This gene encodes a pleckstrin homology (PH) domain-containing protein. The PH domain is found near the N-terminus and contains a putative phosphatidylinositol 3, 4, 5-triphosphate-binding motif (PPBM). Elevated expression of this gene has been observed in some melanomas. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq... See more...

Aliases for PLEKHA4 Gene

Aliases for PLEKHA4 Gene

  • Pleckstrin Homology Domain Containing A4 2 3 5
  • PEPP1 2 3 4
  • Pleckstrin Homology Domain-Containing Family A Member 4 3 4
  • PH Domain-Containing Family A Member 4 3 4
  • Pleckstrin Homology Domain-Containing, Family A (Phosphoinositide Binding Specific) Member 4 2
  • Pleckstrin Homology Domain Containing, Family A (Phosphoinositide Binding Specific) Member 4 3
  • Phosphoinositol 3-Phosphate-Binding PH Domain Protein 1 3
  • Phosphoinositol 3-Phosphate-Binding Protein 1 4
  • PLEKHA4 5
  • PEPP-1 4

External Ids for PLEKHA4 Gene

Previous GeneCards Identifiers for PLEKHA4 Gene

  • GC19M049998
  • GC19M049708
  • GC19M054016
  • GC19M054032
  • GC19M049340
  • GC19M045716

Summaries for PLEKHA4 Gene

Entrez Gene Summary for PLEKHA4 Gene

  • This gene encodes a pleckstrin homology (PH) domain-containing protein. The PH domain is found near the N-terminus and contains a putative phosphatidylinositol 3, 4, 5-triphosphate-binding motif (PPBM). Elevated expression of this gene has been observed in some melanomas. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

GeneCards Summary for PLEKHA4 Gene

PLEKHA4 (Pleckstrin Homology Domain Containing A4) is a Protein Coding gene. Among its related pathways are PI Metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include 1-phosphatidylinositol binding. An important paralog of this gene is PLEKHA7.

UniProtKB/Swiss-Prot Summary for PLEKHA4 Gene

  • Binds specifically to phosphatidylinositol 3-phosphate (PtdIns3P), but not to other phosphoinositides.

Additional gene information for PLEKHA4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PLEKHA4 Gene

Genomics for PLEKHA4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PLEKHA4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J048866 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 605.8 +0.6 649 3.3 ARHGAP35 PRDM10 ZNF512 RFX1 LEF1 IKZF1 ZNF300 PRDM1 MTA2 PKNOX1 PLEKHA4 lnc-TULP2-3 GRWD1 PRR12 PIH1D1 SNORD35A SNRNP70 PTOV1-AS2 ALDH16A1 SNORD35B
GH19J048898 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 12.2 -31.6 -31620 3.8 SP1 CREB1 GATAD2A PRDM10 REST ZNF629 ZNF512 SIX5 IKZF1 NFKBIZ NUCB1 TULP2 PPP1R15A PLEKHA4 BAX FTL DBP SEC1P IRF3
GH19J048844 Enhancer 0.6 ENCODE 12.2 +24.0 23983 0.2 SP1 TEAD4 CTCF SP2 USF1 ZBTB5 TEAD1 NFYA NFYB ZNF384 PLEKHA4 PPP1R15A TULP2 BCAT2 NUCB1 NUCB1-AS1 CGB7 NTF4 NONHSAG026190.2 HSD17B14
GH19J048835 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 0.3 +31.9 31922 3 ARHGAP35 SP1 GATAD2A CTCF TFE3 IKZF1 KDM1A ZNF692 BACH1 JUND HSD17B14 NONHSAG026190.2 lnc-HSD17B14-1 PLEKHA4
GH19J048858 Promoter/Enhancer 1.4 Ensembl ENCODE dbSUPER 0.4 +8.9 8850 2.1 ARHGAP35 ZNF512 SIX5 IKZF1 JUND DDX20 MTA2 PRDM1 ZNF143 PKNOX1 HSD17B14 BCL2L12 NUCB1 RF00017-3052 PLEKHA4 lnc-TULP2-3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PLEKHA4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PLEKHA4

Top Transcription factor binding sites by QIAGEN in the PLEKHA4 gene promoter:
  • AP-1
  • ATF-2
  • ATF6
  • c-Jun
  • CREB
  • deltaCREB
  • IRF-1
  • IRF-7A
  • Sp1

Genomic Locations for PLEKHA4 Gene

Genomic Locations for PLEKHA4 Gene
chr19:48,837,092-48,868,622
(GRCh38/hg38)
Size:
31,531 bases
Orientation:
Minus strand
chr19:49,340,354-49,371,889
(GRCh37/hg19)
Size:
31,536 bases
Orientation:
Minus strand

Genomic View for PLEKHA4 Gene

Genes around PLEKHA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PLEKHA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PLEKHA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PLEKHA4 Gene

Proteins for PLEKHA4 Gene

  • Protein details for PLEKHA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H4M7-PKHA4_HUMAN
    Recommended name:
    Pleckstrin homology domain-containing family A member 4
    Protein Accession:
    Q9H4M7
    Secondary Accessions:
    • Q8N4M8
    • Q8N658

    Protein attributes for PLEKHA4 Gene

    Size:
    779 amino acids
    Molecular mass:
    85401 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAH33832.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PLEKHA4 Gene

    Alternative splice isoforms for PLEKHA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PLEKHA4 Gene

Post-translational modifications for PLEKHA4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for PLEKHA4 Gene

Domains & Families for PLEKHA4 Gene

Gene Families for PLEKHA4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PLEKHA4 Gene

InterPro:
Blocks:
  • Pleckstrin-like
ProtoNet:

Suggested Antigen Peptide Sequences for PLEKHA4 Gene

GenScript: Design optimal peptide antigens:
  • Phosphoinositol 3-phosphate-binding protein 1 (PKHA4_HUMAN)
genes like me logo Genes that share domains with PLEKHA4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for PLEKHA4 Gene

Function for PLEKHA4 Gene

Molecular function for PLEKHA4 Gene

UniProtKB/Swiss-Prot Function:
Binds specifically to phosphatidylinositol 3-phosphate (PtdIns3P), but not to other phosphoinositides.

Phenotypes From GWAS Catalog for PLEKHA4 Gene

Gene Ontology (GO) - Molecular Function for PLEKHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding IDA 31091453
GO:0008289 lipid binding IEA --
GO:0032266 phosphatidylinositol-3-phosphate binding IDA 11001876
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding IDA 31091453
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding IDA 31091453
genes like me logo Genes that share ontologies with PLEKHA4: view
genes like me logo Genes that share phenotypes with PLEKHA4: view

Animal Model Products

CRISPR Products

miRNA for PLEKHA4 Gene

miRTarBase miRNAs that target PLEKHA4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PLEKHA4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for PLEKHA4 Gene

Localization for PLEKHA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PLEKHA4 Gene

Cytoplasm. Membrane. Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PLEKHA4 gene
Compartment Confidence
plasma membrane 5
cytosol 3
cytoskeleton 2
mitochondrion 1
nucleus 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (2)
  • Cytokinetic bridge (2)
  • Cytosol (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PLEKHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane IDA 31091453
genes like me logo Genes that share ontologies with PLEKHA4: view

Pathways & Interactions for PLEKHA4 Gene

genes like me logo Genes that share pathways with PLEKHA4: view

Interacting Proteins for PLEKHA4 Gene

STRING Interaction Network Preview (showing top 1 STRING interactants - click image to see details)
STRING Interaction Network
Selected Interacting proteins: Q9H4M7-PKHA4_HUMAN ENSP00000263265 for PLEKHA4 Gene via UniProtKB STRING IID

Gene Ontology (GO) - Biological Process for PLEKHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006661 phosphatidylinositol biosynthetic process TAS --
GO:0090263 positive regulation of canonical Wnt signaling pathway IMP 31091453
GO:2000096 positive regulation of Wnt signaling pathway, planar cell polarity pathway IMP 31091453
genes like me logo Genes that share ontologies with PLEKHA4: view

No data available for SIGNOR curated interactions for PLEKHA4 Gene

Drugs & Compounds for PLEKHA4 Gene

(1) Drugs for PLEKHA4 Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
inositol 1,3,4,5-tetrakisphosphate Experimental Pharma Target 0
genes like me logo Genes that share compounds with PLEKHA4: view

Transcripts for PLEKHA4 Gene

mRNA/cDNA for PLEKHA4 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PLEKHA4

Alternative Splicing Database (ASD) splice patterns (SP) for PLEKHA4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b · 16c ^ 17 ^ 18 ^ 19 ^ 20
SP1: -
SP2: - -
SP3: - - -
SP4: -
SP5: - -
SP6:
SP7:

Relevant External Links for PLEKHA4 Gene

GeneLoc Exon Structure for
PLEKHA4

Expression for PLEKHA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PLEKHA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PLEKHA4 Gene

This gene is overexpressed in Nerve - Tibial (x14.7).

Protein differential expression in normal tissues from HIPED for PLEKHA4 Gene

This gene is overexpressed in Platelet (24.9), CD4 Tcells (22.1), and Liver, secretome (9.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PLEKHA4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PLEKHA4

SOURCE GeneReport for Unigene cluster for PLEKHA4 Gene:

Hs.9469

mRNA Expression by UniProt/SwissProt for PLEKHA4 Gene:

Q9H4M7-PKHA4_HUMAN
Tissue specificity: Highly expressed in melanoma. Detected at low levels in heart, skeletal muscle, kidney, liver and small intestine.

Evidence on tissue expression from TISSUES for PLEKHA4 Gene

  • Nervous system(4.3)
  • Liver(4.3)
  • Heart(2)
  • Skin(2)
genes like me logo Genes that share expression patterns with PLEKHA4: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PLEKHA4 Gene

Orthologs for PLEKHA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for PLEKHA4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PLEKHA4 31
  • 99 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia PLEKHA4 30 31
  • 85.82 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PLEKHA4 30 31
  • 85.71 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Plekha4 30 17 31
  • 79.13 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Plekha4 30
  • 78.96 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 9 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia PLEKHA4 31
  • 57 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii PLEKHA4 31
  • 17 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG34383 31
  • 5 (a)
OneToMany
Species where no ortholog for PLEKHA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PLEKHA4 Gene

ENSEMBL:
Gene Tree for PLEKHA4 (if available)
TreeFam:
Gene Tree for PLEKHA4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PLEKHA4: view image

Paralogs for PLEKHA4 Gene

Paralogs for PLEKHA4 Gene

(2) SIMAP similar genes for PLEKHA4 Gene using alignment to 6 proteins:

  • PKHA4_HUMAN
  • M0QXD9_HUMAN
  • M0QXJ3_HUMAN
  • M0R0J1_HUMAN
  • M0R0V1_HUMAN
  • M0R2K5_HUMAN
genes like me logo Genes that share paralogs with PLEKHA4: view

Variants for PLEKHA4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PLEKHA4 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs193920946 Uncertain Significance: Malignant tumor of prostate 48,867,592(-) AGGCTGCTGC/A INFRAME_DELETION
rs12460394 - p.Arg597Gln
rs34460869 - p.Thr714Ala
rs35965411 - p.Gly742Val
rs506425 - p.Ile37Val

Additional dbSNP identifiers (rs#s) for PLEKHA4 Gene

Structural Variations from Database of Genomic Variants (DGV) for PLEKHA4 Gene

Variant ID Type Subtype PubMed ID
dgv1794n106 CNV deletion 24896259
nsv470148 CNV gain 18288195
nsv833855 CNV loss 17160897
nsv833856 CNV loss 17160897
nsv9739 CNV gain+loss 18304495

Variation tolerance for PLEKHA4 Gene

Residual Variation Intolerance Score: 97.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.39; 94.24% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PLEKHA4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PLEKHA4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PLEKHA4 Gene

Disorders for PLEKHA4 Gene

Additional Disease Information for PLEKHA4

No disorders were found for PLEKHA4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for PLEKHA4 Gene

Publications for PLEKHA4 Gene

  1. Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities. (PMID: 11001876) Dowler S … Alessi DR (The Biochemical journal 2000) 2 3 4 23
  2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  3. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  4. PLEKHA4/kramer Attenuates Dishevelled Ubiquitination to Modulate Wnt and Planar Cell Polarity Signaling. (PMID: 31091453) Shami Shah A … Baskin JM (Cell reports 2019) 3
  5. Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor. (PMID: 27229929) Daakour S … Twizere JC (BMC cancer 2016) 3

Products for PLEKHA4 Gene

  • Biorbyt antibodies for PLEKHA4

Sources for PLEKHA4 Gene