PLXDC1

Summary

PLXDC1 (plexin domain containing 1, HGNC:20945) is a protein-coding gene on chromosome 17q12, encoding Plexin domain-containing protein 1 (Q8IUK5). Plays a critical role in endothelial cell capillary morphogenesis.

Predicted to be involved in angiogenesis. Part of receptor complex.

Source: NCBI Gene 57125 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_020405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20945
Approved symbol	PLXDC1
Name	plexin domain containing 1
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	TEM3, TEM7
Ensembl gene	ENSG00000161381
Ensembl biotype	protein_coding
OMIM	606826
Entrez	57125

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 10 protein_coding, 6 retained_intron, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000315392, ENST00000394318, ENST00000415163, ENST00000441877, ENST00000444435, ENST00000444911, ENST00000461225, ENST00000493200, ENST00000577838, ENST00000577941, ENST00000578277, ENST00000578390, ENST00000578517, ENST00000578808, ENST00000579190, ENST00000579279, ENST00000579417, ENST00000580667, ENST00000582025, ENST00000583285, ENST00000881056, ENST00000881057, ENST00000961384, ENST00000961385

RefSeq mRNA: 1 — MANE Select: NM_020405 NM_020405

CCDS: CCDS11333

Canonical transcript exons

ENST00000315392 — 14 exons

Exon	Start	End
ENSE00001111379	39079104	39079164
ENSE00001820015	39063313	39067959
ENSE00002721375	39151362	39151637
ENSE00003508734	39069856	39070016
ENSE00003509234	39109248	39109391
ENSE00003511765	39083459	39083540
ENSE00003514899	39072450	39072485
ENSE00003519718	39139654	39139832
ENSE00003546713	39087607	39087702
ENSE00003564921	39105854	39105953
ENSE00003599692	39107407	39107525
ENSE00003681428	39077913	39078048
ENSE00003689255	39108904	39108973
ENSE00003790834	39108123	39108245

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.37.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3686 / max 135.0244, expressed in 473 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165573	1.4922	377
165576	0.2334	104
165574	0.1536	83
165575	0.1446	83
165578	0.1427	65
165577	0.1341	49
165572	0.0571	28
165579	0.0110	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.37	gold quality
tendon of biceps brachii	UBERON:0008188	94.67	gold quality
right ovary	UBERON:0002118	93.96	gold quality
gall bladder	UBERON:0002110	93.80	gold quality
left uterine tube	UBERON:0001303	93.40	gold quality
left ovary	UBERON:0002119	93.05	gold quality
body of uterus	UBERON:0009853	92.80	gold quality
right uterine tube	UBERON:0001302	92.50	gold quality
tibial nerve	UBERON:0001323	92.37	gold quality
mucosa of stomach	UBERON:0001199	90.94	gold quality
right frontal lobe	UBERON:0002810	90.32	gold quality
heart left ventricle	UBERON:0002084	89.97	gold quality
cardiac ventricle	UBERON:0002082	89.77	gold quality
synovial joint	UBERON:0002217	89.64	gold quality
granulocyte	CL:0000094	89.31	gold quality
thymus	UBERON:0002370	89.12	gold quality
putamen	UBERON:0001874	89.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.30	gold quality
lower esophagus	UBERON:0013473	88.27	gold quality
ovary	UBERON:0000992	88.02	gold quality
caudate nucleus	UBERON:0001873	87.26	gold quality
prefrontal cortex	UBERON:0000451	87.12	gold quality
omental fat pad	UBERON:0010414	86.90	gold quality
peritoneum	UBERON:0002358	86.87	gold quality
skin of hip	UBERON:0001554	86.76	gold quality
heart	UBERON:0000948	86.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.46	gold quality
saphenous vein	UBERON:0007318	86.38	gold quality
lymph node	UBERON:0000029	86.26	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	40.69
E-GEOD-137537	yes	21.88
E-MTAB-8410	yes	17.24
E-ANND-3	yes	10.45
E-GEOD-99795	no	84.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting PLXDC1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-129-5P	99.88	70.26	3273

Literature-anchored findings (GeneRIF, showing 11)

• TEM7 expression level closely parallels histology-based prognostication of OGS metastasis and, therefore, it is a therapeutic target. (PMID:17560052)
• TEM7 may play significant role in proliferation and maintenance of neovascular endothelial cells in fibrovascular membranes. TEM7 may be molecular target for new diagnostic and therapeutic strategies for proliferative diabetic retinopathy. (PMID:18316703)
• All osteosarcoma cell lines, 6/9 tumors but none of the bone specimens expressed mRNA of TEM7 secreted forms 1 and 2. (PMID:20032373)
• TEM-7 is a vascular protein associated with angiogenic states. TEM-7 is a novel and attractive target for antiangiogenic therapy. (PMID:21958527)
• PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF. (PMID:25535841)
• Immunohistochemical analysis of 122 gliomas showed that TGLI1 expression was positively correlated with VEGF-C, TEM7 and microvessel density. (PMID:26093087)
• PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice. (PMID:29890852)
• Study revealed that over-expression of PLXDC1 per se was able to change partly the growth features of U87MG glioblastoma cells. Molecularly, PLXDC1 regulated the epithelial to mesenchymal transition program of tumor cells, whereby its silencing increased the mRNA levels of epithelial transcripts, whereas those of mesenchymal marker genes were reduced. (PMID:30414187)
• Serum TEM5 and TEM7 concentrations correlate with clinicopathologic features and poor prognosis of colorectal cancer patients (PMID:31352222)
• Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV). (PMID:33657166)
• PLXDC1 serves as a potential prognostic marker and involves in malignant progression and macrophage polarization in colon cancer. (PMID:39267413)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxdc1	ENSDARG00000078417
mus_musculus	Plxdc1	ENSMUSG00000017417
rattus_norvegicus	Plxdc1	ENSRNOG00000021536
drosophila_melanogaster	l(1)G0289	FBGN0028331
caenorhabditis_elegans		WBGENE00007982

Paralogs (1): PLXDC2 (ENSG00000120594)

Protein

Protein identifiers

Plexin domain-containing protein 1 — Q8IUK5 (reviewed: Q8IUK5)

Alternative names: Tumor endothelial marker 3, Tumor endothelial marker 7

All UniProt accessions (7): B4E173, C9JCL2, C9JWQ3, Q8IUK5, J3KS04, J3QR40, J3QRR7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in endothelial cell capillary morphogenesis.

Subunit / interactions. Interacts with NID1. May interact with CTTN.

Subcellular location. Secreted Cell membrane. Cell junction. Tight junction Secreted Secreted Cytoplasm.

Tissue specificity. Detected in urine (at protein level). Detected in endothelial cells from colorectal cancer, and in endothelial cells from primary cancers of the lung, liver, pancreas, breast and brain. Not detectable in endothelial cells from normal tissue. Expressed in fibrovascular membrane with increased expression in individuals with proliferative diabetic retinopathy.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the plexin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IUK5-1	1, TEM7-M	yes
Q8IUK5-2	2, TEM7-S1
Q8IUK5-3	3, TEM7-S2
Q8IUK5-4	4, TEM7-I

RefSeq proteins (1): NP_065138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002165	Plexin_repeat	Repeat
IPR031152	PLXDC	Family

Pfam: PF01437

UniProt features (22 total): splice variant 5, region of interest 4, compositionally biased region 3, glycosylation site 3, topological domain 2, signal peptide 1, chain 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-Q8IUK5-F1	72.85	0.44

Functional residue map

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

Glycosylation sites (3): 33, 80, 197

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 253 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, LU_TUMOR_VASCULATURE_UP, GOBP_BLOOD_VESSEL_MORPHOGENESIS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, KUNINGER_IGF1_VS_PDGFB_TARGETS_DN, GOCC_NEURON_PROJECTION, GOCC_CELL_CELL_JUNCTION, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, LU_TUMOR_ENDOTHELIAL_MARKERS_UP, LEIN_CEREBELLUM_MARKERS, GAVIN_FOXP3_TARGETS_CLUSTER_P3, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP

GO Biological Process (2): angiogenesis (GO:0001525), spinal cord development (GO:0021510)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), dendrite (GO:0030425), neuronal cell body (GO:0043025), signaling receptor complex (GO:0043235), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
central nervous system development	1
anatomical structure development	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
protein-containing complex	1
cell junction	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXDC1	CD248	Q9HCU0	791
PLXDC1	RASD2	Q96D21	777
PLXDC1	ADGRA2	Q96PE1	661
PLXDC1	ARHGEF17	Q96PE2	640
PLXDC1	ANTXR1	Q9H6X2	544
PLXDC1	HIGD1B	Q9P298	455
PLXDC1	FAM47E	Q6ZV65	417
PLXDC1	PTPRF	P10586	414
PLXDC1	TNS3	Q68CZ2	406
PLXDC1	FBXL20	Q96IG2	401
PLXDC1	IPO5	O00410	400
PLXDC1	OXA1L	Q15070	395
PLXDC1	RARA	P10276	385
PLXDC1	CDK12	Q9NYV4	375
PLXDC1	RPRML	Q8N4K4	364

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LIN7C	ABLIM1	psi-mi:“MI:0914”(association)	0.530
PLXDC1	C5AR2	psi-mi:“MI:0915”(physical association)	0.370
PLXDC1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
PLXDC1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
LIN7B	ABLIM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): PLXDC1 (Two-hybrid), PLXDC1 (Synthetic Lethality), PLXDC1 (Affinity Capture-MS), PLXDC1 (Two-hybrid), PLXDC1 (Two-hybrid), PLXDC1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A291NVT7, A0A4Y5X186, A0A4Y5X1A7, B0VXV3, B0VXV4, O42493, O43278, P01060, P05486, P08163, P0DN42, P0DN43, P0DTJ2, P0DTJ3, P16229, P17668, P48250, P56688, P58990, P67862, Q00945, Q07662, Q07663, Q08E66, Q23247, Q2XXR7, Q2XXR8, Q330K6, Q4R128, Q56R10, Q56R11, Q58T08, Q7M428, Q7TPG5, Q7TPG6, Q7TPG7, Q7TPG8, Q7TQN3, Q7Z5A8, Q7Z5A9

Diamond homologs: Q6DE92, Q6UX71, Q8IUK5, Q91ZV7, Q9DC11

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2903 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39077908:CTTA:C	donor_loss	1.0000
17:39077909:TTACC:T	donor_loss	1.0000
17:39077910:TAC:T	donor_loss	1.0000
17:39077911:A:AC	donor_gain	1.0000
17:39077911:AC:A	donor_gain	1.0000
17:39077911:ACCTT:A	donor_gain	1.0000
17:39077912:C:CT	donor_gain	1.0000
17:39077912:CC:C	donor_gain	1.0000
17:39077912:CCT:C	donor_gain	1.0000
17:39077912:CCTT:C	donor_gain	1.0000
17:39077912:CCTTC:C	donor_gain	1.0000
17:39078045:CTGC:C	acceptor_gain	1.0000
17:39078049:C:CC	acceptor_gain	1.0000
17:39078050:T:A	acceptor_loss	1.0000
17:39079093:A:AC	donor_gain	1.0000
17:39079093:ATG:A	donor_gain	1.0000
17:39079094:T:C	donor_gain	1.0000
17:39079100:TCACC:T	donor_loss	1.0000
17:39079101:CACCT:C	donor_loss	1.0000
17:39079102:A:AT	donor_loss	1.0000
17:39079102:ACCT:A	donor_gain	1.0000
17:39079103:CCTC:C	donor_gain	1.0000
17:39079105:T:TA	donor_gain	1.0000
17:39079161:GCAT:G	acceptor_gain	1.0000
17:39079162:CAT:C	acceptor_gain	1.0000
17:39079162:CATC:C	acceptor_gain	1.0000
17:39079163:AT:A	acceptor_gain	1.0000
17:39079165:C:CC	acceptor_gain	1.0000
17:39079165:CT:C	acceptor_loss	1.0000
17:39079166:T:C	acceptor_loss	1.0000

AlphaMissense

3308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39079128:C:A	W342C	0.998
17:39079128:C:G	W342C	0.998
17:39083476:C:A	W324C	0.998
17:39083476:C:G	W324C	0.998
17:39107503:C:A	W205C	0.998
17:39107503:C:G	W205C	0.998
17:39107505:A:G	W205R	0.998
17:39107505:A:T	W205R	0.998
17:39108241:G:C	F158L	0.998
17:39108241:G:T	F158L	0.998
17:39108243:A:G	F158L	0.998
17:39083473:G:C	C325W	0.996
17:39083474:C:G	C325S	0.996
17:39083475:A:T	C325S	0.996
17:39108170:A:G	F182S	0.996
17:39079130:A:G	W342R	0.995
17:39079130:A:T	W342R	0.995
17:39079162:C:G	C331S	0.995
17:39079163:A:T	C331S	0.995
17:39083475:A:G	C325R	0.995
17:39083478:A:G	W324R	0.995
17:39083478:A:T	W324R	0.995
17:39105896:A:G	S257P	0.995
17:39107455:G:C	F221L	0.995
17:39107455:G:T	F221L	0.995
17:39107457:A:G	F221L	0.995
17:39087675:T:C	Y280C	0.994
17:39105890:C:G	A259P	0.994
17:39107510:A:T	V203D	0.994
17:39108177:C:G	A180P	0.994

dbSNP variants (sampled 300 via entrez): RS1000045226 (17:39086762 T>C), RS1000061948 (17:39143496 C>T), RS1000159533 (17:39120182 G>A), RS1000265804 (17:39068247 C>T), RS1000288126 (17:39109522 C>A,T), RS1000311639 (17:39149728 A>G), RS1000317672 (17:39091685 G>T), RS1000328726 (17:39086057 G>A), RS1000360032 (17:39097924 G>A,C,T), RS1000368294 (17:39144395 C>T), RS1000371536 (17:39091512 G>A), RS1000418898 (17:39144736 G>A), RS1000421442 (17:39132466 C>T), RS1000453047 (17:39126873 C>A,T), RS1000492155 (17:39121796 T>C)

Disease associations

OMIM: gene MIM:606826 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008916_86	Asthma	2.000000e-14
GCST011624_10	Tau burden	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	increases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	increases expression	1
bisphenol A	increases expression	1
terbufos	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, decreases expression	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	increases abundance, decreases expression	1
entinostat	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	increases expression	1
Vorinostat	increases expression	1
Cadmium	decreases expression, increases abundance	1
Diazinon	decreases methylation	1
Fonofos	decreases methylation	1
Hydralazine	increases expression, affects cotreatment	1
Parathion	decreases methylation	1
Phthalic Acids	decreases expression	1
Progesterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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