PODXL

protein-coding

podocalyxin like

Gene summary

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]

MANE transcript

NM_001018111.3

Inheritance

AR, AD

ClinVar variants

P:7U:113B:104

Top phenotype

nephrotic syndrome

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr7:131,500,262-131,558,217

External References & Databases

Ensembl (ENSG00000128567)

Transcript & Mutation Effects

hg38 • Region Span ~58.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

juvenile-onset Parkinson diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0000828

Submitter: PanelApp Australia

nephrotic syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0005377

Submitter: PanelApp Australia

nephrotic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005377

Submitter: PanelApp Australia

young-onset Parkinson diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017279

Submitter: Orphanet

atypical juvenile parkinsonismSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018321

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PODXL variants in ClinVar

9 Conditions Cataloged

not providedTotal: 208

Inborn genetic diseasesTotal: 75

PODXL-related disorderTotal: 25

not specifiedTotal: 7

Parkinson disease, late-onsetTotal: 3

Nephrotic syndromeTotal: 1

Young-onset Parkinson diseaseTotal: 1

Focal segmental glomerulosclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001018111.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	62 clinvar	10 clinvar	73
missense			106 clinvar	28 clinvar	2 clinvar	136
nonsense	3 clinvar					3
start loss						0
frameshift	1 clinvar	1 clinvar	2 clinvar		2 clinvar	6
splice donor/acceptor (+/-2bp)		2 clinvar	4 clinvar			6
Total	4	3	113	90	14	224

Highest pathogenic variant AF is 0.00000929383

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001018111.3	RefSeq	NP_001018121.1	9	MANE Select
ENST00000378555.8	Ensembl	ENSP00000367817.3	9	MANE Select
NM_005397.4	RefSeq	NP_005388.2	8	Standard
ENST00000322985.10	Ensembl	ENSP00000319782.9	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
podxl	Danio rerio	Structure: pronephric glomerular capsule Quality: cystic abnormal

Gene / Model

Organism

Observed Phenotype

podxl

Danio rerio

Structure: pronephric glomerular capsule

Quality: cystic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

cell adhesion
negative regulation of cell adhesion
cell migration
negative regulation of cell-cell adhesion
positive regulation of cell migration

Molecular Function

protein binding

Cellular Component

ruffle
extracellular space
nucleolus
cytoplasm
microtubule organizing center

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378555
Coding exons: 9
Length: 57956
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.672	271	304	0.891	0.0000169	3541
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0901

Intolerance Scores

LoFtool: 0.580
RVIS EVS: 1.38
RVIS percentile EVS: 94.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.450

Gene Damage Prediction

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