SMCR8

Chr 17

SMCR8-C9orf72 complex subunit

Also known as: DENND8A

NCBI Gene: 140775 ENSG00000176994 UniProt: Q8TEV9 OMIM: 617074

SMCR8 encodes a component of the C9orf72-SMCR8 complex that functions as a guanine nucleotide exchange factor and regulates autophagy by promoting RAB GTPase activation and inhibiting ULK1 kinase activity. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.654), suggesting some tolerance for such mutations.

OMIM ResearchSummary from RefSeq, UniProt

Enables GTPase activator activity; protein kinase binding activity; and protein kinase inhibitor activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in negative regulation of gene expression; regulation of TOR signaling; and regulation of macroautophagy. Located in Atg1/ULK1 kinase complex; chromatin; and nucleoplasm. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.65

LOEUF

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Mechanism