SIX3

Chr 2AD

SIX homeobox 3

Also known as: HPE2

NCBI Gene: 6496 ENSG00000138083 UniProt: O95343 OMIM: 603714

This gene encodes a homeobox transcription factor that regulates eye and forebrain development during embryogenesis. Loss-of-function mutations cause holoprosencephaly type 2 and schizencephaly through autosomal dominant inheritance. The protein is intolerant to loss-of-function variants, consistent with its critical role in early brain patterning.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Holoprosencephaly 2MIM #157170

SchizencephalyMIM #269160

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — SIX3