MCF2

Summary

MCF2 (MCF.2 cell line derived transforming sequence, HGNC:6940) is a protein-coding gene on chromosome Xq27.1, encoding Proto-oncogene DBL (P10911). Guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases.

The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.

Source: NCBI Gene 4168 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polymicrogyria, bilateral perisylvian, X-linked (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 184 total
• Druggable target: yes
• MANE Select transcript: NM_001171876

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6940
Approved symbol	MCF2
Name	MCF.2 cell line derived transforming sequence
Location	Xq27.1
Locus type	gene with protein product
Status	Approved
Aliases	DBL, ARHGEF21
Ensembl gene	ENSG00000101977
Ensembl biotype	protein_coding
OMIM	311030
Entrez	4168

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000338585, ENST00000370573, ENST00000370576, ENST00000414978, ENST00000437564, ENST00000446225, ENST00000483690, ENST00000519895, ENST00000520602, ENST00000536274

RefSeq mRNA: 6 — MANE Select: NM_001171876 NM_001099855, NM_001171876, NM_001171877, NM_001171878, NM_001171879, NM_005369

CCDS: CCDS14667, CCDS48175, CCDS55514, CCDS55515, CCDS55516, CCDS55517

Canonical transcript exons

ENST00000519895 — 29 exons

Exon	Start	End
ENSE00000677238	139631395	139631511
ENSE00000677239	139629695	139629844
ENSE00000677240	139626623	139626756
ENSE00000677241	139626193	139626307
ENSE00000677242	139619587	139619706
ENSE00000677243	139617513	139617704
ENSE00000677244	139616282	139616473
ENSE00000677245	139614881	139615052
ENSE00000677249	139605713	139605779
ENSE00000677251	139604869	139604984
ENSE00000677253	139604681	139604750
ENSE00000677255	139602406	139602498
ENSE00000677257	139598406	139598498
ENSE00000677259	139597460	139597585
ENSE00000677262	139596549	139596770
ENSE00000677264	139589835	139589927
ENSE00000677266	139588360	139588438
ENSE00000677268	139587716	139587788
ENSE00000677270	139586378	139586487
ENSE00000677272	139585066	139585178
ENSE00000874427	139632335	139632454
ENSE00001179081	139645568	139645658
ENSE00001179084	139646789	139646903
ENSE00001215378	139607691	139607779
ENSE00001796761	139581770	139582503
ENSE00003600888	139613216	139613263
ENSE00003631565	139651720	139651788
ENSE00003675496	139610301	139610338
ENSE00003978108	139708106	139708167

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 92.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0042 / max 175.8871, expressed in 150 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200709	0.4646	122
200710	0.3501	99
200711	0.1754	77
200712	0.0111	3
200713	0.0030	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	92.74	gold quality
seminal vesicle	UBERON:0000998	92.56	gold quality
endothelial cell	CL:0000115	90.31	gold quality
right adrenal gland cortex	UBERON:0035827	88.29	gold quality
left adrenal gland cortex	UBERON:0035825	87.63	gold quality
left adrenal gland	UBERON:0001234	87.47	gold quality
adrenal cortex	UBERON:0001235	87.19	gold quality
right adrenal gland	UBERON:0001233	86.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.16	gold quality
adrenal gland	UBERON:0002369	86.12	gold quality
right testis	UBERON:0004534	84.60	gold quality
primary visual cortex	UBERON:0002436	83.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.52	gold quality
left testis	UBERON:0004533	83.42	gold quality
testis	UBERON:0000473	82.60	gold quality
hypothalamus	UBERON:0001898	81.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.08	gold quality
prefrontal cortex	UBERON:0000451	80.04	gold quality
occipital lobe	UBERON:0002021	79.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.49	gold quality
substantia nigra	UBERON:0002038	78.94	gold quality
pons	UBERON:0000988	78.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.88	gold quality
middle temporal gyrus	UBERON:0002771	78.21	gold quality
midbrain	UBERON:0001891	78.08	gold quality
frontal cortex	UBERON:0001870	77.33	gold quality
spinal cord	UBERON:0002240	77.21	gold quality
neocortex	UBERON:0001950	77.15	gold quality
nucleus accumbens	UBERON:0001882	76.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

53 targeting MCF2, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-377-3P	99.37	70.18	1905

Literature-anchored findings (GeneRIF, showing 10)

• data describe 4 splicing variants of the human DBL (MCF-2) proto-oncogene that show different tissue distributions and guanine nucleotide exchange factor specificities (PMID:12445822)
• provides fundamental data on the structure of Mcf-2, which regulates a variety of cellular signaling pathways (PMID:13679059)
• These data suggest a mechanism whereby precise spatial guanine nucleotide exchange of Cdc42 by Dbl is dependent on functional ERM proteins and is important for directional cell migration. (PMID:17538024)
• Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain (PMID:17606614)
• Nm23-H1 can negatively regulate cell migration and tumor metastasis by modulating the activity of Cdc42 and possibly other Rho family members through interaction with Dbl-1 (PMID:18728402)
• proto-oncogene dbl is not a major target for sporadic testicular germ cell tumors (PMID:19373475)
• Dbl is regulated by hamartin through association with ezrin. (PMID:21712385)
• Phosphoinositide 3-kinase C2beta regulates RhoA and the actin cytoskeleton through an interaction with Dbl (PMID:22984590)
• Results support a role for Dbl oncogene in mammary epithelial cell differentiation and transformation and suggest the relevance of GEF deregulation in tumor onset and progression. (PMID:25723869)
• we elucidate a mechanism through which the DBL family members MCF2 and VAV1 act to drive drug resistance in human BRAFV600E-mutant melanoma cells (PMID:31416844)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcf2a	ENSDARG00000022895
danio_rerio	mcf2b	ENSDARG00000056603
mus_musculus	Mcf2	ENSMUSG00000031139
rattus_norvegicus	Mcf2	ENSRNOG00000003435

Paralogs (22): TRIO (ENSG00000038382), MCF2L2 (ENSG00000053524), PLEKHG2 (ENSG00000090924), 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), ARHGEF40 (ENSG00000165801), SPATA13 (ENSG00000182957), SESTD1 (ENSG00000187231), PLEKHN1 (ENSG00000187583), PLEKHG4 (ENSG00000196155), ARHGEF25 (ENSG00000240771)

Protein

Protein identifiers

Proto-oncogene DBL — P10911 (reviewed: P10911)

Alternative names: Proto-oncogene MCF-2

All UniProt accessions (4): P10911, A0A2U3TZL4, H0Y662, Q5JYJ5

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. Promotes the conversion of some member of the Rho family GTPase from the GDP-bound to the GTP-bound form. Isoform 1 exhibits no activity toward RHOA, RAC1 or CDC42. Isoform 2 exhibits decreased GEF activity toward CDC42. Isoform 3 exhibits a weak but significant activity toward RAC1 and CDC42. Isoform 4 exhibits significant activity toward RHOA and CDC42. The truncated DBL oncogene is active toward RHOA, RAC1 and CDC42.

Subunit / interactions. Interacts with an array of inositol phospholipids such as phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-phosphate (PI5P). May interact with CCPG1.

Subcellular location. Cytoplasm Membrane Membrane.

Tissue specificity. Isoform 1 is expressed only in brain. Isoform 3 is expressed in heart, kidney, spleen, liver and testis. Isoform 4 is expressed in brain, heart, kidney, testis, placenta, stomach and peripheral blood. The protein is detectable in brain, heart, kidney, intestine, muscle, lung and testis.

Post-translational modifications. Phosphorylation by TNK2 enhances guanine nucleotide exchange factor (GEF) activity toward Rho family proteins.

Disease relevance. MCF2 and DBL represent two activated versions of the same proto-oncogene.

Domain organisation. The CRAL-TRIO domain is involved in interaction with inositol phospholipids. The DH domain is essential for transforming activity and directly catalyzes GDP-GTP exchange activity. It may interact with CCPG1.

Similarity. Belongs to the MCF2 family.

Isoforms (6)

UniProt ID	Names	Canonical?
P10911-1	1, Var.1	yes
P10911-2	2, Var.2
P10911-3	3, Var.3
P10911-4	4, Var.4
P10911-5	5
P10911-6	6

RefSeq proteins (6): NP_001093325, NP_001165347, NP_001165348, NP_001165349, NP_001165350, NP_005360 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001251	CRAL-TRIO_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018159	Spectrin/alpha-actinin	Repeat
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR051336	RhoGEF_Guanine_NuclExch_SF	Family
IPR055251	SOS1_NGEF_PH	Domain
IPR056466	Spectrin_DBS	Domain

Pfam: PF00621, PF13716, PF22697, PF23289

UniProt features (21 total): sequence conflict 8, splice variant 5, chain 3, domain 3, mutagenesis site 1, repeat 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10911-F1	74.74	0.42

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
640–646	transformation capability reduced; no stimulation of gdp dissociation.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-193634	Axonal growth inhibition (RHOA activation)
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-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193697	p75NTR regulates axonogenesis
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: 127 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MODULE_205, WTGAAAT_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (5): dendrite development (GO:0016358), intracellular signal transduction (GO:0035556), negative regulation of axonogenesis (GO:0050771), regulation of small GTPase mediated signal transduction (GO:0051056), cellular response to leukemia inhibitory factor (GO:1990830)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RHO GTPase cycle	8
p75 NTR receptor-mediated signalling	2
Signal Transduction	2
p75NTR regulates axonogenesis	1
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
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
intracellular anatomical structure	2
neuron projection development	1
anatomical structure development	1
signal transduction	1
axonogenesis	1
negative regulation of neuron projection development	1
negative regulation of neurogenesis	1
regulation of axonogenesis	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCF2	PLEK	P08567	977
MCF2	PLEK2	Q9NYT0	969
MCF2	RHOA	P06749	967
MCF2	RABIF	P47224	935
MCF2	CDC42	P21181	901
MCF2	EZR	P15311	836
MCF2	ARHGEF1	Q92888	827
MCF2	AKAP13	Q12802	784
MCF2	ARHGEF12	Q9NZN5	767
MCF2	ARHGEF11	O15085	745
MCF2	NGEF	Q8N5V2	744
MCF2	RHOG	P35238	743
MCF2	ITSN1	Q15811	743
MCF2	ITSN2	Q9NZM3	732
MCF2	RGS21	Q2M5E4	722

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MCF2	RDX	psi-mi:“MI:0915”(physical association)	0.540
RDX	MCF2	psi-mi:“MI:0407”(direct interaction)	0.540
NME1	MCF2	psi-mi:“MI:0914”(association)	0.530
MCF2	NME1	psi-mi:“MI:0914”(association)	0.530
DISC1	MCF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): HSP90AA1 (Affinity Capture-Western), MCF2 (Affinity Capture-Western), STUB1 (Affinity Capture-Western), HSPA8 (Affinity Capture-Western), MCF2 (Affinity Capture-Western), MCF2 (Biochemical Activity), MCF2 (Reconstituted Complex), MCF2 (Affinity Capture-Western), MCF2 (Reconstituted Complex), MCF2 (Reconstituted Complex), MCF2 (Reconstituted Complex), MCF2 (Reconstituted Complex), MCF2 (FRET), MCF2 (FRET), MCF2 (FRET)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8WXF6, E9PT87, F1M0Z1, G4SLH0, O02827, O08875, O43293, O44997, O54784, O60229, O62305, O70150, O75962, O88764, O94768, O94806, P07313, P08414, P10911, P13234, P18652, P18653, P18654, P20689, P22216, P25323, P29294, P51812, P53355, P97924, Q00168, Q0KHT7, Q0KL02, Q14012, Q15139, Q15418

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MCF2	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
MCF2	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
MCF2	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3785 predictions. Top by Δscore:

Variant	Effect	Δscore
X:139585174:CCAAA:C	acceptor_gain	1.0000
X:139585175:CAAAC:C	acceptor_gain	1.0000
X:139585179:C:CC	acceptor_gain	1.0000
X:139586486:TT:T	acceptor_gain	1.0000
X:139587711:CTTA:C	donor_gain	1.0000
X:139587712:TTA:T	donor_loss	1.0000
X:139587713:TAC:T	donor_loss	1.0000
X:139587714:A:AC	donor_gain	1.0000
X:139587714:A:T	donor_loss	1.0000
X:139587714:ACT:A	donor_gain	1.0000
X:139587715:C:CT	donor_gain	1.0000
X:139587715:CT:C	donor_gain	1.0000
X:139587715:CTC:C	donor_gain	1.0000
X:139587715:CTCA:C	donor_gain	1.0000
X:139587715:CTCAT:C	donor_gain	1.0000
X:139587718:AT:A	donor_gain	1.0000
X:139587719:T:C	donor_gain	1.0000
X:139587784:TTTAA:T	acceptor_gain	1.0000
X:139587785:TTAA:T	acceptor_gain	1.0000
X:139587786:TAA:T	acceptor_gain	1.0000
X:139587787:AA:A	acceptor_gain	1.0000
X:139587788:ACTGA:A	acceptor_loss	1.0000
X:139587789:C:CC	acceptor_gain	1.0000
X:139587789:CTGA:C	acceptor_loss	1.0000
X:139589830:CCAA:C	donor_loss	1.0000
X:139589831:CAAC:C	donor_loss	1.0000
X:139589832:AACC:A	donor_loss	1.0000
X:139589833:ACC:A	donor_loss	1.0000
X:139589834:CC:C	donor_loss	1.0000
X:139589854:T:TA	donor_gain	1.0000

AlphaMissense

6667 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:139596655:C:G	R724P	0.998
X:139596721:A:T	V702D	0.998
X:139596561:T:A	K755N	0.997
X:139596561:T:G	K755N	0.997
X:139596618:G:C	C736W	0.997
X:139588411:A:G	W800R	0.996
X:139588411:A:T	W800R	0.996
X:139596620:A:G	C736R	0.996
X:139617604:A:G	L303P	0.996
X:139626221:A:G	L220P	0.996
X:139596563:T:C	K755E	0.995
X:139596615:T:A	K737N	0.995
X:139596615:T:G	K737N	0.995
X:139596646:A:G	F727S	0.995
X:139598434:C:G	R634P	0.995
X:139605762:A:G	L503P	0.995
X:139596616:T:A	K737I	0.994
X:139604691:A:G	F578S	0.994
X:139626262:A:C	F206L	0.994
X:139626262:A:T	F206L	0.994
X:139626264:A:G	F206L	0.994
X:139589839:A:T	V789D	0.993
X:139604877:G:C	F555L	0.993
X:139604877:G:T	F555L	0.993
X:139604879:A:G	F555L	0.993
X:139617667:C:T	G282E	0.993
X:139596572:A:C	Y752D	0.992
X:139596619:C:T	C736Y	0.992
X:139596656:G:C	R724G	0.991
X:139604878:A:G	F555S	0.991

dbSNP variants (sampled 300 via entrez): RS1000006981 (X:139703029 T>C), RS1000016410 (X:139646842 A>G), RS1000086425 (X:139648416 T>C), RS1000098093 (X:139683693 A>C), RS1000159570 (X:139608381 C>T), RS1000174985 (X:139653039 G>T), RS1000193919 (X:139650881 A>G), RS1000213319 (X:139599028 G>A,T), RS1000227498 (X:139652765 C>A), RS1000302199 (X:139694498 G>A,T), RS1000372771 (X:139673200 C>T), RS1000388504 (X:139660391 T>C), RS1000406113 (X:139661147 C>A,G), RS1000443162 (X:139696264 C>A,T), RS1000458627 (X:139661779 A>G)

Disease associations

OMIM: gene MIM:311030 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
polymicrogyria, bilateral perisylvian, X-linked	Limited	X-linked

Mondo (1): polymicrogyria, bilateral perisylvian, X-linked (MONDO:0010314)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST009391_1428	Metabolite levels	6.000000e-06
GCST009391_1616	Metabolite levels	7.000000e-06
GCST009391_1737	Metabolite levels	2.000000e-06
GCST009391_2101	Metabolite levels	4.000000e-07
GCST009391_2111	Metabolite levels	1.000000e-06
GCST009391_815	Metabolite levels	4.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0010407	triacylglycerol 48:4 measurement
EFO:0010378	phosphatidylcholine 34:4 measurement
EFO:0010376	phosphatidylcholine 34:2 measurement
EFO:0010373	phosphatidylcholine 32:1 measurement
EFO:0010381	phosphatidylcholine 36:3 measurement
EFO:0010397	sphingomyelin 24:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523650 (PROTEIN COMPLEX)

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	4
Aflatoxin B1	decreases expression, decreases methylation	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
quinocetone	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Troglitazone	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Endosulfan	decreases reaction, decreases expression	1
Fluorouracil	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	affects cotreatment, decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419742	Binding	Inhibition of GST-tagged human DBL RhoGEF DH-PH module expressed in mouse NIH/3T3 cells assessed as reduction in human full length RhoA (1 to 193 residues) interaction with DBL RhoGEF at 10 to 50 uM incubated for 1 hr by Western blot analys	Small-molecule inhibitors targeting g-protein-coupled rho guanine nucleotide exchange factors

Clinical trials (associated diseases)

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