NOD1

protein-coding

nucleotide binding oligomerization domain containing 1, the group of Caspase recruitment domain containing|NLR family

Gene summary

This gene encodes a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins. The encoded protein plays a role in innate immunity by acting as a pattern-recognition receptor (PRR) that binds bacterial peptidoglycans and initiates inflammation. This protein has also been implicated in the immune response to viral and parasitic infection. Major structural features of this protein include an N-terminal caspase recruitment domain (CARD), a centrally located nucleotide-binding domain (NBD), and 10 tandem leucine-rich repeats (LRRs) in its C terminus. The CARD is involved in apoptotic signaling, LRRs participate in protein-protein interactions, and mutations in the NBD may affect the process of oligomerization and subsequent function of the LRR domain. Mutations in this gene are associated with asthma, inflammatory bowel disease, Behcet disease and sarcoidosis in human patients. [provided by RefSeq, Aug 2017]

Previous symbols:

CARD4

MANE transcript

NM_006092.4

Inheritance

—

ClinVar variants

U:160B:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr7:30,424,527-30,478,784

External References & Databases

Ensembl (ENSG00000106100)

Transcript & Mutation Effects

hg38 • Region Span ~54.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 151

not providedTotal: 36

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006092.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	2 clinvar	2 clinvar	13
missense			147 clinvar	14 clinvar	2 clinvar	163
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	160	16	4	180

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 101 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006092.4	RefSeq	NP_006083.1	11	MANE Select
ENST00000222823.9	Ensembl	ENSP00000222823.4	11	MANE Select
NM_001354849.2	RefSeq	NP_001341778.1	10	Standard
ENST00000411552.5	Ensembl	ENSP00000396046.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nod1	Danio rerio	Structure: whole organism Quality: viability abnormal

Gene / Model

Organism

Observed Phenotype

nod1

Danio rerio

Structure: whole organism

Quality: viability

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pertussis - Homo sapiens (human)
Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
Shigellosis - Homo sapiens (human)
Nucleotide-binding Oligomerization Domain (NOD) pathway

Biological Process

activation of MAPK activity
positive regulation of dendritic cell antigen processing and presentation
apoptotic process
activation of cysteine-type endopeptidase activity involved in apoptotic process
defense response

Molecular Function

protein binding
ATP binding
cysteine-type endopeptidase activator activity involved in apoptotic process
identical protein binding
protein homodimerization activity

Cellular Component

cytoplasm
cytosol
basolateral plasma membrane
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222823
Coding exons: 11
Length: 54258
Individuals with no LoFs: 125399
Homozygous LoFs: 2
Heterozygous LoFs: 347
Defined: 125748
p: 0.00139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.119	566	574	0.986	0.0000371	6246
Missense (PolyPhen)		209	216.62	0.96484		2404
Synonymous	-0.196	262	258	1.02	0.0000171	1942
Loss of Function	0.772	30	34.9	0.859	0.00000158	402

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00078	0.00078	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00027	0.00027	rare
Finnish	0.0090	0.0090	notable
European (Non-Finnish)	0.00086	0.00083	rare
South Asian	0.00049	0.00049	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Enhances caspase-9-mediated apoptosis. Induces NF-kappa- B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shigella effector proteins IpgB2 and OspB. Recruits NLRP10 to the cell membrane following bacterial infection. {ECO:0000269|PubMed:11058605, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:22672233}.;

Recessive Scores

pRec: 0.261

Intolerance Scores

LoFtool: 0.857
RVIS EVS: -0.46
RVIS percentile EVS: 23.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.773

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High