HR Gene - Structure, Function, Mutations, and Associated Diseases

The HR gene encodes a protein that functions as a lysine-specific demethylase and a nuclear receptor corepressor. It is essential for normal hair growth and cycling. Loss-of-function mutations in HR cause congenital atrichia with papular lesions (APL) and alopecia universalis congenita (ALUNC). The protein represses transcription of hair-specific genes by interacting with histone deacetylases and thyroid hormone receptor.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Thyroid hormone signaling pathway (Reactome: R-HSA-376172)

• Transcriptional regulation by the AP-2 family (Reactome: R-HSA-8866907)

• Chromatin modifying enzymes (Reactome: R-HSA-3247509)

The HR protein (UniProt O43593) is a 1189-amino acid nuclear protein containing a JmjC domain that confers lysine demethylase activity specific for histone H3 lysine 4 (H3K4me2/me3). It also contains a C-terminal region that mediates interaction with nuclear receptors and corepressors such as NCOR1 and HDACs. HR represses transcription of genes involved in hair follicle differentiation and cycling. Loss of HR function leads to inability to transition from catagen to telogen, causing permanent hair loss.