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GRHL2

Chr 8q22.3

grainyhead like transcription factor 2

Aliases:
FLJ13782, BOM
MANE:
ENST00000646743.1
OMIM: 608576 ↗NCBI: 79977 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Corneal dystrophy

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • DDG2P

    BIALLELIC, autosomal or pseudoautosomal

  • Ectodermal dysplasia

    BIALLELIC, autosomal or pseudoautosomal

  • Monogenic hearing loss

    BOTH monoallelic and biallelic, autosomal or pseudoautosomal

  • Fetal anomalies

    BIALLELIC, autosomal or pseudoautosomal

  • Congenital fibrosis of the extraocular muscles

    Unknown

Disease associations (Open Targets)

  • nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome

    0.73

  • autosomal dominant nonsyndromic hearing loss 28

    0.64

  • posterior polymorphous corneal dystrophy

    0.62

  • autosomal dominant nonsyndromic hearing loss

    0.46

  • breast carcinoma

    0.46

  • nonsyndromic genetic hearing loss

    0.37

  • neurodegenerative disease

    0.37

  • Non-syndromic genetic deafness

    0.37

  • corneal dystrophy

    0.35

  • stroke disorder

    0.32

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Grainyhead-like protein 2 homolog

Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456, PubMed:29309642). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293)

Diseases associated with GRHL2

Curated MONDO disease pages that list GRHL2 among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.