SIRT1

sirtuin 1

3 disorders 3 no genetic record 10q21.3 gene with protein product

HGNC:14929 Monarch NCBI Gene 23411 ENSG00000096717 UniProt Q96EB6 OMIM 604479

Aliases: SIR2L1.

Normal function · from ai-gene-review (Q96EB6, commit 79fe13b38970) · AI-generated, not KB evidence

NAD-dependent protein deacetylase that catalyzes removal of acetyl groups from lysine residues of histones (preferentially H4K16, H3K9, H3K14) and numerous non-histone proteins including p53, NF-kB RelA/p65, FOXO factors, HIF1alpha/HIF2alpha, and PGC-1alpha. The core enzymatic function couples NAD+ cleavage to lysine deacetylation, producing nicotinamide and 2-O-acetyl-ADP-ribose. Functions in transcriptional regulation through heterochromatin formation and as a transcription corepressor. Has broad pleiotropic effects on metabolism, stress responses, DNA damage response, and aging through deacetylation of diverse substrates.

Primary enzymatic function of SIRT1. Catalyzes NAD-dependent removal of acetyl groups from lysine residues of histones and numerous non-histone proteins. The reaction couples NAD+ cleavage to lysine deacetylation, producing nicotinamide and 2-O-acetyl-ADP-ribose.

molecular function: NAD-dependent protein lysine deacetylase activity

Preferential histone substrate. Deacetylation of H4K16 is a major activity of SIRT1 critical for heterochromatin formation and transcriptional silencing.

molecular function: histone H4K16 deacetylase activity, NAD-dependent

Major histone substrate. H3K9 deacetylation is linked to heterochromatin formation at rDNA and telomeric regions.

molecular function: histone H3K9 deacetylase activity, NAD-dependent

SIRT1 functions as a transcriptional corepressor through histone deacetylation and deacetylation of transcription factors.

molecular function: transcription corepressor activity

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
Alzheimer Disease	no genetic record	mechanism: PARP1-Mediated Parthanatos
Asthma	no genetic record	mechanism: SIRT1-Mediated NAD+ Signaling and Protective Deacetylation
Chronic_Obstructive_Pulmonary_Disease	no genetic record	mechanism: SIRT1-Mediated NAD+ Signaling and Protective Deacetylation

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
monogenic diabetes MONDO:0015967	AD	Limited 2025-04-18	Diabetes mellitus not named

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