NOD2

Chr 16MultiAD

nucleotide binding oligomerization domain containing 2

Also known as: ACUG, BLAU, BLAUS, CARD15, CD, CLR16.3, IBD1, NLRC2

NCBI Gene: 64127 ENSG00000167207 UniProt: Q9HC29 OMIM: 605956

NOD2 encodes a pattern recognition receptor that detects bacterial peptidoglycan fragments (particularly muramyl dipeptide) and activates NF-kappaB signaling to regulate gastrointestinal immunity and maintain the balance between intestinal microbiota and host immune responses. Mutations cause Blau syndrome (autosomal dominant granulomatous inflammatory condition) and contribute to Crohn disease susceptibility (multifactorial inheritance). The gene is extremely tolerant to loss-of-function variants (LOEUF 1.36), suggesting that different mutation types may underlie these distinct clinical presentations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Inflammatory bowel disease 1, Crohn disease}MIM #266600

Multi

{Yao syndrome}MIM #617321

Multi

Blau syndromeMIM #186580

Clinical highlights

Gene-disease validity (ClinGen)

Blau syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

309

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

GOF

Mechanism· G2P