, Q6PFT9, Q70E73, Q71S10, Q7Z5R6, Q8BMC3, Q8R5A3, Q92835, Q9BG88, Q9ES52, Q9JLM9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
RAPH1	“up-regulates activity”	ENAH	binding
RAPH1	“up-regulates activity”	VASP	binding
RAPH1	“up-regulates activity”	EVL	binding
ABL1	“up-regulates activity”	RAPH1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ROBO receptors	6	19.6×	2e-05
Clathrin-mediated endocytosis	7	15.7×	1e-05
Cargo recognition for clathrin-mediated endocytosis	5	13.8×	4e-04
RAC1 GTPase cycle	8	12.9×	9e-06
RHO GTPase cycle	8	12.7×	9e-06
RHO GTPase Effectors	7	12.5×	4e-05
Signaling by Rho GTPases	11	9.9×	1e-06
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	11	9.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
neuron projection development	5	14.2×	3e-03
cell migration	6	8.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	161
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4952 predictions. Top by Δscore:

Variant	Effect	Δscore
2:203396779:CCTCA:C	acceptor_loss	1.0000
2:203396780:CTCAG:C	acceptor_loss	1.0000
2:203396781:TCAG:T	acceptor_loss	1.0000
2:203396782:CA:C	acceptor_loss	1.0000
2:203396783:A:AG	acceptor_gain	1.0000
2:203396783:A:C	acceptor_loss	1.0000
2:203396784:G:GC	acceptor_gain	1.0000
2:203396784:GC:G	acceptor_gain	1.0000
2:203396784:GCC:G	acceptor_gain	1.0000
2:203396784:GCCC:G	acceptor_gain	1.0000
2:203396784:GCCCC:G	acceptor_gain	1.0000
2:203396964:ACAGG:A	donor_loss	1.0000
2:203396965:CAGGT:C	donor_loss	1.0000
2:203396967:GGT:G	donor_loss	1.0000
2:203396968:G:GG	donor_gain	1.0000
2:203396968:GTA:G	donor_loss	1.0000
2:203402571:TTCA:T	acceptor_loss	1.0000
2:203402574:A:AC	acceptor_loss	1.0000
2:203402574:A:AG	acceptor_gain	1.0000
2:203402574:AG:A	acceptor_gain	1.0000
2:203402575:G:GT	acceptor_gain	1.0000
2:203402575:GG:G	acceptor_gain	1.0000
2:203402575:GGT:G	acceptor_gain	1.0000
2:203402575:GGTC:G	acceptor_gain	1.0000
2:203402575:GGTCA:G	acceptor_gain	1.0000
2:203402731:CCAGG:C	donor_loss	1.0000
2:203402732:CAGGT:C	donor_loss	1.0000
2:203402733:AGGT:A	donor_loss	1.0000
2:203402734:GGT:G	donor_loss	1.0000
2:203402735:G:GA	donor_loss	1.0000

AlphaMissense

8098 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:203439684:A:G	L1169P	1.000
2:203448764:A:G	W496R	1.000
2:203448764:A:T	W496R	1.000
2:203455468:C:T	G424D	1.000
2:203455469:C:G	G424R	1.000
2:203455500:C:A	W413C	1.000
2:203455500:C:G	W413C	1.000
2:203455502:A:G	W413R	1.000
2:203455502:A:T	W413R	1.000
2:203459981:A:G	W340R	1.000
2:203459981:A:T	W340R	1.000
2:203459989:A:G	L337P	1.000
2:203459998:A:T	V334D	1.000
2:203461320:A:G	L300P	1.000
2:203461359:A:T	V287E	1.000
2:203461395:A:T	V275D	1.000
2:203461407:A:G	L271P	1.000
2:203461862:C:G	A266P	1.000
2:203461879:A:G	L260P	1.000
2:203461882:G:T	A259D	1.000
2:203461883:C:G	A259P	1.000
2:203461891:A:C	I256S	1.000
2:203490038:A:G	L93P	1.000
2:203495250:A:G	L35P	1.000
2:203495259:A:G	L32P	1.000
2:203495263:A:G	W31R	1.000
2:203495263:A:T	W31R	1.000
2:203439684:A:T	L1169H	0.999
2:203448748:C:G	R501P	0.999
2:203448792:A:C	C486W	0.999

dbSNP variants (sampled 300 via entrez): RS1000021434 (2:203449424 G>A), RS1000025705 (2:203457684 G>A,C), RS1000033377 (2:203457172 T>G), RS1000036707 (2:203503437 A>G), RS1000126091 (2:203509974 A>T), RS1000151665 (2:203503541 T>A,C), RS1000204160 (2:203498223 T>C), RS1000262534 (2:203463826 C>T), RS1000275431 (2:203478009 C>T), RS1000302531 (2:203456544 C>T), RS1000320149 (2:203521800 T>G), RS1000327976 (2:203516821 C>T), RS1000330055 (2:203508962 C>G,T), RS1000375706 (2:203508775 C>T), RS1000417067 (2:203503843 T>A,C)

Disease associations

OMIM: gene MIM:609035 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005752_161	Systemic lupus erythematosus	4.000000e-06
GCST006143_1	Bone mineral density (total hip)	2.000000e-07
GCST010243_79	Apolipoprotein B levels	7.000000e-11
GCST90002383_197	Hematocrit	4.000000e-10
GCST90002384_240	Hemoglobin	8.000000e-10
GCST90002396_179	Mean reticulocyte volume	6.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density
EFO:0004615	apolipoprotein B measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects expression, decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Acetaminophen	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
dicrotophos	increases expression	1
lead acetate	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance	1
ferrous chloride	increases expression	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	decreases expression, increases activity	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Cannabidiol	increases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer