NLRP12

NLR family pyrin domain containing 12, the group of Pyrin domain containing|NLR family

Basic information

Region (hg38): 19:53792139-53824403

Previous symbols: [ "NALP12" ]

Links

ENSG00000142405 ∙ NCBI:91662 ∙ OMIM:609648 ∙ HGNC:22938 ∙ Uniprot:P59046 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial cold autoinflammatory syndrome 2 (Moderate), mode of inheritance: AD
• familial cold autoinflammatory syndrome 2 (Strong), mode of inheritance: AD
• familial cold autoinflammatory syndrome 2 (Supportive), mode of inheritance: AD
• familial cold autoinflammatory syndrome 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Familial cold autoinflammatory syndrome 2	AD	Allergy/Immunology/Infectious	Medical treatment (eg, with prednisone or colchicine) has been reported as effective in reducing fever	Allergy/Immunology/Infectious	18230725; 22753383; 27314497; 27633793

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLRP12 gene.

• Familial cold autoinflammatory syndrome 2 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRP12 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	212	12	234
missense	1		548	22	5	576
nonsense	2	3	22			27
start loss			1			1
frameshift		5	38	2		45
inframe indel			14			14
splice donor/acceptor (+/-2bp)	1	1	5			7
splice region			15	20	1	36
non coding			10	46	47	103
Total	4	9	648	282	64

Highest pathogenic variant AF is 0.00000657

Variants in NLRP12

This is a list of pathogenic ClinVar variants found in the NLRP12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-53793505-G-T			not provided (-)
19-53793578-T-C		Familial cold autoinflammatory syndrome	Likely benign (Jun 14, 2016)
19-53793619-C-T		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 12, 2018)
19-53793626-C-A		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 13, 2018)
19-53793647-C-T		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 12, 2018)
19-53793654-G-A		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 13, 2018)
19-53793664-A-C		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 12, 2018)
19-53793687-C-A		Familial cold autoinflammatory syndrome	Likely benign (Jun 14, 2016)
19-53793706-T-C		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 13, 2018)
19-53793724-AC-A		Familial cold autoinflammatory syndrome	Benign (Jun 14, 2016)
19-53793759-T-G		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 13, 2018)
19-53793783-C-A		Familial cold autoinflammatory syndrome	Benign (Jun 14, 2016)
19-53793820-C-T		Familial cold autoinflammatory syndrome 2	Benign (Jan 12, 2018)
19-53793844-C-T		Familial cold autoinflammatory syndrome 2	Benign (Jan 12, 2018)
19-53793845-G-A		Familial cold autoinflammatory syndrome 2	Benign (Jan 12, 2018)
19-53793846-A-G		Familial cold autoinflammatory syndrome 2	Benign (Jan 12, 2018)
19-53793855-G-A		Familial cold autoinflammatory syndrome 2	Benign (Jan 12, 2018)
19-53793877-G-A		Familial cold autoinflammatory syndrome 2	Benign (Jan 13, 2018)
19-53793888-T-G		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 12, 2018)
19-53793923-C-G		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 13, 2018)
19-53793931-C-T		Familial cold autoinflammatory syndrome 2	Benign (Jan 13, 2018)
19-53793941-A-G		Familial cold autoinflammatory syndrome 2	Uncertain significance (Jan 12, 2018)
19-53793980-G-T		Familial cold autoinflammatory syndrome	Benign (May 14, 2021)
19-53794050-C-T		Familial cold autoinflammatory syndrome 2	Likely benign (Aug 17, 2023)
19-53794054-A-C		Familial cold autoinflammatory syndrome 2	Uncertain significance (Nov 25, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLRP12	protein_coding	protein_coding	ENST00000324134	10	30792

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.65e-28	0.0000633	125009	3	736	125748	0.00294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.71	729	610	1.20	0.0000402	6910
Missense in Polyphen		250	202.5	1.2345		2518
Synonymous	-2.50	326	273	1.19	0.0000195	2164
Loss of Function	-0.258	41	39.3	1.04	0.00000201	461

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0257	0.0257
Ashkenazi Jewish	0.00	0.00
East Asian	0.00169	0.00169
Finnish	0.00	0.00
European (Non-Finnish)	0.00147	0.00142
Middle Eastern	0.00169	0.00169
South Asian	0.00291	0.00291
Other	0.00245	0.00245

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May mediate activation of CASP1 via ASC and promote activation of NF-kappa-B via IKK.
• Disease: DISEASE: Familial cold autoinflammatory syndrome 2 (FCAS2) [MIM:611762]: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. {ECO:0000269|PubMed:18230725}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway (Consensus)

Intolerance Scores

• loftool: 0.275
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.22

Haploinsufficiency Scores

• pHI: 0.126
• hipred: N
• hipred_score: 0.146
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.230

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nlrp12
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype; neoplasm

Gene ontology

• Biological process: activation of cysteine-type endopeptidase activity involved in apoptotic process;signal transduction;negative regulation of signal transduction;negative regulation of protein autophosphorylation;negative regulation of NF-kappaB transcription factor activity;dendritic cell migration;regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of MHC class I biosynthetic process;regulation of interleukin-18 biosynthetic process;negative regulation of interleukin-6 biosynthetic process;negative regulation of Toll signaling pathway;negative regulation of cytokine secretion;negative regulation of interleukin-1 secretion;positive regulation of interleukin-1 beta secretion;negative regulation of inflammatory response;positive regulation of inflammatory response;negative regulation of ERK1 and ERK2 cascade;cellular response to cytokine stimulus;negative regulation of NIK/NF-kappaB signaling;positive regulation of NIK/NF-kappaB signaling
• Cellular component: nucleus;cytoplasm
• Molecular function: protein binding;ATP binding;cysteine-type endopeptidase activator activity involved in apoptotic process