ATF6

Chr 1AR

activating transcription factor 6

Also known as: ACHM7, ATF6A, ATP6alpha

NCBI Gene: 22926 ENSG00000118217 UniProt: P18850 OMIM: 605537

ATF6 encodes a transmembrane transcription factor that serves as an endoplasmic reticulum stress sensor and activates the unfolded protein response by translocating to the nucleus to upregulate ER chaperone genes. Biallelic mutations cause achromatopsia 7, an autosomal recessive condition affecting color vision due to cone photoreceptor dysfunction. The gene is moderately constrained against loss-of-function variants (LOEUF 0.698), and comprehensive clinical information is available in GeneReviews.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Achromatopsia 7MIM #616517

Clinical highlights

Gene-disease validity (ClinGen)

ATF6-related retinopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

513

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

LOF

Mechanism· G2P

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