PODXL2

Summary

PODXL2 (podocalyxin like 2, HGNC:17936) is a protein-coding gene on chromosome 3q21.3, encoding Podocalyxin-like protein 2 (Q9NZ53). Acts as a ligand for vascular selectins.

This gene is a member of the CD34 family of cell surface transmembrane proteins, which are characterized by an N-terminal extracellular mucin domain, globular and stalk domains, a single pass transmembrane region, and a charged cytoplasmic tail. The encoded protein is a ligand for vascular selectins.

Source: NCBI Gene 50512 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_015720

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17936
Approved symbol	PODXL2
Name	podocalyxin like 2
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PODLX2, endoglycan, EG
Ensembl gene	ENSG00000114631
Ensembl biotype	protein_coding
OMIM	616627
Entrez	50512

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000342480, ENST00000890423, ENST00000925822, ENST00000925823, ENST00000952529

RefSeq mRNA: 1 — MANE Select: NM_015720 NM_015720

CCDS: CCDS3044

Canonical transcript exons

ENST00000342480 — 8 exons

Exon	Start	End
ENSE00000777667	127671434	127671613
ENSE00000777668	127669141	127669202
ENSE00000777674	127662237	127662311
ENSE00001122304	127668441	127668597
ENSE00001122309	127660378	127661159
ENSE00001122315	127639245	127639523
ENSE00001559779	127672268	127672802
ENSE00001705832	127629185	127629289

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0511 / max 285.8397, expressed in 1334 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38387	14.4757	1326
38386	0.5754	284

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.91	gold quality
ganglionic eminence	UBERON:0004023	96.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.24	gold quality
cerebellar hemisphere	UBERON:0002245	95.86	gold quality
cerebellar cortex	UBERON:0002129	95.76	gold quality
anterior cingulate cortex	UBERON:0009835	94.82	gold quality
right frontal lobe	UBERON:0002810	94.81	gold quality
ventricular zone	UBERON:0003053	94.65	gold quality
cingulate cortex	UBERON:0003027	94.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.71	gold quality
adenohypophysis	UBERON:0002196	93.66	gold quality
prefrontal cortex	UBERON:0000451	93.22	gold quality
cerebellum	UBERON:0002037	93.17	gold quality
pituitary gland	UBERON:0000007	91.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.66	gold quality
nucleus accumbens	UBERON:0001882	90.49	gold quality
amygdala	UBERON:0001876	90.09	gold quality
neocortex	UBERON:0001950	90.05	gold quality
frontal cortex	UBERON:0001870	89.05	gold quality
caudate nucleus	UBERON:0001873	88.95	gold quality
right testis	UBERON:0004534	88.83	gold quality
hypothalamus	UBERON:0001898	88.79	gold quality
left testis	UBERON:0004533	88.78	gold quality
spinal cord	UBERON:0002240	88.59	gold quality
cerebral cortex	UBERON:0000956	87.42	gold quality
forebrain	UBERON:0001890	86.80	gold quality
telencephalon	UBERON:0001893	86.60	gold quality
brain	UBERON:0000955	86.59	gold quality
putamen	UBERON:0001874	86.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	26.91
E-HCAD-10	yes	18.15
E-GEOD-84465	yes	6.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting PODXL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172
HSA-MIR-1538	85.86	60.08	75
HSA-MIR-4745-3P	83.50	60.58	126

Literature-anchored findings (GeneRIF, showing 5)

• endoglycan functions as an L-selectin ligand through modification with tyrosine sulfation and sialyl Lewis x (PMID:12889478)
• findings indicate that endoglycan can function as a ligand for the vascular selectins. (PMID:18606703)
• PODXL2 maintains cellular stemness and promotes breast cancer development through the Rac1/Akt pathway. (PMID:32669966)
• ITGB6-Knockout Suppresses Cholangiocarcinoma Cell Migration and Invasion with Declining PODXL2 Expression. (PMID:34208313)
• Endoglycan (PODXL2) is proteolytically processed by ADAM10 (a disintegrin and metalloprotease 10) and controls neurite branching in primary neurons. (PMID:34390512)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Podxl2	ENSMUSG00000033152
rattus_norvegicus	Podxl2	ENSRNOG00000016255

Protein

Protein identifiers

Podocalyxin-like protein 2 — Q9NZ53 (reviewed: Q9NZ53)

Alternative names: Endoglycan

All UniProt accessions (1): Q9NZ53

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a ligand for vascular selectins. Mediates rapid rolling of leukocytes over vascular surfaces through high affinity divalent cation-dependent interactions with E-, P- and L-selectins.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with SELL, SELE and SELP.

Subcellular location. Membrane.

Tissue specificity. Expressed in T-cells, B-cells and monocytes. Expression is higher on memory and germinal center cells than on naive B-cells (at protein level). Highly expressed in brain. Moderately expressed in pancreas, kidney and lymphoid node. Weakly expressed in liver. Detected in both endothelial cells and CD34+ bone marrow cells.

Post-translational modifications. O-glycosylated; contains chondroitin sulfate. Displays sialylated O-linked oligosaccharides. Sulfation is necessary for interaction with SELL. Sialylated O-linked oligosaccharides are necessary for interaction with SELL, SELE and SELP.

Similarity. Belongs to the podocalyxin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZ53-1	1	yes
Q9NZ53-2	2

RefSeq proteins (1): NP_056535* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013836	CD34/Podocalyxin	Family
IPR042397	PODXL2	Family

Pfam: PF06365

UniProt features (28 total): compositionally biased region 6, modified residue 4, glycosylation site 4, mutagenesis site 3, region of interest 3, topological domain 2, signal peptide 1, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ53-F1	55.43	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 97, 118, 570, 596

Glycosylation sites (4): 79, 144, 193, 395

Mutagenesis-validated functional residues (3):

Position	Phenotype
97	remains sulfated. not sulfated and reduced rolling of jurkat t-cells by more than 50%; when associated with f-118. the r
118	remains sulfated. not sulfated and reduced rolling of jurkat t-cells by more than 50%; when associated with f-97. the ro
124	reduced sialylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules

MSigDB gene sets: 62 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_ADHESION, GOBP_CELLULAR_EXTRAVASATION, GOBP_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_ADHESION_TO_VASCULAR_ENDOTHELIAL_CELL, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_LEUKOCYTE_CELL_CELL_ADHESION, chr3q21, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, REACTOME_CYTOSOLIC_SULFONATION_OF_SMALL_MOLECULES, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOCC_GOLGI_LUMEN, REACTOME_PHASE_II_CONJUGATION_OF_COMPOUNDS, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3

GO Biological Process (2): leukocyte tethering or rolling (GO:0050901), cell adhesion (GO:0007155)

GO Molecular Function (2): glycosaminoglycan binding (GO:0005539), protein binding (GO:0005515)

GO Cellular Component (3): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular extravasation	1
leukocyte adhesion to vascular endothelial cell	1
cellular process	1
carbohydrate derivative binding	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PODXL2	CFAP100	Q494V2	875
PODXL2	TMCC1	O94876	875
PODXL2	KLF15	Q9UIH9	843
PODXL2	PLXND1	Q9Y4D7	828
PODXL2	PLXNA1	Q9UIW2	722
PODXL2	SELP	P16109	600
PODXL2	SELL	P14151	599
PODXL2	NHERF1	O14745	509
PODXL2	GATA2	P23769	507
PODXL2	SELE	P16111	479
PODXL2	MAP6D1	Q9H9H5	468
PODXL2	KIRREL1	Q96J84	454
PODXL2	CCL21	O00585	451
PODXL2	COMTD1	Q86VU5	451
PODXL2	CD34	P28906	447

IntAct

59 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
TNIP1	COCH	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
RAET1E	GOLIM4	psi-mi:“MI:0914”(association)	0.350
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.350
VCAM1	APOA1	psi-mi:“MI:0914”(association)	0.350
CEACAM21	MET	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
TNFSF18	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SLC47A1	FAM234B	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): PODXL2 (Affinity Capture-RNA), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), PODXL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: O00592, O57604, Q04864, Q28645, Q52S86, Q8CAE9, Q9NZ53, Q9R0M4, Q9WTQ2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	12	6.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	6	16.3×	1e-03
transport across blood-brain barrier	5	14.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1750 predictions. Top by Δscore:

Variant	Effect	Δscore
3:127639481:G:GT	donor_gain	1.0000
3:127662233:A:AG	acceptor_gain	1.0000
3:127662233:ACAG:A	acceptor_gain	1.0000
3:127662234:C:G	acceptor_gain	1.0000
3:127662234:CAGG:C	acceptor_loss	1.0000
3:127662235:A:T	acceptor_loss	1.0000
3:127662235:AGGT:A	acceptor_gain	1.0000
3:127662236:GGT:G	acceptor_gain	1.0000
3:127662236:GGTG:G	acceptor_gain	1.0000
3:127662307:ACTGT:A	donor_gain	1.0000
3:127662308:CTGT:C	donor_gain	1.0000
3:127662310:GT:G	donor_gain	1.0000
3:127662312:G:GG	donor_gain	1.0000
3:127668593:GCAGG:G	donor_gain	1.0000
3:127668596:GG:G	donor_gain	1.0000
3:127668597:GG:G	donor_gain	1.0000
3:127669139:AGG:A	acceptor_gain	1.0000
3:127669140:GGG:G	acceptor_gain	1.0000
3:127669199:GGAG:G	donor_gain	1.0000
3:127669200:G:GT	donor_gain	1.0000
3:127669200:GAGGT:G	donor_loss	1.0000
3:127669201:AGGTA:A	donor_loss	1.0000
3:127669202:GGTAA:G	donor_loss	1.0000
3:127669203:GTA:G	donor_loss	1.0000
3:127669204:T:G	donor_loss	1.0000
3:127671432:AGATT:A	acceptor_gain	1.0000
3:127671433:GATT:G	acceptor_gain	1.0000
3:127671433:GATTG:G	acceptor_gain	1.0000
3:127671611:GTG:G	donor_gain	1.0000
3:127671612:TGG:T	donor_loss	1.0000

AlphaMissense

3927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:127671534:G:A	G509E	0.999
3:127671542:T:C	C512R	0.999
3:127662243:T:A	C380S	0.998
3:127662243:T:C	C380R	0.998
3:127662244:G:A	C380Y	0.998
3:127662244:G:C	C380S	0.998
3:127662286:T:C	L394P	0.998
3:127668571:T:C	L446P	0.998
3:127671533:G:A	G509R	0.998
3:127671533:G:C	G509R	0.998
3:127672315:C:A	N551K	0.998
3:127672315:C:G	N551K	0.998
3:127662245:C:G	C380W	0.997
3:127662254:G:C	W383C	0.997
3:127662254:G:T	W383C	0.997
3:127662309:T:C	C402R	0.997
3:127662310:G:A	C402Y	0.997
3:127668448:T:G	F405C	0.997
3:127668541:T:C	L436P	0.997
3:127671441:T:C	I478T	0.997
3:127672289:T:C	F543L	0.997
3:127672291:C:A	F543L	0.997
3:127672291:C:G	F543L	0.997
3:127662286:T:A	L394Q	0.996
3:127668448:T:C	F405S	0.996
3:127668535:T:A	I434N	0.996
3:127668543:A:C	S437R	0.996
3:127668545:C:A	S437R	0.996
3:127668545:C:G	S437R	0.996
3:127668574:T:C	L447P	0.996

dbSNP variants (sampled 300 via entrez): RS1000002380 (3:127657800 A>C,G), RS1000013907 (3:127661024 C>T), RS1000148757 (3:127652050 G>A), RS1000187507 (3:127667471 T>A), RS1000286891 (3:127635259 C>T), RS1000308542 (3:127628636 C>T), RS1000328890 (3:127672812 T>A,C), RS1000395122 (3:127629408 T>C,G), RS1000400505 (3:127664690 T>A), RS1000427026 (3:127672939 G>A,T), RS1000575679 (3:127629619 C>T), RS1000577598 (3:127641448 A>G), RS1000608170 (3:127667754 C>T), RS1000612487 (3:127636525 C>T), RS1000728312 (3:127647132 C>T)

Disease associations

OMIM: gene MIM:616627 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_438	Refractive error	9.000000e-21

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	increases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cytarabine	increases expression	1
Lead	affects expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Tunicamycin	decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.