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PLEKHG6

gene
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Also known as FLJ10665MYOGEFARHGEF46

Summary

PLEKHG6 (pleckstrin homology and RhoGEF domain containing G6, HGNC:25562) is a protein-coding gene on chromosome 12p13.31, encoding Pleckstrin homology domain-containing family G member 6 (Q3KR16). Guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation.

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome.

Source: NCBI Gene 55200 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 196 total
  • MANE Select transcript: NM_001384598

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:25562
Approved symbolPLEKHG6
Namepleckstrin homology and RhoGEF domain containing G6
Location12p13.31
Locus typegene with protein product
StatusApproved
AliasesFLJ10665, MYOGEF, ARHGEF46
Ensembl geneENSG00000008323
Ensembl biotypeprotein_coding
OMIM611743
Entrez55200

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000011684, ENST00000304581, ENST00000396988, ENST00000449001, ENST00000535616, ENST00000536531, ENST00000538208, ENST00000543000, ENST00000544743, ENST00000684764, ENST00000898443, ENST00000898444, ENST00000898445, ENST00000898446, ENST00000898447, ENST00000898448, ENST00000928829, ENST00000928830, ENST00000965576, ENST00000965577, ENST00000965579

RefSeq mRNA: 10 — MANE Select: NM_001384598 NM_001144856, NM_001144857, NM_001384598, NM_001384599, NM_001384600, NM_001384601, NM_001384602, NM_001384603, NM_001384604, NM_018173

CCDS: CCDS8541, CCDS91644

Canonical transcript exons

ENST00000684764 — 16 exons

ExonStartEnd
ENSE0000036930163150056315169
ENSE0000071492863136296313784
ENSE0000071492963155546315649
ENSE0000071493063158696315919
ENSE0000071493163162556316404
ENSE0000071493263173036317413
ENSE0000071493363175476317696
ENSE0000071493563178576317994
ENSE0000071493763183016318420
ENSE0000071493863187456318877
ENSE0000071494063264286326573
ENSE0000116696663272546327946
ENSE0000137553463121596312364
ENSE0000222018463281366328506
ENSE0000362240763189936319108
ENSE0000392047863106826310848

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 96.04.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2971 / max 81.8979, expressed in 496 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1236401.3313423
1236410.8730285
1236420.054426
1236390.038418

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499196.04gold quality
lower esophagus mucosaUBERON:003583494.69gold quality
ileal mucosaUBERON:000033193.40gold quality
esophagus mucosaUBERON:000246988.70gold quality
transverse colonUBERON:000115787.40gold quality
tongue squamous epitheliumUBERON:000691986.53silver quality
duodenumUBERON:000211486.39gold quality
rectumUBERON:000105285.85gold quality
small intestine Peyer’s patchUBERON:000345485.68gold quality
small intestineUBERON:000210884.78gold quality
jejunal mucosaUBERON:000039984.02gold quality
buccal mucosa cellCL:000233683.76silver quality
colonic epitheliumUBERON:000039783.52gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047382.86gold quality
minor salivary glandUBERON:000183082.23gold quality
skin of abdomenUBERON:000141681.81gold quality
mouth mucosaUBERON:000372981.77gold quality
saliva-secreting glandUBERON:000104481.11gold quality
adipose tissue of abdominal regionUBERON:000780880.54gold quality
omental fat padUBERON:001041480.28gold quality
peritoneumUBERON:000235880.21gold quality
skin of legUBERON:000151180.15gold quality
placentaUBERON:000198779.93gold quality
olfactory segment of nasal mucosaUBERON:000538679.77gold quality
colonic mucosaUBERON:000031779.65gold quality
adipose tissueUBERON:000101379.47gold quality
vaginaUBERON:000099678.93gold quality
oral cavityUBERON:000016778.92gold quality
intestineUBERON:000016078.87gold quality
zone of skinUBERON:000001478.75gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes6.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting PLEKHG6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-450A-1-3P100.0069.331837
HSA-MIR-4283100.0066.422097
HSA-MIR-450099.9972.722367
HSA-MIR-428299.9975.366408
HSA-LET-7A-5P99.9872.291790
HSA-LET-7B-5P99.9872.311790
HSA-LET-7C-5P99.9872.291790
HSA-LET-7E-5P99.9872.291790
HSA-LET-7F-5P99.9872.561784
HSA-LET-7G-5P99.9872.371784
HSA-LET-7I-5P99.9872.371788
HSA-MIR-98-5P99.9872.331787
HSA-LET-7D-5P99.9671.761632
HSA-MIR-445899.9671.641650
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-153-5P99.8973.866317
HSA-MIR-3151-5P99.8663.831069
HSA-MIR-383-3P99.8565.841359
HSA-MIR-4446-5P99.7269.192544
HSA-MIR-430699.7270.503630
HSA-MIR-317599.6566.302031
HSA-MIR-1212299.5669.331672
HSA-MIR-443799.5265.291266
HSA-MIR-582-5P99.4770.792635
HSA-MIR-6731-5P99.2867.422375
HSA-MIR-808599.2867.562362
HSA-MIR-66199.0965.942062
HSA-MIR-7151-3P99.0469.722370
HSA-MIR-939-3P98.9765.072347
HSA-MIR-445198.8268.171455

Literature-anchored findings (GeneRIF, showing 9)

  • ezrin allows the local activation of RhoG at the apical pole of epithelial cells by recruiting upstream and downstream regulators of RhoG and that both PLEKHG6 and ezrin are required for efficient macropinocytosis (PMID:17881735)
  • Plk1 can regulate MyoGEF activity and localization, contributing to the regulation of cytokinesis (PMID:18694934)
  • MyoGEF cooperates with nonmuscle myosin IIA to regulate the polarity and invasion activity of breast cancer cells through activation of RhoA and RhoC. (PMID:19421144)
  • GIPC1-MyoGEF complex formation plays an important role in regulating MDA-MB-231 breast cancer cell polarization and invasion. (PMID:20634288)
  • Taken together, these results suggest that aurora B coordinates with Plk1 to regulate MyoGEF activation and localization, thus contributing to the regulation of cytokinesis. (PMID:24482237)
  • Intramolecular interactions between MyoGEF domains act as an autoinhibitory mechanism for the regulation of MyoGEF functions. (PMID:25336641)
  • Ezrin interacts with MYOGEF and recruits it to retracting blebs, where MYOGEF activates RhoA and promotes the reassembly of the cortical actomyosin network at the bleb membrane, thus contributing to the regulation of bleb retraction. (PMID:29321250)
  • PLEKHG6 isoform is an example of a primate-specific genomic element supporting brain development. (PMID:30517861)
  • Genetic Predisposition to Colon and Rectal Adenocarcinoma Is Mediated by a Super-enhancer Polymorphism Coactivating CD9 and PLEKHG6. (PMID:31988071)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_rerioplekhg6ENSDARG00000086056
mus_musculusPlekhg6ENSMUSG00000038167
rattus_norvegicusPlekhg6ENSRNOG00000019528
drosophila_melanogasterRhoGEF2FBGN0023172
drosophila_melanogastercystFBGN0032796
caenorhabditis_elegansWBGENE00006468
caenorhabditis_elegansprhg-1WBGENE00022391

Paralogs (8): ARHGEF1 (ENSG00000076928), ARHGEF18 (ENSG00000104880), ARHGEF2 (ENSG00000116584), ARHGEF11 (ENSG00000132694), ARHGEF3 (ENSG00000163947), NET1 (ENSG00000173848), ARHGEF12 (ENSG00000196914), ARHGEF28 (ENSG00000214944)

Protein

Protein identifiers

Pleckstrin homology domain-containing family G member 6 — Q3KR16 (reviewed: Q3KR16)

Alternative names: Myosin-interacting guanine nucleotide exchange factor

All UniProt accessions (3): Q3KR16, A0A2X0TW08, F5H731

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation. Also activates RHOG. Does not activate RAC1, or to a much lower extent than RHOA and RHOG. Part of a functional unit, involving PLEKHG6, MYH10 and RHOA, at the cleavage furrow to advance furrow ingression during cytokinesis. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with EZR, required for normal macropinocytosis.

Subunit / interactions. Interacts with MYH10. Interacts with ELMO1 and EZR (in an open conformation). Interacts with CSPP1.

Subcellular location. Cell projection. Microvillus. Cytoplasm. Cytoskeleton. Spindle. Spindle pole. Cleavage furrow.

Tissue specificity. Highest expression in the placenta. Low levels in small intestine, lung, liver, kidney, thymus and heart.

Isoforms (3)

UniProt IDNamesCanonical?
Q3KR16-11yes
Q3KR16-22
Q3KR16-33

RefSeq proteins (10): NP_001138328, NP_001138329, NP_001371527, NP_001371528, NP_001371529, NP_001371530, NP_001371531, NP_001371532, NP_001371533, NP_060643 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000219DH_domDomain
IPR001849PH_domainDomain
IPR011993PH-like_dom_sfHomologous_superfamily
IPR035899DBL_dom_sfHomologous_superfamily
IPR042918PLEKHG6Family

Pfam: PF00621

UniProt features (18 total): compositionally biased region 4, region of interest 4, splice variant 3, domain 2, sequence conflict 2, chain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q3KR16-F168.360.45

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):

PositionPhenotype
351loss of exchange activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-8980692RHOA GTPase cycle
R-HSA-9013149RAC1 GTPase cycle

MSigDB gene sets: 93 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GATA3_01, TCF11_01, HNF4_DR1_Q3, ARGGGTTAA_UNKNOWN, GATA1_04, GATA1_02, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GATA_Q6, GOCC_SPINDLE, GOCC_MICROVILLUS, GOCC_CELL_DIVISION_SITE, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (1): regulation of small GTPase mediated signal transduction (GO:0051056)

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

GO Cellular Component (10): spindle pole (GO:0000922), centrosome (GO:0005813), cytosol (GO:0005829), microvillus (GO:0005902), cell junction (GO:0030054), cleavage furrow (GO:0032154), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
RHO GTPase cycle2

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure5
GTPase regulator activity2
intracellular membraneless organelle2
small GTPase-mediated signal transduction1
regulation of intracellular signal transduction1
GTP binding1
GDP binding1
GTPase activity1
enzyme activator activity1
binding1
spindle1
centriole1
microtubule organizing center1
cytoplasm1
actin filament bundle1
actin-based cell projection1
cell division site1
plasma membrane region1
intracellular anatomical structure1
microtubule cytoskeleton1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PLEKHG6RHOGP35238718
PLEKHG6RHOAP06749652
PLEKHG6CSPP1Q1MSJ5642
PLEKHG6EZRP15311604
PLEKHG6PLEK2Q9NYT0481
PLEKHG6PLEKP08567478
PLEKHG6TRNP1Q6NT89448
PLEKHG6ARHGEF33A8MVX0447
PLEKHG6ARHGEF11O15085432
PLEKHG6TMEM14BQ9NUH8428
PLEKHG6RABIFP47224425
PLEKHG6ARHGEF19Q8IW93418
PLEKHG6ARHGEF15O94989415
PLEKHG6FGD3Q5JSP0404
PLEKHG6PLEKHG4BQ96PX9396

IntAct

12 interactions, top by confidence:

ABTypeScore
CEP55PLEKHG6psi-mi:“MI:0915”(physical association)0.780
PLEKHG6CEP55psi-mi:“MI:0915”(physical association)0.780
PLEKHG6CST4psi-mi:“MI:0914”(association)0.530
PLEKHG4DDX39Apsi-mi:“MI:0914”(association)0.350
PLEKHG6CEP55psi-mi:“MI:0915”(physical association)0.000

BioGRID (55): PLEKHG6 (Two-hybrid), PCDHGA5 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), CST1 (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), CST5 (Affinity Capture-MS), PIGR (Affinity Capture-MS), IGJ (Affinity Capture-MS), ZG16B (Affinity Capture-MS), GSN (Affinity Capture-MS), ACTB (Affinity Capture-MS), AMY1C (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), TMOD2 (Affinity Capture-MS)

ESM2 similar proteins: A2ARS0, A5PKW4, A6QQ91, B7ZNG0, C9JTQ0, D3ZG83, F1MUS9, O14523, O14559, O75064, O75427, O95996, P0C5W1, P46062, P58660, Q02779, Q16584, Q2KI85, Q2M1P5, Q2TAL5, Q3KR16, Q3U0S6, Q3U1Y4, Q3UHC7, Q3UMT1, Q5BJT1, Q5DTT2, Q5U464, Q5U651, Q5VWQ8, Q66HA1, Q66K74, Q66L42, Q69YU3, Q6P730, Q80XI6, Q80YF9, Q86VW2, Q86YV0, Q8C052

Diamond homologs: O94827, Q3KR16, Q66T02, Q6RFZ7, Q8R0J1, Q92888, Q9Z1I6, O75962, Q1LUA6, A2CG49, A8DYP0, E2RP94, F1M0Z1, M0R4F8, O15068, O60229, P10911, P97924, Q0KL02, Q58EX7, Q63406, Q64096, Q6KAU7, Q6P720, Q80U35, Q86VW2, Q96PX9, Q9CWR0, Q9H7P9

SIGNOR signaling

4 interactions.

AEffectBMechanism
PLK1up-regulatesPLEKHG6phosphorylation
AURKBup-regulatesPLEKHG6phosphorylation
PLEKHG6“up-regulates activity”RHOA“guanine nucleotide exchange factor”
PLEKHG6“up-regulates activity”RAC1“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance167
Likely benign15
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2676 predictions. Top by Δscore:

VariantEffectΔscore
12:6312361:GCTG:Gdonor_gain1.0000
12:6312362:CTGGT:Cdonor_loss1.0000
12:6312363:TGG:Tdonor_loss1.0000
12:6312365:G:GGdonor_gain1.0000
12:6312365:GTGA:Gdonor_loss1.0000
12:6312366:T:Gdonor_loss1.0000
12:6315000:CCCA:Cacceptor_loss1.0000
12:6315002:CA:Cacceptor_loss1.0000
12:6315003:A:AGacceptor_gain1.0000
12:6315003:AG:Aacceptor_gain1.0000
12:6315003:AGG:Aacceptor_loss1.0000
12:6315004:G:Aacceptor_loss1.0000
12:6315004:G:GGacceptor_gain1.0000
12:6315004:GG:Gacceptor_gain1.0000
12:6315004:GGA:Gacceptor_gain1.0000
12:6315004:GGAA:Gacceptor_gain1.0000
12:6315529:T:Aacceptor_gain1.0000
12:6315552:A:AGacceptor_gain1.0000
12:6315552:AG:Aacceptor_gain1.0000
12:6315553:G:GAacceptor_gain1.0000
12:6315553:G:GCacceptor_loss1.0000
12:6315553:GG:Gacceptor_gain1.0000
12:6315553:GGA:Gacceptor_gain1.0000
12:6315553:GGAGA:Gacceptor_gain1.0000
12:6315648:AT:Adonor_gain1.0000
12:6315649:TGTGA:Tdonor_loss1.0000
12:6315650:G:GGdonor_gain1.0000
12:6315651:T:Adonor_loss1.0000
12:6315866:CA:Cacceptor_loss1.0000
12:6315867:A:AGacceptor_gain1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000169249 (12:6308942 G>A), RS1000404929 (12:6313221 G>A,T), RS1000652319 (12:6312196 G>C), RS1000739497 (12:6308386 G>A), RS1000754569 (12:6313365 C>G), RS1000783203 (12:6312787 G>A), RS1000894525 (12:6324056 G>A), RS1001058218 (12:6322402 C>G), RS1001104136 (12:6328436 C>A,T), RS1001407308 (12:6322712 C>A,T), RS1001662616 (12:6324170 C>A,T), RS1001674121 (12:6328906 A>G), RS1001733900 (12:6314321 G>T), RS1001918575 (12:6308777 C>A), RS1002141734 (12:6312669 C>G,T)

Disease associations

OMIM: gene MIM:611743 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST001762_933Obesity-related traits9.000000e-06
GCST002454_10Colorectal cancer6.000000e-10
GCST003129_16Primary biliary cholangitis2.000000e-09
GCST004866_8Alopecia areata8.000000e-06
GCST007856_2Colorectal cancer or advanced adenoma1.000000e-08
GCST011656_3Lung cancer9.000000e-07

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0005116urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases methylation, increases expression2
Calcitriolincreases expression, affects cotreatment2
Valproic Acidaffects cotreatment, increases expression2
aristolochic acid Iincreases expression1
triphenyl phosphateaffects expression1
sodium arseniteincreases expression1
ferrous chlorideincreases expression1
aflatoxin B2decreases methylation1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, affects cotreatment1
perfluorooctane sulfonic acidincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
dorsomorphinincreases expression, affects cotreatment1
licochalcone Bdecreases expression1
(+)-JQ1 compounddecreases expression1
Arsenic Trioxidedecreases response to substance1
Arsenicaffects methylation1
Estradiolaffects cotreatment, decreases expression1
Lipopolysaccharidesincreases expression, affects response to substance, affects cotreatment1
Testosteroneaffects cotreatment, increases expression1
Urethanedecreases expression1
Aflatoxin B1decreases expression1
Okadaic Acidincreases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot