PODXL

Chr 7

podocalyxin like

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

NCBI Gene: 5420ENSG00000128567UniProt: O00592OMIM: 602632

The protein encoded by this gene is a sialomucin that functions as both an anti-adhesive molecule maintaining open filtration pathways between podocyte foot processes in glomerular filtration and a pro-adhesive molecule regulating cell migration and epithelial polarization during renal tubulogenesis. Mutations cause autosomal recessive focal segmental glomerulosclerosis, primarily affecting kidney function with onset typically in childhood. The gene shows low constraint to loss-of-function variation (pLI = 0.001), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.69
Clinical Summary— PODXL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 104 VUS of 200 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.001
Z-score 2.69
OE 0.39 (0.24–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.67Z-score
OE missense 0.89 (0.81–0.99)
271 obs / 304.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.24–0.69)
0≤0.351.4
Missense OE0.89 (0.81–0.99)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 9 / 22.9Missense obs/exp: 271 / 304.0Syn Z: 0.12
DN
0.6743th %ile
GOF
0.6735th %ile
LOF
0.2872th %ile

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

GOFprediction above median
DNprediction 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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS104
Likely Benign64
Benign11
Conflicting7
6
Pathogenic
1
Likely Pathogenic
104
VUS
64
Likely Benign
11
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
3
0
6
Likely Pathogenic
1
0
0
0
1
VUS
4
95
4
1
104
Likely Benign
0
9
15
40
64
Benign
0
1
6
4
11
Conflicting
—7
Total81052845193

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Neurochondrin drives colorectal cancer progression by modulating the PODXL-Ezrin axis and mitochondrial function.
Garranzo-Asensio M et al.·Cell Death Dis
2026
Development and Characterization of a Novel Chronic Thromboembolic Pulmonary Hypertension Rat Model: Identifying Sell-Podxl as Potential Regulators.
Liu J et al.·Hypertension
2026Functional
Asperosaponin VI Promotes Osteoporotic Fracture Healing by Targeting Piezo1 to Enhance the Coupling of LEPR+ BMSCs and PODXL+ ECs.
Dong R et al.·Phytother Res
2025
Novel Truncating Variants in PODXL Represent a New Entity to Be Explored Among Podocytopathies.
García-Aznar JM et al.·Genes (Basel)
2025Open Access
Tumor endothelium-derived PODXL correlates with immunosuppressive microenvironment and poor prognosis in cervical cancer patients receiving radiotherapy or chemoradiotherapy.
Huang R et al.·Biomark Res
2024Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients