MRC2

Summary

MRC2 (mannose receptor C-type 2, HGNC:16875) is a protein-coding gene on chromosome 17q23.2, encoding C-type mannose receptor 2 (Q9UBG0). May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity.

This gene encodes a member of the mannose receptor family of proteins that contain a fibronectin type II domain and multiple C-type lectin-like domains. The encoded protein plays a role in extracellular matrix remodeling by mediating the internalization and lysosomal degradation of collagen ligands. Expression of this gene may play a role in the tumorigenesis and metastasis of several malignancies including breast cancer, gliomas and metastatic bone disease.

Source: NCBI Gene 9902 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiac rhythm disease (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 217 total — 1 likely-pathogenic
• MANE Select transcript: NM_006039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16875
Approved symbol	MRC2
Name	mannose receptor C-type 2
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0709, ENDO180, CLEC13E, CD280
Ensembl gene	ENSG00000011028
Ensembl biotype	protein_coding
OMIM	612264
Entrez	9902

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000303375, ENST00000446119, ENST00000579432, ENST00000580916, ENST00000583597, ENST00000584265, ENST00000584682

RefSeq mRNA: 1 — MANE Select: NM_006039 NM_006039

CCDS: CCDS11634

Canonical transcript exons

ENST00000303375 — 30 exons

Exon	Start	End
ENSE00001241322	62692231	62693597
ENSE00002202312	62680418	62680453
ENSE00002204537	62627670	62627920
ENSE00002248600	62680170	62680308
ENSE00002258512	62677269	62677486
ENSE00002271993	62680800	62680960
ENSE00002308032	62678504	62678646
ENSE00002310320	62676383	62676531
ENSE00003469071	62675790	62675905
ENSE00003502057	62681837	62681937
ENSE00003539549	62679800	62679902
ENSE00003563084	62664548	62664949
ENSE00003569511	62671649	62671837
ENSE00003572665	62689894	62690062
ENSE00003580105	62689522	62689760
ENSE00003583417	62671998	62672152
ENSE00003589656	62666757	62666870
ENSE00003590367	62690949	62691128
ENSE00003591367	62682235	62682377
ENSE00003591852	62692112	62692138
ENSE00003606370	62667390	62667533
ENSE00003617130	62688852	62688960
ENSE00003621541	62688501	62688664
ENSE00003628871	62674063	62674170
ENSE00003629690	62681062	62681129
ENSE00003636917	62688289	62688403
ENSE00003640633	62666094	62666267
ENSE00003648549	62690642	62690761
ENSE00003652925	62666455	62666619
ENSE00003671847	62690156	62690305

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.8950 / max 2427.4745, expressed in 1689 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162117	95.0291	1614
162119	9.7383	1225
162118	5.9833	1133
208304	4.4682	910
208303	1.3721	591
162127	0.3785	221
162129	0.3327	66
162128	0.3191	59
208307	0.1773	82
162125	0.0963	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.60	gold quality
stromal cell of endometrium	CL:0002255	99.18	gold quality
tibia	UBERON:0000979	98.57	gold quality
periodontal ligament	UBERON:0008266	98.54	gold quality
synovial joint	UBERON:0002217	97.92	gold quality
vena cava	UBERON:0004087	97.72	gold quality
pericardium	UBERON:0002407	97.68	gold quality
layer of synovial tissue	UBERON:0007616	97.17	gold quality
ascending aorta	UBERON:0001496	97.01	gold quality
right ovary	UBERON:0002118	96.96	gold quality
thoracic aorta	UBERON:0001515	96.95	gold quality
descending thoracic aorta	UBERON:0002345	96.95	gold quality
urethra	UBERON:0000057	96.86	gold quality
left ovary	UBERON:0002119	96.46	gold quality
left uterine tube	UBERON:0001303	96.31	gold quality
nipple	UBERON:0002030	96.31	gold quality
trigeminal ganglion	UBERON:0001675	96.30	gold quality
saphenous vein	UBERON:0007318	96.27	gold quality
skin of hip	UBERON:0001554	96.26	gold quality
apex of heart	UBERON:0002098	95.86	gold quality
right coronary artery	UBERON:0001625	95.77	gold quality
cartilage tissue	UBERON:0002418	95.45	gold quality
cardia of stomach	UBERON:0001162	95.42	gold quality
body of uterus	UBERON:0009853	95.31	gold quality
myometrium	UBERON:0001296	95.27	gold quality
gall bladder	UBERON:0002110	95.24	gold quality
endocervix	UBERON:0000458	95.19	gold quality
ectocervix	UBERON:0012249	95.01	gold quality
ventricular zone	UBERON:0003053	94.92	gold quality
right atrium auricular region	UBERON:0006631	94.86	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	374.73
E-GEOD-135922	yes	51.79
E-ANND-3	yes	21.59
E-CURD-112	yes	16.00
E-ENAD-27	yes	6.94
E-MTAB-7037	no	521.31
E-MTAB-6075	no	65.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting MRC2, 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-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-873-5P	98.84	66.90	1348

Literature-anchored findings (GeneRIF, showing 29)

• Investigation of the role of Endo180/urokinase-type plasminogen activator receptor-associated protein as a collagenase 3 (matrix metalloproteinase 13) receptor (PMID:11903048)
• Endo180 was found to be distinct within the mannose receptor family in that the tyrosine-based motif is not required for efficient delivery to and recycling from early endosomes (PMID:12068012)
• Mannose receptor activity is up-regulated by surfactant protein A on monocyte-derived macrophages. (PMID:12244146)
• characterization of the monosaccharide binding sites (PMID:12399458)
• Approximately 60% of the initial association of HIV with macrophages that lack expression of DC-SIGN (a dendritic cell-specific ICAM-3 receptor/HIV-1-binding protein) is mediated by the macrophage mannose receptor. (PMID:12645947)
• By using cell isolates from uPARAP deficient mice, it is demonstrated that uPARAP is a collagen receptor. Thus uPARAP deficient fibroblasts can not internalize collagen and show a reduced adhesion/migration on collagen surfaces (PMID:12668656)
• Results suggest that Endo180 is a crucial link between urokinase-type plasminogen activator and its receptor and setting of the internal cellular compass. (PMID:12952933)
• Endo180 plays a physiological role in mediating collagen matrix remodelling during tissue development and homeostasis (PMID:12972549)
• Data suggest that uPARAP/Endo180 participates in the connective tissue destruction during head and neck squamous cell carcinoma progression by mediating cellular uptake and lysosomal degradation of collagen. (PMID:17189524)
• To investigate the consequence of Endo180 up-regulation, MCF7 cells transfected with Endo180 were inoculated into immunocompromised mice; expression of wild-type Endo180, but not an internalization-defective Endo180 mutant, showed enhanced tumor growth. (PMID:17974964)
• Endo180 is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. (PMID:19861500)
• fibrillar collagen deposition and the collagen internalization receptor endo180 have roles in glioma invasion (PMID:20339555)
• Our present study suggests that uPARAP may be involved in glioma cell invasiveness through actin cytoskeletal rearrangement (PMID:20845060)
• A novel functional role of collagen glycosylation: interaction with the endocytic collagen receptor uparap/ENDO180. (PMID:21768090)
• TGFbeta1-Endo180-dependent collagen deposition is dysregulated at the tumour-stromal interface in bone metastasis. (PMID:22072289)
• Our findings correlate for the first time impaired collagen uptake via Endo180 with the pericellular accumulation of collagen fragments during photoaging. (PMID:23433549)
• MRC2 is downregulated by UVA irradiation and reduces collagen internalization; this can be recovered by all-trans retinoic acid (PMID:24161566)
• Study identifies the interaction between lectin domain in Endo180 and CD147 as an Epithelial-to-mesenchymal transition suppressor and indicates that stabilization of this molecular complex improves prostate cancer survival rates. (PMID:25381222)
• AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed prostate epithelial cells via Endo180 pathway linked to cancer progression. (PMID:25408555)
• The positive correlation between suPLAUR expression and body mass index, suggests that leukocyte recruitment in obese tissue may be regulated, at least in part, through the splicing of the PLAUR transcript. (PMID:26284904)
• Our findings identify sarcoma cell-resident uPARAP/Endo180 as a central player in the bone degeneration of advanced osteosarcoma (PMID:26466547)
• A model of the ligand-binding region of uPARAP was obtained by molecular replacement. (PMID:26527274)
• results provide a molecular mechanism to support the structural flexibility of uPARAP, and shed light on the structural flexibility of other members of the MR family (PMID:27247422)
• Endo180 knockdown in pancreatic stellate cells (PSCs) attenuated the invasive abilities of PSCs and co-cultured pancreatic cancer cells, and decreased the expression level of phosphorylated myosin light chain 2 (MLC2). (PMID:29061505)
• In lung tissue from idiopathic pulmonary fibrosis patients, a strong up-regulation of uPARAP was observed in fibroblasts adjacent to regions with SP-D secretion. (PMID:30366943)
• These results indicate that a substance secreted from UVB-exposed keratinocytes regulates Endo180 expression and that IL-1alpha may play an important role in the maintenance of Endo180. (PMID:31376337)
• Mathematical modelling of the role of Endo180 network in the development of metastatic bone disease in prostate cancer. (PMID:32072971)
• MRC2 Promotes Proliferation and Inhibits Apoptosis of Diabetic Nephropathy. (PMID:34012764)
• The Collagen Receptor uPARAP in Malignant Mesothelioma: A Potential Diagnostic Marker and Therapeutic Target. (PMID:34768883)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrc2	ENSDARG00000078135
mus_musculus	Mrc2	ENSMUSG00000020695
rattus_norvegicus	Mrc2	ENSRNOG00000006548

Paralogs (4): LY75 (ENSG00000054219), PLA2R1 (ENSG00000153246), CD302 (ENSG00000241399), MRC1 (ENSG00000260314)

Protein

Protein identifiers

C-type mannose receptor 2 — Q9UBG0 (reviewed: Q9UBG0)

Alternative names: C-type lectin domain family 13 member E, Endocytic receptor 180, Macrophage mannose receptor 2, Urokinase-type plasminogen activator receptor-associated protein

All UniProt accessions (4): Q9UBG0, E7EME3, J3KRF1, J3QQZ6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity. Internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via clathrin-mediated endocytosis. May be involved in plasminogen activation system controlling the extracellular level of PLAUR/PLAU, and thus may regulate protease activity at the cell surface. May contribute to cellular uptake, remodeling and degradation of extracellular collagen matrices. May play a role during cancer progression as well as in other chronic tissue destructive diseases acting on collagen turnover. May participate in remodeling of extracellular matrix cooperating with the matrix metalloproteinases (MMPs).

Subunit / interactions. Interacts with C-terminal region of type I collagen/COL1A1. Interacts directly with PLAUR/UPAR and PLAU/pro-UPA to form a tri-molecular complex. Interacts with collagen V.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous with low expression in brain, placenta, lung, kidney, pancreas, spleen, thymus and colon. Expressed in endothelial cells, fibroblasts and macrophages. Highly expressed in fetal lung and kidney.

Post-translational modifications. N-glycosylated.

Domain organisation. C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine. C-type lectin domain 2 is responsible for sugar-binding in a calcium-dependent manner. Fibronectin type-II domain mediates collagen-binding. Ricin B-type lectin domain contacts with the second C-type lectin domain.

RefSeq proteins (1): NP_006030* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000562	FN_type2_dom	Domain
IPR000772	Ricin_B_lectin	Domain
IPR001304	C-type_lectin-like	Domain
IPR013806	Kringle-like	Homologous_superfamily
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033989	CD209-like_CTLD	Domain
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR036943	FN_type2_sf	Homologous_superfamily
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00040, PF00059, PF24562

UniProt features (98 total): strand 30, disulfide bond 16, turn 14, domain 10, helix 8, glycosylation site 7, mutagenesis site 4, topological domain 2, sequence variant 2, signal peptide 1, chain 1, region of interest 1, transmembrane region 1, cross-link 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5EW6	X-RAY DIFFRACTION	2.29
5E4L	X-RAY DIFFRACTION	2.44
5AO5	X-RAY DIFFRACTION	2.48
5E4K	X-RAY DIFFRACTION	2.58
5AO6	X-RAY DIFFRACTION	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBG0-F1	77.72	0.27

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): 1142

Disulfide bonds (16): 54–68, 93–112, 187–213, 201–228, 266–359, 335–351, 410–504, 481–496, 618–635, 704–808, 785–800, 853–950, 927–942, 1078–1098, 1220–1234, 1369–1384

Glycosylation sites (7): 69, 140, 364, 588, 954, 1029, 1350

Mutagenesis-validated functional residues (4):

Position	Phenotype
472	reduced sugar-binding activity.
1452	no alteration of distribution and trafficking.
1464	increased cell surface distribution.
1468–1469	reduction of endocytotic activity; distribution almost restricted to the cell surface.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 193 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, FISCHER_G1_S_CELL_CYCLE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_VESICLE_MEDIATED_TRANSPORT, TTGGGAG_MIR150, MODULE_331, MARTINEZ_RB1_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, E4F1_Q6, GOBP_OSSIFICATION, EGR1_01, ROSS_AML_WITH_PML_RARA_FUSION, SOX5_01

GO Biological Process (3): osteoblast differentiation (GO:0001649), endocytosis (GO:0006897), collagen catabolic process (GO:0030574)

GO Molecular Function (4): collagen binding (GO:0005518), carbohydrate binding (GO:0030246), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): focal adhesion (GO:0005925), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Antigen processing-Cross presentation	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
ossification	1
cell differentiation	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
catabolic process	1
collagen metabolic process	1
protein-containing complex binding	1
molecular transducer activity	1
cell-substrate junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRC2	PLAUR	Q03405	851
MRC2	PLAU	P00749	828
MRC2	ITGA2	P17301	481
MRC2	CD163L1	Q9NR16	481
MRC2	BGN	P13247	476
MRC2	ZNF557	Q8N988	438
MRC2	ZNF358	Q9NW07	424
MRC2	RABEPK	Q7Z6M1	422
MRC2	MMP14	P50281	418
MRC2	FCER1G	P30273	400
MRC2	LRRC8E	Q6NSJ5	385
MRC2	TTC8	Q8TAM2	383
MRC2	ALDH6A1	Q02252	371
MRC2	FCRLB	Q6BAA4	327
MRC2	FN1	P02751	316

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MRC2	Col1a1	psi-mi:“MI:0407”(direct interaction)	0.560
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
CER1	POTEF	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
MRC2	EEF1G	psi-mi:“MI:0915”(physical association)	0.400
MRC2	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
AKT1	MRC2	psi-mi:“MI:0915”(physical association)	0.370
MRC2	BAG4	psi-mi:“MI:0915”(physical association)	0.370
BRMS1	MRC2	psi-mi:“MI:0915”(physical association)	0.370
MRC2	ESR2	psi-mi:“MI:0915”(physical association)	0.370
MRC2	PALB2	psi-mi:“MI:0915”(physical association)	0.370
MRC2	PAX2	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	MRC2	psi-mi:“MI:0915”(physical association)	0.370
MRC2	PTPN1	psi-mi:“MI:0915”(physical association)	0.370
RAF1	MRC2	psi-mi:“MI:0915”(physical association)	0.370
RB1CC1	MRC2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (91): MRC2 (Affinity Capture-MS), MRC2 (Affinity Capture-MS), MRC2 (Affinity Capture-MS), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Two-hybrid), MRC2 (Affinity Capture-MS)

ESM2 similar proteins: A5D8T8, O35217, O75078, O75882, O75900, O88272, O88507, O88676, O95633, P08887, P0C7M8, P0C7M9, P26992, P78539, Q00961, Q01098, Q08406, Q0ZCA7, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5VV63, Q63769, Q642A6, Q6A051, Q6IA17, Q6P1D5, Q6PCB0, Q6UXF7, Q71DR4, Q7TNS7, Q7TSQ1, Q8NCF0, Q8R2Z5, Q8R366, Q91XD7, Q96FT7, Q96HD1

Diamond homologs: A0ZT93, B0VXV2, B4XT08, B5U6Y6, B5U6Y7, C0HKZ7, O60449, P05140, P06027, P06734, P0DJL5, P10716, P13611, P14371, P20693, P34472, P55066, P55067, P81018, P81282, P81996, Q01758, Q02988, Q26627, Q28062, Q28670, Q28858, Q4PRD0, Q4TU93, Q4V885, Q61830, Q62059, Q64449, Q66S03, Q6X5S2, Q6X5S3, Q6X5S5, Q6X5S6, Q6X5S7, Q6X5S8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	182
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
978816	Single allele	Likely pathogenic

SpliceAI

5305 predictions. Top by Δscore:

Variant	Effect	Δscore
17:62664922:G:GT	donor_gain	1.0000
17:62664925:GACC:G	donor_gain	1.0000
17:62664947:ACGGT:A	donor_loss	1.0000
17:62664949:GGTG:G	donor_loss	1.0000
17:62664950:G:C	donor_loss	1.0000
17:62664951:T:A	donor_loss	1.0000
17:62666225:GAC:G	donor_gain	1.0000
17:62666265:AGA:A	donor_gain	1.0000
17:62666266:GA:G	donor_gain	1.0000
17:62666266:GAG:G	donor_gain	1.0000
17:62666268:G:GG	donor_gain	1.0000
17:62666617:ACG:A	donor_gain	1.0000
17:62666617:ACGGT:A	donor_loss	1.0000
17:62666619:GGT:G	donor_loss	1.0000
17:62666620:G:GG	donor_gain	1.0000
17:62666620:G:T	donor_loss	1.0000
17:62666868:GTG:G	donor_gain	1.0000
17:62667532:AGG:A	donor_loss	1.0000
17:62667534:G:GA	donor_loss	1.0000
17:62667534:G:GG	donor_gain	1.0000
17:62667535:T:A	donor_loss	1.0000
17:62671833:GCAAG:G	donor_gain	1.0000
17:62671838:G:GA	donor_loss	1.0000
17:62671838:G:GG	donor_gain	1.0000
17:62671984:T:TA	acceptor_gain	1.0000
17:62671987:T:TA	acceptor_gain	1.0000
17:62671990:A:AG	acceptor_gain	1.0000
17:62671991:C:G	acceptor_gain	1.0000
17:62671993:CCCA:C	acceptor_loss	1.0000
17:62671996:A:AG	acceptor_gain	1.0000

AlphaMissense

9761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:62664660:G:C	W77C	1.000
17:62664660:G:T	W77C	1.000
17:62664666:G:C	W79C	1.000
17:62664666:G:T	W79C	1.000
17:62664706:T:A	C93S	1.000
17:62664706:T:C	C93R	1.000
17:62664707:G:C	C93S	1.000
17:62666111:G:A	G180R	1.000
17:62666111:G:C	G180R	1.000
17:62666112:G:T	G180V	1.000
17:62666124:G:A	G184E	1.000
17:62666124:G:T	G184V	1.000
17:62666132:T:A	C187S	1.000
17:62666132:T:C	C187R	1.000
17:62666133:G:A	C187Y	1.000
17:62666133:G:C	C187S	1.000
17:62666133:G:T	C187F	1.000
17:62666134:C:G	C187W	1.000
17:62666142:C:A	P190H	1.000
17:62666144:T:C	F191L	1.000
17:62666145:T:G	F191C	1.000
17:62666146:C:A	F191L	1.000
17:62666146:C:G	F191L	1.000
17:62666174:T:A	C201S	1.000
17:62666174:T:C	C201R	1.000
17:62666175:G:C	C201S	1.000
17:62666207:T:A	W212R	1.000
17:62666207:T:C	W212R	1.000
17:62666209:G:C	W212C	1.000
17:62666209:G:T	W212C	1.000

dbSNP variants (sampled 300 via entrez): RS1000046747 (17:62666659 C>G,T), RS1000176795 (17:62637046 T>C), RS1000194030 (17:62679387 G>T), RS1000197333 (17:62659976 G>A), RS1000231282 (17:62653994 C>T), RS1000258733 (17:62636626 G>A,T), RS1000281221 (17:62629399 G>A), RS1000360874 (17:62643184 T>A), RS1000367818 (17:62655504 T>C), RS1000408997 (17:62649730 G>A), RS1000466672 (17:62689884 C>G), RS1000546560 (17:62666853 A>T), RS1000647873 (17:62655178 C>A,G,T), RS1000666987 (17:62673319 C>T), RS1000712462 (17:62653719 G>T)

Disease associations

OMIM: gene MIM:612264 | disease phenotypes: MIM:618050

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiac rhythm disease	Limited	Autosomal dominant

Mondo (2): intellectual disability, autosomal dominant 57 (MONDO:0054837), cardiac rhythm disease (MONDO:0007263)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004278_13	Pulse pressure	3.000000e-12
GCST004280_1	Diastolic blood pressure	1.000000e-07
GCST006979_515	Heel bone mineral density	6.000000e-19
GCST007267_244	Systolic blood pressure	3.000000e-08
GCST007268_64	Diastolic blood pressure	7.000000e-10
GCST007269_127	Pulse pressure	3.000000e-25

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	2
Nickel	decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases methylation, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases expression, increases oxidation, increases abundance, affects cotreatment	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	increases expression, increases acetylation	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
coumarin	increases phosphorylation	1
JP8 aviation fuel	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	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, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00146822	PHASE4	COMPLETED	REFLEx Study (ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance
NCT00187239	PHASE4	COMPLETED	Reduce Ventricular Pacing in Dual Chamber Implantable Cardioverter Defibrillators Using AutoIntrinsic Conduction Search Study
NCT00247533	PHASE4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00282620	PHASE4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00290056	PHASE4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	PHASE4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	PHASE4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	PHASE4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	PHASE4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
NCT01819064	PHASE4	COMPLETED	Heart Rate Response to Atropine Doses Less Than 0.1mg IV to Anesthetized Infants
NCT01834872	PHASE4	UNKNOWN	Safety and Feasibility of Arrhythmia Ablation Using the Amigo Remote Robotic System as Compared With Manual Ablation
NCT01841242	PHASE4	COMPLETED	Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation
NCT01991223	PHASE4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02203630	PHASE4	TERMINATED	Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
NCT02565069	PHASE4	COMPLETED	Identification for the Treatment of Complex Arrhythmias
NCT03273634	PHASE4	COMPLETED	The Effect of Proton Pump Inhibition on Palpitations
NCT03289429	PHASE4	UNKNOWN	Antiarrhythmic and Cardioprotective Effects of Atorvastatin Versus Magnesium Sulfate in Cardiac Valve Replacement Surgery
NCT03895411	PHASE4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05486377	PHASE4	COMPLETED	Remimazolam vs Desflurane for General Anesthesia for Ablation of Arrhythmia
NCT06574555	PHASE4	COMPLETED	Norepinephrine ED90 Bolus After Spinal Anesthesia in Cesarean Section
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000476	PHASE3	COMPLETED	Digitalis Investigation Group (DIG)
NCT00000480	PHASE3	COMPLETED	Multicenter Unsustained Tachycardia Trial (MUSTT)
NCT00000492	PHASE3	COMPLETED	Beta-Blocker Heart Attack Trial (BHAT)
NCT00000502	PHASE3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000517	PHASE3	COMPLETED	Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF)
NCT00000518	PHASE3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00000531	PHASE3	COMPLETED	Antiarrhythmics Versus Implantable Defibrillators (AVID)
NCT00000540	PHASE3	COMPLETED	Coronary Artery Bypass Graft (CABG) Patch Trial
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00000561	PHASE3	COMPLETED	Mode Selection Trial in Sinus Node Dysfunction (MOST)
NCT00000609	PHASE3	COMPLETED	Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
NCT00004559	PHASE3	COMPLETED	Fatty Acid Antiarrhythmia Trial (FAAT)
NCT00004560	PHASE3	COMPLETED	Public Access Defibrillation (PAD) Community Trial
NCT00035490	PHASE3	COMPLETED	Efficacy and Safety Evaluation of Azimilide Dihydrochloride in Patients With Implantable Cardioverter Defibrillators