ECSCR

Summary

ECSCR (endothelial cell surface expressed chemotaxis and apoptosis regulator, HGNC:35454) is a protein-coding gene on chromosome 5q31.2, encoding Endothelial cell-specific chemotaxis regulator (Q19T08). Regulates endothelial chemotaxis and tube formation. In precision oncology, ECSCR EXPRESSION confers sensitivity to Angiogenesis Inhibitor in Cancer (CIViC Level B).

The protein encoded by this gene is primarily found in endothelial cells and blood vessels, where it is involved in cell shape changes and EGF-induced cell migration. It can enhance the activation of vascular endothelial growth factor receptor-2/kinase insert domain receptor and also promote the proteolysis of internalized kinase insert domain receptor. This gene may play a role in angiogenesis-related diseases. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 641700 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 2 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001077693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35454
Approved symbol	ECSCR
Name	endothelial cell surface expressed chemotaxis and apoptosis regulator
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	ECSM2, ARIA
Ensembl gene	ENSG00000249751
Ensembl biotype	protein_coding
OMIM	615736
Entrez	641700

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000618155, ENST00000857214, ENST00000857215, ENST00000857216, ENST00000857217, ENST00000857218, ENST00000857219, ENST00000857220, ENST00000857221, ENST00000917018, ENST00000941547

RefSeq mRNA: 2 — MANE Select: NM_001077693 NM_001077693, NM_001293739

CCDS: CCDS75317

Canonical transcript exons

ENST00000618155 — 10 exons

Exon	Start	End
ENSE00002040593	139448560	139448908
ENSE00002048816	139462610	139462743
ENSE00002050044	139449078	139449174
ENSE00003716404	139456474	139456518
ENSE00003732727	139454825	139454923
ENSE00003733014	139455323	139455436
ENSE00003743645	139457545	139457604
ENSE00003746623	139454602	139454638
ENSE00003755852	139457757	139457807
ENSE00003756009	139458139	139458183

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 95.85.

FANTOM5 (CAGE): breadth broad, TPM avg 31.1898 / max 1139.4804, expressed in 693 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63760	31.1898	693

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	95.85	gold quality
placenta	UBERON:0001987	95.52	gold quality
apex of heart	UBERON:0002098	95.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.17	gold quality
adipose tissue	UBERON:0001013	94.96	gold quality
lung	UBERON:0002048	94.91	gold quality
smooth muscle tissue	UBERON:0001135	94.84	gold quality
omental fat pad	UBERON:0010414	94.76	gold quality
right lung	UBERON:0002167	94.56	gold quality
left uterine tube	UBERON:0001303	94.22	gold quality
myometrium	UBERON:0001296	93.66	gold quality
thoracic mammary gland	UBERON:0005200	93.62	gold quality
right lobe of thyroid gland	UBERON:0001119	93.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.86	gold quality
thyroid gland	UBERON:0002046	92.86	gold quality
left lobe of thyroid gland	UBERON:0001120	92.77	gold quality
body of uterus	UBERON:0009853	92.50	gold quality
heart left ventricle	UBERON:0002084	92.25	gold quality
mucosa of stomach	UBERON:0001199	91.87	gold quality
heart	UBERON:0000948	91.80	gold quality
tibial nerve	UBERON:0001323	91.63	gold quality
calcaneal tendon	UBERON:0003701	91.61	gold quality
right atrium auricular region	UBERON:0006631	91.41	gold quality
right coronary artery	UBERON:0001625	91.36	gold quality
left coronary artery	UBERON:0001626	91.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.11	gold quality
lower esophagus	UBERON:0013473	91.05	gold quality
fallopian tube	UBERON:0003889	90.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.69	gold quality
gall bladder	UBERON:0002110	90.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	85.75
E-ANND-3	yes	32.55
E-MTAB-6678	yes	14.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting ECSCR, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-203A-5P	96.33	65.03	714

Literature-anchored findings (GeneRIF, showing 7)

• Characterize a novel cell surface protein ECSM2 that regulates endothelial chemotaxis and tube formation, and interacts with filamin A. (PMID:18556573)
• ECSM2 is involved in cell-shape changes and actin cytoskeletal rearrangement, suppresses tyrosine phosphorylation signaling and ECSM2 can cross-talk with EGFR to attenuate the EGF-induced cell migration. (PMID:19267780)
• Knockdown of ARIA in HUVECs significantly reduced endothelial apoptosis without affecting either cell migration or proliferation. ARIA knockdown significantly increased inhibitor of apoptosis cIAP-1 and cIAP-2 protein expression (PMID:19416853)
• ECSM2 modulated bFGF-directed endothelial cell motility via the FGF receptor (FGFR)-extracellular regulated kinase (ERK)-focal adhesion kinase (FAK) pathway. (PMID:21720547)
• identification of three novel full-length splice variants potentially encoding different protein isoforms (PMID:23147565)
• Endothelial cell-specific chemotaxis receptor (ECSCR) enhances vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain receptor (KDR) activation and promotes proteolysis of internalized KDR. (PMID:23393131)
• Low expression level of ECSCR is associated with evasive resistance and disease progression in cancer. (PMID:26956051)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ecscr	ENSMUSG00000073599
rattus_norvegicus	Ecscr	ENSRNOG00000039593

Protein

Protein identifiers

Endothelial cell-specific chemotaxis regulator — Q19T08 (reviewed: Q19T08)

Alternative names: Apoptosis regulator through modulating IAP expression, Endothelial cell-specific molecule 2

All UniProt accessions (1): Q19T08

UniProt curated annotations — full annotation on UniProt →

Function. Regulates endothelial chemotaxis and tube formation. Has a role in angiogenesis and apoptosis via modulation of the actin cytoskeleton and facilitation of proteasomal degradation of the apoptosis inhibitors BIRC3/IAP1 and BIRC2/IAP2.

Subunit / interactions. Interacts with FLNA. Interacts with the 20S proteasome subunit PSMA7.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Highest expression in endothelial cells. Also detected in vascular smooth muscle, macrophages, lymphocytes, and mast cells.

Post-translational modifications. May be heavily O-glycosylated.

Similarity. Belongs to the ECSCR family.

RefSeq proteins (2): NP_001071161, NP_001280668 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026247	ECSCR	Family

Pfam: PF15820

UniProt features (12 total): compositionally biased region 3, topological domain 2, region of interest 2, signal peptide 1, chain 1, modified residue 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q19T08-F1	57.07	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 (1): 198

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TAXIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (7): angiogenesis (GO:0001525), apoptotic process (GO:0006915), chemotaxis (GO:0006935), negative regulation of angiogenesis (GO:0016525), cell differentiation (GO:0030154), positive regulation of proteasomal protein catabolic process (GO:1901800), positive regulation of endothelial cell apoptotic process (GO:2000353)

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

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to chemical	1
taxis	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cellular developmental process	1
proteasomal protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
positive regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECSCR	SPATA24	Q86W54	483
ECSCR	DNAJC18	Q9H819	479
ECSCR	FLNA	P21333	454
ECSCR	RILPL1	Q5EBL4	431
ECSCR	ZSCAN30	Q86W11	428
ECSCR	GALNT9	Q9HCQ5	427
ECSCR	ROBO4	Q8WZ75	419
ECSCR	CAPN8	A6NHC0	418
ECSCR	DLGAP4	Q9Y2H0	409
ECSCR	PROB1	E7EW31	403
ECSCR	SMIM33	A0A1B0GW64	403
ECSCR	PTN	P21246	401
ECSCR	CCNB3	Q8WWL7	391
ECSCR	FAM20C	Q8IXL6	387
ECSCR	R3HDM2	Q9Y2K5	379

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ECSCR	PSMA7	psi-mi:“MI:0915”(physical association)	0.510
PSMA7	ECSCR	psi-mi:“MI:0915”(physical association)	0.510
ECSCR	PTEN	psi-mi:“MI:0915”(physical association)	0.510
ECSCR	Pten	psi-mi:“MI:0915”(physical association)	0.400
ECSCR	PCNA	psi-mi:“MI:0915”(physical association)	0.370
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
ECSCR	RABGAP1L	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): PTEN (Affinity Capture-Western), ECSCR (Affinity Capture-Western), SOAT1 (Affinity Capture-MS), RABGAP1 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), RABGAP1L (Affinity Capture-MS), DUPD1 (Affinity Capture-MS), GALNT10 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), RAB4A (Affinity Capture-MS), ECSCR (Affinity Capture-MS), ECSCR (Affinity Capture-Western), PSMA7 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GW64, A4FUY1, A4IFL2, A6QPH9, A8MVS5, O54693, P0C8R9, P16070, P19438, P20944, P26051, P26842, P49772, P50555, Q0VAQ4, Q13261, Q14CZ8, Q19T08, Q29435, Q2KIX5, Q3TZW0, Q3U2E2, Q4R3D6, Q4V9L6, Q5BJT4, Q5T1S8, Q60522, Q640R3, Q6A044, Q6GTX8, Q6P6J9, Q6P9G4, Q6UX15, Q7TPF1, Q7YR73, Q7Z692, Q8C6Z1, Q8MI01, Q8N387, Q8R0A6

Diamond homologs: P0C8R9, Q19T08, Q2KIX5, Q3TZW0

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139454913:G:C	S129R	0.999
5:139454913:G:T	S129R	0.999
5:139454915:T:G	S129R	0.999
5:139454923:C:T	G126D	0.995
5:139455323:C:G	G126R	0.991
5:139454862:G:C	S146R	0.990
5:139454862:G:T	S146R	0.990
5:139454864:T:G	S146R	0.990
5:139454899:A:T	L134Q	0.990
5:139454878:A:T	L141Q	0.988
5:139454899:A:C	L134R	0.988
5:139454853:G:C	F149L	0.987
5:139454853:G:T	F149L	0.987
5:139454855:A:G	F149L	0.987
5:139455328:G:T	A124E	0.986
5:139455331:G:T	A123D	0.986
5:139449136:A:G	L184P	0.985
5:139455324:A:C	F125L	0.985
5:139455324:A:T	F125L	0.985
5:139455326:A:G	F125L	0.985
5:139454878:A:G	L141P	0.984
5:139454878:A:C	L141R	0.983
5:139454899:A:G	L134P	0.980
5:139454920:A:T	V127D	0.978
5:139449136:A:T	L184H	0.977
5:139454866:A:T	V145D	0.975
5:139454908:A:T	I131N	0.975
5:139454887:A:T	V138E	0.973
5:139454893:A:T	V136D	0.969
5:139454910:G:C	F130L	0.968

dbSNP variants (sampled 300 via entrez): RS1000344935 (5:139457176 C>A), RS1000366322 (5:139457870 G>C,T), RS1001205036 (5:139451064 C>G,T), RS1001278213 (5:139463331 C>T), RS1001310819 (5:139463023 C>T), RS1001582451 (5:139456307 C>T), RS1001825445 (5:139456655 C>T), RS1001885119 (5:139451291 TG>T,TGG), RS1001967600 (5:139449854 T>C), RS1002003490 (5:139449482 C>T), RS1002307810 (5:139462548 G>A,T), RS1002560955 (5:139457913 C>A,T), RS1002606816 (5:139449315 G>A), RS1003229792 (5:139455371 T>G), RS1003504839 (5:139462336 A>G)

Disease associations

OMIM: gene MIM:615736 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001538_15	Immune reponse to smallpox (secreted IFN-alpha)	3.000000e-14
GCST005951_151	Body mass index	6.000000e-07
GCST010725_68	Malaria	4.000000e-07
GCST010725_7	Malaria	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
ECSCR EXPRESSION	Angiogenesis Inhibitor	Cancer	Sensitivity/Response	CIViC B	EID1165

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
ascorbate-2-phosphate	affects binding, affects cotreatment, decreases expression	1
triadimefon	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Chir 99021	affects cotreatment, decreases expression, affects binding	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
bisphenol S	decreases expression	1
XAV939	affects binding, affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1
2,6-dichloro-(1,4)benzoquinone	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Ascorbic Acid	affects cotreatment, decreases expression, affects binding	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Hydrocortisone	decreases expression, affects cotreatment	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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