NLRC3

NLR family CARD domain containing 3, the group of NLR family

Basic information

Region (hg38): 16:3539033-3577403

Links

ENSG00000167984 ∙ NCBI:197358 ∙ OMIM:615648 ∙ HGNC:29889 ∙ Uniprot:Q7RTR2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLRC3 gene.

• not_specified (159 variants)
• not_provided (45 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000178844.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	3	1	11
missense			158	17	3	178
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2			2
Total	0	0	167	20	4

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLRC3	polymorphic_pseudogene	protein_coding	ENST00000448023	19	38369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.23e-25	0.000749	124411	2	238	124651	0.000963

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.494	705	669	1.05	0.0000425	7053
Missense in Polyphen		137	130.91	1.0465		1573
Synonymous	-1.24	339	311	1.09	0.0000221	2351
Loss of Function	0.288	39	41.0	0.951	0.00000190	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00379	0.00378
Ashkenazi Jewish	0.0000997	0.0000994
East Asian	0.000473	0.000445
Finnish	0.000432	0.000418
European (Non-Finnish)	0.000567	0.000549
Middle Eastern	0.000473	0.000445
South Asian	0.00121	0.00114
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of the innate immune response (PubMed:15705585, PubMed:22863753, PubMed:25277106). Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (By similarity) (PubMed:22863753). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'- linked ubiquitination and leaving unchanged the degradative 'Lys- 48'-linked ubiquitination (PubMed:22863753). Inhibits the PI3K- AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells (By similarity). May also affect NOD1- or NOD2-mediated NF-kappa-B activation (PubMed:25277106). Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation (PubMed:25277106). {ECO:0000250|UniProtKB:Q5DU56, ECO:0000269|PubMed:15705585, ECO:0000269|PubMed:22863753, ECO:0000269|PubMed:25277106}.
• Pathway: STING mediated induction of host immune responses;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;Cytosolic sensors of pathogen-associated DNA (Consensus)

Recessive Scores

• pRec: 0.112

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.251

Essentials

• essential_gene_CRISPR2: N

Mouse Genome Informatics

• Gene name: Nlrc3
• Phenotype: hematopoietic system phenotype; immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: I-kappaB kinase/NF-kappaB signaling;negative regulation of phosphatidylinositol 3-kinase signaling;negative regulation of NF-kappaB transcription factor activity;negative regulation of interferon-alpha production;negative regulation of interferon-beta production;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;intracellular signal transduction;T cell activation;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of innate immune response;negative regulation of fibroblast proliferation;negative regulation of epithelial cell proliferation;negative regulation of inflammatory response;negative regulation of cytokine production involved in inflammatory response;negative regulation of NLRP3 inflammasome complex assembly;negative regulation of NIK/NF-kappaB signaling
• Cellular component: cytoplasm;microtubule organizing center;cytosol;perinuclear region of cytoplasm
• Molecular function: molecular_function;protein binding;ATP binding;phosphatidylinositol 3-kinase regulatory subunit binding