ATF6

activating transcription factor 6

2 disorders 2 causative 1q23.3 gene with protein product

HGNC:791 Monarch NCBI Gene 22926 ENSG00000118217 UniProt P18850 OMIM 605537

Aliases: ATF6A, ATP6alpha.

Normal function · from ai-gene-review (P18850, commit 79fe13b38970) · AI-generated, not KB evidence

ATF6 is a basic leucine zipper transcription factor synthesized as a type II endoplasmic-reticulum membrane protein. During ER stress, the precursor moves to the Golgi, where MBTPS1 and MBTPS2 cleave it to release the N-terminal transcription factor. The released product enters the nucleus, binds ER-stress response regulatory DNA and activates genes encoding chaperones, folding machinery and components of ER-associated degradation. ATF6 also induces XBP1 transcription, coordinating branches of the unfolded protein response. Biallelic pathogenic ATF6 variants cause achromatopsia with impaired cone function and foveal development.

The released N-terminal ATF6 transcription factor binds ER-stress response regulatory DNA and activates RNA polymerase II transcription of adaptive unfolded-protein-response genes. Chaperone and quality-control gene induction increases ER folding capacity, while XBP1 transcription coordinates the response with the IRE1 branch. The active DNA-binding product acts in the nucleus after stress-dependent ER-to-Golgi trafficking and proteolytic release of the membrane precursor.

molecular function: DNA-binding transcription activator activity, RNA polymerase II-specific · directly involved in: ATF6-mediated unfolded protein response · locations: nucleus

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Achromatopsia	causative germline	mechanism: ATF6 Signaling Dysregulation subtype: ACHM7 scoped to subtype: ACHM7
ATF6-Related Retinopathy	causative germline	mechanism: ATF6 Unfolded Protein Response Impairment

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
ATF6-related retinopathy MONDO:0100447	AR	Definitive 2021-10-07	ATF6-Related Retinopathy causative

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.