PYDC2

Summary

PYDC2 (pyrin domain containing 2, HGNC:33512) is a protein-coding gene on chromosome 3q28, encoding Pyrin domain-containing protein 2 (Q56P42). May play a role in innate immunity by disrupting the interaction between PYCARD and NLRP3, thereby regulating the NLRP3 inflammasome.

Involved in negative regulation of inflammatory response; negative regulation of signal transduction; and regulation of gene expression. Located in cytosol; nucleolus; and nucleoplasm.

Source: NCBI Gene 152138 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001083308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33512
Approved symbol	PYDC2
Name	pyrin domain containing 2
Location	3q28
Locus type	gene with protein product
Status	Approved
Aliases	POP2
Ensembl gene	ENSG00000253548
Ensembl biotype	protein_coding
OMIM	615701
Entrez	152138

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000518817

RefSeq mRNA: 1 — MANE Select: NM_001083308 NM_001083308

Canonical transcript exons

ENST00000518817 — 1 exons

Exon	Start	End
ENSE00002291388	191461163	191461456

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 80.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.73	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
urinary bladder	UBERON:0001255	30.39	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.78	gold quality
monocyte	CL:0000576	29.50	gold quality
leukocyte	CL:0000738	29.33	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.34	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
uterine cervix	UBERON:0000002	25.42	silver quality
right lobe of liver	UBERON:0001114	25.18	silver quality
frontal cortex	UBERON:0001870	25.13	gold quality
muscle of leg	UBERON:0001383	25.10	silver quality
primary visual cortex	UBERON:0002436	24.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.35

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• POP2 inhibits both the interaction of ASC with various NLR pyrin domains and inhibits NF-kappaB p65 (RelA). (PMID:17339483)
• POP2 inhibits inflammasome priming and activation (PMID:28580931)
• PYDC2 inhibits NF-kB activation through the non-canonical kinase IKK epsilon. PYDC2 interferes with ASC oligomerization and with ASC-inflammasome activation resulting in reduced production of Interleukin-1-beta and reduced IL-18 secretion, as well as reduced pyroptosis. (PMID:28580931)
• Association of NOD1, NOD2, PYDC1 and PYDC2 genes with Behcet’s disease susceptibility and clinical manifestations. (PMID:34294014)

Cross-species orthologs

0 orthologs

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), 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)

Protein

Protein identifiers

Pyrin domain-containing protein 2 — Q56P42 (reviewed: Q56P42)

Alternative names: Pyrin-only protein 2, cellular POP2

All UniProt accessions (1): Q56P42

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in innate immunity by disrupting the interaction between PYCARD and NLRP3, thereby regulating the NLRP3 inflammasome. May also inhibit NF-kappa-B signaling distally by affecting the nuclear accumulation of RELA.

Subunit / interactions. Interacts with PYCARD/ASC (via pyrin domain). Interacts with NLRP2 (via pyrin domain).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Predominantly expressed in peripheral blood. Weakly expressed in testis.

RefSeq proteins (1): NP_001076777* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004020	DAPIN	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily

Pfam: PF02758

UniProt features (3 total): chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q56P42-F1	74.80	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_NEGATIVE_REGULATION_OF_NF_KAPPAB_TRANSCRIPTION_FACTOR_ACTIVITY, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (11): inflammatory response (GO:0006954), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of interleukin-1 beta production (GO:0032691), innate immune response (GO:0045087), negative regulation of inflammatory response (GO:0050728), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), immune system process (GO:0002376), negative regulation of signal transduction (GO:0009968), regulation of interleukin-1 beta production (GO:0032651)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
interleukin-1 beta production	2
nuclear lumen	2
defense response	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
immune response	1
defense response to symbiont	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
biological_process	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of interleukin-1 production	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

379 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYDC2	MEFV	O15553	629
PYDC2	PYDC1	Q8WXC3	606
PYDC2	CARD17P	Q5XLA6	516
PYDC2	NAIP	Q13075	478
PYDC2	CARD8	Q9Y2G2	463
PYDC2	CASP5	P51878	450
PYDC2	CNOT1	A5YKK6	445
PYDC2	DAPK1	P53355	400
PYDC2	CARD16	Q5EG05	398
PYDC2	OR10S1	Q8NGN2	394
PYDC2	CARD18	P57730	381
PYDC2	CIITA	P33076	380
PYDC2	CASP1	P29466	327
PYDC2	AIM2	O14862	325
PYDC2	NLRC4	Q9NPP4	322

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PYCARD	PYDC2	psi-mi:“MI:0915”(physical association)	0.600
PYDC2	NLRP2	psi-mi:“MI:0915”(physical association)	0.600
PYDC2	PYCARD	psi-mi:“MI:0915”(physical association)	0.600
NLRP2	PYDC2	psi-mi:“MI:0915”(physical association)	0.600
PYDC2	PYCARD	psi-mi:“MI:0403”(colocalization)	0.600
NLRP2	PYDC2	psi-mi:“MI:0403”(colocalization)	0.600
NLRP4	PYDC2	psi-mi:“MI:0915”(physical association)	0.370
NLRP12	PYDC2	psi-mi:“MI:0915”(physical association)	0.370
PYDC2	NLRP1	psi-mi:“MI:0915”(physical association)	0.370

ESM2 similar proteins: A4IIK1, C6FG12, E7FH61, F5HEZ4, F6R2G2, F6S215, P30429, Q01001, Q01044, Q07440, Q16548, Q1L8H0, Q1LVQ2, Q20CR4, Q29IM7, Q32NG6, Q3C2I0, Q3MHH2, Q4R6F2, Q4V9P9, Q4VSN5, Q56P42, Q5RB52, Q5RBY8, Q5T6L9, Q5TBC7, Q5U228, Q60Z52, Q66674, Q6DFV1, Q6NU22, Q6NU51, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZN28, Q7KLI1, Q86XI2, Q8AXQ3, Q8IRY7

Diamond homologs: P0DMW2, Q56P42, Q8WX94, Q9NX02, Q96MN2, A1Z198, A6QLE5, B0FPE9, D4A523, E9Q5R7, P10775, P29315, P59046, P59047, Q288C4, Q3TKR3, Q647I9, Q66X19, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8HZP9, Q8R4B8, Q91VI7, Q96P20, Q9C000, Q9R1M5, A0A2H5Q1B8, D9I2F9, D9I2G1, D9I2G3, D9I2H0, P13489, P59045, Q2LKU9, Q66X01

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

96 predictions. Top by Δscore:

Variant	Effect	Δscore
3:191461223:GA:G	donor_gain	0.9100
3:191461238:TTC:T	donor_gain	0.8800
3:191461222:GGA:G	donor_gain	0.8700
3:191461224:A:G	donor_gain	0.8400
3:191461224:A:AG	donor_gain	0.8300
3:191461229:T:G	donor_gain	0.7500
3:191461214:C:G	donor_gain	0.7300
3:191461296:CAGAG:C	donor_loss	0.7300
3:191461297:AGAG:A	donor_loss	0.7300
3:191461298:G:GT	donor_gain	0.7300
3:191461299:AGG:A	donor_loss	0.7300
3:191461300:GGT:G	donor_loss	0.7300
3:191461301:GT:G	donor_loss	0.7300
3:191461302:T:A	donor_loss	0.7300
3:191461234:C:T	donor_gain	0.7200
3:191461270:A:T	donor_gain	0.7200
3:191461239:TCA:T	donor_gain	0.6900
3:191461274:GAGC:G	donor_gain	0.6900
3:191461298:GAG:G	donor_gain	0.6900
3:191461277:C:G	donor_gain	0.6700
3:191461310:GC:G	donor_loss	0.6600
3:191461318:G:T	donor_gain	0.6600
3:191461274:G:GT	donor_loss	0.6500
3:191461303:A:C	donor_loss	0.6500
3:191461228:GTTGA:G	donor_gain	0.6200
3:191461310:GCTAA:G	donor_gain	0.6000
3:191461318:G:GT	donor_gain	0.5900
3:191461357:C:G	donor_gain	0.5800
3:191461224:A:T	donor_gain	0.5600
3:191461324:ACT:A	donor_loss	0.5500

AlphaMissense

641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:191461238:T:C	F26L	0.930
3:191461240:C:A	F26L	0.930
3:191461240:C:G	F26L	0.930
3:191461243:G:C	K27N	0.919
3:191461243:G:T	K27N	0.919
3:191461239:T:C	F26S	0.838
3:191461310:G:C	A50P	0.793
3:191461187:T:C	F9L	0.774
3:191461189:C:A	F9L	0.774
3:191461189:C:G	F9L	0.774
3:191461230:T:C	L23S	0.739
3:191461241:A:G	K27E	0.718
3:191461242:A:T	K27M	0.715
3:191461388:T:C	F76L	0.705
3:191461390:T:A	F76L	0.705
3:191461390:T:G	F76L	0.705
3:191461239:T:G	F26C	0.666
3:191461248:T:C	L29P	0.660
3:191461398:T:C	M79T	0.651
3:191461242:A:C	K27T	0.647
3:191461215:T:C	L18P	0.635
3:191461363:G:C	W67C	0.633
3:191461363:G:T	W67C	0.633
3:191461326:T:A	L55Q	0.630
3:191461206:T:A	L15Q	0.614
3:191461326:T:C	L55P	0.613
3:191461376:G:C	A72P	0.610
3:191461335:T:C	I58T	0.599
3:191461338:T:C	F59S	0.594
3:191461377:C:A	A72D	0.590

dbSNP variants (sampled 300 via entrez): RS1003703006 (3:191460552 C>T), RS1003744685 (3:191460199 C>T), RS1005997679 (3:191460157 T>A,C), RS1007212205 (3:191460903 C>A,G), RS1008519994 (3:191459183 T>C), RS1009542150 (3:191461565 A>C,G), RS1010577372 (3:191460576 T>G), RS1012373447 (3:191460128 A>G), RS1015662296 (3:191460177 G>A), RS1016130041 (3:191459853 A>G), RS1016712256 (3:191461200 C>A), RS1016994588 (3:191461199 G>A), RS1018261454 (3:191461939 G>A), RS1019291841 (3:191460918 A>G,T), RS1019523538 (3:191459403 C>A)

Disease associations

OMIM: gene MIM:615701 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005648_38	Serum metabolite concentrations in chronic kidney disease	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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