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
• GTEx eGene: eQTL in 10 tissues, sQTL in 2 (q < 0.05)
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.27 (unconstrained)
• 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: 18 — 15 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000618155

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000618155, ENST00000857214, ENST00000857215, ENST00000857216, ENST00000857217, ENST00000857218, ENST00000857219, ENST00000857220, ENST00000857221, ENST00000917018, ENST00000941547, ENST00000988585, ENST00001017866, ENST00001017867, ENST00001017868, ENST00001110788, ENST00001116297, ENST00001137505

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.

Highest expression (Bgee): upper lobe of left lung, placenta, apex of heart, subcutaneous adipose tissue, adipose tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ECSCR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	3.9e-12	-0.48	5:139461879:T:C
Muscle Skeletal	eqtl	1.1e-04	-0.20	5:139545512:C:T
Nerve Tibial	eqtl	2.4e-04	-0.36	5:139432413:T:C
Skin Sun Exposed Lower leg	eqtl	2.5e-04	-0.11	5:139471320:G:A
Esophagus Gastroesophageal Junction	eqtl	3.7e-04	-0.31	5:139327344:C:CTA
Stomach	sqtl	4.3e-03	+1.20	5:139913989:C:CA
Adipose Subcutaneous	eqtl	7.9e-03	+0.17	5:138591195:A:G
Colon Sigmoid	eqtl	2.3e-02	-0.40	5:140220945:C:T
Brain Cerebellum	eqtl	3.4e-02	-0.66	5:138663298:G:A
Spleen	eqtl	4.3e-02	-0.87	5:138714159:C:T
Brain Hypothalamus	sqtl	4.7e-02	+1.23	5:139849706:T:C
Brain Nucleus accumbens basal ganglia	eqtl	5.0e-02	-0.79	5:140032593:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
63760	31.1898	693

Top tissues by expression

showing 100 of 133 tissues 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
endocervix	UBERON:0000458	90.35	gold quality
metanephros cortex	UBERON:0010533	90.21	gold quality
ectocervix	UBERON:0012249	90.09	gold quality
lymph node	UBERON:0000029	89.26	gold quality
vagina	UBERON:0000996	88.93	gold quality
vermiform appendix	UBERON:0001154	88.54	gold quality
fundus of stomach	UBERON:0001160	88.23	gold quality
spleen	UBERON:0002106	87.92	gold quality
esophagus	UBERON:0001043	87.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.68	gold quality
urinary bladder	UBERON:0001255	87.64	gold quality
uterine cervix	UBERON:0000002	87.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.36	gold quality
muscle tissue	UBERON:0002385	86.25	gold quality
minor salivary gland	UBERON:0001830	85.86	gold quality
adult mammalian kidney	UBERON:0000082	85.78	gold quality
skin of leg	UBERON:0001511	85.74	gold quality
skin of abdomen	UBERON:0001416	85.69	gold quality
zone of skin	UBERON:0000014	85.53	gold quality
ascending aorta	UBERON:0001496	85.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.30	gold quality
thoracic aorta	UBERON:0001515	85.23	gold quality
prostate gland	UBERON:0002367	85.11	gold quality
rectum	UBERON:0001052	85.09	gold quality
saliva-secreting gland	UBERON:0001044	85.03	gold quality
muscle of leg	UBERON:0001383	85.03	gold quality
tibial artery	UBERON:0007610	85.02	gold quality
popliteal artery	UBERON:0002250	84.98	gold quality
small intestine	UBERON:0002108	84.73	gold quality
esophagus mucosa	UBERON:0002469	84.68	gold quality
colon	UBERON:0001155	84.35	gold quality
intestine	UBERON:0000160	84.33	gold quality
gastrocnemius	UBERON:0001388	84.22	gold quality
cortex of kidney	UBERON:0001225	84.19	gold quality
kidney	UBERON:0002113	84.17	gold quality
descending thoracic aorta	UBERON:0002345	83.74	gold quality
colonic epithelium	UBERON:0000397	83.60	gold quality
skeletal muscle tissue	UBERON:0001134	83.34	gold quality
body of stomach	UBERON:0001161	83.17	gold quality
transverse colon	UBERON:0001157	82.57	gold quality
stomach	UBERON:0000945	82.45	gold quality
left adrenal gland cortex	UBERON:0035825	82.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.24	gold quality
right adrenal gland	UBERON:0001233	82.15	gold quality
adrenal gland	UBERON:0002369	81.78	gold quality
left adrenal gland	UBERON:0001234	81.68	gold quality
substantia nigra	UBERON:0002038	81.68	gold quality
islet of Langerhans	UBERON:0000006	81.54	gold quality
right ovary	UBERON:0002118	80.93	gold quality
right adrenal gland cortex	UBERON:0035827	80.79	gold quality
multicellular organism	UBERON:0000468	80.68	gold quality
duodenum	UBERON:0002114	79.64	gold quality
ganglionic eminence	UBERON:0004023	79.18	gold quality
right uterine tube	UBERON:0001302	79.08	gold quality
Ammon’s horn	UBERON:0001954	78.86	gold quality
adenohypophysis	UBERON:0002196	78.24	gold quality
hypothalamus	UBERON:0001898	78.21	gold quality
pancreas	UBERON:0001264	78.07	gold quality
ovary	UBERON:0000992	77.97	gold quality
left ovary	UBERON:0002119	77.60	gold quality
lower esophagus mucosa	UBERON:0035834	77.44	gold quality
mucosa of transverse colon	UBERON:0004991	77.42	gold quality
putamen	UBERON:0001874	77.30	gold quality
tonsil	UBERON:0002372	77.07	gold quality
amygdala	UBERON:0001876	76.92	gold quality
body of pancreas	UBERON:0001150	76.85	gold quality
pituitary gland	UBERON:0000007	76.84	gold quality
temporal lobe	UBERON:0001871	76.76	gold quality
adrenal tissue	UBERON:0018303	76.37	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Placenta	tissue	31.5
Vagina	tissue	25.3
Adipose tissue	tissue	24.1
Smooth muscle	tissue	22.8
Lung	tissue	22.8
Heart muscle	tissue	18.9
Tongue	tissue	16.0
Breast	tissue	15.4
Urinary bladder	tissue	14.9
Fallopian tube	tissue	12.9
Endometrium 1	tissue	12.5
Cervix	tissue	12.4
Ovary	tissue	11.5
Gallbladder	tissue	11.4
Lymph node	tissue	10.9
Thyroid gland	tissue	10.7
Appendix	tissue	10.5
Skeletal muscle	tissue	10.4
Esophagus	tissue	9.1
Spleen	tissue	8.4
Frontal cortex	tissue	8.0
Caudate putamen	tissue	7.8
Rectum	tissue	7.5
Pituitary gland	tissue	7.1
Epididymis	tissue	7.0
Seminal vesicle	tissue	6.9
Tonsil	tissue	6.8
Colon	tissue	6.7
Skin 1	tissue	5.9
Kidney	tissue	5.4
Parathyroid gland	tissue	4.4
Liver	tissue	4.4
Duodenum	tissue	4.3
Prostate	tissue	4.3
Small intestine	tissue	4.1
Spinal cord	tissue	4.0
Adrenal gland	tissue	3.9
Substantia nigra	tissue	3.8
Superior colliculi	tissue	3.5
Stomach 1	tissue	3.2
Thymus	tissue	3.2
Choroid plexus	tissue	2.8
Midbrain	tissue	2.7
Locus coeruleus	tissue	2.7
Salivary gland	tissue	2.6
Thalamus	tissue	2.5
Medulla oblongata	tissue	2.4
Hippocampus	tissue	2.2
Pons	tissue	2.0
Cerebral cortex	tissue	1.7
Pancreas	tissue	1.7
Hippocampal formation	tissue	1.7
Entorhinal cortex	tissue	1.7
Retrosplenial and cingulate cortex	tissue	1.7
Prefrontal cortex	tissue	1.6
Testis	tissue	1.6
Septum	tissue	1.6
Insular cortex	tissue	1.6
Motor cortex	tissue	1.5
Nucleus accumbens	tissue	1.5

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (38.6), Posterior thalamic nucleus (5.7), Dorsal tegmental nucleus (5.0), Dorsal cochlear nucleus (4.8), Anterior thalamic nucleus, ventral (4.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ECSCR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.0033, LOEUF 1.27, missense Z -0.289 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000618155 — one region, missense o/e 1.05.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915795) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal thymus morphology	1
small thymus	1
abnormal spinal cord morphology	1
small seminal vesicle	1
increased circulating triglyceride level	1
increased circulating free fatty acids level	1
hemorrhage	1
abnormal seminal vesicle morphology	1
abnormal kidney morphology	1
abnormal epididymis morphology	1
enlarged kidney	1
increased circulating glycerol level	1
abnormal vascular endothelial cell migration	1
pathological neovascularization	1
enlarged epididymis	1
abnormal white adipose tissue physiology	1
enhanced lipolysis	1
decreased vascular endothelial cell apoptosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Canis lupus familiaris	P0C8R9	75.6%	Diamond
Bos taurus	Q2KIX5	57.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SMIM33	protein-coding	111064649
DNAJC18-AS1	ncRNA	124901082
SPATA24	protein-coding	202051
DNAJC18	protein-coding	202052
PROB1	protein-coding	389333
STING1	protein-coding	340061
MZB1	protein-coding	51237

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q19T08-F1	57.07	0.03

Human Protein Atlas

Protein class: Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; vesicles; nucleoplasm

Antibody reliability (HPA): IF supported

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)

Type	Positions
Phosphoserine	198

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (3): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

GO top-level categories

23 GO namespaces:

Category	Terms
cellular anatomical structure	2
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
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of angiogenesis	BP	mutant phenotype
positive regulation of endothelial cell apoptotic process	BP	mutant phenotype
positive regulation of proteasomal protein catabolic process	BP	mutant phenotype
cytosol	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 19 of 570 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECSCR	DNAJC18	Q9H819	486
ECSCR	SPATA24	Q86W54	479
ECSCR	PROB1	E7EW31	442
ECSCR	PTN	P21246	428
ECSCR	ZSCAN30	Q86W11	420
ECSCR	R3HDM2	Q9Y2K5	385
ECSCR	CST8	O60676	370
ECSCR	ASXL2	Q76L83	370
ECSCR	KAT6B	Q8WYB5	370
ECSCR	CAPN2	P17655	370
ECSCR	FAM20C	Q8IXL6	370
ECSCR	GALNT17	Q6IS24	370
ECSCR	GALNT9	Q9HCQ5	370
ECSCR	SHANK2	Q9UPX8	370
ECSCR	CAPN8	A6NHC0	370
ECSCR	DLGAP4	Q9Y2H0	370
ECSCR	CCNB3	Q8WWL7	370
ECSCR	RILPL1	Q5EBL4	370
ECSCR	C1R	P00736	370

IntAct

Human interaction partners of ECSCR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
PTEN	physical association	0.510	4
PSMA7	physical association	0.510	3
PCNA	physical association	0.370	1
RABGAP1L	association	0.350	1

BioGRID (14 interactions; top human partners by supporting records): PSMA7 (Affinity Capture-Western; 2 records), PTEN (Affinity Capture-Western; 2 records), COPS5 (Affinity Capture-MS), DUPD1 (Affinity Capture-MS), GALNT10 (Affinity Capture-MS), RAB4A (Affinity Capture-MS), RABGAP1 (Affinity Capture-MS), RABGAP1L (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ECSCR-KDR receptor complex	2	ECSCR, KDR

Disease & clinical

Genetic variants

Variant evidence for ECSCR: 2 ClinVar records (0 pathogenic / likely pathogenic); 1 CIViC cancer variant; 4 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 666):

Position(s)	Effect	Δscore	Sites
5:139454924–139454925	acceptor_loss	1.0000	6
5:139462608–139462609	donor_loss	1.0000	3
5:139449077	donor_loss	0.9900
5:139454823–139454824	donor_loss	0.9900	5
5:139456907	donor_gain	0.9900
5:139462608–139462609	donor_loss	0.9900	2
5:139449076–139449077	donor_loss	0.9800	4
5:139449080	donor_gain	0.9800
5:139449173	acceptor_gain	0.9800
5:139449175–139449176	acceptor_loss	0.9800	6

AlphaMissense

223 missense substitutions predicted likely pathogenic (of 1,331 scored), across 59 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F130	8	0.895	0.968
F125	8	0.876	0.985
F149	7	0.930	0.987
C151	7	0.843	0.940
M187	6	0.916	0.931
K188	6	0.851	0.934
V138	6	0.831	0.973
L184	6	0.826	0.985
V137	6	0.745	0.965
T183	6	0.692	0.766
V127	5	0.889	0.978
S146	5	0.887	0.990
A124	5	0.885	0.986
L141	5	0.867	0.988
R148	5	0.855	0.907
L134	5	0.851	0.990
I182	5	0.834	0.949
V145	5	0.830	0.975
G126	5	0.825	0.995
K162	5	0.731	0.790

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.19e-06
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	3.64e-05

Disease associations

OMIM: gene MIM:615736 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST001538_1	Immune reponse to smallpox (secreted IFN-alpha)	3e-14
GCST010725_43	Malaria	4e-7
GCST005951_96	Body mass index	6e-7
GCST010725_82	Malaria	2e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

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

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

EXPRESSION.

PharmGKB: 1 entry (CPIC guideline: no)

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 cotreatment, decreases expression, affects binding	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	decreases expression, affects binding, affects cotreatment	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 binding, affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Hydrocortisone	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.