PODXL

Chr 7

podocalyxin like

Also known as: Gp200, PC, PCLP, PCLP-1, PDX, PODXL1, gp135

NCBI Gene: 5420ENSG00000128567UniProt: O00592

This gene encodes a member of the sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin. [provided by RefSeq, Jul 2008]

320
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PODXL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 126 VUS of 320 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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.
0.69LOEUF
pLI 0.001
Z-score 2.69
OE 0.39 (0.24–0.69)
Tolerant

Typical tolerance to LoF variation

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.
0.67Z-score
OE missense 0.89 (0.81–0.99)
271 obs / 304.0 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.0.39 (0.24–0.69)
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 (0.81–0.99)
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.0.99
0≤1.21.6
LoF obs/exp: 9 / 22.9Missense obs/exp: 271 / 304.0Syn Z: 0.12

ClinVar Variant Classifications

320 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS126
Likely Benign93
Benign53
Conflicting15
30
Pathogenic
3
Likely Pathogenic
126
VUS
93
Likely Benign
53
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
29
0
30
Likely Pathogenic
2
0
1
0
3
VUS
3
105
17
1
126
Likely Benign
0
13
19
61
93
Benign
2
7
30
14
53
Conflicting
—15
Total81259676320

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

View in ClinVar →

Protein Context — Lollipop Plot

PODXL · 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
PODOCALYXIN-LIKE; PODXL
MIM #602632 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of specific markers for human pluripotent stem cell-derived small extracellular vesicles.
Chen Z et al.·J Extracell Vesicles
2024
CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression.
Lewis MW et al.·Cancer Res
2024
Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer.
Cao Y et al.·Arch Immunol Ther Exp (Warsz)
2023Review
Novel Truncating Variants in PODXL Represent a New Entity to Be Explored Among Podocytopathies.
García-Aznar JM et al.·Genes (Basel)
2025
PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer.
Zhang J et al.·Gastric Cancer
2019
Antibody-Drug Conjugates Targeting Tumor-Specific Mucin Glycoepitopes.
Brassard J et al.·Front Biosci (Landmark Ed)
2022Review
The genetic landscape of Parkinson's disease.
Lunati A et al.·Rev Neurol (Paris)
2018Review
Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.
Schulten HJ et al.·PLoS One
2019Meta-analysis
PODXL promotes malignant progression of hepatocellular carcinoma by activating PI3K/AKT pathway.
Ding Y et al.·J Mol Histol
2024
First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis.
Lin FJ et al.·Clin Sci (Lond)
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Diabetic Kidney Disease

Role of Finerenone in African American Veterans With Diabetic Kidney Disease

NOT YET RECRUITING
NCT07155694Phase PHASE4Washington D.C. Veterans Affairs Medical CenterStarted 2025-09
Finerenone 10 MGEmpagliflozin 10 MG

External Resources

Links to major genomics databases and tools