PYCARD

Chr 16

PYD and CARD domain containing

Also known as: ASC, CARD5, TMS, TMS-1, TMS1

NCBI Gene: 29108ENSG00000103490UniProt: Q9ULZ3

This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

39
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— PYCARD
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 20 VUS of 39 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.90LOEUF
pLI 0.000
Z-score -0.44
OE 1.24 (0.61–1.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.89 (0.76–1.05)
103 obs / 115.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.24 (0.61–1.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.76–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 5 / 4.0Missense obs/exp: 103 / 115.2Syn Z: -0.74

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS20
Likely Benign1
Benign1
9
Pathogenic
1
Likely Pathogenic
20
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
13
7
0
20
Likely Benign
0
0
0
1
1
Benign
0
0
0
1
1
Total01317232

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PYCARD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in age-related macular degeneration.
Kaarniranta K et al.·Autophagy
2023Review
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.
Larabi A et al.·Autophagy
2020Review
Activity of caspase-8 determines plasticity between cell death pathways.
Newton K et al.·Nature
2019
PYCARD gene polymorphisms and susceptibility to periodontal and coronary heart diseases.
Daily ZA et al.·J Med Life
2024
Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.
Geng XL et al.·Eur J Med Res
2024Cohort
Expression of a PYCARD/ASC variant lacking exon 2 in Japanese patients with palindromic rheumatism increases interleukin-1β secretion.
Suganuma Y et al.·Asian Pac J Allergy Immunol
2022Cohort
[Changes in expression of PYCARD gene and its transcript variant mRNA in peripheral blood mononuclear cells of patients with primary gout].
Dang WT et al.·Sichuan Da Xue Xue Bao Yi Xue Ban
2015Cohort
Research Progress on the Role of Inflammasomes in Kidney Disease.
Chi K et al.·Mediators Inflamm
2020Review
Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.
McElvania Tekippe E et al.·PLoS One
2010
Expression of PYCARD gene transcript variant mRNA in peripheral blood mononuclear cells of primary gout patients with different Chinese medicine syndromes.
Dang WT et al.·Chin J Integr Med
2018Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrative transcriptomic and machine learning analysis identifies PYCARD and IFI30 as immune-lysosomal biomarkers of ANCA-associated glomerulonephritis.
Bei L et al.·Ren Fail
2026🔓 Open Access
Integrative transcriptomic and structural modeling reveal CASP1, TLR3, PYCARD, and CD274 as immune-modulatory drivers in breast cancer.
Meng G et al.·Naunyn Schmiedebergs Arch Pharmacol
2026Functional
Neutrophils- and Pyroptosis-Related Genes IL1B and PYCARD as Diagnostic Biomarkers for Systemic Lupus Erythematosus.
Li Y et al.·Exp Dermatol
2025
Comprehensive multiomics analysis identifies PYCARD as a key pyroptosis-related gene in osteoarthritis synovial macrophages.
Yao Z et al.·Front Immunol
2025🔓 Open Access
The inflammasome adaptor pycard is essential for immunity against Mycobacterium marinum infection in adult zebrafish.
Uusi-Mäkelä M et al.·Dis Model Mech
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Periodontitis, Adult

Non-surgical Periodontal Treatment in Smokers on SIRT-1, NLRP3 Inflammasome and LncRNAs

NOT YET RECRUITING
NCT06351722Necmettin Erbakan UniversityStarted 2024-05-15
Before non-surgical periodontal treatmentnon-surgical periodontal treatment3rd month after non-surgical periodontal treatment
Cigarette Smoking-Related CarcinomaLung Carcinoma

Evaluation of Canakinumab in High-Risk Former-Smokers

ACTIVE NOT RECRUITING
NCT06038526Phase PHASE2Peter ShieldsStarted 2024-03-11
Biospecimen CollectionBronchoscopyCanakinumab
Familial Mediterranean Fever

Health-related Quality of Life, Electrocardiographic and Holter Findings in Children With Familial Mediterranean Fever

ACTIVE NOT RECRUITING
NCT07128225Sohag UniversityStarted 2025-03-01

External Resources

Links to major genomics databases and tools