ARHGEF40

Summary

ARHGEF40 (Rho guanine nucleotide exchange factor 40, HGNC:25516) is a protein-coding gene on chromosome 14q11.2, encoding Rho guanine nucleotide exchange factor 40 (Q8TER5). Acts as a guanine nucleotide exchange factor (GEF) for RHOA and RHOC.

This gene encodes a protein similar to guanosine nucleotide exchange factors for Rho GTPases. The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. Alternatively spliced transcripts that encode different proteins have been described.

Source: NCBI Gene 55701 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 301 total — 1 pathogenic
• MANE Select transcript: NM_018071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25516
Approved symbol	ARHGEF40
Name	Rho guanine nucleotide exchange factor 40
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	solo, FLJ10357
Ensembl gene	ENSG00000165801
Ensembl biotype	protein_coding
OMIM	610018
Entrez	55701

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 38 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000298694, ENST00000553709, ENST00000554514, ENST00000555038, ENST00000555052, ENST00000555232, ENST00000556399, ENST00000557498, ENST00000877988, ENST00000877989, ENST00000877990, ENST00000877991, ENST00000877992, ENST00000877993, ENST00000877994, ENST00000877995, ENST00000877996, ENST00000877997, ENST00000877998, ENST00000918624, ENST00000918625, ENST00000918626, ENST00000918627, ENST00000918628, ENST00000918629, ENST00000918630, ENST00000918631, ENST00000918632, ENST00000918633, ENST00000918634, ENST00000918635, ENST00000918636, ENST00000918637, ENST00000918638, ENST00000918639, ENST00000950135, ENST00000950136, ENST00000950137, ENST00000950138, ENST00000950139, ENST00000950140, ENST00000950141, ENST00000950142, ENST00000950143

RefSeq mRNA: 3 — MANE Select: NM_018071 NM_001278529, NM_001278530, NM_018071

CCDS: CCDS32041

Canonical transcript exons

ENST00000298694 — 24 exons

Exon	Start	End
ENSE00001593451	21073932	21075180
ENSE00001673027	21075332	21075499
ENSE00001681573	21073045	21073242
ENSE00001724654	21075645	21075765
ENSE00002451351	21070304	21070399
ENSE00002523611	21089014	21090248
ENSE00003459243	21081509	21082119
ENSE00003499391	21082244	21082478
ENSE00003506992	21084753	21084923
ENSE00003512687	21076360	21076456
ENSE00003545694	21082831	21082917
ENSE00003552531	21078177	21078272
ENSE00003600145	21076774	21076890
ENSE00003604515	21085689	21085866
ENSE00003606423	21078373	21078488
ENSE00003612807	21087320	21087463
ENSE00003614635	21080660	21080782
ENSE00003628730	21088830	21088876
ENSE00003647073	21076563	21076643
ENSE00003648260	21087968	21088098
ENSE00003664809	21083835	21084050
ENSE00003676785	21087001	21087105
ENSE00003685332	21078884	21079010
ENSE00003690196	21080873	21081016

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5963 / max 132.5984, expressed in 1638 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138509	7.1861	1487
138508	3.4630	1333
138510	1.0545	687
138506	0.7829	439
138504	0.6271	220
138507	0.2586	102
138505	0.2242	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.39	gold quality
tendon of biceps brachii	UBERON:0008188	97.99	gold quality
right adrenal gland	UBERON:0001233	97.40	gold quality
sural nerve	UBERON:0015488	97.40	gold quality
adrenal cortex	UBERON:0001235	97.24	gold quality
left adrenal gland cortex	UBERON:0035825	97.18	gold quality
right adrenal gland cortex	UBERON:0035827	97.17	gold quality
left adrenal gland	UBERON:0001234	97.15	gold quality
pancreatic ductal cell	CL:0002079	96.78	gold quality
tibial nerve	UBERON:0001323	96.34	gold quality
seminal vesicle	UBERON:0000998	96.24	gold quality
adrenal gland	UBERON:0002369	96.16	gold quality
spleen	UBERON:0002106	95.57	gold quality
parotid gland	UBERON:0001831	95.48	gold quality
trigeminal ganglion	UBERON:0001675	95.47	gold quality
ventricular zone	UBERON:0003053	94.99	gold quality
dorsal root ganglion	UBERON:0000044	94.89	gold quality
endocervix	UBERON:0000458	94.56	gold quality
right lobe of liver	UBERON:0001114	94.21	gold quality
adipose tissue	UBERON:0001013	94.18	gold quality
blood	UBERON:0000178	93.94	gold quality
right ovary	UBERON:0002118	93.93	gold quality
connective tissue	UBERON:0002384	93.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.61	gold quality
cartilage tissue	UBERON:0002418	93.47	gold quality
body of pancreas	UBERON:0001150	93.45	gold quality
left uterine tube	UBERON:0001303	93.13	gold quality
corpus epididymis	UBERON:0004359	93.05	gold quality
apex of heart	UBERON:0002098	93.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	yes	1067.76
E-ANND-3	yes	7.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting ARHGEF40, 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-6798-5P	100.00	65.77	699
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-186-3P	99.51	66.24	1685

Literature-anchored findings (GeneRIF, showing 4)

• Solo mRNA is ubiquitously expressed but enriched in brain, and it undergoes extensive alternative splicing. (PMID:16143467)
• Keratin binding domain is critical for Solo localization and its function in regulating mechanotransduction. (PMID:30929300)
• High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma. (PMID:32276436)
• ARHGEF40 promotes non-small cell lung cancer proliferation and invasion via the AKT-Wnt axis by binding to RhoA. (PMID:36000254)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arhgef40	ENSMUSG00000004562
rattus_norvegicus	Arhgef40	ENSRNOG00000052354

Paralogs (22): TRIO (ENSG00000038382), MCF2L2 (ENSG00000053524), PLEKHG2 (ENSG00000090924), MCF2 (ENSG00000101977), ARHGEF7 (ENSG00000102606), PLEKHG1 (ENSG00000120278), MCF2L (ENSG00000126217), ARHGEF6 (ENSG00000129675), ARHGEF9 (ENSG00000131089), VAV3 (ENSG00000134215), VAV1 (ENSG00000141968), TIAM2 (ENSG00000146426), KIAA1755 (ENSG00000149633), PLEKHG4B (ENSG00000153404), TIAM1 (ENSG00000156299), KALRN (ENSG00000160145), VAV2 (ENSG00000160293), SPATA13 (ENSG00000182957), SESTD1 (ENSG00000187231), PLEKHN1 (ENSG00000187583), PLEKHG4 (ENSG00000196155), ARHGEF25 (ENSG00000240771)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 40 — Q8TER5 (reviewed: Q8TER5)

Alternative names: Protein SOLO, Scambio

All UniProt accessions (4): Q8TER5, G3V3N2, G3V485, G3V5C1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a guanine nucleotide exchange factor (GEF) for RHOA and RHOC. Promotes actin stress fiber formation, force-induced stress fiber reinforcement and organization of KRT8/KRT18 networks via activation of RHOA/ROCK signaling, which is mediated by N-terminus KRT18 binding. Regulates the formation or maintenance of properly elongated morphology of epithelial tubules, via mediation of the organization and orientation of KRT18 filaments. Promotes RHOA-dependent, cell-cell contact mediated reorientation of endothelial cells and their actin stress fibers in response to mechanotransduction. Positively regulates hemidesmosome formation via acting as a linker protein that anchors keratin filaments to hemidesmosomes. Also required for JUP localization at cell-cell adhesion junctions.

Subunit / interactions. Interacts with KRT8/KRT18 heterodimers; the interaction is via N-terminal, central and C-terminal domains with KRT18. The interaction facilitates actin stress fiber formation, force-induced stress fiber reinforcement and organization of KRT8/KRT18 networks. Interacts with activated RAC3. Interacts (via central region) with ITGB4 (via C-terminus); the interaction may facilitate ITGB4 localization to hemidesmosomes and act as a linker to anchor keratin filaments to ITGB4 in hemidesmosomes.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Hemidesmosome.

Tissue specificity. Expressed at higher level in the central nervous system and skeletal muscle and greater abundance in fetal than adult brain (at protein level).

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TER5-1	1	yes
Q8TER5-2	2
Q8TER5-3	3
Q8TER5-4	4

RefSeq proteins (3): NP_001265458, NP_001265459, NP_060541* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR052231	Rho_GEF_signaling-related	Family
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00621, PF22697

UniProt features (49 total): modified residue 10, region of interest 9, compositionally biased region 8, sequence variant 8, mutagenesis site 5, splice variant 3, domain 2, coiled-coil region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TER5-F1	64.28	0.17

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 (10): 262, 371, 419, 931, 961, 1082, 1433, 1438, 1474, 1492

Mutagenesis-validated functional residues (5):

Position	Phenotype
14	disrupts n-terminus mediated interaction and colocalization with krt18; when associated with r-17. decreases formation o
17	disrupts n-terminus mediated interaction and colocalization with krt18; when associated with r-14. decreases formation o
49	disrupts n-terminus mediated interaction and colocalization with krt18; when associated with r-52. decreases formation o
52	disrupts n-terminus mediated interaction and colocalization with krt18; when associated with r-49. decreases formation o
1217	abolishes gef activity and reduces force-induced actin stress fiber formation, organization, and focal adhesion formatio

Function

Pathways and Gene Ontology

Reactome pathways

13 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-9013106	RHOC 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: 131 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, TATTATA_MIR374, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS, GTGCCTT_MIR506, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, ONDER_CDH1_TARGETS_2_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ACTTTAT_MIR1425P, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (2): axon guidance (GO:0007411), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (1): guanyl-nucleotide exchange factor activity (GO:0005085)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), extrinsic component of membrane (GO:0019898)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signal Transduction	3
RHO GTPase cycle	2
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	3
membrane	2
axonogenesis	1
neuron projection guidance	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
intracellular anatomical structure	1
cytoplasm	1
cell periphery	1

Protein interactions and networks

STRING

596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF40	PLEK2	Q9NYT0	541
ARHGEF40	PLEK	P08567	537
ARHGEF40	SMC3	Q9UQE7	508
ARHGEF40	BRCA1	P38398	479
ARHGEF40	PARP1	P09874	478
ARHGEF40	ARHGEF17	Q96PE2	472
ARHGEF40	ARHGEF33	A8MVX0	456
ARHGEF40	C19orf44	Q9H6X5	454
ARHGEF40	A0A2R8Y809	A0A2R8Y809	447
ARHGEF40	TBCE	Q15813	447
ARHGEF40	HTN3	P15516	434
ARHGEF40	HTN1	P15515	406
ARHGEF40	ARHGEF28	Q8N1W1	404
ARHGEF40	ARHGEF37	A1IGU5	396
ARHGEF40	ARHGEF35	A5YM69	388

IntAct

28 interactions, top by confidence:

A	B	Type	Score
INSRR	INSR	psi-mi:“MI:0914”(association)	0.650
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
ARHGEF40	P4HA1	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
SPANXN2	ZNF320	psi-mi:“MI:0914”(association)	0.350
P2RY10	POTEF	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
HNRNPCL2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
H2BW1	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
P4HA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
P4HA3	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
SPANXN3	OGA	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350
ARHGEF40	STC2	psi-mi:“MI:0915”(physical association)	0.000
MYCBP	ARHGEF40	psi-mi:“MI:0915”(physical association)	0.000
TAC1	ARHGEF40	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (87): SPERT (Two-hybrid), ARHGEF40 (Affinity Capture-MS), ARHGEF40 (Affinity Capture-MS), ARHGEF40 (Proximity Label-MS), ARHGEF40 (Affinity Capture-MS), ARHGEF40 (Affinity Capture-RNA), ARHGEF40 (Affinity Capture-MS), ARHGEF40 (Two-hybrid), STC2 (Two-hybrid), ARHGEF40 (Two-hybrid), ARHGEF11 (Affinity Capture-Western), ARHGEF40 (Affinity Capture-MS), ARHGEF40 (Affinity Capture-MS), ARHGEF11 (Affinity Capture-MS), AZGP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0A494C0Y3, A0JNH6, A0JNN8, A1A5D9, A2ARS0, A5A769, A5PJP1, A6NC98, A7YWC8, C9JTQ0, O15049, O35764, O95502, P0C7N4, P0DPE3, P58660, Q0P5D1, Q1HCM0, Q2TAC2, Q3LUD3, Q3LUD4, Q3TMW1, Q3UMT1, Q4QRL3, Q5BLP8, Q5JTB6, Q6QNY0, Q6QZQ4, Q8BP01, Q8C7U1, Q8CHW5, Q8K262, Q8N283, Q8N6Y0, Q8TAT2, Q8TER5, Q8TF21, Q91XV7

Diamond homologs: Q3UPH7, Q58EX7, Q5JYT7, Q8BWG4, Q8TER5, A1L390, A2CG49, E2RP94, F1M0Z1, M0R4F8, O60229, O75962, P10911, P97924, Q0KL02, Q13009, Q1LUA6, Q4VAC9, Q60610, Q63406, Q64096, Q6KAU7, Q6P720, Q6TXD4, Q6XZF7, Q86VW2, Q96PX9, Q9CWR0, Q9H7P9, Q9ULL1, O43307, Q3UTH8, Q58DL7, Q5RDK0, Q7TNR9, Q9QX73

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	250
Likely benign	16
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57747	GRCh38/hg38 14q11.2(chr14:20908863-21576473)x1	Pathogenic

SpliceAI

3430 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21070397:ATGG:A	donor_loss	1.0000
14:21070398:TGGT:T	donor_loss	1.0000
14:21070400:G:GA	donor_loss	1.0000
14:21070401:T:G	donor_loss	1.0000
14:21073234:G:GT	donor_gain	1.0000
14:21075319:T:TA	acceptor_gain	1.0000
14:21075321:T:TA	acceptor_gain	1.0000
14:21075325:T:TA	acceptor_gain	1.0000
14:21075330:A:AG	acceptor_gain	1.0000
14:21075330:AG:A	acceptor_gain	1.0000
14:21075331:G:A	acceptor_loss	1.0000
14:21075331:G:GA	acceptor_gain	1.0000
14:21075331:GG:G	acceptor_gain	1.0000
14:21075331:GGA:G	acceptor_gain	1.0000
14:21075331:GGAC:G	acceptor_gain	1.0000
14:21075331:GGACA:G	acceptor_gain	1.0000
14:21075495:GACGG:G	donor_gain	1.0000
14:21075498:GG:G	donor_gain	1.0000
14:21075499:GG:G	donor_gain	1.0000
14:21075500:GTCA:G	donor_gain	1.0000
14:21075503:A:AG	donor_gain	1.0000
14:21075504:G:GG	donor_gain	1.0000
14:21078164:AT:A	acceptor_gain	1.0000
14:21078164:ATGT:A	acceptor_gain	1.0000
14:21078164:ATGTG:A	acceptor_gain	1.0000
14:21078165:T:G	acceptor_gain	1.0000
14:21078168:G:A	acceptor_gain	1.0000
14:21078176:GGAA:G	acceptor_gain	1.0000
14:21078267:G:GT	donor_gain	1.0000
14:21078269:AGAGG:A	donor_loss	1.0000

AlphaMissense

9610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21073968:T:A	W80R	1.000
14:21073968:T:C	W80R	1.000
14:21073082:T:A	L14H	0.999
14:21073970:G:C	W80C	0.999
14:21073970:G:T	W80C	0.999
14:21074044:T:C	F105S	0.999
14:21074046:T:G	Y106D	0.999
14:21074164:T:C	F145S	0.999
14:21074175:T:A	W149R	0.999
14:21074175:T:C	W149R	0.999
14:21074262:T:A	W178R	0.999
14:21074262:T:C	W178R	0.999
14:21074264:G:C	W178C	0.999
14:21074264:G:T	W178C	0.999
14:21085705:T:C	L1326P	0.999
14:21085746:T:A	W1340R	0.999
14:21085746:T:C	W1340R	0.999
14:21085815:T:A	W1363R	0.999
14:21085815:T:C	W1363R	0.999
14:21073082:T:C	L14P	0.998
14:21073196:T:C	L52P	0.998
14:21074041:A:T	D104V	0.998
14:21074043:T:C	F105L	0.998
14:21074045:C:A	F105L	0.998
14:21074045:C:G	F105L	0.998
14:21074092:T:A	L121H	0.998
14:21074223:T:C	C165R	0.998
14:21084802:T:A	V1280D	0.998
14:21084864:A:C	S1301R	0.998
14:21084866:C:A	S1301R	0.998

dbSNP variants (sampled 300 via entrez): RS1000201074 (14:21084998 T>C), RS1000226191 (14:21076328 A>G), RS1000324285 (14:21066019 C>T), RS1000332570 (14:21083054 G>C), RS1000438847 (14:21065775 C>A), RS1000688099 (14:21080027 G>C), RS1000803144 (14:21086554 T>G), RS1000938776 (14:21061210 G>A,T), RS1000955476 (14:21065065 G>C), RS1001121671 (14:21071161 AC>A), RS1001151890 (14:21086220 T>A), RS1001346094 (14:21067364 T>A,C), RS1001412557 (14:21071475 A>C,G), RS1001514789 (14:21070339 G>T), RS1001663044 (14:21077138 T>C)

Disease associations

OMIM: gene MIM:610018 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (3): myoepithelial tumor (MONDO:0002380), prostate cancer (MONDO:0008315), neurodevelopmental disorder (MONDO:0700092)

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

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003818_18	Resting heart rate	4.000000e-20
GCST004604_59	Hematocrit	3.000000e-09
GCST004943_1	Pediatric nonalcoholic steatohepatitis	7.000000e-06
GCST010083_196	Hemoglobin levels	2.000000e-14
GCST010320_48	PR interval	3.000000e-08
GCST010321_82	PR interval	9.000000e-10
GCST011053_4	Neuroblastoma (pediatric)	5.000000e-16
GCST90000025_1059	Appendicular lean mass	2.000000e-38
GCST90002383_252	Hematocrit	3.000000e-18
GCST90002384_331	Hemoglobin	6.000000e-15
GCST90002400_129	Plateletcrit	2.000000e-12
GCST90002403_499	Red blood cell count	9.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004462	PR interval
EFO:0004980	appendicular lean mass
EFO:0007985	platelet crit
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D065886	Neurodevelopmental Disorders	F03.625
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cyclosporine	decreases expression	3
Tretinoin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
zinc chromate	increases abundance, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
muconaldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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