NLRP12

Protein identityUniProt · HPA

UniProt accession

P59046

Gene

NLRP12

Ensembl

ENSG00000142405

Chromosome

19

Canonical length

1061 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

Canonical amino-acid sequenceUniProt

1061 residues, UniProt reviewed canonical sequence.

>P59046|NLRP12
     1  MLRTAGRDGL CRLSTYLEEL EAVELKKFKL YLGTATELGE GKIPWGSMEK AGPLEMAQLL
    61  ITHFGPEEAW RLALSTFERI NRKDLWERGQ REDLVRDTPP GGPSSLGNQS TCLLEVSLVT
   121  PRKDPQETYR DYVRRKFRLM EDRNARLGEC VNLSHRYTRL LLVKEHSNPM QVQQQLLDTG
   181  RGHARTVGHQ ASPIKIETLF EPDEERPEPP RTVVMQGAAG IGKSMLAHKV MLDWADGKLF
   241  QGRFDYLFYI NCREMNQSAT ECSMQDLIFS CWPEPSAPLQ ELIRVPERLL FIIDGFDELK
   301  PSFHDPQGPW CLCWEEKRPT ELLLNSLIRK KLLPELSLLI TTRPTALEKL HRLLEHPRHV
   361  EILGFSEAER KEYFYKYFHN AEQAGQVFNY VRDNEPLFTM CFVPLVCWVV CTCLQQQLEG
   421  GGLLRQTSRT TTAVYMLYLL SLMQPKPGAP RLQPPPNQRG LCSLAADGLW NQKILFEEQD
   481  LRKHGLDGED VSAFLNMNIF QKDINCERYY SFIHLSFQEF FAAMYYILDE GEGGAGPDQD
   541  VTRLLTEYAF SERSFLALTS RFLFGLLNEE TRSHLEKSLC WKVSPHIKMD LLQWIQSKAQ
   601  SDGSTLQQGS LEFFSCLYEI QEEEFIQQAL SHFQVIVVSN IASKMEHMVS SFCLKRCRSA
   661  QVLHLYGATY SADGEDRARC SAGAHTLLVQ LPERTVLLDA YSEHLAAALC TNPNLIELSL
   721  YRNALGSRGV KLLCQGLRHP NCKLQNLRLK RCRISSSACE DLSAALIANK NLTRMDLSGN
   781  GVGFPGMMLL CEGLRHPQCR LQMIQLRKCQ LESGACQEMA SVLGTNPHLV ELDLTGNALE
   841  DLGLRLLCQG LRHPVCRLRT LWLKICRLTA AACDELASTL SVNQSLRELD LSLNELGDLG
   901  VLLLCEGLRH PTCKLQTLRL GICRLGSAAC EGLSVVLQAN HNLRELDLSF NDLGDWGLWL
   961  LAEGLQHPAC RLQKLWLDSC GLTAKACENL YFTLGINQTL TDLYLTNNAL GDTGVRLLCK
  1021  RLSHPGCKLR VLWLFGMDLN KMTHSRLAAL RVTKPYLDIG C

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NLRP12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

5.7 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NLRP12.

Disease | AllUniProt

Conditions NLRP12 is implicated in, by any mechanism.

• Familial cold autoinflammatory syndrome 2 (FCAS2) MIM:611762

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 1,456 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial cold autoinflammatory syndrome 2
• See cases
• Autoinflammatory syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.36

gnomAD pLI

0

gnomAD missense Z

-1.71

DepMap mean gene effect

0.13

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to cytokine stimulus
• dendritic cell migration
• ERK1 and ERK2 cascade
• negative regulation of canonical NF-kappaB signal transduction
• negative regulation of cytokine production
• negative regulation of ERK1 and ERK2 cascade
• negative regulation of inflammatory response
• negative regulation of interleukin-1 production
• negative regulation of interleukin-6 production
• negative regulation of non-canonical NF-kappaB signal transduction
• negative regulation of signal transduction
• negative regulation of Toll signaling pathway
• positive regulation of inflammatory response
• positive regulation of interleukin-1 beta production
• positive regulation of MHC class I biosynthetic process
• positive regulation of non-canonical NF-kappaB signal transduction
• regulation of canonical NF-kappaB signal transduction
• regulation of inflammatory response
• signal transduction
• regulation of interleukin-18 production

Molecular functions

• ATP binding
• cysteine-type endopeptidase activator activity
• protein-macromolecule adaptor activity

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Leucine-rich repeat
• DAPIN domain
• NACHT nucleoside triphosphatase
• Death-like domain superfamily
• P-loop containing nucleoside triphosphate hydrolase
• NACHT-associated domain
• Leucine-rich repeat domain superfamily
• NOD1/2, winged helix domain
• NACHT, LRR and PYD domains-containing protein, helical domain HD2
• NLRP family, innate immunity and inflammation regulators
• PAAD/DAPIN/Pyrin domain
• NACHT domain
• Leucine Rich repeat
• Fish-specific NACHT associated domain
• NLRC4 helical domain HD2
• NOD2 winged helix domain

KeywordsUniProt

• ATP-binding
• Cytoplasm
• Leucine-rich repeat
• Nucleotide-binding
• Repeat

InteractionsUniProt · HPA

Protein binding partners of NLRP12 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HSP90AA1
• HSPA1A
• HSPA8
• MAP3K14
• NOD2
• TRIM25