This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009] See more...

Aliases for GRHL1 Gene

Aliases for GRHL1 Gene

  • Grainyhead Like Transcription Factor 1 2 3 5
  • Transcription Factor CP2-Like 2 2 3 4
  • Grainyhead-Like Protein 1 Homolog 3 4
  • Transcription Factor LBP-32 3 4
  • Mammalian Grainyhead 3 4
  • TFCP2L2 3 4
  • LBP32 3 4
  • NH32 3 4
  • MGR 3 4
  • Grainyhead-Like 1 (Drosophila) 2
  • Grainyhead-Like 1 3
  • LBP Protein 32 3

External Ids for GRHL1 Gene

Previous HGNC Symbols for GRHL1 Gene

  • TFCP2L2

Previous GeneCards Identifiers for GRHL1 Gene

  • GC02P010043
  • GC02P010085

Summaries for GRHL1 Gene

Entrez Gene Summary for GRHL1 Gene

  • This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009]

GeneCards Summary for GRHL1 Gene

GRHL1 (Grainyhead Like Transcription Factor 1) is a Protein Coding gene. Diseases associated with GRHL1 include Deafness, Autosomal Dominant 28 and Jaw Cancer. Among its related pathways are Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Metabolism. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is GRHL2.

UniProtKB/Swiss-Prot Summary for GRHL1 Gene

  • Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity).
  • [Isoform 1]: Functions as transcription activator.
  • [Isoform 2]: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed.

Additional gene information for GRHL1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GRHL1 Gene

Genomics for GRHL1 Gene

GeneHancer (GH) Regulatory Elements for GRHL1 Gene

Promoters and enhancers for GRHL1 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
GH02J009950 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 516.2 +0.3 274 3.1 HNRNPK ZNF217 NRF1 POLR2G PHF8 ZBTB11 ZBTB26 CTBP1 SKI REST GRHL1 ENSG00000287305 LOC105373422 lnc-CYS1-6
GH02J009970 Enhancer 1.2 Ensembl ENCODE dbSUPER 27.3 +22.1 22138 7.2 ZSCAN5C JUND FOS ZNF639 ZNF10 ATF2 ZEB1 RBM25 NFIC SP2 HE856245 GRHL1 ENSG00000188525 CYS1 ENSG00000233502 lnc-CYS1-6
GH02J009966 Enhancer 1.2 Ensembl ENCODE dbSUPER 16.1 +16.2 16166 2.3 NRF1 EP300 TOE1 MYC CTBP1 BCL11A RELA ZNF384 NR3C1 POLR2A GRHL1 ENSG00000233502 HE856245 lnc-CYS1-6
GH02J009914 Enhancer 1.1 Ensembl ENCODE 11.7 -37.0 -36961 1.4 CTCF TCF12 JUND FOS ZBTB11 AFF1 TARDBP REST MYC RAD21 TAF1B GRHL1 ENSG00000269973 lnc-CYS1-8 piR-40110-357
GH02J010040 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 4.9 +91.6 91642 5.3 SIN3A NRF1 USF1 SP1 PHF8 JUND TEAD4 ZFX POLR2A ZBTB11 KLF11 LOC101929882 ENSG00000260077 ENSG00000233502 GRHL1 lnc-KLF11-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GRHL1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GRHL1

Top Transcription factor binding sites by QIAGEN in the GRHL1 gene promoter:
  • AREB6
  • CUTL1
  • Elk-1
  • FOXI1
  • HFH-3
  • Hlf
  • POU3F2

Genomic Locations for GRHL1 Gene

Genomic Locations for GRHL1 Gene
chr2:9,951,663-10,002,284
(GRCh38/hg38)
Size:
50,622 bases
Orientation:
Plus strand
chr2:10,085,341-10,142,412
(GRCh37/hg19)
Size:
57,072 bases
Orientation:
Plus strand

Genomic View for GRHL1 Gene

Genes around GRHL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRHL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GRHL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRHL1 Gene

Proteins for GRHL1 Gene

  • Protein details for GRHL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NZI5-GRHL1_HUMAN
    Recommended name:
    Grainyhead-like protein 1 homolog
    Protein Accession:
    Q9NZI5
    Secondary Accessions:
    • A6NLA4
    • B2R7E4
    • B5MEC2
    • Q53T93
    • Q6NWN7
    • Q6NWN8
    • Q6NWN9
    • Q8NI33

    Protein attributes for GRHL1 Gene

    Size:
    618 amino acids
    Molecular mass:
    70113 Da
    Quaternary structure:
    • Binds DNA as homodimer (PubMed:29309642). Homodimer, also forms heterodimers with GRHL2 or GRHL3 (PubMed:12175488, PubMed:12549979, PubMed:29309642).
    Miscellaneous:
    • GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal 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.

    Three dimensional structures from OCA and Proteopedia for GRHL1 Gene

    Alternative splice isoforms for GRHL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRHL1 Gene

Post-translational modifications for GRHL1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for GRHL1 Gene

Domains & Families for GRHL1 Gene

Gene Families for GRHL1 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for GRHL1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GRHL1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51493, highly similar to Grainyhead-like protein 1 (B7Z1S6_HUMAN)
  • Transcription factor LBP-32 (GRHL1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NZI5

UniProtKB/Swiss-Prot:

GRHL1_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 GRHL1: view

Function for GRHL1 Gene

Molecular function for GRHL1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity).
UniProtKB/Swiss-Prot Function:
[Isoform 1]: Functions as transcription activator.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed.

Phenotypes From GWAS Catalog for GRHL1 Gene

Gene Ontology (GO) - Molecular Function for GRHL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 12175488
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IMP 29309642
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IBA 21873635
genes like me logo Genes that share ontologies with GRHL1: view
genes like me logo Genes that share phenotypes with GRHL1: view

Animal Models for GRHL1 Gene

MGI Knock Outs for GRHL1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GRHL1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GRHL1 Gene

Localization for GRHL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRHL1 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 GRHL1 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 2
golgi apparatus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GRHL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IDA,IBA 18288204
GO:0005654 nucleoplasm TAS --
GO:0005794 Golgi apparatus IDA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with GRHL1: view

Pathways & Interactions for GRHL1 Gene

genes like me logo Genes that share pathways with GRHL1: view

Gene Ontology (GO) - Biological Process for GRHL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002934 desmosome organization IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007275 multicellular organism development IEA --
GO:0008544 epidermis development ISS --
GO:0019216 regulation of lipid metabolic process TAS --
genes like me logo Genes that share ontologies with GRHL1: view

No data available for SIGNOR curated interactions for GRHL1 Gene

Drugs & Compounds for GRHL1 Gene

No Compound Related Data Available

Transcripts for GRHL1 Gene

mRNA/cDNA for GRHL1 Gene

1 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
8 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 GRHL1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GRHL1 Gene

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

ExUns: 17c · 17d
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for GRHL1 Gene

GeneLoc Exon Structure for
GRHL1

Expression for GRHL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GRHL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GRHL1 Gene

This gene is overexpressed in Esophagus - Mucosa (x12.4), Skin - Not Sun Exposed (Suprapubic) (x7.6), Skin - Sun Exposed (Lower leg) (x7.0), Vagina (x6.0), and Minor Salivary Gland (x4.6).

Protein differential expression in normal tissues from HIPED for GRHL1 Gene

This gene is overexpressed in Plasma (58.9) and Placenta (9.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GRHL1 Gene



Protein tissue co-expression partners for GRHL1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GRHL1

SOURCE GeneReport for Unigene cluster for GRHL1 Gene:

Hs.418493

mRNA Expression by UniProt/SwissProt for GRHL1 Gene:

Q9NZI5-GRHL1_HUMAN
Tissue specificity: Isoform 1 is highly expressed in brain, pancreas, tonsil, placenta and kidney. Isoform 2 is highly expressed in brain and liver. Expressed at very low levels in non-steroidogenic cells.

Evidence on tissue expression from TISSUES for GRHL1 Gene

  • Nervous system(4)
  • Skin(2.4)
genes like me logo Genes that share expression patterns with GRHL1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for GRHL1 Gene

Orthologs for GRHL1 Gene

This gene was present in the common ancestor of animals.

Orthologs for GRHL1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRHL1 31 30
  • 99.46 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRHL1 31
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GRHL1 31
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GRHL1 31 30
  • 91.64 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grhl1 30
  • 88.46 (n)
cow
(Bos Taurus)
Mammalia GRHL1 31 30
  • 88.33 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Grhl1 17 31 30
  • 88.08 (n)
chicken
(Gallus gallus)
Aves GRHL1 31 30
  • 80.29 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRHL1 31
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grhl1 30
  • 75.11 (n)
Str.17745 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.25460 30
zebrafish
(Danio rerio)
Actinopterygii grhl1 31 30
  • 69.57 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta grh 31
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grh-1 31
  • 31 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 41 (a)
OneToMany
Species where no ortholog for GRHL1 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 GRHL1 Gene

ENSEMBL:
Gene Tree for GRHL1 (if available)
TreeFam:
Gene Tree for GRHL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GRHL1: view image

Paralogs for GRHL1 Gene

Paralogs for GRHL1 Gene

(3) SIMAP similar genes for GRHL1 Gene using alignment to 5 proteins:

  • GRHL1_HUMAN
  • B7Z1S6_HUMAN
  • C9JYY8_HUMAN
  • F8WFB0_HUMAN
  • J3KPZ1_HUMAN
genes like me logo Genes that share paralogs with GRHL1: view

Variants for GRHL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GRHL1 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
785957 Benign: not provided 9,955,068(+) C/G SYNONYMOUS_VARIANT
rs16867256 - p.Asn191Ser
rs2303920 - p.Val397Ile

Additional dbSNP identifiers (rs#s) for GRHL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for GRHL1 Gene

Variant ID Type Subtype PubMed ID
esv1497328 CNV insertion 17803354
nsv1071972 CNV deletion 25765185
nsv1126540 CNV deletion 24896259
nsv1138748 CNV deletion 24896259
nsv213438 CNV insertion 16902084
nsv828297 CNV loss 20364138

Variation tolerance for GRHL1 Gene

Residual Variation Intolerance Score: 15.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.11; 84.55% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GRHL1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRHL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRHL1 Gene

Disorders for GRHL1 Gene

MalaCards: The human disease database

(7) MalaCards diseases for GRHL1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
deafness, autosomal dominant 28
  • dfna28
jaw cancer
  • jaw neoplasm
maxillary cancer
  • maxillary neoplasm
orofacial cleft 15
  • ofc15
van der woude syndrome 1
  • vws1
- elite association - COSMIC cancer census association via MalaCards
Search GRHL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GRHL1

genes like me logo Genes that share disorders with GRHL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GRHL1 Gene

Publications for GRHL1 Gene

  1. A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead. (PMID: 12175488) Wilanowski T … Jane SM (Mechanisms of development 2002) 2 3 4 54
  2. Cloning of factors related to HIV-inducible LBP proteins that regulate steroidogenic factor-1-independent human placental transcription of the cholesterol side-chain cleavage enzyme, P450scc. (PMID: 10644752) Huang N … Miller WL (The Journal of biological chemistry 2000) 2 3 4 54
  3. Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family. (PMID: 29309642) Ming Q … Heinemann U (Nucleic acids research 2018) 3 4 54
  4. Perturbed desmosomal cadherin expression in grainy head-like 1-null mice. (PMID: 18288204) Wilanowski T … Jane SM (The EMBO journal 2008) 3 4 54
  5. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4 54

Products for GRHL1 Gene

Sources for GRHL1 Gene