PLEKHG7

Summary

PLEKHG7 (pleckstrin homology and RhoGEF domain containing G7, HGNC:33829) is a protein-coding gene on chromosome 12q22, encoding Pleckstrin homology domain-containing family G member 7 (Q6ZR37).

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Rho protein signal transduction.

Source: NCBI Gene 440107 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001377329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33829
Approved symbol	PLEKHG7
Name	pleckstrin homology and RhoGEF domain containing G7
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46688
Ensembl gene	ENSG00000187510
Ensembl biotype	protein_coding
Entrez	440107

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000344636, ENST00000397833, ENST00000544406, ENST00000549856, ENST00000647865, ENST00000898649, ENST00000898650

RefSeq mRNA: 3 — MANE Select: NM_001377329 NM_001037671, NM_001178097, NM_001377329

CCDS: CCDS41819, CCDS53818, CCDS91737

Canonical transcript exons

ENST00000344636 — 17 exons

Exon	Start	End
ENSE00001363878	92764041	92764194
ENSE00001367929	92755825	92755940
ENSE00001368162	92736482	92736577
ENSE00001376087	92761752	92761831
ENSE00001382936	92770088	92772455
ENSE00001385251	92756298	92756391
ENSE00001386333	92754090	92754264
ENSE00001389724	92768983	92769080
ENSE00001530410	92706471	92707138
ENSE00002386565	92728993	92729120
ENSE00002404210	92732233	92732273
ENSE00003361463	92740853	92740948
ENSE00003365295	92745478	92745591
ENSE00003415441	92741491	92741592
ENSE00003804649	92737378	92737521
ENSE00003833174	92707650	92707672
ENSE00003916193	92702989	92703132

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 85.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1439 / max 19.6882, expressed in 41 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127337	0.0883	30
127336	0.0556	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	85.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.38	gold quality
right uterine tube	UBERON:0001302	82.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.89	silver quality
sural nerve	UBERON:0015488	64.62	gold quality
vermiform appendix	UBERON:0001154	62.78	gold quality
nasal cavity mucosa	UBERON:0001826	62.44	gold quality
lymph node	UBERON:0000029	61.02	gold quality
bone marrow cell	CL:0002092	59.72	silver quality
tibial nerve	UBERON:0001323	57.95	gold quality
caecum	UBERON:0001153	57.86	gold quality
mucosa of transverse colon	UBERON:0004991	56.34	gold quality
right lung	UBERON:0002167	55.38	gold quality
fallopian tube	UBERON:0003889	55.35	gold quality
left uterine tube	UBERON:0001303	55.09	gold quality
colonic epithelium	UBERON:0000397	54.99	gold quality
gall bladder	UBERON:0002110	53.40	gold quality
body of pancreas	UBERON:0001150	53.31	gold quality
endometrium	UBERON:0001295	52.90	gold quality
rectum	UBERON:0001052	52.40	gold quality
spleen	UBERON:0002106	52.27	gold quality
tonsil	UBERON:0002372	51.94	gold quality
pancreas	UBERON:0001264	51.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	51.71	gold quality
small intestine	UBERON:0002108	50.63	gold quality
lower lobe of lung	UBERON:0008949	50.63	silver quality
adult mammalian kidney	UBERON:0000082	49.57	gold quality
islet of Langerhans	UBERON:0000006	49.49	gold quality
right lobe of liver	UBERON:0001114	48.75	gold quality
liver	UBERON:0002107	47.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.98
E-MTAB-6678	no	2.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting PLEKHG7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhg7	ENSDARG00000062855
caenorhabditis_elegans		WBGENE00006476

Paralogs (1): PLEKHG5 (ENSG00000171680)

Protein

Protein identifiers

Pleckstrin homology domain-containing family G member 7 — Q6ZR37 (reviewed: Q6ZR37)

All UniProt accessions (3): Q6ZR37, A0A3B3ISE0, R4GMP4

UniProt curated annotations — full annotation on UniProt →

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZR37-1	1	yes
Q6ZR37-2	2
Q6ZR37-3	3

RefSeq proteins (3): NP_001032760, NP_001171568, NP_001364258* (*=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
IPR040181	PKHG5/7	Family

Pfam: PF00621, PF15720

UniProt features (12 total): splice variant 4, domain 2, sequence variant 2, region of interest 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZR37-F1	63.60	0.15

Functional residue map

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

Glycosylation sites (1): 395

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): chr12q22, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, HSF2_TARGET_GENES, ZNF92_TARGET_GENES, MIR8485, MIR3646, MIR4659A_3P_MIR4659B_3P, MIR513A_3P_MIR513C_3P, MIR511_5P, MIR519E_5P, MIR515_5P, MIR519D_5P

GO Biological Process (1): Rho protein signal transduction (GO:0007266)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small GTPase-mediated signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHG7	TMEM213	A2RRL7	478
PLEKHG7	ZNF485	Q8NCK3	475
PLEKHG7	FER1L6	Q2WGJ9	462
PLEKHG7	CLXN	Q9HAE3	460
PLEKHG7	ARHGEF33	A8MVX0	460
PLEKHG7	KBTBD12	Q3ZCT8	448
PLEKHG7	ARHGEF38	Q9NXL2	438
PLEKHG7	RIMS2	Q9UQ26	436
PLEKHG7	ZNF483	Q8TF39	431
PLEKHG7	WDFY3	Q8IZQ1	418
PLEKHG7	FAM184B	Q9ULE4	415
PLEKHG7	NXPH3	O95157	412
PLEKHG7	LCORL	Q8N3X6	400
PLEKHG7	PLEKHG3	A1L390	393
PLEKHG7	VPS4A	Q9UN37	371

IntAct

231 interactions, top by confidence:

A	B	Type	Score
PLEKHG7	HTRA2	psi-mi:“MI:0407”(direct interaction)	0.590
PRKAB2	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
AGXT	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	APBB2	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	DMWD	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7		psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRN	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	GSN	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	NF2	psi-mi:“MI:0915”(physical association)	0.560
PRKN	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	PMP22	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	PPT1	psi-mi:“MI:0915”(physical association)	0.560
TSC1	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	WFS1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	RAB7A	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	SPTLC1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	CCT5	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	RNF11	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG7	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SNCA	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560
HTT	PLEKHG7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (23): CORO1B (Proximity Label-MS), PLEKHG7 (Proximity Label-MS), ANKFY1 (Affinity Capture-MS), BYSL (Affinity Capture-MS), CTNND1 (Affinity Capture-MS), DLAT (Affinity Capture-MS), MAGED1 (Affinity Capture-MS), MAT2A (Affinity Capture-MS), MYCBP (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), EIF3G (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CIRBP (Affinity Capture-MS), CPSF2 (Affinity Capture-MS), DYRK1B (Affinity Capture-MS)

ESM2 similar proteins: A2A690, A2AWP8, A2RRU4, F1LQY6, F1LTE0, F1LXF1, O88842, O94827, O95267, P11274, P49797, Q0P5I0, Q14161, Q14CM0, Q29RM4, Q3B7L5, Q3UHE1, Q5JSP0, Q5R5M3, Q5R5T1, Q5T6S3, Q5XIS9, Q66H91, Q66T02, Q68FF6, Q6PAJ1, Q6RFZ7, Q6ZN54, Q6ZPY2, Q6ZR37, Q76JQ2, Q7Z6G3, Q80YA9, Q8BZ03, Q8R1S4, Q8TBP0, Q8TCU6, Q8WXI2, Q91ZP9, Q96JH8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Assembly and cell surface presentation of NMDA receptors	7	26.5×	1e-06
Neurexins and neuroligins	9	26.4×	1e-08
Protein-protein interactions at synapses	5	19.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to synapse	5	43.0×	3e-05
establishment or maintenance of epithelial cell apical/basal polarity	6	39.2×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	39.0×	4e-07
adult locomotory behavior	5	16.9×	9e-04
cell-cell adhesion	8	9.1×	5e-04
protein-containing complex assembly	6	7.7×	7e-03
negative regulation of neuron apoptotic process	6	7.5×	7e-03
chemical synaptic transmission	7	6.1×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2450 predictions. Top by Δscore:

Variant	Effect	Δscore
12:92737478:G:GG	donor_gain	1.0000
12:92740849:A:AG	acceptor_gain	1.0000
12:92740850:A:G	acceptor_gain	1.0000
12:92745592:G:GG	donor_gain	1.0000
12:92754088:A:AG	acceptor_gain	1.0000
12:92754088:AGT:A	acceptor_gain	1.0000
12:92754089:G:GG	acceptor_gain	1.0000
12:92754089:GTG:G	acceptor_gain	1.0000
12:92754265:G:GG	donor_gain	1.0000
12:92754278:A:G	donor_gain	1.0000
12:92756283:C:A	acceptor_gain	1.0000
12:92756295:AAGT:A	acceptor_gain	1.0000
12:92756296:A:G	acceptor_gain	1.0000
12:92703101:GC:G	donor_gain	0.9900
12:92703128:TACAG:T	donor_loss	0.9900
12:92703129:ACAGG:A	donor_loss	0.9900
12:92703130:CAG:C	donor_loss	0.9900
12:92703131:AGG:A	donor_loss	0.9900
12:92703132:GG:G	donor_loss	0.9900
12:92703133:G:GA	donor_loss	0.9900
12:92706470:GAT:G	acceptor_gain	0.9900
12:92736570:GTCT:G	donor_gain	0.9900
12:92736571:TCTT:T	donor_gain	0.9900
12:92736574:TAAG:T	donor_loss	0.9900
12:92736578:GT:G	donor_loss	0.9900
12:92737371:T:G	acceptor_gain	0.9900
12:92737518:GATG:G	donor_gain	0.9900
12:92740851:A:AG	acceptor_gain	0.9900
12:92740852:G:GG	acceptor_gain	0.9900
12:92741489:A:AG	acceptor_gain	0.9900

AlphaMissense

4507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:92706740:T:C	F37L	0.986
12:92706742:T:A	F37L	0.986
12:92706742:T:G	F37L	0.986
12:92741494:A:C	S35R	0.977
12:92741496:C:A	S35R	0.977
12:92741496:C:G	S35R	0.977
12:92770094:T:A	W347R	0.970
12:92770094:T:C	W347R	0.970
12:92761800:T:C	L250P	0.968
12:92755896:T:A	W188R	0.966
12:92755896:T:C	W188R	0.966
12:92740922:T:C	F25L	0.965
12:92740924:T:A	F25L	0.965
12:92740924:T:G	F25L	0.965
12:92764129:T:A	V290E	0.965
12:92764141:C:A	P294H	0.957
12:92764141:C:G	P294R	0.954
12:92740930:C:A	N27K	0.950
12:92740930:C:G	N27K	0.950
12:92761800:T:G	L250R	0.950
12:92769010:T:A	I321K	0.946
12:92754178:T:C	L135S	0.945
12:92706787:G:C	R52S	0.943
12:92706787:G:T	R52S	0.943
12:92764144:T:A	I295N	0.943
12:92761785:T:C	L245P	0.942
12:92761806:T:A	V252D	0.941
12:92745574:T:C	F100L	0.937
12:92745576:T:A	F100L	0.937
12:92745576:T:G	F100L	0.937

dbSNP variants (sampled 300 via entrez): RS1000051737 (12:92758365 T>C), RS1000062714 (12:92754425 A>G), RS1000076229 (12:92710379 T>C), RS1000137474 (12:92729791 G>A), RS1000146403 (12:92713876 G>A), RS1000174517 (12:92703401 TAAAG>T), RS1000191553 (12:92710799 T>A,C), RS1000202512 (12:92740114 G>A), RS1000233437 (12:92751981 C>A), RS1000252878 (12:92736667 C>A,T), RS1000258420 (12:92701177 C>G,T), RS1000335032 (12:92748898 G>C), RS1000340126 (12:92765495 G>A,T), RS1000419978 (12:92716302 T>A,G), RS1000478431 (12:92743221 T>C,G)

Disease associations

OMIM: gene `` | 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):

Study	Trait	p-value
GCST001102_6	Sudden cardiac arrest	5.000000e-06
GCST002127_12	Periodontitis (Mean PAL)	7.000000e-06
GCST006193_5	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-11
GCST006194_7	Diastolic blood pressure x smoking status (current vs non-current) interaction (1df test)	3.000000e-07
GCST006195_90	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-08
GCST006269_899	General cognitive ability	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
FR900359	increases phosphorylation	1
tebuconazole	decreases expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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