This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010] See more...

Aliases for GRHL3 Gene

Aliases for GRHL3 Gene

  • Grainyhead Like Transcription Factor 3 2 3 5
  • Transcription Factor CP2-Like 4 2 3 4
  • Grainyhead-Like Protein 3 Homolog 3 4
  • Sister Of Mammalian Grainyhead 3 4
  • TFCP2L4 3 4
  • SOM 3 4
  • Grainyhead-Like 3 (Drosophila) 2
  • Transcription Factor HSOM1 3
  • VWS2 3

External Ids for GRHL3 Gene

Previous HGNC Symbols for GRHL3 Gene

  • TFCP2L4

Previous GeneCards Identifiers for GRHL3 Gene

  • GC01P024392
  • GC01P024518
  • GC01P024645
  • GC01P022898

Summaries for GRHL3 Gene

Entrez Gene Summary for GRHL3 Gene

  • This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

GeneCards Summary for GRHL3 Gene

GRHL3 (Grainyhead Like Transcription Factor 3) is a Protein Coding gene. Diseases associated with GRHL3 include Van Der Woude Syndrome 2 and Van Der Woude Syndrome 1. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and DNA-binding transcription factor activity, RNA polymerase II-specific. An important paralog of this gene is GRHL1.

UniProtKB/Swiss-Prot Summary for GRHL3 Gene

  • Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin (By similarity). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (PubMed:21081122, PubMed:25347468). xhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair (By similarity). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair but is essential to form the epidermal barrier with TGM3 as critical direct target gene among others. Despite being dispensable during normal epidermal homeostasis in the adulthood, is again required for barrier repair after immune-mediated epidermal damage, regulates distinct gene batteries in embryonic epidermal differentiation and adult epidermal barrier reformation after injury. Plays unique and cooperative roles with GRHL2 in establishing distinct zones of primary neurulation. Essential for spinal closure, functions cooperatively with GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122).

Additional gene information for GRHL3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GRHL3 Gene

Genomics for GRHL3 Gene

GeneHancer (GH) Regulatory Elements for GRHL3 Gene

Promoters and enhancers for GRHL3 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
GH01J024316 Promoter/Enhancer 2 EPDnew Ensembl ENCODE dbSUPER 750.6 +0.8 824 7.9 ZBTB40 ZBTB6 SMARCE1 RUNX1 L3MBTL2 MAX MNT TEAD4 SP1 ZNF148 ENSG00000232298 GRHL3 GRHL3-AS1 piR-42832 piR-62044
GH01J024149 Enhancer 1.2 FANTOM5 ENCODE CraniofacialAtlas 24.6 -167.9 -167947 3.8 CTCF SMARCE1 CREB1 NFYC RAD21 TEAD4 ELF3 SP1 SMARCA4 SP5 IFNLR1 GRHL3 MYOM3 ENSG00000232298 NCMAP IL22RA1 PNRC2 piR-34822-005
GH01J024183 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 12.4 -130.7 -130716 9.8 ZNF24 SP1 ZBTB6 SMARCE1 USF2 NR2F6 ZNF133 MYC NFYC ETV6 IFNLR1 SRRM1 LINC01355 SRSF10 HNRNPR LINC02800 E2F2 PNRC2 GRHL3 ZNF436-AS1
GH01J024390 Promoter/Enhancer 1.3 Ensembl ENCODE dbSUPER 11.2 +73.3 73254 3.4 SP1 CTCF CC2D1A ETV6 RELA MAX RAD21 SP7 CREM IKZF1 STPG1 NIPAL3 IFNLR1 ENSG00000232298 GRHL3 NCMAP lnc-STPG1-2 piR-42832
GH01J024362 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 10.4 +45.2 45179 3.8 SMARCE1 POLR2A PRDM1 CREM FOSL2 IKZF1 ZIC2 PKNOX1 ZNF629 CEBPB STPG1 NIPAL3 GRHL3 PNRC2 piR-42832
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GRHL3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GRHL3 gene promoter:
  • ARP-1
  • c-Myb
  • E2F
  • E2F-1
  • FOXF2
  • Roaz

Genomic Locations for GRHL3 Gene

Genomic Locations for GRHL3 Gene
chr1:24,319,322-24,364,482
(GRCh38/hg38)
Size:
45,161 bases
Orientation:
Plus strand
chr1:24,645,812-24,690,972
(GRCh37/hg19)
Size:
45,161 bases
Orientation:
Plus strand

Genomic View for GRHL3 Gene

Genes around GRHL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRHL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GRHL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRHL3 Gene

Proteins for GRHL3 Gene

  • Protein details for GRHL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TE85-GRHL3_HUMAN
    Recommended name:
    Grainyhead-like protein 3 homolog
    Protein Accession:
    Q8TE85
    Secondary Accessions:
    • A2A297
    • B2RCL1
    • G3XAF0
    • Q5TH78
    • Q86Y06
    • Q8N407

    Protein attributes for GRHL3 Gene

    Size:
    626 amino acids
    Molecular mass:
    70345 Da
    Quaternary structure:
    • Homodimer, also forms heterodimers with GRHL1 and GRHL2 (PubMed:12549979). Interacts with LMO4 (By similarity).
    Miscellaneous:
    • GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxical lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related, but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.
    SequenceCaution:
    • Sequence=AAH36890.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG37608.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for GRHL3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRHL3 Gene

Post-translational modifications for GRHL3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for GRHL3 Gene

Domains & Families for GRHL3 Gene

Gene Families for GRHL3 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins
  • Transcription factors

Protein Domains for GRHL3 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GRHL3 Gene

GenScript: Design optimal peptide antigens:
  • Transcription factor CP2-like 4 (GRHL3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TE85

UniProtKB/Swiss-Prot:

GRHL3_HUMAN :
  • Belongs to the grh/CP2 family. Grainyhead subfamily.
Family:
  • Belongs to the grh/CP2 family. Grainyhead subfamily.
genes like me logo Genes that share domains with GRHL3: view

Function for GRHL3 Gene

Molecular function for GRHL3 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin (By similarity). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (PubMed:21081122, PubMed:25347468). xhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair (By similarity). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair but is essential to form the epidermal barrier with TGM3 as critical direct target gene among others. Despite being dispensable during normal epidermal homeostasis in the adulthood, is again required for barrier repair after immune-mediated epidermal damage, regulates distinct gene batteries in embryonic epidermal differentiation and adult epidermal barrier reformation after injury. Plays unique and cooperative roles with GRHL2 in establishing distinct zones of primary neurulation. Essential for spinal closure, functions cooperatively with GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122).

Phenotypes From GWAS Catalog for GRHL3 Gene

Gene Ontology (GO) - Molecular Function for GRHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 23685552
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IBA 21873635
GO:0005515 protein binding IPI 23455924
genes like me logo Genes that share ontologies with GRHL3: view
genes like me logo Genes that share phenotypes with GRHL3: view

Human Phenotype Ontology for GRHL3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GRHL3 Gene

MGI Knock Outs for GRHL3:

Animal Model Products

CRISPR Products

miRNA for GRHL3 Gene

miRTarBase miRNAs that target GRHL3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GRHL3 Gene

Localization for GRHL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRHL3 Gene

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 GRHL3 gene
Compartment Confidence
nucleus 5
cytoskeleton 2
endoplasmic reticulum 2
plasma membrane 1
mitochondrion 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GRHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IBA 21081122
GO:0005654 nucleoplasm IDA --
genes like me logo Genes that share ontologies with GRHL3: view

Pathways & Interactions for GRHL3 Gene

PathCards logo

SuperPathways for GRHL3 Gene

No Data Available

Gene Ontology (GO) - Biological Process for GRHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001736 establishment of planar polarity IEA --
GO:0001843 neural tube closure ISS --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007389 pattern specification process IEA --
GO:0007398 ectoderm development IEA --
genes like me logo Genes that share ontologies with GRHL3: view

No data available for Pathways by source and SIGNOR curated interactions for GRHL3 Gene

Drugs & Compounds for GRHL3 Gene

No Compound Related Data Available

Transcripts for GRHL3 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GRHL3 Gene

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

Relevant External Links for GRHL3 Gene

GeneLoc Exon Structure for
GRHL3
ECgene alternative splicing isoforms for
GRHL3

Expression for GRHL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GRHL3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GRHL3 Gene

This gene is overexpressed in Esophagus - Mucosa (x18.9), Skin - Not Sun Exposed (Suprapubic) (x7.1), Vagina (x6.6), Skin - Sun Exposed (Lower leg) (x6.4), and Minor Salivary Gland (x5.5).

Protein differential expression in normal tissues from HIPED for GRHL3 Gene

This gene is overexpressed in Adipocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GRHL3 Gene



Protein tissue co-expression partners for GRHL3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of GRHL3 Gene:

GRHL3

SOURCE GeneReport for Unigene cluster for GRHL3 Gene:

Hs.657920

mRNA Expression by UniProt/SwissProt for GRHL3 Gene:

Q8TE85-GRHL3_HUMAN
Tissue specificity: Expressed in brain, colon, pancreas, placenta and kidney. Isoform 1 is expressed in lung and tonsil. Isoform 2 is prostate-specific.

Evidence on tissue expression from TISSUES for GRHL3 Gene

  • Eye(4)
  • Kidney(4)
  • Nervous system(3.4)
  • Skin(2.7)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GRHL3 Gene

Germ Layers:
  • ectoderm
  • endoderm
Systems:
  • digestive
  • integumentary
  • skeleton
Regions:
Head and neck:
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • pharynx
  • skull
  • tooth
General:
  • skin
genes like me logo Genes that share expression patterns with GRHL3: view

Orthologs for GRHL3 Gene

This gene was present in the common ancestor of animals.

Orthologs for GRHL3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRHL3 33 32
  • 99.39 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GRHL3 33 32
  • 90.68 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GRHL3 33 32
  • 90.09 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grhl3 32
  • 87.13 (n)
mouse
(Mus musculus)
Mammalia Grhl3 17 33 32
  • 86.93 (n)
oppossum
(Monodelphis domestica)
Mammalia GRHL3 33
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRHL3 33
  • 57 (a)
OneToOne
chicken
(Gallus gallus)
Aves GRHL3 33 32
  • 75.18 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRHL3 33
  • 69 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grhl3 32
  • 66.95 (n)
Str.3072 32
African clawed frog
(Xenopus laevis)
Amphibia Xl.5446 32
zebrafish
(Danio rerio)
Actinopterygii grhl3 33 32
  • 58.9 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta grh 33
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grh-1 33
  • 27 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 35 (a)
OneToMany
Species where no ortholog for GRHL3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • 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 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)
  • wheat (Triticum aestivum)

Evolution for GRHL3 Gene

ENSEMBL:
Gene Tree for GRHL3 (if available)
TreeFam:
Gene Tree for GRHL3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GRHL3: view image

Paralogs for GRHL3 Gene

Paralogs for GRHL3 Gene

(2) SIMAP similar genes for GRHL3 Gene using alignment to 3 proteins:

  • GRHL3_HUMAN
  • E9PLG9_HUMAN
  • E9PLT6_HUMAN
genes like me logo Genes that share paralogs with GRHL3: view

Variants for GRHL3 Gene

Sequence variations from dbSNP and Humsavar for GRHL3 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs116396279 benign, Van der Woude syndrome 2 24,344,928(+) A/G coding_sequence_variant, missense_variant
rs1553172687 pathogenic, Van der Woude syndrome 2 24,338,050(+) G/A coding_sequence_variant, stop_gained
rs34637004 benign, Van der Woude syndrome 2, - 24,336,694(+) T/C coding_sequence_variant, missense_variant
rs41268753 benign, Van der Woude syndrome 2 24,342,967(+) C/T coding_sequence_variant, missense_variant
rs752673677 pathogenic, Van der Woude syndrome 2, Van der Woude syndrome 2 (VWS2) [MIM:606713] 24,338,044(+) G/A coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for GRHL3 Gene

Variant ID Type Subtype PubMed ID
esv1739869 CNV insertion 17803354
esv1745617 CNV insertion 17803354
esv2745486 CNV deletion 23290073
esv2745497 CNV deletion 23290073
esv3426242 CNV insertion 20981092
nsv469575 CNV loss 16826518
nsv834447 CNV loss 17160897
nsv950302 CNV deletion 24416366

Variation tolerance for GRHL3 Gene

Residual Variation Intolerance Score: 90.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.14; 92.30% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GRHL3 Gene

Human Gene Mutation Database (HGMD)
GRHL3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRHL3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRHL3 Gene

Disorders for GRHL3 Gene

MalaCards: The human disease database

(15) MalaCards diseases for GRHL3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
van der woude syndrome 2
  • vws2
van der woude syndrome 1
  • vws1
submucosal cleft palate
cleft hard palate
  • cleft of hard palate
cleft soft palate
  • cleft velum
- elite association - COSMIC cancer census association via MalaCards
Search GRHL3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GRHL3_HUMAN
  • Van der Woude syndrome 2 (VWS2) [MIM:606713]: An autosomal dominant developmental disorder characterized by lower lip pits, cleft lip and/or cleft palate. {ECO:0000269 PubMed:24360809}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GRHL3

genes like me logo Genes that share disorders with GRHL3: view

No data available for Genatlas for GRHL3 Gene

Publications for GRHL3 Gene

  1. The identification and characterization of human Sister-of-Mammalian Grainyhead (SOM) expands the grainyhead-like family of developmental transcription factors. (PMID: 12549979) Ting SB … Jane SM (The Biochemical journal 2003) 2 3 4 56
  2. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. (PMID: 24360809) Peyrard-Janvid M … Schutte BC (American journal of human genetics 2014) 3 4 56
  3. Two isoforms of Sister-Of-Mammalian Grainyhead have opposing functions in endothelial cells and in vivo. (PMID: 23685552) Haendeler J … Altschmied J (Arteriosclerosis, thrombosis, and vascular biology 2013) 2 3 56
  4. The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity. (PMID: 21081122) Boglev Y … Jane SM (Developmental biology 2011) 3 4 56
  5. Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration. (PMID: 18814840) Guardiola-Serrano F … Altschmied J (Biochemical and biophysical research communications 2008) 3 23 56

Products for GRHL3 Gene

Sources for GRHL3 Gene