PIERCE1

Chr 9

piercer of microtubule wall 1

The protein is a microtubule inner protein that attaches outer dynein arms to doublet microtubules in cilia axonemes, which is essential for motile cilia beating and the initial establishment of left-right asymmetry in visceral organs. Based on the provided data, the gene appears to have high tolerance to loss-of-function variants (very low pLI and high LOEUF scores), but no specific disease associations or inheritance patterns are documented in the available information. The predicted dominant-negative mechanism suggests mutations could potentially disrupt normal cilia function.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 1.93
Clinical SummaryPIERCE1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.000
Z-score -0.85
OE 1.45 (0.741.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.53Z-score
OE missense 0.83 (0.691.02)
69 obs / 82.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.45 (0.741.93)
00.351.4
Missense OE0.83 (0.691.02)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 6 / 4.1Missense obs/exp: 69 / 82.7Syn Z: -0.68
DN
0.7035th %ile
GOF
0.6444th %ile
LOF
0.3550th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PIERCE1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC