PROCR

Summary

PROCR (protein C receptor, HGNC:9452) is a protein-coding gene on chromosome 20q11.22, encoding Endothelial protein C receptor (Q9UNN8). Binds activated protein C.

The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer.

Source: NCBI Gene 10544 — RefSeq curated summary.

At a glance

• GWAS associations: 37
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_006404

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9452
Approved symbol	PROCR
Name	protein C receptor
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	EPCR, CCD41, CD201
Ensembl gene	ENSG00000101000
Ensembl biotype	protein_coding
OMIM	600646
Entrez	10544

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000216968, ENST00000634509, ENST00000635377, ENST00000852804, ENST00000852805, ENST00000930190

RefSeq mRNA: 1 — MANE Select: NM_006404 NM_006404

CCDS: CCDS13248

Canonical transcript exons

ENST00000216968 — 4 exons

Exon	Start	End
ENSE00000661565	35174702	35174953
ENSE00000661566	35176168	35176446
ENSE00000860180	35176698	35177362
ENSE00001049003	35172072	35172224

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.6688 / max 1130.3585, expressed in 1657 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184288	49.1736	1637
184283	1.6884	918
184285	1.0457	365
184286	0.5881	384
184289	0.5014	317
184287	0.3426	199
184284	0.3291	134

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	98.17	gold quality
germinal epithelium of ovary	UBERON:0001304	97.40	gold quality
tendon of biceps brachii	UBERON:0008188	96.49	gold quality
omental fat pad	UBERON:0010414	95.95	gold quality
peritoneum	UBERON:0002358	95.91	gold quality
mucosa of stomach	UBERON:0001199	95.76	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.13	gold quality
right coronary artery	UBERON:0001625	94.45	gold quality
parietal pleura	UBERON:0002400	94.29	gold quality
synovial joint	UBERON:0002217	94.23	gold quality
vena cava	UBERON:0004087	93.49	gold quality
left uterine tube	UBERON:0001303	92.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.51	gold quality
calcaneal tendon	UBERON:0003701	92.32	gold quality
tendon	UBERON:0000043	92.25	gold quality
descending thoracic aorta	UBERON:0002345	91.80	gold quality
left coronary artery	UBERON:0001626	91.40	gold quality
right atrium auricular region	UBERON:0006631	91.30	gold quality
thoracic aorta	UBERON:0001515	91.17	gold quality
layer of synovial tissue	UBERON:0007616	91.17	gold quality
decidua	UBERON:0002450	91.11	gold quality
ascending aorta	UBERON:0001496	91.10	gold quality
coronary artery	UBERON:0001621	90.99	gold quality
body of uterus	UBERON:0009853	90.86	gold quality
placenta	UBERON:0001987	90.77	gold quality
adipose tissue	UBERON:0001013	90.66	gold quality
cardiac atrium	UBERON:0002081	90.28	gold quality
connective tissue	UBERON:0002384	90.24	gold quality
tibial nerve	UBERON:0001323	89.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.64	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	802.47
E-HCAD-13	yes	503.97
E-MTAB-10662	yes	200.81
E-HCAD-11	yes	54.69
E-HCAD-1	yes	20.43
E-GEOD-135922	yes	9.95
E-MTAB-7052	no	119.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

32 targeting PROCR, 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-126-5P	100.00	72.71	3180
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-299-3P	97.73	66.67	773

Literature-anchored findings (GeneRIF, showing 40)

• A 23bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function. Since protein C activation depends on the concentration of EPCR, patients with the EPCR insertion could have a diminished protein C activation capacity. (PMID:11686350)
• Our findings showed that the EPCR 23bp insertion is very rare in both patients with VTE and the general population and failed to support an association between the EPCR 23bp insertion and an increased risk of VTE. (PMID:11776299)
• Functional analysis of a hypersensitive site in the 5’ flanking region of the hEPCR gene in endothelial cells identified multiple regions, containing high and low homology consensus Sp1 binding sequences, that were protected from methylation. (PMID:12560236)
• data suggest that activated protein C regulates calcium concentration in human brain endothelium and in human umbilical vein endothelial cells by binding to endothelial protein C receptor and signaling via protease activated receptor-1 (PMID:12586611)
• Endothelial protein C receptor expressed by eosinophils activated with protein C or activated protein C arrests directed migration (PMID:12897745)
• Endothelial protein C receptor may play an important inflammation-related role in plaque development. (PMID:15080580)
• individuals carrying the 4600AG EPCR genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism (PMID:15116250)
• Anti-EPCR autoantibodies can be detected in antiphospholid syndrome patients and are independent risk factors for fetal death. (PMID:15150078)
• Review. TM, APC, & EPCR impact coagulation, inflammation, fibrinolysis, & cell proliferation. We review the functions of this complex multimolecular system & how its components maintain homeostasis under hypercoagulable &/or proinflammatory conditions. (PMID:15178554)
• this study does not show a strong association between EPCR haplotypes and thrombosis risk, but low sEPCR levels may reduce the risk of deep venous thrombosis (PMID:15304035)
• protein C binding to sEPCR and phospholipids is broadly dependent on correct Gla domain folding, but can be selectively influenced by judicious mutation (PMID:15634335)
• endothelial protein C receptor ligation and sphingosine 1-phosphate receptor transactivation results in endothelial cell cytoskeletal rearrangement and barrier protection through activated protein C (PMID:15710622)
• EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219Gly EPCR phenotype. (PMID:15921688)
• the vascular dysfunction characteristic of systemic lupus erythematosus may be related to a dramatically altered distribution of EPCR, both soluble and membrane-bound forms (PMID:15954900)
• protein C receptor autoantibodies may have a role in acute myocardial infarction in young women (PMID:15978102)
• EPCR 4600A/G and 4678G/C polymorphisms may be involved in venous thromboembolism in carriers of factor V Leiden (PMID:16113830)
• CRP significantly decreases the expression of thrombomodulin and EPCR in human endothelial cells, thereby promoting thrombogenic conditions. (PMID:16153429)
• In vascular endotheliumt, binds activated protein C, generating an anti-inflammatory response. (PMID:16354176)
• In cultured keratinocytes, EPCR expression was upregulated by the addition of activated protein C and inhibited by tumor necrosis factor-alpha (PMID:16354200)
• the A3 haplotype does promote cellular shedding in either 293 or endothelial cells and therefore is likely directly contributory to the higher soluble EPCR levels seen in patients carrying this haplotype (PMID:16409473)
• study confirms that there is a strong association between A3 haplotype and elevated sEPCR levels; we suggest that elevated sEPCR levels might increase the risk of stroke at pediatric age (PMID:17027065)
• possible role for high levels of thrombomodulin as a marker of HCC development in patients with cirrhosis, whereas high levels of EPCR are a possible marker of worse HCC prognosis, being a sign of endothelial damage of large vessels (PMID:17049585)
• Gamma-carboxyglutamic acid–> Lysine mutation causes a significant reduction in the binding force between this protein and protein C. (PMID:17054378)
• Release of EPCR into the conditioned medium was inhibited by the metalloproteinase inhibitors TAPI and GM6001, indicating that the shedding of EPCR from the alveolar epithelium is mediated by a metalloproteinase. (PMID:17099142)
• mutations in the EPCR are not a major cause of recurrent miscarriage although they may exert a modifier effect in combination with other variants (PMID:17099210)
• the EPCR sequence requirement for shedding is amino acids from residue 193 to residue 200. ADAM17 is responsible for EPCR shedding. (PMID:17155946)
• EPCR expression is detected in smooth muscle cells in the fibrous cap of human carotid artery plaques. (PMID:17170365)
• EPCR serves as a cellular binding site for FVII/FVIIa (PMID:17327234)
• the presence of anti-EPCR autoantibodies is a moderate risk factor for deep vein thrombosis in the general population (PMID:17439632)
• Homozygous 23-bp insertion of endothelial protein c receptor gene is associated with fatal sepsis (PMID:17454790)
• relationship between plasma sEPCR levels and development of arteriovenous fistula thromboses (PMID:17570903)
• when EPCR is bound by protein C, the PAR-1 cleavage-dependent protective signaling responses in endothelial cells can be mediated by either thrombin or APC. (PMID:17823308)
• Highlights the different mutations/polymorphisms reported in the EPCR gene and their association with the risk of thrombosis. (PMID:17849044)
• the sEPCRisoform could contribute to the regulatory effect of sEPCR in plasma. (PMID:18073349)
• Failed to validate association of EPCR gene polymorphisms with venous thromboembolism amoung Californians of European ancestry. (PMID:18278202)
• in 20210A carriers the venous thromboembolism risk is influenced both by the actual prothrombin levels and by the EPCR A3 haplotype, via its effect on sEPCR levels (PMID:18403391)
• tEPCR behaves as sEPCR generated by shedding of the cellular endothelial cell protein C receptor (PMID:18443268)
• The EPCR A1 haplotype reduced the risk for recurrent miscarriage in carriers of FV Leiden. (PMID:18539144)
• Expression of protein-C receptor in vascular endothelium is activated by aldesterone. (PMID:18555797)
• Possible role of soluble EPCR in the pathogenesis of Behcet’s disease. Studies of mutations and polymorphisms in EPCR gene in patients with Behcet’s disease might bring to light pathogenic mechanism of ocular and systemic vascular complications. (PMID:18604550)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Procr	ENSMUSG00000027611
rattus_norvegicus	Procr	ENSRNOG00000019330

Protein

Protein identifiers

Endothelial protein C receptor — Q9UNN8 (reviewed: Q9UNN8)

Alternative names: Activated protein C receptor, Endothelial cell protein C receptor

All UniProt accessions (3): Q9UNN8, A0A0U1RQQ4, A0A0U1RRC4

UniProt curated annotations — full annotation on UniProt →

Function. Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation.

Subcellular location. Membrane.

Tissue specificity. Expressed strongly in the endothelial cells of arteries and veins in heart and lung, less intensely in capillaries in the lung and skin, and not at all in the endothelium of small vessels of the liver and kidney.

Post-translational modifications. N-glycosylated. A soluble form exists; probably released by a metalloprotease. Seems to have the same activity as the membrane-bound form.

RefSeq proteins (1): NP_006395* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR015669	Endothetial_C_recpt	Family
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily

Pfam: PF16497

UniProt features (31 total): strand 10, helix 6, glycosylation site 4, sequence conflict 2, topological domain 2, turn 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, disulfide bond 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1LQV	X-RAY DIFFRACTION	1.6
3JTC	X-RAY DIFFRACTION	1.6
7Q5D	X-RAY DIFFRACTION	1.8
7OKV	X-RAY DIFFRACTION	1.85
7OKS	X-RAY DIFFRACTION	1.95
7OKT	X-RAY DIFFRACTION	1.95
7OKU	X-RAY DIFFRACTION	1.95
1L8J	X-RAY DIFFRACTION	2
4V3D	X-RAY DIFFRACTION	2.65
4V3E	X-RAY DIFFRACTION	2.9
9TJX	X-RAY DIFFRACTION	3
6SNY	X-RAY DIFFRACTION	3.11
8C44	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNN8-F1	87.27	0.70

Functional residue map

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

Disulfide bonds (1): 118–186

Glycosylation sites (4): 47, 64, 136, 172

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140875

MSigDB gene sets: 264 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_52, GOBP_REGULATION_OF_COAGULATION, BECKER_TAMOXIFEN_RESISTANCE_UP, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOCC_CELL_SURFACE, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GGGTGGRR_PAX4_03, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GERY_CEBP_TARGETS

GO Biological Process (3): blood coagulation (GO:0007596), negative regulation of coagulation (GO:0050819), hemostasis (GO:0007599)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), centrosome (GO:0005813), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
coagulation	2
hemostasis	1
wound healing	1
regulation of coagulation	1
negative regulation of multicellular organismal process	1
regulation of body fluid levels	1
molecular transducer activity	1
binding	1
centriole	1
microtubule organizing center	1
membrane	1
cell periphery	1
cell-substrate junction	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROCR	THBD	P07204	998
PROCR	F2R	P25116	978
PROCR	F10	P00742	958
PROCR	CMC2	Q9NRP2	928
PROCR	NSL1	Q96IY1	922
PROCR	F7	P08709	915
PROCR	TFPI	P10646	853
PROCR	PROC	P04070	846
PROCR	CD36	P16671	832
PROCR	SCARB2	Q14108	832
PROCR	SCARB1	Q8WTV0	828
PROCR	PRTN3	P15637	771
PROCR	PITRM1	Q5JRX3	771
PROCR	CPB2	Q96IY4	724
PROCR	ICAM1	P05362	721

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PROCR	F2R	psi-mi:“MI:0915”(physical association)	0.640
PROCR	F2R	psi-mi:“MI:0914”(association)	0.640
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APC	PROCR	psi-mi:“MI:0407”(direct interaction)	0.440
PSMD9	PROCR	psi-mi:“MI:0407”(direct interaction)	0.440
ARID4A	PROCR	psi-mi:“MI:0915”(physical association)	0.400
ALKBH5	PROCR	psi-mi:“MI:0915”(physical association)	0.400
	RAP1BL	psi-mi:“MI:0915”(physical association)	0.400
PROCR	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.400
		psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
PCDHGC3	HRAS	psi-mi:“MI:0914”(association)	0.350
SHC1	KDM1A	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
F2R	CAV1	psi-mi:“MI:0914”(association)	0.350
CAV1	F2R	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350
DMTN	PROCR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS), PROCR (Affinity Capture-MS)

ESM2 similar proteins: A2ASA8, A5PJJ5, A6NE52, A6NHZ5, B6CZ46, E9QAM5, G7PWZ3, P08571, P10810, P33076, P52824, P79621, P86243, Q15048, Q15345, Q1L8H0, Q28680, Q32PG9, Q3U1Y4, Q3UJB3, Q3UWY1, Q3V1N1, Q3V3V9, Q3ZBI5, Q569B5, Q5BK65, Q5DU56, Q5M936, Q63035, Q63691, Q640Z9, Q66H52, Q68EF8, Q6F5E8, Q6GPH6, Q6P5E8, Q6QNU9, Q6R5P0, Q7RTR2, Q80VA5

Diamond homologs: Q28105, Q4V8I1, Q64695, Q9UNN8, P23043

SIGNOR signaling

0 interactions.

Disease & clinical

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	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

746 predictions. Top by Δscore:

Variant	Effect	Δscore
20:35172154:G:GT	donor_gain	1.0000
20:35172221:GATG:G	donor_gain	1.0000
20:35174949:GGCCT:G	donor_gain	1.0000
20:35174950:GCCT:G	donor_gain	1.0000
20:35174950:GCCTG:G	donor_gain	1.0000
20:35174953:TG:T	donor_loss	1.0000
20:35174954:G:C	donor_loss	1.0000
20:35174954:G:GG	donor_gain	1.0000
20:35176166:A:AG	acceptor_gain	1.0000
20:35176167:G:GA	acceptor_gain	1.0000
20:35176167:GTT:G	acceptor_gain	1.0000
20:35176167:GTTC:G	acceptor_gain	1.0000
20:35176443:AAAGG:A	donor_loss	1.0000
20:35176444:AAGGT:A	donor_loss	1.0000
20:35176447:G:GA	donor_loss	1.0000
20:35176448:T:A	donor_loss	1.0000
20:35172222:ATGGT:A	donor_loss	0.9900
20:35172223:TGGT:T	donor_loss	0.9900
20:35172225:G:GG	donor_gain	0.9900
20:35172225:GTGA:G	donor_loss	0.9900
20:35174951:CCT:C	donor_gain	0.9900
20:35174952:CT:C	donor_gain	0.9900
20:35174956:GA:G	donor_gain	0.9900
20:35174958:G:GG	donor_gain	0.9900
20:35176162:CCACA:C	acceptor_loss	0.9900
20:35176163:CACA:C	acceptor_loss	0.9900
20:35176164:ACAG:A	acceptor_loss	0.9900
20:35176165:CA:C	acceptor_loss	0.9900
20:35176166:A:T	acceptor_loss	0.9900
20:35176167:GT:G	acceptor_gain	0.9900

AlphaMissense

1523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:35174868:G:C	W79C	0.996
20:35174868:G:T	W79C	0.996
20:35176295:G:C	W150C	0.996
20:35176295:G:T	W150C	0.996
20:35176293:T:A	W150R	0.990
20:35176293:T:C	W150R	0.990
20:35176272:T:C	F143L	0.989
20:35176273:T:G	F143C	0.989
20:35176274:C:A	F143L	0.989
20:35176274:C:G	F143L	0.989
20:35176273:T:C	F143S	0.985
20:35176386:T:C	F181L	0.985
20:35176388:C:A	F181L	0.985
20:35176388:C:G	F181L	0.985
20:35176387:T:G	F181C	0.983
20:35174773:G:C	A48P	0.980
20:35174953:T:C	F108L	0.980
20:35176169:T:A	F108L	0.980
20:35176169:T:G	F108L	0.980
20:35176751:A:C	S219R	0.977
20:35176753:T:A	S219R	0.977
20:35176753:T:G	S219R	0.977
20:35176187:C:G	C114W	0.976
20:35176402:G:A	C186Y	0.974
20:35174767:G:C	G46R	0.971
20:35176168:T:G	F108C	0.970
20:35176387:T:C	F181S	0.970
20:35176185:T:C	C114R	0.969
20:35176233:T:C	F130L	0.969
20:35176235:C:A	F130L	0.969

dbSNP variants (sampled 300 via entrez): RS1000032424 (20:35188934 C>T), RS1000108047 (20:35212590 C>G), RS1000207485 (20:35182896 C>G), RS1000311052 (20:35172641 G>A,C,T), RS1000418473 (20:35170866 G>A), RS1000454336 (20:35205332 G>A), RS1000518926 (20:35179358 A>G), RS1000524478 (20:35186767 T>C), RS1000775061 (20:35192823 T>C,G), RS1000811735 (20:35212245 G>T), RS1000875654 (20:35200306 G>A), RS1000911654 (20:35204364 C>T), RS1000947247 (20:35199864 A>G), RS1001061536 (20:35207316 C>T), RS1001145159 (20:35193252 T>A)

Disease associations

OMIM: gene MIM:600646 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000625_2	Factor VII levels	6.000000e-37
GCST000780_3	Protein C levels	2.000000e-200
GCST001049_5	D-dimer levels	4.000000e-06
GCST001365_6	Anticoagulant levels	4.000000e-09
GCST001378_3	Hemostatic factors and hematological phenotypes	2.000000e-06
GCST001378_9	Hemostatic factors and hematological phenotypes	4.000000e-34
GCST001573_2	Prothrombin time	5.000000e-13
GCST001728_18	Ulcerative colitis	2.000000e-08
GCST001956_51	Height	1.000000e-15
GCST002337_169	Amyotrophic lateral sclerosis (sporadic)	4.000000e-06
GCST002686_2	Protein C levels	1.000000e-64
GCST002808_10	Venous thromboembolism	2.000000e-08
GCST003390_7	Thrombosis	7.000000e-09
GCST005195_15	Coronary artery disease	7.000000e-12
GCST005196_244	Coronary artery disease	5.000000e-12
GCST005956_31	Waist-to-hip ratio adjusted for BMI	8.000000e-08
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST006017_9	Prothrombin time	6.000000e-24
GCST006020_23	Diastolic blood pressure	4.000000e-08
GCST006119_3	Protein C levels	6.000000e-57
GCST006119_9	Protein C levels	9.000000e-237
GCST007401_11	Factor VII activity	3.000000e-64
GCST007401_34	Factor VII activity	9.000000e-17
GCST007401_35	Factor VII activity	3.000000e-59
GCST007402_2	Factor VII activity or levels	7.000000e-64
GCST008070_109	HDL cholesterol levels	6.000000e-06
GCST008075_86	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-07
GCST008084_180	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-06
GCST008084_87	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004619	factor VII measurement
EFO:0004633	protein C measurement
EFO:0004507	D dimer measurement
EFO:0004503	hematological measurement
EFO:0008390	prothrombin time measurement
EFO:0003907	deep vein thrombosis
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006336	diastolic blood pressure
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0008111	diet measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1415774	PROCR		0.00	0
rs9574	PROCR		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	7
Valproic Acid	increases expression, affects expression, affects cotreatment	6
Aflatoxin B1	affects expression, increases expression	5
Vorinostat	affects cotreatment, increases expression, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Tetradecanoylphorbol Acetate	increases secretion, decreases reaction, increases expression, affects localization, decreases cleavage (+3 more)	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
entinostat	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Dexamethasone	increases expression, affects cotreatment	2
Methyl Methanesulfonate	increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methyleugenol	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases expression	1
withaferin A	increases reaction, decreases reaction, increases cleavage	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8N6	Abcam HCT 116 PROCR KO	Cancer cell line	Male
CVCL_B9AR	Abcam MCF-7 PROCR KO	Cancer cell line	Female
CVCL_B9QG	Abcam A-549 PROCR KO	Cancer cell line	Male
CVCL_TH17	HAP1 PROCR (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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