PODXL

podocalyxin like

Basic information

Region (hg38): 7:131500261-131558217

Links

ENSG00000128567 ∙ NCBI:5420 ∙ OMIM:602632 ∙ HGNC:9171 ∙ Uniprot:O00592 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• young-onset Parkinson disease (Supportive), mode of inheritance: AR
• atypical juvenile parkinsonism (Supportive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PODXL gene.

• not provided (152 variants)
• Inborn genetic diseases (25 variants)
• Parkinson disease, late-onset (3 variants)
• Autosomal recessive juvenile Parkinson disease 2 (1 variants)
• not specified (1 variants)
• PODXL-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PODXL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	26	16	45
missense			53	14	9	76
nonsense	2					2
start loss						0
frameshift		1	1		2	4
inframe indel			5	1	3	9
splice donor/acceptor (+/-2bp)						0
splice region			1	3	2	6
non coding				5	20	25
Total	2	1	62	46	50

Variants in PODXL

This is a list of pathogenic ClinVar variants found in the PODXL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-131504303-A-C		PODXL-related disorder	Likely benign (Dec 13, 2022)
7-131504305-A-C		PODXL-related disorder	Likely benign (Dec 13, 2022)
7-131504335-A-G			Benign (Mar 20, 2022)
7-131504336-T-C		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
7-131504346-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 16, 2021)
7-131504348-T-C			Likely benign (May 01, 2023)
7-131504351-G-A		Inborn genetic diseases	Uncertain significance (Apr 08, 2022)
7-131504353-C-T			Likely benign (Oct 27, 2021)
7-131504370-C-T		PODXL-related disorder	Likely benign (Dec 11, 2023)
7-131504377-G-A			Likely benign (Jan 20, 2023)
7-131504381-T-C			Likely benign (Apr 23, 2021)
7-131504382-C-T			Uncertain significance (Feb 24, 2022)
7-131504383-C-A			Benign (Jan 28, 2024)
7-131504411-T-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
7-131504412-T-C		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
7-131504415-TCTC-T			Likely benign (Aug 06, 2022)
7-131504424-T-C		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
7-131504428-A-C			Likely benign (Mar 28, 2018)
7-131504431-A-G			Likely benign (Jun 14, 2021)
7-131504449-C-T		PODXL-related disorder	Benign/Likely benign (Jan 18, 2024)
7-131504451-G-T			Uncertain significance (Oct 17, 2022)
7-131504464-A-G			Likely benign (Aug 20, 2023)
7-131504482-T-C			Benign (Mar 27, 2023)
7-131504504-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
7-131504505-G-A			Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PODXL	protein_coding	protein_coding	ENST00000378555	9	57956

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00103	0.997	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.672	271	304	0.891	0.0000169	3541
Missense in Polyphen		65	82.487	0.78801		1003
Synonymous	0.121	135	137	0.987	0.00000892	1196
Loss of Function	2.69	9	22.9	0.394	0.00000135	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the regulation of both adhesion and cell morphology and cancer progression. Function as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell- cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR- dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells. {ECO:0000269|PubMed:17616675, ECO:0000269|PubMed:18456258}.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Primary Focal Segmental Glomerulosclerosis FSGS;Ectoderm Differentiation;Hepatitis C and Hepatocellular Carcinoma (Consensus)

Recessive Scores

• pRec: 0.0901

Intolerance Scores

• loftool: 0.580
• rvis_EVS: 1.38
• rvis_percentile_EVS: 94.6

Haploinsufficiency Scores

• pHI: 0.263
• hipred: N
• hipred_score: 0.372
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.450

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Podxl
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype

Zebrafish Information Network

• Gene name: podxl
• Affected structure: pronephric glomerular capsule
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: cell adhesion;negative regulation of cell adhesion;cell migration;negative regulation of cell-cell adhesion;positive regulation of cell migration;regulation of microvillus assembly;positive regulation of cell-cell adhesion mediated by integrin;glomerular visceral epithelial cell development;epithelial tube formation
• Cellular component: ruffle;extracellular space;nucleolus;cytoplasm;microtubule organizing center;plasma membrane;integral component of plasma membrane;apical plasma membrane;lamellipodium;filopodium;microvillus membrane;slit diaphragm;intracellular membrane-bounded organelle;membrane raft;extracellular exosome
• Molecular function: protein binding