GRHL2

Chr 8ADAR

grainyhead like transcription factor 2

Also known as: BOM, DFNA28, ECTDS, PPCD4, TFCP2L3

NCBI Gene: 79977 ENSG00000083307 UniProt: Q6ISB3 OMIM: 608576

This gene encodes a transcription factor that binds to specific DNA sequences to regulate epithelial development, primary neurulation, and expression of tight junction proteins including claudins. Mutations cause autosomal dominant non-syndromic sensorineural deafness (DFNA28), posterior polymorphous corneal dystrophy type 4, and autosomal recessive ectodermal dysplasia with short stature. The pathogenic mechanism involves loss of function, as the protein is highly intolerant to loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Corneal dystrophy, posterior polymorphous, 4MIM #618031

Deafness, autosomal dominant 28MIM #608641

Ectodermal dysplasia/short stature syndromeMIM #616029

Clinical highlights

Gene-disease validity (ClinGen)

nonsyndromic genetic hearing loss · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.27

LOEUF· LoF intol.

LOF

Mechanism· predicted

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GeneReview available — GRHL2