NLRC5

Summary

NLRC5 (NLR family CARD domain containing 5, HGNC:29933) is a protein-coding gene on chromosome 16q13, encoding Protein NLRC5 (Q86WI3). Probable regulator of the NF-kappa-B and type I interferon signaling pathways.

This gene encodes a member of the caspase recruitment domain-containing NLR family. This gene plays a role in cytokine response and antiviral immunity through its inhibition of NF-kappa-B activation and negative regulation of type I interferon signaling pathways.

Source: NCBI Gene 84166 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 368 total
• MANE Select transcript: NM_001384950

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29933
Approved symbol	NLRC5
Name	NLR family CARD domain containing 5
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	NOD27, CLR16.1, FLJ21709
Ensembl gene	ENSG00000140853
Ensembl biotype	protein_coding
OMIM	613537
Entrez	84166

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 12 protein_coding, 12 retained_intron, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000262510, ENST00000399221, ENST00000534927, ENST00000534931, ENST00000535284, ENST00000535658, ENST00000536231, ENST00000537056, ENST00000538059, ENST00000538110, ENST00000538273, ENST00000538453, ENST00000538778, ENST00000538805, ENST00000538930, ENST00000539144, ENST00000539881, ENST00000540182, ENST00000541020, ENST00000543030, ENST00000543049, ENST00000543103, ENST00000543141, ENST00000543402, ENST00000544189, ENST00000544641, ENST00000545081, ENST00000545349, ENST00000688547, ENST00000877315, ENST00000877316, ENST00000959497

RefSeq mRNA: 26 — MANE Select: NM_001384950 NM_001330552, NM_001384950, NM_001384951, NM_001384952, NM_001384953, NM_001384954, NM_001384955, NM_001384956, NM_001384957, NM_001384958, NM_001384959, NM_001384960, NM_001384961, NM_001384962, NM_001384963, NM_001384964, NM_001384965, NM_001384966, NM_001384967, NM_001384968, NM_001384969, NM_001384970, NM_001384971, NM_001384972, NM_001384973, NM_032206

CCDS: CCDS10773, CCDS81985

Canonical transcript exons

ENST00000688547 — 49 exons

Exon	Start	End
ENSE00001108788	57055433	57055519
ENSE00001482473	57017074	57017188
ENSE00001636366	57028072	57028155
ENSE00001639321	57022256	57022315
ENSE00001654511	57023785	57023853
ENSE00001783106	57025368	57027018
ENSE00002698154	57020701	57021007
ENSE00003461782	57061448	57061531
ENSE00003462294	57043515	57043604
ENSE00003464142	57039781	57039849
ENSE00003464349	57076819	57076902
ENSE00003475553	57051538	57051621
ENSE00003484614	57045448	57045492
ENSE00003484784	57055032	57055094
ENSE00003487526	57059467	57059532
ENSE00003496177	57077943	57078020
ENSE00003500583	57077719	57077802
ENSE00003502566	57067736	57067828
ENSE00003507029	57065212	57065298
ENSE00003515817	57058972	57059061
ENSE00003517984	57036100	57036183
ENSE00003518326	57034168	57034251
ENSE00003519440	57033604	57033669
ENSE00003522350	57079546	57079629
ENSE00003531523	57028302	57028385
ENSE00003531798	57047545	57047628
ENSE00003534576	57061618	57061701
ENSE00003544620	57041982	57042065
ENSE00003548372	57074600	57074683
ENSE00003556539	57040650	57040718
ENSE00003569088	57067387	57067470
ENSE00003592389	57079221	57079292
ENSE00003608639	57029995	57030084
ENSE00003611449	57054751	57054840
ENSE00003621846	57058065	57058148
ENSE00003629976	57041485	57041574
ENSE00003647083	57066534	57066614
ENSE00003657084	57069836	57069919
ENSE00003658903	57029773	57029856
ENSE00003659580	57046552	57046641
ENSE00003660967	57081527	57081610
ENSE00003663538	57070535	57070618
ENSE00003669668	57077296	57077379
ENSE00003671379	57037195	57037284
ENSE00003676578	57079050	57079133
ENSE00003678260	57031404	57031463
ENSE00003682566	57081098	57081181
ENSE00003924466	57082417	57083520
ENSE00003937537	56989557	56989617

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0733 / max 409.0325, expressed in 1520 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154301	15.0352	1436
154300	1.7140	920
154299	1.2802	667
154304	0.0439	24

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.01	gold quality
spleen	UBERON:0002106	97.71	gold quality
bone marrow cell	CL:0002092	97.67	gold quality
blood	UBERON:0000178	97.14	gold quality
vermiform appendix	UBERON:0001154	96.84	gold quality
lymph node	UBERON:0000029	96.60	gold quality
leukocyte	CL:0000738	95.70	gold quality
monocyte	CL:0000576	95.67	gold quality
ileal mucosa	UBERON:0000331	94.62	gold quality
trabecular bone tissue	UBERON:0002483	94.21	gold quality
epithelium of nasopharynx	UBERON:0001951	93.91	gold quality
pancreatic ductal cell	CL:0002079	93.79	silver quality
bone marrow	UBERON:0002371	93.72	gold quality
caecum	UBERON:0001153	92.86	gold quality
sural nerve	UBERON:0015488	92.85	gold quality
upper lobe of left lung	UBERON:0008952	92.78	gold quality
skin of abdomen	UBERON:0001416	92.49	gold quality
bone element	UBERON:0001474	92.49	gold quality
colonic epithelium	UBERON:0000397	92.45	gold quality
apex of heart	UBERON:0002098	92.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.42	gold quality
tonsil	UBERON:0002372	91.85	gold quality
upper lobe of lung	UBERON:0008948	91.61	gold quality
rectum	UBERON:0001052	91.49	gold quality
skin of leg	UBERON:0001511	91.37	gold quality
mucosa of transverse colon	UBERON:0004991	91.18	gold quality
zone of skin	UBERON:0000014	90.79	gold quality
pituitary gland	UBERON:0000007	90.78	gold quality
adenohypophysis	UBERON:0002196	90.59	gold quality
small intestine	UBERON:0002108	90.54	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	36.48
E-MTAB-9067	yes	12.83
E-ANND-3	yes	9.52
E-MTAB-7381	no	716.00
E-GEOD-100618	no	74.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting NLRC5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-592	96.59	67.59	817

Literature-anchored findings (GeneRIF, showing 40)

• NLRC5 may represent a molecular switch of interferon (IFN)-gamma activation sequence and IFN-specific response element signaling pathways contributing to antiviral defense mechanisms. (PMID:20061403)
• Study identifies NLRC5 as a negative regulator that blocks two central components of the NF-kappaB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity. (PMID:20434986)
• function for NLRC5 in anti-viral innate immune responses (PMID:20538593)
• NLRC5 is identified and characterized as a key regulator of proinflammatory pathways in immune cells. (PMID:20610642)
• suggest that NLRC5 is a transcriptional regulator, orchestrating the concerted expression of critical components in the MHC class I pathway. (PMID:20639463)
• NLRC5 is a critical component of inflammasome-dependent interleukin (IL)-1beta secretion in response to a repertoire of stimuli that also activate NLRP3. (PMID:21191067)
• NLRC5 was proposed to function as a positive and as a negative regulator of IFN, NF-kappaB, AP-1 signaling and antiviral immunity. (Review) (PMID:22024701)
• NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. (PMID:22310711)
• NLRC5 acts as a key transcriptional regulator of MHC I in lymphocytes and support an essential role for NLRs in directing not only innate but also adaptive immune responses. (PMID:22412192)
• Expression of NLRC5 positively correlates with histocompatibility class I expression in human tissues. (PMID:22490867)
• NLRC5 can cooperate with X1 box-binding transcription factor RFX and X2 box-binding transcription factor ATF1 in activation of histocompatibility class I promoter region. (PMID:22490869)
• rhinovirus ion channel protein 2B triggers NLRP3 and NLRC5 inflammasome activation and IL-1beta secretion in bronchial cells (PMID:23815151)
• A model for full-length human NLRC5 was prepared and, besides the closed conformation of monomeric NLRC5, a heptameric platform was also modeled for the opened conformational NLRC5 monomers. (PMID:24044430)
• Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain. (PMID:24815518)
• This study presents a detailed functional study of the domains of NLRC5 revealing that the N-terminal domain of human NLRC5 has intrinsic transcriptional activity. (PMID:25127861)
• a novel role for NLRC5 in RIG-I-mediated antiviral host responses against influenza virus infection, distinguished from the role of NLRC5 in MHC class I gene regulation. (PMID:25404059)
• In a transformed cell line, NLRC5 plays a significant role in IL-6 and IL-1Beta secretion. (PMID:25820389)
• RSV infection of lung epithelial cells induces expression of RIG-I, NLRC5, and subsequent upregulation of HLA-A, HLA-B and HLA-C. (PMID:25972545)
• NLRC5 regulates TGFB1-induced proliferation and activation of hepatic stellate cells during hepatic fibrosis. (PMID:26592197)
• NLRC5 function is shaped by reversible ubiquitination, which modulates the NF-kappaB activation switch (PMID:26620909)
• NLRC5 not only positively correlates with the increase of beta-catenin but also coordinates the activation of downstream Wnt/beta-catenin signaling pathway, regulating cell proliferation, migration and invasion in hepatocellular carcinoma. (PMID:26975630)
• CITA/NLRC5 and CIITA are transcriptional regulators that orchestrate the concerted expression of critical components in the MHC class I and class II pathways, respectively. [review] (PMID:27087581)
• NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers. (PMID:27162338)
• These results demonstrate that NLRC5 promotes hepatocellular carcinoma progression via the AKT/VEGF-A signaling pathway (PMID:27338800)
• NLRC5 interacts with miR-34a.NLRC5 role in HPV16 persistence. (PMID:27423514)
• silencing NLRC5 reduced extracellular matrix expression in keloid fibroblasts through inhibiting the TGF-beta1/Smad signaling pathway. (PMID:27525969)
• Our study, for the first time, identified the possible involvement of a polymorphism within NLRC5 gene as a possible biomarker for periodontitis condition susceptibility among Italian individuals from genetic isolates. (PMID:28122660)
• NLRC5 performed a crucial role in the process of cardiac fibrosis (PMID:28780973)
• the methylation profile combination of HKR1, ROD1, and NLRC5 could be a promising biomarker for aging in Hainan centenarians (PMID:29394898)
• obtained 18 pair-wise interactions within and between the NLRC5 ad PD-L1 genes and 6 more when IFNGR variants were added (PMID:29408916)
• NLRC5 may act as a key mediator in renal fibroblast activation and fibrogenesis (PMID:29608899)
• knockdown of NLRC5 attenuates renal ischemia/reperfusion injury in vitro through the activation of PI3K/Akt signaling pathway. (PMID:29655162)
• frameshift mutations in DTX1 and NLRC5, two genes involved in immune regulation, were identified in a family with familial pityriasis rubra pilaris. (PMID:29704870)
• Genetic polymorphisms in NLRC5 may be used as prognostic markers of survival of colorectal cancer patients, as well as for survival in response to 5-FU treatment. (PMID:29762254)
• The expression of NLRC5 in the ectopic and eutopic endometrium of endometriosis groups was significantly higher than that in the endometrium of leiomyoma group. (PMID:30316442)
• NLRC5 could potentially be a diagnostic index and represents a prognostic factor in IgA nephritis patients. (PMID:30453994)
• High NLRC5 expression is associated with clear cell renal cell carcinoma. (PMID:30543814)
• This study evaluated the effect of Orientia tsutsugamushi on the internal immunological systems of HeLa and aortic endothelial cells. (PMID:30559222)
• present an overview on NLRC5, addressing its underlying molecular mechanisms and implications in host defense, inflammatory response, and associated cancers (PMID:30867141)
• The expression of NOD2 and NLRC5 was associated with the severity of renal lesions in anti-neutrophil cytoplasmic antibody-associated vasculitis. (PMID:31186034)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nlrc5	ENSMUSG00000074151
rattus_norvegicus	Nlrc5	ENSRNOG00000048222

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

Protein NLRC5 — Q86WI3 (reviewed: Q86WI3)

Alternative names: Caterpiller protein 16.1, Nucleotide-binding oligomerization domain protein 27, Nucleotide-binding oligomerization domain protein 4

All UniProt accessions (12): Q86WI3, F5GYP0, F5H274, H0YF88, H0YFG4, H0YFT1, H0YFT3, H0YG32, H0YGE2, H0YGM1, H0YGT6, H0YGV6

UniProt curated annotations — full annotation on UniProt →

Function. Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms.

Subunit / interactions. Interacts with CHUK and IKBKB; prevents CHUK and IKBKB phosphorylation and inhibits their kinase activity. Interacts with RIGI and IFIH1; blocks the interaction of MAVS to RIGI.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in spleen, thymus, lung, brain, tonsil, heart and prostate.

Induction. By IFNG/IFN-gamma.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the NLRP family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86WI3-1	1	yes
Q86WI3-2	2
Q86WI3-3	3
Q86WI3-4	4
Q86WI3-5	5
Q86WI3-6	6

RefSeq proteins (26): NP_001317481, NP_001371879, NP_001371880, NP_001371881, NP_001371882, NP_001371883, NP_001371884, NP_001371885, NP_001371886, NP_001371887, NP_001371888, NP_001371889, NP_001371890, NP_001371891, NP_001371892, NP_001371893, NP_001371894, NP_001371895, NP_001371896, NP_001371897, NP_001371898, NP_001371899, NP_001371900, NP_001371901, NP_001371902, NP_115582 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR006553	Leu-rich_rpt_Cys-con_subtyp	Repeat
IPR007111	NACHT_NTPase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041210	NLRC5_atypical_Card	Domain
IPR041267	NLRP_HD2	Domain

Pfam: PF05729, PF13516, PF17776, PF18461

UniProt features (52 total): repeat 26, sequence variant 9, splice variant 8, sequence conflict 5, chain 1, domain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WI3-F1	73.96	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 228–235

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-9758274	Regulation of NF-kappa B signaling

MSigDB gene sets: 252 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, RICKMAN_METASTASIS_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_UP

GO Biological Process (11): response to bacterium (GO:0009617), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), regulation of kinase activity (GO:0043549), innate immune response (GO:0045087), positive regulation of MHC class I biosynthetic process (GO:0045345), positive regulation of transcription by RNA polymerase II (GO:0045944), defense response to virus (GO:0051607), positive regulation of type II interferon-mediated signaling pathway (GO:0060335), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), immune system process (GO:0002376)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), ATP binding (GO:0005524), nucleotide binding (GO:0000166), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
TAK1-dependent IKK and NF-kappa-B activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine-mediated signaling pathway	2
type I interferon-mediated signaling pathway	2
regulation of type I interferon-mediated signaling pathway	2
cellular anatomical structure	2
response to other organism	1
kinase activity	1
regulation of phosphorylation	1
regulation of transferase activity	1
immune response	1
defense response to symbiont	1
positive regulation of macromolecule biosynthetic process	1
MHC class I biosynthetic process	1
regulation of MHC class I biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
defense response	1
response to virus	1
positive regulation of response to type II interferon	1
type II interferon-mediated signaling pathway	1
regulation of type II interferon-mediated signaling pathway	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of innate immune response	1
positive regulation of innate immune response	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1

Protein interactions and networks

STRING

1763 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRC5	RIGI	O95786	985
NLRC5	IFIH1	Q9BYX4	981
NLRC5	CHUK	O15111	966
NLRC5	NLRC4	Q9NPP4	955
NLRC5	NLRP3	Q96P20	926
NLRC5	MAVS	Q7Z434	860
NLRC5	IKBKB	O14920	851
NLRC5	NLRP6	P59044	851
NLRC5	AIM2	O14862	807
NLRC5	NLRP7	Q8WX94	799
NLRC5	NLRP1	Q9C000	791
NLRC5	CASP1	P29466	736
NLRC5	RFXAP	O00287	728
NLRC5	RFXANK	O14593	725
NLRC5	IRF1	P10914	644

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CHUK	IKBKB	psi-mi:“MI:0915”(physical association)	0.960
NLRC5	IKBKB	psi-mi:“MI:0915”(physical association)	0.520
NLRC5	KPNA1	psi-mi:“MI:0915”(physical association)	0.400
NLRC5	KPNA6	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
NLRC5	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): NLRC5 (Affinity Capture-RNA), NLRC5 (Affinity Capture-RNA), NDUFAF7 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), NLRC5 (Proximity Label-MS), NLRC5 (Affinity Capture-Western), WHSC1 (Affinity Capture-Western), NLRC5 (Affinity Capture-Western), CALCOCO2 (Affinity Capture-Western), TOLLIP (Affinity Capture-Western), SQSTM1 (Affinity Capture-Western), NLRC5 (Affinity Capture-Western), NLRC5 (Affinity Capture-RNA), MMS19 (Affinity Capture-MS), ATAD3A (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A4FV42, A4FV98, A6NDG6, D3YWP0, D3ZVU9, O15315, O35719, O70277, O75382, O94759, P21964, P57775, P81799, Q2TBS1, Q3UGX3, Q4R3I0, Q5E9V4, Q5H879, Q5RJL2, Q5SUV1, Q6DC64, Q7Z624, Q86WI3, Q86XA0, Q8BNV1, Q8C436, Q8CIW5, Q8IZ69, Q8N8L6, Q8N9F0, Q8VCX6, Q8WXB1, Q96AZ1, Q96FB5, Q96RR1, Q9BQD7, Q9BRQ3, Q9BUU2, Q9CQL0

Diamond homologs: C3VPR6, Q86WI3, A9JR78, D4A615, P59046, Q0P5G1, Q6NZL6, Q6UY01, Q96HA7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

368 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	211
Likely benign	27
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

8107 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56989594:GG:G	donor_gain	1.0000
16:56989595:GG:G	donor_gain	1.0000
16:57017189:G:GG	donor_gain	1.0000
16:57020696:TCCAG:T	acceptor_loss	1.0000
16:57020697:CCA:C	acceptor_loss	1.0000
16:57020698:CA:C	acceptor_loss	1.0000
16:57020699:A:AC	acceptor_loss	1.0000
16:57020699:A:AG	acceptor_gain	1.0000
16:57020699:AG:A	acceptor_gain	1.0000
16:57020699:AGG:A	acceptor_gain	1.0000
16:57020700:G:GG	acceptor_gain	1.0000
16:57020700:G:GT	acceptor_loss	1.0000
16:57020700:GG:G	acceptor_gain	1.0000
16:57020700:GGG:G	acceptor_gain	1.0000
16:57020700:GGGC:G	acceptor_gain	1.0000
16:57020700:GGGCT:G	acceptor_gain	1.0000
16:57020983:C:G	donor_gain	1.0000
16:57023849:GCTAG:G	donor_gain	1.0000
16:57023852:AGGT:A	donor_loss	1.0000
16:57023853:GGT:G	donor_loss	1.0000
16:57023855:T:G	donor_loss	1.0000
16:57025367:GA:G	acceptor_gain	1.0000
16:57029993:A:AG	acceptor_gain	1.0000
16:57029994:G:GG	acceptor_gain	1.0000
16:57029994:GCCT:G	acceptor_gain	1.0000
16:57030081:CCAG:C	donor_loss	1.0000
16:57030083:AG:A	donor_loss	1.0000
16:57030084:GG:G	donor_loss	1.0000
16:57030085:G:GC	donor_loss	1.0000
16:57030086:T:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000109662 (16:57050315 G>A), RS1000113122 (16:57006524 C>T), RS1000120582 (16:57011544 G>A), RS1000156980 (16:56998252 A>C), RS1000219279 (16:57038423 A>C,G,T), RS1000221310 (16:57006007 T>C,G), RS1000271922 (16:57006221 A>G), RS1000371957 (16:56995126 A>G), RS1000382556 (16:57055710 A>C), RS1000460282 (16:57038946 A>C), RS1000572629 (16:57066193 T>C,G), RS1000592699 (16:56995319 C>G,T), RS1000596904 (16:57045068 G>C,T), RS1000728580 (16:57027310 G>A), RS1000753887 (16:56989711 G>T)

Disease associations

OMIM: gene MIM:613537 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001567_6	Bipolar disorder and schizophrenia	3.000000e-06
GCST001757_15	Schizophrenia	8.000000e-06
GCST001904_2	HDL cholesterol	1.000000e-24
GCST004627_161	Lymphocyte count	2.000000e-14
GCST004632_48	Lymphocyte percentage of white cells	4.000000e-14
GCST009597_6	Multiple sclerosis	4.000000e-09
GCST010241_300	Apolipoprotein A1 levels	1.000000e-08
GCST90002381_90	Eosinophil count	5.000000e-20
GCST90002382_441	Eosinophil percentage of white cells	7.000000e-23
GCST90002388_168	Lymphocyte count	2.000000e-24
GCST90002389_310	Lymphocyte percentage of white cells	5.000000e-25
GCST90002393_271	Monocyte count	8.000000e-17
GCST90002398_299	Neutrophil count	9.000000e-11
GCST90002399_266	Neutrophil percentage of white cells	1.000000e-09
GCST90002407_557	White blood cell count	4.000000e-16

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression, increases expression	3
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	3
sodium arsenite	affects expression, increases expression	2
Cisplatin	decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression, increases methylation	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases phosphorylation, increases secretion, decreases reaction, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1GL	Abcam A-549 NLRC5 KO	Cancer cell line	Male
CVCL_E2E1	HAP1 NLRC5 (-) 1	Cancer cell line	Male
CVCL_E2E2	HAP1 NLRC5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.