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 (Strong), mode of inheritance: AD
familial cold autoinflammatory syndrome 2 (Supportive), 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 (1099 variants)
not_provided (200 variants)
Inborn_genetic_diseases (150 variants)
Autoinflammatory_syndrome (134 variants)
NLRP12-related_disorder (50 variants)
not_specified (25 variants)
Familial_cold_autoinflammatory_syndrome (6 variants)
Multisystem_inflammatory_syndrome_in_children (2 variants)
See_cases (2 variants)
Autoimmune_interstitial_lung_disease-arthritis_syndrome (1 variants)
Childhood-onset_schizophrenia (1 variants)
NLRP12-associated_autoinflammatory_disease (1 variants)
Periodic_fever_syndrome (1 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. These statistics are base on transcript: NM_000144687.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	266 clinvar	11 clinvar	286
missense		1 clinvar	658 clinvar	66 clinvar	6 clinvar	731
nonsense	1 clinvar	5 clinvar	27 clinvar	1 clinvar		34
start loss			3			3
frameshift		13 clinvar	45 clinvar	2 clinvar		60
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	7 clinvar			10
Total	2	21	749	335	17

Highest pathogenic variant AF is 0.0000427628

Loading clinvar variants...

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