SIX1 (Homeobox protein SIX1) variants and mutations

SIX1 (also known as Homeobox protein SIX1) is a human protein-coding gene encoding a homeobox protein. It regulates developmental programs in the ear, kidney, craniofacial structures, and skeletal muscle together with EYA-family cofactors. Heterozygous pathogenic variants cause branchio-otic or branchio-oto-renal syndrome with hearing loss and variable branchial or renal abnormalities. This analysis covers 721 SIX1 variants and mutations. Of these, 94% have computational variant effect predictions. Disease context includes Branchio-otic syndrome, autosomal dominant nonsyndromic hearing loss, and branchiootic syndrome. Example SIX1 variants include M1I, M1L, and S2*.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SIX1 variants

Examples include M1I, M1L, S2*, S2L, S2W, M3I, L4P, P5A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.