Human Gene PLEKHG5 (ENST00000400913.6) from GENCODE V44
  Description: Homo sapiens pleckstrin homology and RhoGEF domain containing G5 (PLEKHG5), transcript variant 5, mRNA. (from RefSeq NM_001042665)
RefSeq Summary (NM_001042665): This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012].
Gencode Transcript: ENST00000400913.6
Gencode Gene: ENSG00000171680.23
Transcript (Including UTRs)
   Position: hg38 chr1:6,467,122-6,485,954 Size: 18,833 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg38 chr1:6,467,563-6,477,571 Size: 10,009 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:6,467,122-6,485,954)mRNA (may differ from genome)Protein (1006 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Pleckstrin homology domain-containing family G member 5; Short=PH domain-containing family G member 5; AltName: Full=Guanine nucleotide exchange factor 720; Short=GEF720;
FUNCTION: Activates the NF-kappa-B signaling pathway and RHOA. Appears to be involved in the control of neuronal cell differentiation.
SUBUNIT: Interacts with GIPC1/synectin and RHOA (By similarity).
SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region. Note=Predominantly cytoplasmic, however when cells are stimulated found in perinuclear regions (By similarity).
TISSUE SPECIFICITY: Predominantly expressed in the peripheral nervous system and brain. Highest expression is observed in heart, lung, kidney, testis and moderate expression is present in spleen, pancreas, skeletal muscle, ovary and liver. Weakly expressed in glioblastoma cells (GBM cell lines).
DISEASE: Defects in PLEKHG5 are the cause of distal spinal muscular atrophy autosomal recessive type 4 (DSMA4) [MIM:611067]. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent.
SIMILARITY: Contains 1 DH (DBL-homology) domain.
SIMILARITY: Contains 1 PH domain.
SEQUENCE CAUTION: Sequence=BAA34440.2; Type=Erroneous initiation; Sequence=BAC77354.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing; Sequence=BAC85124.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: PLEKHG5
Diseases sorted by gene-association score: spinal muscular atrophy, distal, autosomal recessive, 4* (1550), charcot-marie-tooth disease, recessive intermediate c* (1550), plekhg5-related intermediate charcot-marie-tooth neuropathy c* (500), distal spinal muscular atrophy 4* (100), autosomal recessive intermediate charcot-marie-tooth disease (19), spinal muscular atrophy (11), muscular atrophy (10), retinal perforation (9), charcot-marie-tooth disease (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 92.61 RPKM in Brain - Cerebellum
Total median expression: 612.90 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -91.10206-0.442 Picture PostScript Text
3' UTR -159.00441-0.361 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000219 - DH-domain
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology

Pfam Domains:
PF00621 - RhoGEF domain

ModBase Predicted Comparative 3D Structure on O94827
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity

Biological Process:
GO:0007186 G-protein coupled receptor signaling pathway
GO:0035023 regulation of Rho protein signal transduction
GO:0035767 endothelial cell chemotaxis
GO:0043065 positive regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043542 endothelial cell migration
GO:0051056 regulation of small GTPase mediated signal transduction

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0016020 membrane
GO:0030027 lamellipodium
GO:0030054 cell junction
GO:0030139 endocytic vesicle
GO:0042995 cell projection
GO:0048471 perinuclear region of cytoplasm

-  Descriptions from all associated GenBank mRNAs
  AK131074 - Homo sapiens mRNA for FLJ00260 protein.
AB018263 - Homo sapiens KIAA0720 mRNA for KIAA0720 protein.
BC042606 - Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, mRNA (cDNA clone IMAGE:4750645), with apparent retained intron.
AK096347 - Homo sapiens cDNA FLJ39028 fis, clone NT2RP7006395, highly similar to Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, transcript variant 1, mRNA.
BC036671 - Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, mRNA (cDNA clone IMAGE:4811640).
AK128021 - Homo sapiens cDNA FLJ46140 fis, clone TESTI2052799.
AK299523 - Homo sapiens cDNA FLJ56148 complete cds, highly similar to Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, transcript variant 1, mRNA.
AK125550 - Homo sapiens cDNA FLJ43562 fis, clone PUAEN2005930.
AK091201 - Homo sapiens cDNA FLJ33882 fis, clone CTONG2007175, highly similar to Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, transcript variant 1, mRNA.
AB097001 - Homo sapiens mRNA for putative NFkB activating protein, complete cds, clone: 015N.
BC015231 - Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, mRNA (cDNA clone MGC:17838 IMAGE:3900065), complete cds.
AK024676 - Homo sapiens cDNA: FLJ21023 fis, clone CAE06432.
JD100043 - Sequence 81067 from Patent EP1572962.
JD157546 - Sequence 138570 from Patent EP1572962.
JD474732 - Sequence 455756 from Patent EP1572962.
AK301239 - Homo sapiens cDNA FLJ59769 complete cds, highly similar to Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, transcript variant 1, mRNA.
AK294875 - Homo sapiens cDNA FLJ59684 complete cds, highly similar to Homo sapiens pleckstrin homology domain containing, family G (with RhoGef domain) member 5, transcript variant 1, mRNA.
AB385374 - Synthetic construct DNA, clone: pF1KA0720, Homo sapiens PLEKHG5 gene for pleckstrin homology domain-containing protein, family G member 5 isoform b, complete cds, without stop codon, in Flexi system.
KJ902953 - Synthetic construct Homo sapiens clone ccsbBroadEn_12347 PLEKHG5 gene, encodes complete protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O94827 (Reactome details) participates in the following event(s):

R-HSA-194913 GEFs activate Rho GTPase:GDP
R-HSA-419166 GEFs activate RhoA,B,C
R-HSA-205039 p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-193648 NRAGE signals death through JNK
R-HSA-194315 Signaling by Rho GTPases
R-HSA-388396 GPCR downstream signalling
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-162582 Signal Transduction
R-HSA-372790 Signaling by GPCR
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-73887 Death Receptor Signalling

-  Other Names for This Gene
  Alternate Gene Symbols: B3KU07, ENST00000400913.1, ENST00000400913.2, ENST00000400913.3, ENST00000400913.4, ENST00000400913.5, KIAA0720, NM_001042665, O94827, PKHG5_HUMAN, Q5SY17, Q5T8W5, Q5T8W9, Q6ZNM0, Q7Z436, Q86YD8, Q96BS1, uc001ank.1, uc001ank.2
UCSC ID: ENST00000400913.6
RefSeq Accession: NM_001042665
Protein: O94827 (aka PKHG5_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.