ARHGEF15

Summary

ARHGEF15 (Rho guanine nucleotide exchange factor 15, HGNC:15590) is a protein-coding gene on chromosome 17p13.1, encoding Rho guanine nucleotide exchange factor 15 (O94989). Guanine nucleotide exchange factor (GEF) that activates RhoA, playing a role in the regulation of actin cytoskeleton organization.

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene.

Source: NCBI Gene 22899 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 725 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_173728

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15590
Approved symbol	ARHGEF15
Name	Rho guanine nucleotide exchange factor 15
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0915, Vsm-RhoGEF, ARGEF15, FLJ13791, MGC44868
Ensembl gene	ENSG00000198844
Ensembl biotype	protein_coding
OMIM	608504
Entrez	22899

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000361926, ENST00000421050, ENST00000455564, ENST00000578286, ENST00000579439, ENST00000581809, ENST00000582060, ENST00000583529, ENST00000647883, ENST00000852584, ENST00000852585, ENST00000852586

RefSeq mRNA: 2 — MANE Select: NM_173728 NM_025014, NM_173728

CCDS: CCDS11139

Canonical transcript exons

ENST00000361926 — 16 exons

Exon	Start	End
ENSE00000683831	8318570	8318662
ENSE00000683836	8318387	8318461
ENSE00000683841	8316019	8316148
ENSE00000683846	8315755	8315907
ENSE00000683858	8314906	8314964
ENSE00000683862	8313501	8313555
ENSE00000683865	8312922	8313254
ENSE00000683868	8311991	8312640
ENSE00000855084	8319499	8319603
ENSE00000855085	8319312	8319394
ENSE00000855086	8319007	8319159
ENSE00000949000	8318750	8318910
ENSE00001232401	8310241	8310343
ENSE00001777337	8320842	8322511
ENSE00003606899	8315066	8315277
ENSE00003632789	8315414	8315574

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 95.51.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1200 / max 190.0813, expressed in 324 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159485	1.4419	257
159482	1.1804	250
159483	0.2623	149
159484	0.2354	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.51	gold quality
omental fat pad	UBERON:0010414	94.06	gold quality
peritoneum	UBERON:0002358	93.98	gold quality
pancreatic ductal cell	CL:0002079	93.48	silver quality
adipose tissue of abdominal region	UBERON:0007808	92.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.51	gold quality
right lung	UBERON:0002167	89.96	gold quality
heart left ventricle	UBERON:0002084	89.32	gold quality
upper lobe of left lung	UBERON:0008952	88.88	gold quality
sural nerve	UBERON:0015488	88.82	gold quality
cardiac ventricle	UBERON:0002082	88.77	gold quality
upper lobe of lung	UBERON:0008948	87.91	gold quality
adipose tissue	UBERON:0001013	87.26	gold quality
buccal mucosa cell	CL:0002336	86.41	gold quality
connective tissue	UBERON:0002384	86.19	gold quality
metanephros cortex	UBERON:0010533	86.19	gold quality
right lobe of thyroid gland	UBERON:0001119	85.60	gold quality
heart	UBERON:0000948	85.49	gold quality
right atrium auricular region	UBERON:0006631	85.18	gold quality
mucosa of stomach	UBERON:0001199	85.16	gold quality
tendon of biceps brachii	UBERON:0008188	84.54	gold quality
body of uterus	UBERON:0009853	84.29	gold quality
cardiac atrium	UBERON:0002081	84.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.04	gold quality
left uterine tube	UBERON:0001303	83.96	gold quality
gall bladder	UBERON:0002110	83.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.91	gold quality
lower esophagus	UBERON:0013473	82.84	gold quality
left lobe of thyroid gland	UBERON:0001120	82.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.16
E-GEOD-81608	no	88.66
E-MTAB-6678	no	2.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFDP3

miRNA regulators (miRDB)

58 targeting ARHGEF15, 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-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4260	98.78	65.37	848

Literature-anchored findings (GeneRIF, showing 4)

• This paper presents functional studies determined in rat, mouse, and human tissues and cell lines. (PMID:12775584)
• Arhgef15 acts as an endothelial cell-specific GEF to mediate VEGF-induced Cdc42 activation and potentiate RhoJ inactivation, thereby promoting actin polymerization and cell motility. (PMID:23029280)
• upregulation of ARHGEF15 contributes to the development of aggressive PDAC by increasing the growth and motility of the pancreatic cancer cells, thereby worsening the prognosis of these patients. (PMID:27145964)
• pathological elevation of Ephexin5 expression critically drives Abeta-induced memory impairment (PMID:28346227)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgef15b	ENSDARG00000061844
danio_rerio	arhgef15a	ENSDARG00000100293
mus_musculus	Arhgef15	ENSMUSG00000052921
rattus_norvegicus	Arhgef15	ENSRNOG00000004566
caenorhabditis_elegans		WBGENE00019487

Paralogs (6): ARHGEF5 (ENSG00000050327), NGEF (ENSG00000066248), ARHGEF26 (ENSG00000114790), ARHGEF16 (ENSG00000130762), ARHGEF19 (ENSG00000142632), ARHGEF35 (ENSG00000213214)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 15 — O94989 (reviewed: O94989)

Alternative names: Ephexin-5, Vsm-RhoGEF

All UniProt accessions (7): O94989, A0A0S2Z543, A0A0S2Z547, A0A3B3IUF8, J3KT46, J3QQS4, J3QS60

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) that activates RhoA, playing a role in the regulation of actin cytoskeleton organization. Is involved in the regulation of vascular smooth muscle contractility. Additionally, it negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2. Does not activate RAC1 or CDC42.

Subunit / interactions. Interacts with EPHB2. Interacts with EPHA4.

Subcellular location. Cell projection. Dendrite.

Tissue specificity. Expressed in the vascular smooth muscle of coronary artery.

Post-translational modifications. Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-dependent phosphorylation at Tyr-353 triggers UBE3A-mediated ubiquitination. Ubiquitinated; UBE3A-mediated ubiquitination and degradation by the proteasome promotes EFNB1-dependent synapse formation.

Disease relevance. Brain small vessel disease 5 with osteoporosis (BSVD5) [MIM:621331] An autosomal dominant, adult form of brain small vessel disease, a cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD5 features include cognitive decline, psychiatric disturbances, and cerebral infarctions associated with brain imaging abnormalities such as microbleeds, enlarged perivascular spaces, white matter abnormalities, and brain atrophy. Patients have osteoporosis and increased bone fracture tendency. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_079290, NP_776089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR047270	PH_ephexin	Domain
IPR047271	Ephexin-like	Family

Pfam: PF00621

UniProt features (20 total): sequence variant 8, region of interest 4, modified residue 3, compositionally biased region 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94989-F1	62.96	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 (3): 109, 353, 107

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): regulation of actin cytoskeleton organization (GO:0032956), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of stress fiber assembly (GO:0051496), retina vasculature morphogenesis in camera-type eye (GO:0061299), regulation of postsynapse assembly (GO:0150052), negative regulation of synapse maturation (GO:2000297)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), dendrite (GO:0030425), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase cycle	3
Signal Transduction	3
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
GTPase regulator activity	2
synapse	2
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
anatomical structure morphogenesis	1
retina vasculature development in camera-type eye	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
negative regulation of developmental process	1
synapse maturation	1
regulation of synapse maturation	1
negative regulation of synapse organization	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF15	UBE3A	P78355	827
ARHGEF15	EPHA4	P54764	783
ARHGEF15	MCF2	P10911	708
ARHGEF15	RHOA	P06749	657
ARHGEF15	EFNB1	P98172	637
ARHGEF15	EFNB3	Q15768	627
ARHGEF15	EFNB2	P52799	601
ARHGEF15	CSAD	Q9Y600	521
ARHGEF15	FGD5	Q6ZNL6	504
ARHGEF15	ARHGEF33	A8MVX0	503
ARHGEF15	SEMA3G	Q9NS98	489
ARHGEF15	PLEK2	Q9NYT0	487
ARHGEF15	GADL1	Q6ZQY3	487
ARHGEF15	MEOX1	P50221	469
ARHGEF15	PLEK	P08567	455
ARHGEF15	POU6F1	Q14863	455

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ARHGEF15	CEP55	psi-mi:“MI:0915”(physical association)	0.810
CEP55	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.810
ARHGEF15	PIN1	psi-mi:“MI:0915”(physical association)	0.560
LASP1	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.560
PIN1	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF15	PRKG1	psi-mi:“MI:0915”(physical association)	0.560
	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF15	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
H1-5	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.400
BICD2	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.400
ARHGEF15	MOB4	psi-mi:“MI:0915”(physical association)	0.370
ARHGEF15	CSTPP1	psi-mi:“MI:0915”(physical association)	0.370
ARHGEF15	DNAJC5	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PRKG1	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.000
ARHGEF15		psi-mi:“MI:0915”(physical association)	0.000
ARHGEF15	CEP55	psi-mi:“MI:0915”(physical association)	0.000
ARHGEF15	GORASP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): ARHGEF15 (Two-hybrid), ARHGEF15 (Two-hybrid), CEP55 (Two-hybrid), MOB4 (Two-hybrid), C11orf49 (Two-hybrid), CEP55 (Two-hybrid), EPHA4 (Affinity Capture-Western), DNAJC5 (FRET), ARHGEF15 (Two-hybrid), ARHGEF15 (Two-hybrid), ARHGEF15 (Two-hybrid), ARHGEF15 (Two-hybrid), HIST1H1B (Proximity Label-MS), BICD2 (Proximity Label-MS), ARHGEF15 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A2AKB4, A2APT9, A5PJC7, B1ASB6, O94761, O94989, P51617, P60924, Q14154, Q32LQ1, Q3TYX8, Q3U381, Q494U1, Q4KLY2, Q5F267, Q5FWH6, Q5R866, Q5RA50, Q5RA67, Q5SXM2, Q5SYB0, Q5T7N3, Q5VTJ3, Q6PCP7, Q6ZMQ8, Q6ZMY3, Q6ZUX3, Q6ZVH7, Q7Z3H0, Q80VJ8, Q80YE4, Q86V42, Q8BG26, Q8BG80, Q8BWA8, Q8BZW2, Q8C886, Q8IW93, Q8IY92

Diamond homologs: A5YM69, E9Q7D5, O94989, Q12774, Q3U5C8, Q5BKC9, Q5FWH6, Q5RDX5, Q5VV41, Q8BWA8, Q8C120, Q8CHT1, Q8IW93, Q8N5V2, Q96DR7, Q8TEJ3, O42287, Q15811, Q9Z0R6, A1IGU3, A1IGU4, A1IGU5, Q62417, Q9NZM3, O60229, Q498M5, Q8BZT2, Q8IVI9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ARHGEF15	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
ARHGEF15	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
EPHB2	“down-regulates quantity by destabilization”	ARHGEF15	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	442
Likely benign	225
Benign	32

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1460382	NC_000017.10:g.(?8136214)(8285628_?)del	Pathogenic
4082148	ARHGEF15, VAL360MET	Pathogenic
4082149	ARHGEF15, ARG21CYS	Pathogenic
4082150	ARHGEF15, GLN683TER	Pathogenic
495290	NM_173728.4(ARHGEF15):c.709_723del (p.Val237_Ala241del)	Likely pathogenic

SpliceAI

2398 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8313552:G:T	donor_gain	1.0000
17:8313553:G:GT	donor_gain	1.0000
17:8313553:G:T	donor_gain	1.0000
17:8314960:GGATG:G	donor_gain	1.0000
17:8314961:GATGG:G	donor_gain	1.0000
17:8315261:A:T	donor_gain	1.0000
17:8315275:G:GT	donor_gain	1.0000
17:8315410:CTA:C	acceptor_loss	1.0000
17:8315411:TA:T	acceptor_loss	1.0000
17:8315412:A:AG	acceptor_gain	1.0000
17:8315412:AG:A	acceptor_loss	1.0000
17:8315413:G:GA	acceptor_gain	1.0000
17:8315413:G:GC	acceptor_loss	1.0000
17:8315413:GA:G	acceptor_gain	1.0000
17:8315413:GAGT:G	acceptor_gain	1.0000
17:8315413:GAGTC:G	acceptor_gain	1.0000
17:8315560:GGGA:G	donor_gain	1.0000
17:8315561:GGAG:G	donor_gain	1.0000
17:8315572:GCG:G	donor_gain	1.0000
17:8315575:G:GG	donor_gain	1.0000
17:8315600:G:T	donor_gain	1.0000
17:8315797:C:G	acceptor_gain	1.0000
17:8315798:A:AG	acceptor_gain	1.0000
17:8315799:T:G	acceptor_gain	1.0000
17:8315885:G:GT	donor_gain	1.0000
17:8315903:CTCAT:C	donor_gain	1.0000
17:8315904:TCAT:T	donor_gain	1.0000
17:8315905:CAT:C	donor_gain	1.0000
17:8315906:AT:A	donor_gain	1.0000
17:8315906:ATGT:A	donor_loss	1.0000

AlphaMissense

5333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8315203:T:A	W396R	1.000
17:8315203:T:C	W396R	1.000
17:8315205:G:C	W396C	1.000
17:8315205:G:T	W396C	1.000
17:8316098:T:C	F552L	1.000
17:8316100:C:A	F552L	1.000
17:8316100:C:G	F552L	1.000
17:8316119:C:A	R559S	1.000
17:8318622:T:C	L611P	1.000
17:8318648:T:C	F620L	1.000
17:8318649:T:C	F620S	1.000
17:8318650:C:A	F620L	1.000
17:8318650:C:G	F620L	1.000
17:8318883:A:T	D669V	1.000
17:8318886:T:C	L670P	1.000
17:8318889:T:C	L671P	1.000
17:8318892:T:C	L672P	1.000
17:8319051:T:A	V693D	1.000
17:8319093:T:C	F707S	1.000
17:8319328:T:A	W735R	1.000
17:8319328:T:C	W735R	1.000
17:8315204:G:C	W396S	0.999
17:8315420:T:C	F423L	0.999
17:8315422:C:A	F423L	0.999
17:8315422:C:G	F423L	0.999
17:8315435:T:C	S428P	0.999
17:8315436:C:A	S428Y	0.999
17:8315436:C:T	S428F	0.999
17:8315447:T:G	Y432D	0.999
17:8315460:T:C	L436P	0.999

dbSNP variants (sampled 300 via entrez): RS1000074039 (17:8308325 A>T), RS1000806593 (17:8318275 T>C), RS1001074363 (17:8317912 C>CA), RS1001341552 (17:8318195 C>T), RS1001385485 (17:8321339 T>C), RS1002313590 (17:8310244 A>G), RS1002449399 (17:8309988 G>A), RS1002632914 (17:8315338 A>G), RS1002790669 (17:8314665 C>T), RS1002848901 (17:8318068 G>T), RS1002849596 (17:8314154 G>A), RS1002880883 (17:8314426 G>A), RS1003081547 (17:8320776 C>A,T), RS1003135228 (17:8308998 T>C), RS1003180551 (17:8316807 G>A,C)

Disease associations

OMIM: gene MIM:608504 | disease phenotypes: MIM:105650, MIM:621331

GenCC curated gene-disease

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Limited	Autosomal dominant
schizophrenia	No Known Disease Relationship	Unknown

Mondo (7): early-infantile DEE (MONDO:0800491), developmental and epileptic encephalopathy (MONDO:0100620), Diamond-Blackfan anemia (MONDO:0015253), prostate cancer (MONDO:0008315), brain small vessel disease 5 with osteoporosis (MONDO:0979880), genetic developmental and epileptic encephalopathy (MONDO:0100062), schizophrenia (MONDO:0005090)

Orphanet (4): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Diamond-Blackfan anemia (Orphanet:124), Familial prostate cancer (Orphanet:1331), Early myoclonic encephalopathy (Orphanet:1935)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000716	Depression
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000939	Osteoporosis
HP:0001268	Mental deterioration
HP:0001279	Syncope
HP:0001342	Cerebral hemorrhage
HP:0002354	Memory impairment
HP:0002445	Tetraplegia
HP:0003596	Middle age onset
HP:0011462	Young adult onset
HP:0012444	Brain atrophy
HP:0012520	Dilation of Virchow-Robin spaces
HP:0030892	Deep cerebral white matter hyperintensities
HP:0031589	Suicidal ideation
HP:0032325	Lacunar stroke
HP:0100754	Mania

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004139_15	Bipolar disorder	2.000000e-07
GCST006612_40	LDL cholesterol	2.000000e-08
GCST006614_69	Total cholesterol levels	2.000000e-08
GCST010083_96	Hemoglobin levels	5.000000e-15
GCST90002383_62	Hematocrit	2.000000e-17
GCST90002384_404	Hemoglobin	2.000000e-20
GCST90002387_21	Immature fraction of reticulocytes	3.000000e-12
GCST90002401_581	Platelet distribution width	3.000000e-25
GCST90020025_1385	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020027_548	Waist-hip index	8.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007984	platelet component distribution width
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D029503	Anemia, Diamond-Blackfan	C15.378.050.085.080.090; C15.378.050.750.500; C15.378.190.223.500.500.090; C16.320.077.090
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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
muconaldehyde	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carcinogens	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1
Mutagens	increases expression	1
Silicon Dioxide	increases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety