PYDC1

Summary

PYDC1 (pyrin domain containing 1, HGNC:30261) is a protein-coding gene on chromosome 16p11.2, encoding Pyrin domain-containing protein 1 (Q8WXC3). Associates with PYCARD/ASC and modulates its ability to collaborate with MEFV/pyrin and NLRP3/cryopyrin in NF-kappa-B and pro-caspase-1 activation. It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

Enables protein serine/threonine kinase binding activity and protein serine/threonine kinase inhibitor activity. Involved in innate immune response; negative regulation of signal transduction; and positive regulation of interleukin-1 beta production. Located in cytosol and nucleus. Part of IkappaB kinase complex.

Source: NCBI Gene 260434 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_152901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30261
Approved symbol	PYDC1
Name	pyrin domain containing 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	ASC2, POP1
Ensembl gene	ENSG00000169900
Ensembl biotype	protein_coding
OMIM	615700
Entrez	260434

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000302964, ENST00000568383, ENST00000928116

RefSeq mRNA: 1 — MANE Select: NM_152901 NM_152901

CCDS: CCDS10710

Canonical transcript exons

ENST00000302964 — 2 exons

Exon	Start	End
ENSE00001172467	31216743	31217135
ENSE00003899232	31215962	31216157

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 85.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	85.87	gold quality
cerebellar cortex	UBERON:0002129	85.54	gold quality
cerebellar hemisphere	UBERON:0002245	85.46	gold quality
cerebellum	UBERON:0002037	83.55	gold quality
skin of leg	UBERON:0001511	82.12	gold quality
skin of abdomen	UBERON:0001416	79.23	gold quality
gastrocnemius	UBERON:0001388	78.95	gold quality
nucleus accumbens	UBERON:0001882	78.36	gold quality
amygdala	UBERON:0001876	78.16	gold quality
zone of skin	UBERON:0000014	77.83	gold quality
muscle of leg	UBERON:0001383	77.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.82	gold quality
anterior cingulate cortex	UBERON:0009835	74.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.42	gold quality
right frontal lobe	UBERON:0002810	71.31	gold quality
hypothalamus	UBERON:0001898	71.12	gold quality
prefrontal cortex	UBERON:0000451	70.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.68	gold quality
temporal lobe	UBERON:0001871	67.82	gold quality
frontal cortex	UBERON:0001870	67.54	gold quality
neocortex	UBERON:0001950	67.16	gold quality
upper leg skin	UBERON:0004262	65.59	gold quality
cerebral cortex	UBERON:0000956	64.67	gold quality
myocardium	UBERON:0002349	64.36	gold quality
brain	UBERON:0000955	64.07	gold quality
cerebellar vermis	UBERON:0004720	63.48	gold quality
penis	UBERON:0000989	63.14	silver quality
putamen	UBERON:0001874	62.95	gold quality
caudate nucleus	UBERON:0001873	62.34	gold quality
forebrain	UBERON:0001890	62.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting PYDC1, 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-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-346	97.01	66.97	662

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• NMR assignment of human ASC2, a self contained protein interaction domain involved in apoptosis and inflammation. (PMID:12153040)
• POP1/ASC2 associates with ASC via PAAD-PAAD interactions and modulates NF-kappa B and pro-caspase-1 regulation by this adapter protein (PMID:12656673)
• analysis of the 3D structure of human ASC2 protein involved in apoptosis and inflammation (PMID:16403450)
• ASC2 is a pyrin domain-only protein that regulates inflammatory signaling (PMID:16905547)
• X-ray diffraction data were collected to a resolution of 3.6 A from a crystal belonging to the cubic space group P23 with unit-cell parameters a=b=c=94.12 A, alpha=beta=gamma=90.00 degrees . (PMID:23519807)
• Changes in the tertiary structure of mutated pyrin B30.2 domain interrupting the formation of the pyrin-caspase-1 complex are related to the manifestations of Mediterranean familial fever. (PMID:26510601)
• PYDC1 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Association of NOD1, NOD2, PYDC1 and PYDC2 genes with Behcet’s disease susceptibility and clinical manifestations. (PMID:34294014)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	casp8	ENSDARG00000058325
danio_rerio	casp3l	ENSDARG00000086266
danio_rerio	casp20	ENSDARG00000104367
danio_rerio		ENSDARG00000112575
drosophila_melanogaster	Dronc	FBGN0026404
drosophila_melanogaster	Decay	FBGN0028381
caenorhabditis_elegans		WBGENE00000417
caenorhabditis_elegans		WBGENE00000819
caenorhabditis_elegans		WBGENE00000820
caenorhabditis_elegans	csp-3	WBGENE00000821

Paralogs (16): CASP10 (ENSG00000003400), CFLAR (ENSG00000003402), CASP8 (ENSG00000064012), PYCARD (ENSG00000103490), CASP14 (ENSG00000105141), CASP2 (ENSG00000106144), CASP9 (ENSG00000132906), CASP1 (ENSG00000137752), CASP5 (ENSG00000137757), CASP6 (ENSG00000138794), CASP3 (ENSG00000164305), CASP7 (ENSG00000165806), CASP4 (ENSG00000196954), CARD16 (ENSG00000204397), CASP12 (ENSG00000204403), CARD18 (ENSG00000255501)

Protein

Protein identifiers

Pyrin domain-containing protein 1 — Q8WXC3 (reviewed: Q8WXC3)

Alternative names: PAAD-only protein 1, Pyrin-only protein 1, cellular POP1

All UniProt accessions (1): Q8WXC3

UniProt curated annotations — full annotation on UniProt →

Function. Associates with PYCARD/ASC and modulates its ability to collaborate with MEFV/pyrin and NLRP3/cryopyrin in NF-kappa-B and pro-caspase-1 activation. Suppresses kinase activity of NF-kappa-B inhibitor kinase (IKK) complex, expression of NF-kappa-B inducible genes and inhibits NF-kappa-B activation by cytokines and LPS.

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

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in monocytes, macrophages and granulocytes.

Post-translational modifications. Phosphorylated.

RefSeq proteins (1): NP_690865* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004020	DAPIN	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily

Pfam: PF02758

UniProt features (9 total): helix 6, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4QOB	X-RAY DIFFRACTION	2.7
2HM2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXC3-F1	89.29	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 319 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_INTERLEUKIN_1_PRODUCTION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (9): negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), positive regulation of interleukin-1 beta production (GO:0032731), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), negative regulation of interleukin-1-mediated signaling pathway (GO:2000660), immune system process (GO:0002376), negative regulation of signal transduction (GO:0009968), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), defense response to other organism (GO:0098542)

GO Molecular Function (3): protein serine/threonine kinase inhibitor activity (GO:0030291), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), IkappaB kinase complex (GO:0008385), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cytokine-mediated signaling pathway	2
tumor necrosis factor-mediated signaling pathway	2
cellular anatomical structure	2
regulation of tumor necrosis factor-mediated signaling pathway	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
interleukin-1-mediated signaling pathway	1
regulation of interleukin-1-mediated signaling pathway	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 cytokine-mediated signaling pathway	1
defense response	1
response to other organism	1
protein serine/threonine kinase activity	1
protein kinase inhibitor activity	1
protein kinase binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytosol	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYDC1	NLRP1	Q9C000	935
PYDC1	AIM2	O14862	921
PYDC1	NLRP6	P59044	912
PYDC1	CASP1	P29466	847
PYDC1	NLRC4	Q9NPP4	837
PYDC1	F2RL2	O00254	827
PYDC1	NLRP3	Q96P20	802
PYDC1	PYCARD	Q9ULZ3	788
PYDC1	NLRP7	Q8WX94	781
PYDC1	NLRP12	P59046	740
PYDC1	ADCY10	Q96PN6	720
PYDC1	NAIP	Q13075	663
PYDC1	F2R	P25116	648
PYDC1	CARD8	Q9Y2G2	612
PYDC1	PYDC2	Q56P42	606

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PYCARD	PYDC1	psi-mi:“MI:0915”(physical association)	0.460
PYCARD	PYDC1	psi-mi:“MI:0403”(colocalization)	0.460

BioGRID (2): PYDC1 (Affinity Capture-MS), PYDC1 (Affinity Capture-MS)

ESM2 similar proteins: A6QLE5, B0FPE9, D4A523, O08736, O14862, O35732, O62640, O77736, O89110, O95786, P25445, P29452, P43527, P55865, P55867, P57730, P70343, Q13158, Q14790, Q15121, Q153Z0, Q504J1, Q5R529, Q5RAV7, Q5U318, Q61160, Q62048, Q63199, Q645M6, Q6GZR1, Q6Q899, Q7RTR0, Q8HXK9, Q8IXQ6, Q8R4B8, Q8WXC3, Q91VJ1, Q920D5, Q92851, Q96P20

Diamond homologs: A0JN74, A4QPC6, A6NK02, A6NLU0, A6QLE5, B0FPE9, B1H278, D4ABM4, F8RKW2, F8S122, F8VTS6, K7N6K2, O00478, O00481, O00635, O15344, O15553, O19085, O75677, O75678, O75679, P14373, P18892, P19474, P82885, P83234, Q13410, Q1XHU0, Q27J48, Q2T9Z0, Q2XXL4, Q495X7, Q587N6, Q58DK8, Q5D7I9, Q5E9G4, Q5NCC9, Q5R7W8, Q5R996, Q62158

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

333 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31216742:CCAG:C	donor_gain	1.0000
16:31216738:CGTA:C	donor_loss	0.9800
16:31216740:TAC:T	donor_loss	0.9800
16:31216741:A:C	donor_loss	0.9800
16:31216742:C:CA	donor_loss	0.9800
16:31216787:T:TA	donor_gain	0.9800
16:31216737:ACGT:A	donor_loss	0.9700
16:31216741:A:AC	donor_gain	0.9700
16:31216742:C:CC	donor_gain	0.9700
16:31217005:G:GT	donor_gain	0.9500
16:31217126:G:T	donor_gain	0.9300
16:31216155:CTC:C	acceptor_gain	0.9100
16:31216156:TCCTA:T	acceptor_loss	0.9100
16:31216157:CCT:C	acceptor_loss	0.9100
16:31216158:C:A	acceptor_loss	0.9100
16:31216159:T:A	acceptor_loss	0.9100
16:31216687:G:T	donor_gain	0.9000
16:31217126:G:GT	donor_gain	0.8800
16:31216741:ACCAG:A	donor_gain	0.8700
16:31216742:CCAGC:C	donor_gain	0.8700
16:31216331:AAGAC:A	donor_gain	0.8600
16:31216330:TAAG:T	donor_gain	0.8500
16:31216331:AAGA:A	donor_gain	0.8500
16:31216158:C:CC	acceptor_gain	0.8400
16:31216368:T:TA	donor_gain	0.8200
16:31216839:AGT:A	donor_gain	0.8200
16:31216742:CCA:C	donor_gain	0.8100
16:31216981:TGTC:T	donor_gain	0.8100
16:31216757:C:A	donor_gain	0.8000
16:31216765:AG:A	donor_gain	0.8000

AlphaMissense

562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31216921:A:C	F36L	0.913
16:31216921:A:T	F36L	0.913
16:31216923:A:G	F36L	0.913
16:31216957:C:A	K24N	0.907
16:31216957:C:G	K24N	0.907
16:31216960:G:C	F23L	0.904
16:31216960:G:T	F23L	0.904
16:31216962:A:G	F23L	0.904
16:31216961:A:G	F23S	0.884
16:31216913:A:G	I39T	0.860
16:31216874:A:G	L52P	0.787
16:31216966:C:A	K21N	0.785
16:31216966:C:G	K21N	0.785
16:31216985:A:G	L15P	0.775
16:31216913:A:C	I39S	0.753
16:31216874:A:T	L52H	0.743
16:31216835:G:T	A65E	0.720
16:31216859:A:T	V57D	0.717
16:31216823:A:T	V69D	0.713
16:31216862:A:T	L56Q	0.709
16:31217006:A:G	I8T	0.704
16:31216862:A:C	L56R	0.698
16:31216871:G:A	T53I	0.696
16:31217016:G:T	R5S	0.680
16:31216970:A:G	L20P	0.675
16:31216991:T:A	E13V	0.669
16:31216961:A:C	F23C	0.668
16:31216811:A:T	L73Q	0.667
16:31216862:A:G	L56P	0.660
16:31217006:A:C	I8S	0.656

dbSNP variants (sampled 300 via entrez): RS1000961838 (16:31216457 C>A,T), RS1002294610 (16:31215490 G>A), RS1003355331 (16:31219064 C>A,T), RS1003471655 (16:31218571 A>G), RS1005139861 (16:31216840 G>C), RS1006604590 (16:31217268 A>G), RS1008267320 (16:31215793 C>T), RS1009570069 (16:31215603 C>A), RS1010715803 (16:31218141 G>A,T), RS1011057897 (16:31218515 T>C), RS1011608567 (16:31218843 C>T), RS1012320148 (16:31216799 C>A,T), RS1012807049 (16:31216524 G>A,C), RS1015149556 (16:31216858 G>T), RS1016818669 (16:31215485 C>T)

Disease associations

OMIM: gene MIM:615700 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Allethrins	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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