PACS2

Chr 14

phosphofurin acidic cluster sorting protein 2

Also known as: DEE66, EIEE66, PACS-2, PACS1L

NCBI Gene: 23241 ENSG00000179364 UniProt: Q86VP3

PACS2 encodes a protein that maintains endoplasmic reticulum calcium homeostasis and tethers mitochondria to the endoplasmic reticulum. Loss-of-function mutations cause developmental and epileptic encephalopathy 66, inherited in an autosomal dominant pattern. The pathogenic mechanism involves disrupted cellular calcium regulation and impaired mitochondrial-ER communication.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Predicted to enable transmembrane transporter binding activity. Involved in endoplasmic reticulum calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and protein localization to plasma membrane. Acts upstream of or within protein localization to phagophore assembly site. Located in endoplasmic reticulum and mitochondrion. Implicated in developmental and epileptic encephalopathy 66. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 66

Clinical highlights

Gene-disease validity (ClinGen)

genetic developmental and epileptic encephalopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429