PCOLCE

Summary

PCOLCE (procollagen C-endopeptidase enhancer, HGNC:8738) is a protein-coding gene on chromosome 7q22.1, encoding Procollagen C-endopeptidase enhancer 1 (Q15113). Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity.

Fibrillar collagen types I-III are synthesized as precursor molecules known as procollagens. These precursors contain amino- and carboxyl-terminal peptide extensions known as N- and C-propeptides, respectively, which are cleaved, upon secretion of procollagen from the cell, to yield the mature triple helical, highly structured fibrils. This gene encodes a glycoprotein which binds and drives the enzymatic cleavage of type I procollagen and heightens C-proteinase activity.

Source: NCBI Gene 5118 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_002593

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8738
Approved symbol	PCOLCE
Name	procollagen C-endopeptidase enhancer
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PCPE, PCPE1
Ensembl gene	ENSG00000106333
Ensembl biotype	protein_coding
OMIM	600270
Entrez	5118

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 7 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000223061, ENST00000460002, ENST00000462260, ENST00000468214, ENST00000472348, ENST00000482863, ENST00000486440, ENST00000487172, ENST00000490909, ENST00000496269, ENST00000862594, ENST00000862595, ENST00000937380, ENST00000965183, ENST00000965184, ENST00000965185

RefSeq mRNA: 1 — MANE Select: NM_002593 NM_002593

CCDS: CCDS5700

Canonical transcript exons

ENST00000223061 — 9 exons

Exon	Start	End
ENSE00000710689	100605676	100605812
ENSE00000710690	100605091	100605215
ENSE00001861120	100602363	100602551
ENSE00001871599	100607937	100608175
ENSE00003524395	100607452	100607523
ENSE00003528702	100606416	100606630
ENSE00003592467	100603959	100604217
ENSE00003626772	100607637	100607807
ENSE00003687690	100603430	100603538

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 219.7107 / max 4445.8183, expressed in 1619 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80011	204.2556	1078
80012	8.4480	776
80019	1.8669	925
80021	1.6855	765
80013	1.1775	545
80022	1.1558	496
80017	0.4814	259
80020	0.4396	244
80016	0.2004	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.54	gold quality
periodontal ligament	UBERON:0008266	99.50	gold quality
endocervix	UBERON:0000458	98.84	gold quality
tendon of biceps brachii	UBERON:0008188	98.67	gold quality
tibia	UBERON:0000979	98.60	gold quality
cartilage tissue	UBERON:0002418	98.57	gold quality
apex of heart	UBERON:0002098	98.37	gold quality
gall bladder	UBERON:0002110	98.25	gold quality
right coronary artery	UBERON:0001625	98.11	gold quality
layer of synovial tissue	UBERON:0007616	97.96	gold quality
body of uterus	UBERON:0009853	97.92	gold quality
nerve	UBERON:0001021	97.84	gold quality
tibial nerve	UBERON:0001323	97.84	gold quality
right ovary	UBERON:0002118	97.81	gold quality
descending thoracic aorta	UBERON:0002345	97.77	gold quality
synovial joint	UBERON:0002217	97.75	gold quality
coronary artery	UBERON:0001621	97.66	gold quality
left coronary artery	UBERON:0001626	97.63	gold quality
ectocervix	UBERON:0012249	97.60	gold quality
metanephros cortex	UBERON:0010533	97.57	gold quality
right atrium auricular region	UBERON:0006631	97.56	gold quality
left uterine tube	UBERON:0001303	97.52	gold quality
decidua	UBERON:0002450	97.45	gold quality
pericardium	UBERON:0002407	97.43	gold quality
thoracic aorta	UBERON:0001515	97.32	gold quality
left ovary	UBERON:0002119	97.32	gold quality
omental fat pad	UBERON:0010414	97.32	gold quality
ascending aorta	UBERON:0001496	97.30	gold quality
peritoneum	UBERON:0002358	97.26	gold quality
parietal pleura	UBERON:0002400	97.20	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2777.31
E-MTAB-6701	yes	1945.60
E-MTAB-8322	yes	1621.10
E-MTAB-6678	yes	1503.00
E-HCAD-10	yes	1229.07
E-MTAB-10287	yes	929.59
E-GEOD-124472	yes	756.99
E-GEOD-114530	yes	713.89
E-ANND-5	yes	617.67
E-GEOD-135922	yes	589.82
E-HCAD-56	yes	565.94
E-HCAD-1	yes	97.45
E-MTAB-8410	yes	71.35
E-HCAD-11	yes	56.72
E-HCAD-4	yes	23.26

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 30)

• PCPE binds to sites on either side of the procollagen cleavage site, thereby facilitating the action of procollagen C-proteinases. (PMID:12105202)
• PCPE1 and PCPE2 were found to be collagen-binding proteins, capable of binding at multiple sites on the triple helical portions of fibrillar collagens and also capable of competing for such binding with procollagen C-proteinases (PMID:12393877)
• procollagen C-proteinase enhancer is an elongated multidomain glycoprotein as shown by small angle x-ray scattering (PMID:12486138)
• the three-dimensional structure of the NTR domain of human PCOLCE1 is the first example of a structural domain with the canonical features of an NTR module (PMID:12670942)
• chordinase activity of BMP1 is not enhanced by PCPE-1 (PMID:15817489)
• tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains (PMID:16507574)
• PCPE-stimulating activity requires a calcium binding motif in the CUB1 domain that is highly conserved among CUB-containing proteins (PMID:17446170)
• in bone fracture patients, 12 proteins were related to bone/cartilage metabolism, including: TGF-beta induced protein IG-H(3), cartilage acidic protein 1, procollagen C proteinase enhancer protein and TGF-beta receptor III. (PMID:17602227)
• PCPE-1 interacts with beta2-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues (PMID:18164932)
• Procollagen I mRNA expression was decreased by synovial fluid from patients with prosthesis loosening. (PMID:18350290)
• the sPCPE1 glycopattern appears to be associated with the physiological and pathological states of bone (PMID:19361460)
• Data show that only those containing both PCPE1 CUB1 and CUB2 were capable of enhancing BMP-1 activity and binding to a mini-procollagen substrate with nanomolar affinity. (PMID:19801683)
• Role of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity. (PMID:20207734)
• procollagen C-proteinase enhancer-1 (PCPE-1) binds to heparin/heparan sulfate and has a role in interaction with cells (PMID:20729553)
• data generated by our system, support our hypothesis that combined data on PCPE concentration and isoforms may be useful for the diagnosis and follow-up of bone diseases (PMID:21569766)
• Procollagen C-proteinase enhancer stimulates procollagen processing by binding to the C-propeptide region only. (PMID:21940633)
• Procollagen C-proteinase enhancer grasps the stalk of the C-propeptide trimer to boost collagen precursor maturation. (PMID:23550162)
• The results of this study suggested that nuclear entrapment of PCOLCE and its extracellular depletion represents a novel molecular mechanism in late-onset muscle fibrosis. (PMID:23815790)
• The analysis of the PCPE-1 interaction network based on Gene Ontology terms suggests that, besides its role in collagen deposition, PCPE-1 might be involved in tumour growth, neurodegenerative diseases and angiogenesis. (PMID:24117177)
• Results suggest that PCPE-1 binding to syndecans and/or fibronectin may control collagen fibril assembly on the cell surface. (PMID:25286301)
• Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis in chronic hepatitis B. (PMID:29683980)
• Study shows that the two CUB domains bind to two different chains of C-propeptide trimer of procollagen III (CPIII) and that the N-terminal region of one CPIII chain, close to the proteolytic cleavage site, lies in the cleft between CUB1 and CUB2. This suggests that enhancing activity involves unraveling of this chain from the rest of the trimer, thus facilitating the action of the proteinase involved. (PMID:30078642)
• PCPE-1 levels are elevated in chronic kidney disease patients and that this elevation associated with declining glomerular filtration rate. (PMID:30393914)
• Up-regulation of PCOLCE by TWIST1 promotes metastasis in Osteosarcoma. (PMID:31285765)
• Procollagen C-Proteinase Enhancer-1 (PCPE-1) deficiency in mice reduces liver fibrosis but not NASH progression. (PMID:35148334)
• Procollagen C-proteinase enhancer-1 and renal failure in multiple myeloma. (PMID:36173536)
• Expression of procollagen C-proteinase enhancer 1 in human trabecular meshwork tissues and cells. (PMID:36252654)
• A pan-cancer analysis of the oncogenic role of procollagen C-endopeptidase enhancer (PCOLCE) in human. (PMID:36596064)
• High expression of PCOLCE gene indicate poor prognosis in patients and are associated with immune infiltration in glioma. (PMID:36882457)
• SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma. (PMID:38436832)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcolceb	ENSDARG00000052057
danio_rerio	pcolcea	ENSDARG00000056913
mus_musculus	Pcolce	ENSMUSG00000029718
rattus_norvegicus	Pcolce	ENSRNOG00000025001

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Procollagen C-endopeptidase enhancer 1 — Q15113 (reviewed: Q15113)

Alternative names: Procollagen COOH-terminal proteinase enhancer 1, Type 1 procollagen C-proteinase enhancer protein, Type I procollagen COOH-terminal proteinase enhancer

All UniProt accessions (1): Q15113

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity. C-terminal processed part of PCPE (CT-PCPE) may have an metalloproteinase inhibitory activity.

Subunit / interactions. Interacts with EFEMP2.

Subcellular location. Secreted.

Post-translational modifications. C-terminally processed at multiple positions.

RefSeq proteins (1): NP_002584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000859	CUB_dom	Domain
IPR001134	Netrin_domain	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR018933	Netrin_module_non-TIMP	Domain
IPR035814	NTR_PCOLCE	Domain
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily

Pfam: PF00431, PF01759

UniProt features (52 total): strand 25, disulfide bond 7, site 5, domain 3, turn 3, helix 3, glycosylation site 2, signal peptide 1, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9EN2	X-RAY DIFFRACTION	2.2
6FZV	X-RAY DIFFRACTION	2.7
6FZW	X-RAY DIFFRACTION	2.78
1UAP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15113-F1	79.96	0.45

Antibody-complex structures (SAbDab): 1 — 9EN2

Functional residue map

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

Catalytic / active sites (5): 303–304 (cleavage); 287–288 (cleavage); 288–289 (cleavage); 293–294 (cleavage); 299–300 (cleavage)

Post-translational modifications (1): 50

Disulfide bonds (7): 37–63, 90–112, 159–186, 213–236, 318–386, 322–389, 333–437

Glycosylation sites (2): 29, 431

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2243919	Crosslinking of collagen fibrils

MSigDB gene sets: 210 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, RNGTGGGC_UNKNOWN, MODULE_52, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MARTINEZ_RB1_TARGETS_UP, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, ROZANOV_MMP14_TARGETS_UP

GO Biological Process (2): proteolysis (GO:0006508), collagen biosynthetic process (GO:0032964)

GO Molecular Function (5): collagen binding (GO:0005518), heparin binding (GO:0008201), peptidase activator activity (GO:0016504), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Collagen formation	1
Assembly of collagen fibrils and other multimeric structures	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
biosynthetic process	1
collagen metabolic process	1
protein-containing complex binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
enzyme activator activity	1
peptidase activity	1
peptidase regulator activity	1
structural molecule activity	1
extracellular matrix	1
binding	1
cellular anatomical structure	1
extracellular vesicle	1
external encapsulating structure	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCOLCE	COL1A2	P02464	897
PCOLCE	NTSR1	P30989	771
PCOLCE	COL5A1	P20908	721
PCOLCE	BGN	P13247	683
PCOLCE	COL11A2	P13942	636
PCOLCE	THBS1	P07996	618
PCOLCE	COL5A2	P05997	614
PCOLCE	FN1	P02751	577
PCOLCE	COL6A1	P12109	573
PCOLCE	COL11A1	P12107	560
PCOLCE	SERPINH1	P29043	537
PCOLCE	BMP1	P13497	536
PCOLCE	IGFBP7	Q16270	506
PCOLCE	PLS1	Q14651	497
PCOLCE	LTBP1	P22064	490

IntAct

52 interactions, top by confidence:

A	B	Type	Score
APP	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.680
PCOLCE	APP	psi-mi:“MI:0407”(direct interaction)	0.680
	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.620
PCOLCE	COL18A1	psi-mi:“MI:0407”(direct interaction)	0.620
COL18A1	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.620
BMP1	PCOLCE	psi-mi:“MI:0915”(physical association)	0.610
PCOLCE	BMP1	psi-mi:“MI:0407”(direct interaction)	0.610
PCOLCE	Sdc2	psi-mi:“MI:0915”(physical association)	0.580
Sdc2	PCOLCE	psi-mi:“MI:0914”(association)	0.580
PCOLCE	FN1	psi-mi:“MI:0407”(direct interaction)	0.560
PCOLCE	THBS1	psi-mi:“MI:0407”(direct interaction)	0.560
THBS1	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.560
BMP1	COL5A1	psi-mi:“MI:0915”(physical association)	0.540
COL5A1	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.530
COL5A1	PCOLCE	psi-mi:“MI:0915”(physical association)	0.530
PCOLCE	Sdc1	psi-mi:“MI:0915”(physical association)	0.500
Sdc1	PCOLCE	psi-mi:“MI:0914”(association)	0.500
PCOLCE	MMP2	psi-mi:“MI:0194”(cleavage reaction)	0.440
PCOLCE	ACAN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (6): PCOLCE (Affinity Capture-MS), PCOLCE (Two-hybrid), PCOLCE (Affinity Capture-RNA), PCOLCE (Affinity Capture-MS), PCOLCE (Proximity Label-MS), PCOLCE (Two-hybrid)

ESM2 similar proteins: A0EQL2, A2AJ76, A2AJA7, A6H8M9, A8T650, A8T682, A8T688, A8T6A6, D3ZLH5, F1QVU0, O08628, O75173, O88839, P04278, P08514, P08689, P0DV84, P15196, P20701, P29376, P32970, P38570, P60882, P80012, P97497, P97793, Q13444, Q15113, Q5RFQ8, Q5TM20, Q61398, Q63191, Q6UXC1, Q7Z304, Q7Z442, Q7Z7M0, Q8BNJ2, Q8CG85, Q8K1S7, Q8NBP7

Diamond homologs: B3EX01, B8JI71, B8VIV4, C6KFA3, F1RWC3, O08628, O08859, O14786, O35276, O35375, O57382, O60462, O60494, O70244, O75074, O88204, P07898, P13497, P28824, P35443, P42662, P42664, P42674, P49744, P56677, P60882, P70412, P78504, P79795, P79953, P82279, P97333, P97607, P98065, P98066, P98069, P98072, P98074, Q06441, Q15113

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
ECM proteoglycans	6	42.9×	9e-07
Degradation of the extracellular matrix	5	28.0×	4e-05
Platelet degranulation	5	20.9×	1e-04
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	5	20.6×	1e-04
Extracellular matrix organization	6	18.0×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
angiogenesis	5	13.0×	4e-03
cell adhesion	7	10.9×	1e-03
proteolysis	6	8.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1326 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100603992:C:CA	acceptor_gain	1.0000
7:100604167:G:GT	donor_gain	1.0000
7:100604170:G:GT	donor_gain	1.0000
7:100605786:G:GT	donor_gain	1.0000
7:100605786:G:T	donor_gain	1.0000
7:100606400:C:A	acceptor_gain	1.0000
7:100606627:CCTGG:C	donor_loss	1.0000
7:100606628:CTGGT:C	donor_loss	1.0000
7:100606629:TGGTG:T	donor_loss	1.0000
7:100606630:GGTG:G	donor_loss	1.0000
7:100606631:G:GC	donor_loss	1.0000
7:100606632:T:G	donor_loss	1.0000
7:100607632:CACAG:C	acceptor_loss	1.0000
7:100607633:ACAGT:A	acceptor_gain	1.0000
7:100607634:CA:C	acceptor_loss	1.0000
7:100607635:A:AG	acceptor_gain	1.0000
7:100607635:A:C	acceptor_loss	1.0000
7:100607635:AGT:A	acceptor_gain	1.0000
7:100607635:AGTG:A	acceptor_gain	1.0000
7:100607636:G:GA	acceptor_gain	1.0000
7:100607636:GT:G	acceptor_gain	1.0000
7:100607636:GTG:G	acceptor_gain	1.0000
7:100607636:GTGG:G	acceptor_gain	1.0000
7:100607636:GTGGT:G	acceptor_gain	1.0000
7:100607803:GAAAG:G	donor_gain	1.0000
7:100607805:AAGG:A	donor_loss	1.0000
7:100607806:AGGT:A	donor_loss	1.0000
7:100607807:GGTAA:G	donor_loss	1.0000
7:100607808:GT:G	donor_loss	1.0000
7:100607809:T:A	donor_loss	1.0000

AlphaMissense

2864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100605191:G:C	W188C	1.000
7:100605191:G:T	W188C	1.000
7:100606487:T:G	F266C	1.000
7:100603529:G:C	W65C	0.999
7:100603529:G:T	W65C	0.999
7:100604175:G:T	G141C	0.999
7:100604179:T:G	F142C	0.999
7:100605183:T:A	C186S	0.999
7:100605184:G:C	C186S	0.999
7:100605686:T:C	L200P	0.999
7:100605692:T:G	F202C	0.999
7:100605733:G:C	D216H	0.999
7:100605733:G:T	D216Y	0.999
7:100605734:A:C	D216A	0.999
7:100605734:A:T	D216V	0.999
7:100605740:T:A	V218D	0.999
7:100606442:T:C	L251P	0.999
7:100606448:T:A	V253D	0.999
7:100606463:A:T	D258V	0.999
7:100606483:G:T	G265C	0.999
7:100606486:T:C	F266L	0.999
7:100606487:T:C	F266S	0.999
7:100606488:C:A	F266L	0.999
7:100606488:C:G	F266L	0.999
7:100606498:T:G	Y270D	0.999
7:100603443:T:A	C37S	0.998
7:100603444:G:C	C37S	0.998
7:100603482:A:C	S50R	0.998
7:100603484:T:A	S50R	0.998
7:100603484:T:G	S50R	0.998

dbSNP variants (sampled 300 via entrez): RS1000708457 (7:100604738 C>G), RS1000761053 (7:100605061 C>G,T), RS1001110009 (7:100604647 C>G,T), RS1001561291 (7:100604926 C>T), RS1001704068 (7:100606259 G>A,C), RS1002609997 (7:100601108 C>G,T), RS1002628543 (7:100608507 G>A), RS1002762712 (7:100607980 C>T), RS1003155927 (7:100602394 C>T), RS1003569320 (7:100601758 A>G), RS1003775309 (7:100602182 C>G,T), RS1004559378 (7:100603618 G>A,C,T), RS1005120300 (7:100602171 G>A,C), RS1005185098 (7:100605862 G>A,C), RS1005520680 (7:100600401 C>T)

Disease associations

OMIM: gene MIM:600270 | 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
GCST003818_36	Resting heart rate	1.000000e-41
GCST006585_107	Blood protein levels	2.000000e-12
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	increases expression, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
bisphenol AF	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
jinfukang	increases expression	1
Arsenic Trioxide	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carmustine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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