PLEKHG2

Summary

PLEKHG2 (pleckstrin homology and RhoGEF domain containing G2, HGNC:29515) is a protein-coding gene on chromosome 19q13.2, encoding Pleckstrin homology domain-containing family G member 2 (Q9H7P9). May be a transforming oncogene with exchange activity for CDC42.

The protein encoded by this gene is a RhoGTPase that can activate CDC42 by promoting exchange of GDP for GTP on CDC42. The encoded protein is activated by binding to the beta and gamma subunits of heterotrimeric guanine nucleotide-binding protein. Defects in this gene have been associated with leukodystrophy and acquired microcephaly with or without dystonia.

Source: NCBI Gene 64857 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy and acquired microcephaly with or without dystonia; (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 622 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_022835

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29515
Approved symbol	PLEKHG2
Name	pleckstrin homology and RhoGEF domain containing G2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CLG, FLJ00018, ARHGEF42
Ensembl gene	ENSG00000090924
Ensembl biotype	protein_coding
OMIM	611893
Entrez	64857

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 retained_intron

ENST00000205135, ENST00000409797, ENST00000425673, ENST00000438123, ENST00000451354, ENST00000458508, ENST00000474449, ENST00000478523, ENST00000594124, ENST00000594161, ENST00000594307, ENST00000595920, ENST00000596339, ENST00000596443, ENST00000598238, ENST00000600210, ENST00000942561, ENST00000942562

RefSeq mRNA: 3 — MANE Select: NM_022835 NM_001351693, NM_001351694, NM_022835

CCDS: CCDS33022, CCDS86766, CCDS86767

Canonical transcript exons

ENST00000425673 — 19 exons

Exon	Start	End
ENSE00000705943	39417555	39417692
ENSE00000705945	39417905	39418105
ENSE00000705997	39422115	39422288
ENSE00000706022	39422732	39423653
ENSE00000952130	39416850	39417000
ENSE00001631984	39415339	39415439
ENSE00001701866	39416348	39416414
ENSE00001782082	39423733	39428415
ENSE00001834377	39412669	39413412
ENSE00002225428	39414065	39414195
ENSE00002227472	39414992	39415260
ENSE00003515908	39420751	39420852
ENSE00003531989	39420626	39420659
ENSE00003576308	39418734	39418826
ENSE00003577877	39420949	39420996
ENSE00003583646	39421283	39421299
ENSE00003623498	39421075	39421113
ENSE00003644377	39418917	39419003
ENSE00003788068	39416551	39416597

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4292 / max 195.7712, expressed in 1794 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175759	6.0061	1580
175758	4.3300	1544
175757	3.9418	1472
175761	3.7870	1098
175760	0.7510	447
175765	0.6579	342
175763	0.2544	99
175762	0.2196	83
175764	0.2174	86
208804	0.1389	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.58	gold quality
descending thoracic aorta	UBERON:0002345	95.18	gold quality
right coronary artery	UBERON:0001625	94.89	gold quality
left uterine tube	UBERON:0001303	94.72	gold quality
thoracic aorta	UBERON:0001515	94.20	gold quality
ascending aorta	UBERON:0001496	94.13	gold quality
tibial nerve	UBERON:0001323	93.89	gold quality
vermiform appendix	UBERON:0001154	93.88	gold quality
ganglionic eminence	UBERON:0004023	93.62	gold quality
mucosa of stomach	UBERON:0001199	93.58	gold quality
bone marrow cell	CL:0002092	93.54	gold quality
stromal cell of endometrium	CL:0002255	93.42	gold quality
apex of heart	UBERON:0002098	93.38	gold quality
left coronary artery	UBERON:0001626	92.92	gold quality
aorta	UBERON:0000947	92.77	gold quality
upper lobe of left lung	UBERON:0008952	92.64	gold quality
omental fat pad	UBERON:0010414	92.61	gold quality
body of uterus	UBERON:0009853	92.60	gold quality
peritoneum	UBERON:0002358	92.54	gold quality
tibial artery	UBERON:0007610	91.96	gold quality
popliteal artery	UBERON:0002250	91.94	gold quality
coronary artery	UBERON:0001621	91.90	gold quality
cortical plate	UBERON:0005343	91.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.38	gold quality
smooth muscle tissue	UBERON:0001135	91.18	gold quality
lower esophagus	UBERON:0013473	91.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.04	gold quality
right lung	UBERON:0002167	91.00	gold quality
upper lobe of lung	UBERON:0008948	90.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.40
E-ENAD-17	no	182.49
E-MTAB-5061	no	1.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

137 targeting PLEKHG2, 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-3134	100.00	66.43	777
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4648	99.91	67.00	710

Literature-anchored findings (GeneRIF, showing 12)

• Activation of clg, a novel dbl family guanine nucleotide exchange factor gene, by proviral insertion at evi24, a common integration site in B cell and myeloid leukemias (PMID:11839748)
• signaling pathway by which G(i)-coupled receptor specifically induces Rac and Cdc42 activation through direct interaction of Gbetagamma with FLJ00018. (PMID:18045877)
• The binding of Rho family specific guanine nucleotide exchange factor(FLJ00018), at least two actin binding regions of FLJ00018, and actin negatively regulates for FLJ00018 function. (PMID:23000341)
• These results suggest that FLJ00018 is targeted via its pleckstrin homology domain to cellular membranes. (PMID:23811570)
• PLEKHG2 may serve as a key Gbeta-gamma-stimulated RhoGEF that regulates lymphocyte chemotaxis via Rac and Cdc42 activation and actin polymerization. (PMID:24001768)
• The tyrosine phosphorylation of PLEKHG2 plays an important role in EphB2 signaling, which is closely related to cell growth and the proliferation of tumor. (PMID:24378532)
• results provide evidence that stimulation of the Ras/MAPK pathway by EGFR results in FLJ00018 phosphorylation at Thr-680, which in turn controls changes in cell shape. (PMID:24554703)
• Autoantibodies binding to Plekhg2 were found in 19 of 29 patients (66%) with active mycobacterial infections. (PMID:25213431)
• Role of PLEKHG2 in actin polymerization and clinical and radiological findings in PLEKHG2 deficiency. (PMID:26573021)
• results provide evidence that FHL1A interacts with PLEKHG2 and regulates cell morphological change through the activity of PLEKHG2. (PMID:27765816)
• This is the first report to show that PLEKHG2 is a novel effector of Galphas, and is negatively regulated by the Galphas subunit through direct interaction. (PMID:28108261)
• results suggest that FHL1A specifically interacts with PLEKHG2 to regulate a function of PLEKHG2 that is modified by the interaction of Gbetagamma and Galphas. (PMID:28489964)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plekhg2	ENSMUSG00000037552
rattus_norvegicus	Plekhg2	ENSRNOG00000030266

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

Protein

Protein identifiers

Pleckstrin homology domain-containing family G member 2 — Q9H7P9 (reviewed: Q9H7P9)

All UniProt accessions (12): Q9H7P9, C9J7S4, C9JVL3, E7ESZ3, H7BXC7, M0QX05, M0QZT7, M0R0V0, M0R348, M0R391, M0R3G5, M0R3J0

UniProt curated annotations — full annotation on UniProt →

Function. May be a transforming oncogene with exchange activity for CDC42. May be a guanine-nucleotide exchange factor (GEF) for RAC1 and CDC42. Activated by the binding to subunits beta and gamma of the heterotrimeric guanine nucleotide-binding protein (G protein). Involved in the regulation of actin polymerization.

Disease relevance. Leukodystrophy and acquired microcephaly with or without dystonia (LDAMD) [MIM:616763] An autosomal recessive neurologic disorder characterized by profound intellectual disability, dystonia, postnatal microcephaly, and white matter abnormalities consistent with leukodystrophy. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H7P9-1	1	yes
Q9H7P9-2	2
Q9H7P9-3	3

RefSeq proteins (3): NP_001338622, NP_001338623, NP_073746* (*=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
IPR043324	PH_PLEKHG1_G2_G3	Domain
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00621, PF22697

UniProt features (39 total): region of interest 11, modified residue 9, compositionally biased region 7, sequence variant 7, domain 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7P9-F1	48.39	0.16

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 (9): 90, 445, 450, 469, 911, 1049, 1257, 1261, 1310

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 221 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, LIAO_METASTASIS, KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_LENGTH, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215

GO Biological Process (1): regulation of actin filament polymerization (GO:0030833)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	2
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHG2	CHRM2	P08172	648
PLEKHG2	RABIF	P47224	616
PLEKHG2	CDC42	P21181	563
PLEKHG2	GNB1	P04697	551
PLEKHG2	GNG2	P59768	549
PLEKHG2	GNAI1	P04898	544
PLEKHG2	PIK3R3	Q92569	529
PLEKHG2	PLEK	P08567	460
PLEKHG2	RHOA	P06749	445
PLEKHG2	GNAS	Q5JWF2	424
PLEKHG2	LGI4	Q8N135	366
PLEKHG2	PAK1	Q13153	325
PLEKHG2	FBXW10B	O95170	308
PLEKHG2	SPATS2	Q86XZ4	308
PLEKHG2	FHL1	Q13642	307

IntAct

17 interactions, top by confidence:

A	B	Type	Score
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
PIN1	PLEKHG2	psi-mi:“MI:0915”(physical association)	0.560
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
TSC22D1	KRT1	psi-mi:“MI:0914”(association)	0.460
ACTN3	PLEKHG2	psi-mi:“MI:0915”(physical association)	0.370
PLEKHG2	CDK1	psi-mi:“MI:0914”(association)	0.350
PLEKHG2	DCK	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
P4HA3	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
PIN1	PLEKHG2	psi-mi:“MI:0915”(physical association)	0.000
dxs	PLEKHG2	psi-mi:“MI:0915”(physical association)	0.000
PLEKHG2	inhA	psi-mi:“MI:0915”(physical association)	0.000
PLEKHG2		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): PLEKHG2 (Two-hybrid), PLEKHG2 (Affinity Capture-MS), PLEKHG2 (Reconstituted Complex), FHL1 (Affinity Capture-Western), GNB1 (Affinity Capture-Western), PLEKHG2 (Affinity Capture-Western), PLEKHG2 (Affinity Capture-RNA), PLEKHG2 (Proximity Label-MS), ACTN3 (Two-hybrid), PIN1 (Two-hybrid), FHL1 (Affinity Capture-Western), GNAS (Affinity Capture-Western), SKP2 (Affinity Capture-MS), TCTEX1D2 (Affinity Capture-MS), MCRS1 (Affinity Capture-MS)

ESM2 similar proteins: A1YGK1, A2T7E6, A4D1S0, A9YTQ3, B1WBS3, I7HJS4, O43593, O43918, O60304, O75593, O95201, P0C6A0, P0C7X2, P97609, Q2MHN3, Q3B7M4, Q3SY56, Q3U133, Q58DK7, Q5JPB2, Q5SXI5, Q5T619, Q61645, Q6KAU7, Q6NUN9, Q6ZMS7, Q76NI1, Q7Z6P3, Q8BZ34, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8NBB4, Q8NDX1, Q8NHY3, Q91X45, Q96PX9, Q99558

Diamond homologs: A1L390, F1M0Z1, O43307, O75962, P91620, P91621, Q0KL02, Q13009, Q1ZXH8, Q3UTH8, Q4VAC9, Q58DL7, Q58EX7, Q5DU57, Q5RDK0, Q60610, Q6KAU7, Q6P720, Q6ZPF3, Q7TNR9, Q96N96, Q9H7P9, Q9NR80, Q9QX73, Q9ULL1, A1IGU3, A1IGU4, A2CG49, A8MVU1, E7F1U2, F1M707, O15068, O60229, O77774, P10911, P97924, Q09014, Q1LUA6, Q63406, Q64096

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SRC	unknown	PLEKHG2	phosphorylation
SRC	“up-regulates activity”	PLEKHG2	phosphorylation
PLEKHG2	“up-regulates activity”	PIK3R3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	354
Likely benign	174
Benign	39

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
6828	NM_203486.3(DLL3):c.599_603dup (p.Pro202fs)	Pathogenic
2584971	NM_022835.3(PLEKHG2):c.1270C>T (p.Gln424Ter)	Likely pathogenic
4845727	NM_022835.3(PLEKHG2):c.1383del (p.Arg463fs)	Likely pathogenic

SpliceAI

2540 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39415260:GGTA:G	donor_loss	1.0000
19:39415261:GTAAG:G	donor_loss	1.0000
19:39415262:T:G	donor_loss	1.0000
19:39416343:TGTA:T	acceptor_loss	1.0000
19:39416344:GTAGC:G	acceptor_loss	1.0000
19:39416346:A:AG	acceptor_gain	1.0000
19:39416346:A:T	acceptor_loss	1.0000
19:39416346:AGC:A	acceptor_gain	1.0000
19:39416347:G:GT	acceptor_gain	1.0000
19:39416347:GC:G	acceptor_gain	1.0000
19:39416347:GCG:G	acceptor_gain	1.0000
19:39416347:GCGA:G	acceptor_gain	1.0000
19:39416411:GAGG:G	donor_gain	1.0000
19:39416412:AGG:A	donor_gain	1.0000
19:39416413:GG:G	donor_gain	1.0000
19:39416413:GGG:G	donor_gain	1.0000
19:39416414:GG:G	donor_gain	1.0000
19:39416414:GGT:G	donor_loss	1.0000
19:39416415:G:GA	donor_loss	1.0000
19:39416415:G:GG	donor_gain	1.0000
19:39416848:A:AG	acceptor_gain	1.0000
19:39416849:G:GT	acceptor_gain	1.0000
19:39416849:GCT:G	acceptor_gain	1.0000
19:39416849:GCTC:G	acceptor_gain	1.0000
19:39416849:GCTCC:G	acceptor_gain	1.0000
19:39417000:GGT:G	donor_loss	1.0000
19:39417001:G:C	donor_loss	1.0000
19:39417702:GG:G	donor_gain	1.0000
19:39417703:GG:G	donor_gain	1.0000
19:39417728:G:GT	donor_gain	1.0000

AlphaMissense

8849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39415244:T:C	L121P	1.000
19:39415223:A:T	E114V	0.999
19:39415244:T:A	L121H	0.999
19:39416404:T:C	F179S	0.999
19:39416560:T:C	F186L	0.999
19:39416562:T:A	F186L	0.999
19:39416562:T:G	F186L	0.999
19:39416963:C:A	P236H	0.999
19:39416966:T:A	V237D	0.999
19:39416970:G:C	Q238H	0.999
19:39416970:G:T	Q238H	0.999
19:39416990:T:C	L245P	0.999
19:39417637:T:A	V276D	0.999
19:39417640:C:A	A277D	0.999
19:39417649:T:A	I280N	0.999
19:39418035:T:C	F338S	0.999
19:39418780:T:C	F377S	0.999
19:39418944:T:A	W402R	0.999
19:39418944:T:C	W402R	0.999
19:39415435:A:C	S159R	0.998
19:39415437:C:A	S159R	0.998
19:39415437:C:G	S159R	0.998
19:39416353:T:C	L162P	0.998
19:39416403:T:C	F179L	0.998
19:39416405:C:A	F179L	0.998
19:39416405:C:G	F179L	0.998
19:39416578:T:G	Y192D	0.998
19:39416583:C:G	C193W	0.998
19:39416954:T:C	L233P	0.998
19:39416961:A:C	K235N	0.998

dbSNP variants (sampled 300 via entrez): RS1000198214 (19:39417373 G>A), RS1000374028 (19:39420214 C>A,T), RS1000466550 (19:39410593 CCTT>C), RS1000507624 (19:39418267 A>G), RS1000538738 (19:39418395 G>A), RS1000644800 (19:39413336 C>G,T), RS1000764481 (19:39419977 T>C), RS1000805376 (19:39422459 G>A), RS1000958798 (19:39405932 T>C), RS1001299622 (19:39404951 G>A), RS1001372786 (19:39409597 G>C), RS1001391754 (19:39414891 G>A), RS1001448193 (19:39409767 G>A), RS1001528316 (19:39428629 C>T), RS1001544964 (19:39411622 G>A)

Disease associations

OMIM: gene MIM:611893 | disease phenotypes: MIM:616763, MIM:277300

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy and acquired microcephaly with or without dystonia;	Strong	Autosomal recessive
epilepsy	Limited	Autosomal dominant

Mondo (5): leukodystrophy and acquired microcephaly with or without dystonia; (MONDO:0014766), spondylocostal dysostosis 1, autosomal recessive (MONDO:0020692), syndactyly (MONDO:0021002), microcephaly (MONDO:0001149), epilepsy (MONDO:0005027)

Orphanet (1): Autosomal recessive spondylocostal dysostosis (Orphanet:2311)

HPO phenotypes

13 total (14 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0002415	Leukodystrophy
HP:0003593	Infantile onset
HP:0005484	Secondary microcephaly
HP:0007204	Diffuse white matter abnormalities
HP:0010864	Severe intellectual disability
HP:0012736	Profound global developmental delay
HP:0001159	Syndactyly

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D013576	Syndactyly	C05.116.099.370.894.819; C05.660.585.800; C05.660.906.819; C16.131.621.585.800; C16.131.621.906.819

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Valproic Acid	increases methylation, affects expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
potassium chromate(VI)	decreases expression	1
coumarin	affects phosphorylation	1
muconaldehyde	decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Endosulfan	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	increases expression	1
Asbestos, Serpentine	decreases methylation	1
Okadaic Acid	increases expression	1
Genistein	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy