CD177

Summary

CD177 (CD177 molecule, HGNC:30072) is a protein-coding gene on chromosome 19q13.31, encoding CD177 antigen (Q8N6Q3). In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF primed neutrophils including degranulation and superoxide production.

This gene encodes a glycosyl-phosphatidylinositol (GPI)-linked cell surface glycoprotein that plays a role in neutrophil activation. The protein can bind platelet endothelial cell adhesion molecule-1 and function in neutrophil transmigration. Mutations in this gene are associated with myeloproliferative diseases. Over-expression of this gene has been found in patients with polycythemia rubra vera. Autoantibodies against the protein may result in pulmonary transfusion reactions, and it may be involved in Wegener’s granulomatosis. A related pseudogene, which is adjacent to this gene on chromosome 19, has been identified.

Source: NCBI Gene 57126 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_020406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30072
Approved symbol	CD177
Name	CD177 molecule
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Aliases	HNA-2, PRV1, HNA2A, NB1
Ensembl gene	ENSG00000204936
Ensembl biotype	protein_coding
OMIM	162860
Entrez	57126

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000378012, ENST00000607855, ENST00000618265, ENST00000878421, ENST00000878422, ENST00000878423, ENST00000878424, ENST00000961941

RefSeq mRNA: 1 — MANE Select: NM_020406 NM_020406

CCDS: CCDS62700

Canonical transcript exons

ENST00000618265 — 9 exons

Exon	Start	End
ENSE00001475873	43355661	43355783
ENSE00002291620	43353686	43353766
ENSE00002311232	43354207	43354392
ENSE00003718978	43362088	43363172
ENSE00003725008	43361143	43361328
ENSE00003738019	43361445	43361579
ENSE00003738600	43353853	43353993
ENSE00003741603	43360265	43360405
ENSE00003746808	43355992	43356108

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 97.93.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1092 / max 1540.5572, expressed in 234 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176183	3.1092	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	97.93	gold quality
colonic mucosa	UBERON:0000317	95.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.43	gold quality
mucosa of transverse colon	UBERON:0004991	91.76	gold quality
bone marrow	UBERON:0002371	90.80	gold quality
bone marrow cell	CL:0002092	87.00	gold quality
cervix squamous epithelium	UBERON:0006922	85.88	silver quality
spleen	UBERON:0002106	82.83	gold quality
transverse colon	UBERON:0001157	82.39	gold quality
trabecular bone tissue	UBERON:0002483	80.64	gold quality
prostate gland	UBERON:0002367	80.31	gold quality
cervix epithelium	UBERON:0004801	80.07	gold quality
blood	UBERON:0000178	79.96	gold quality
upper lobe of left lung	UBERON:0008952	77.74	gold quality
right lung	UBERON:0002167	77.72	gold quality
palpebral conjunctiva	UBERON:0001812	77.61	gold quality
gingiva	UBERON:0001828	76.98	gold quality
upper lobe of lung	UBERON:0008948	76.71	gold quality
vermiform appendix	UBERON:0001154	75.19	gold quality
tibial nerve	UBERON:0001323	73.76	gold quality
large intestine	UBERON:0000059	73.71	gold quality
colon	UBERON:0001155	73.05	gold quality
nasal cavity epithelium	UBERON:0005384	72.02	silver quality
gingival epithelium	UBERON:0001949	71.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.03	gold quality
caecum	UBERON:0001153	69.01	gold quality
monocyte	CL:0000576	67.15	gold quality
colonic epithelium	UBERON:0000397	67.14	silver quality
mononuclear cell	CL:0000842	67.05	gold quality
periodontal ligament	UBERON:0008266	66.51	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	7348.71
E-GEOD-125970	yes	29.56
E-ANND-3	yes	10.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting CD177, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-6847-5P	97.93	66.74	1808

Literature-anchored findings (GeneRIF, showing 40)

• biochemical characterization; overexpressed in polycythemia rubra vera (PMID:12239154)
• overexpression of PRV-1 to discrimitate essential thrombocythemia and polycythemia vera from secondary thrombocytosis and secondary erythrocytosis (PMID:12377969)
• No evidence for a PRV-1 gene rearrangement was found in metaphase or interphase cells in polycythemia vera and thus, overexpression of PRV-1 in granulocytes in PV is related to mechanisms that do not involve structural genetic changes. (PMID:12591276)
• review of gene structure, gene expression, polymorphisms, and relevance to diseases (PMID:12617169)
• Comparing cDNA sequences of donors with a large (> 60%) and those with a small (< 40%) NB1 GP-expressing subpopulation, we found 6 polymorphisms. 3 were significantly associated with a small NB1 GP-expressing subpopulation. (PMID:12623849)
• association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia and the effect of platelet lowering treatment on the ratio (PMID:12756017)
• This review summarizes and evaluates recent advances in our understanding of molecular aberrations in PV. (PMID:12901344)
• PRV-1 and NB1 are alleles of polymorphic gene CD177. The most common single nucleotide polymorphisms in bp 42 predicted an amino acid change that may have an effect on protein expression. (PMID:14692971)
• neutrophil PRV-1 up-regulation is a characteristic feature of polycythemia vera that may not be affected by fibrotic transformation (PMID:14701686)
• Change in the number of neutrophils and monocytes is related to HNA-2a expression during pregnancy and postpartum. Both decrease postpartum and in threatened premature labor. (PMID:15043575)
• The PRV1 protein altered expression provide an opportunity to diagnose and identify subpopulations of MPD patients. (PMID:15572213)
• PRV-1 overexpression is associated with a significantly increased risk of thrombosis, whereas decreased c-Mpl expression is not (PMID:15951300)
• Presence of the Janus kinase 2 V617F mutation was very highly correlated with polycythemia rubra vera 1 overexpression (PMID:15985544)
• RT-PCR is the most rapid, reliable, and feasible method for the detection of PRV-1 overexpression in highly purified peripheral blood granulocytes in polycythemia rubra vera and essential thrombocythemia. (PMID:16502591)
• FISH study showed no cytogenetic abnormalities in any of the analyzed cases. (PMID:16682284)
• Proteinase 3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. (PMID:17244676)
• neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1 (PMID:17580308)
• DNA methylation regulates PRV-1 expression under physiologic and pathologic conditions (PMID:17976520)
• a novel function for Prv-1 as a signaling molecule in cytokine signaling cascades and may lead to a greater understanding of the mechanism of overexpression of Prv-1 in myeloproliferative disorders. (PMID:17980909)
• The NB1-bound PR3 was active and was cleared from the surface by alpha-1-protease inhibitor (PMID:18854317)
• elevated percentage of CD177 expressing neutrophils in patients with ANCA-associated vasculitis and systemic lupus erythematosus (PMID:19185066)
• Testins for PRV-1 expression is useful in the diagnosis of essential thrombocythaemia, but not in the diagnosis of polycythaemia vera. (PMID:19999391)
• heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner. (PMID:20194726)
• The increased membrane expression of PR3 found in ANCA-associated systemic vasculitis is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene. (PMID:20491791)
• pivotal role of the NB1-Mac-1 receptor interaction for PR3-ANCA-mediated neutrophil activation (PMID:21193407)
• NB1-proteinase 3 interactions may play a role in aiding neutrophil transmigration. (PMID:22266279)
• PRV1 overexpression is associated with Essential Thrombocythemia and Myelofibrosis. (PMID:22300941)
• CD177/PECAM-1 adhesive interaction, while contributing to neutrophil-endothelial cell interaction in neutrophil transendothelial migration, does not contribute to or is redundant in platelet-neutrophil interactions (PMID:22690867)
• This is the first report showing a prognostic correlation between CD177 expression and solid tumor behavior. (PMID:23899160)
• Skewed low neutrophil CD177(%) is highly associated with clonal myeloid disorders, particularly myelodysplasia, and may be useful for detecting clonal myeloid disorders. (PMID:24124144)
• the CD177 SNP is the primary genetic determinant for HNA-2 deficiency and expression variations. The mechanistic delineation of HNA-2 genetics will enable the development of genetic tests for diagnosis and prognosis of HNA-2-related human diseases. (PMID:26024230)
• Data indicate that high percentage of CD177 antigen-positive neutrophils undergo dynamic change during sepsis. (PMID:26829180)
• Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed (PMID:27227454)
• our results have highlighted for the first time an up-regulated transcriptomics and phenotypic expression of neutrophil CD177 in septic shock patients compared to healthy volunteers. (PMID:27568821)
• Characterization of the CD177 interaction with the ANCA antigen proteinase 3 responsible for autoimmune diseases has been reported. (PMID:28240246)
• Data show that CD177 protein is monoallelically expressed in neutrophils and neutrophil-differentiated hematopoietic stem cells (HSCs). (PMID:28559244)
• CD177 signals in a beta2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration. (PMID:28807980)
• High CD177 expression is associated with Biliary Atresia. (PMID:30201498)
• Our findings implicate CD177 as a biomarker for bevacizumab and suggest VEGF/Ang2 inhibition as a strategy to overcome neutrophil associated resistance to anti-angiogenic treatment. (PMID:30377339)
• These results suggested that the increase of CD177(pos) neutrophils was associated with Kawasaki disease. (PMID:30674924)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd177	ENSMUSG00000052212
rattus_norvegicus	Cd177	ENSRNOG00000022669

Paralogs (2): TEX101 (ENSG00000131126), LYPD4 (ENSG00000273111)

Protein

Protein identifiers

CD177 antigen — Q8N6Q3 (reviewed: Q8N6Q3)

Alternative names: Human neutrophil alloantigen 2a, NB1 glycoprotein, Polycythemia rubra vera protein 1

All UniProt accessions (3): A0A087WVM2, A0A087X113, Q8N6Q3

UniProt curated annotations — full annotation on UniProt →

Function. In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF primed neutrophils including degranulation and superoxide production. In addition, by preventing beta-2 integrin internalization and attenuating chemokine signaling favors adhesion over migration. Heterophilic interaction with PECAM1 on endothelial cells plays a role in neutrophil transendothelial migration in vitro. However, appears to be dispensable for neutrophil recruitment caused by bacterial infection in vivo. Acts as a receptor for the mature form of protease PRTN3 allowing its display at the cell surface of neutrophils. By displaying PRTN3 at the neutrophil cell surface, may play a role in enhancing endothelial cell junctional integrity and thus vascular integrity during neutrophil diapedesis.

Subunit / interactions. Found in a complex with integrin ITGAM/CD11b and ITGB2/CD18. Interacts with PECAM1 (via Ig-like C2-type domain 6); the interaction is Ca(2+)-dependent; the interaction is direct. Interacts with serine protease PRTN3/myeloblastin; the interaction tethers PRTN3 to the cell surface; the interaction is direct.

Subcellular location. Cell membrane. Membrane raft. Secreted. Cytoplasmic granule membrane. Cell projection. Lamellipodium.

Tissue specificity. Highly expressed in normal bone marrow and weakly expressed in fetal liver. During neutrophil differentiation, expression begins at the metamyelocyte stage and continues throughout the subsequent stages (at protein level). Expressed by a subset of mature neutrophils (at protein level). The percentage of neutrophils expressing CD177 varies across the population. Expressed in granulocytes of patients with polycythemia vera (PV) and with essential thrombocythemia (ET).

Post-translational modifications. N-glycosylated. A soluble form may also be produced by proteolytic cleavage at the cell surface (shedding).

Induction. By CSF3/G-CSF in resting granulocytes. Induced during CSF3/G-CSF-mediated neutrophil differentiation. Induced during pregnancy. Induced in patients with polycythemia vera (PV) and with essential thrombocythemia (ET).

Polymorphism. There is a significant association between the variants Ala-3, Leu-251 and Thr-348 and a low expression of CD177 on neutrophils. Expression of CD177 on neutrophils is a trait determined by ratio of CD177/CD177P1 alleles. The phenotype of CD177 null neutrophils is due to recombination between exon 7 of CD177 and the pseudogene CD177P1 through gene conversion, changing Lys-263 codon into stop codon. The lack of CD177 expression affects 1-10 percent of the population placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia.

Miscellaneous. Associated with CD177-negative phenotype. Associated with CD177-negative phenotype.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N6Q3-1	1	yes
Q8N6Q3-2	2
Q8N6Q3-3	3

RefSeq proteins (1): NP_065139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR051899	Fert-Immune_med_protein	Family

Pfam: PF00021

UniProt features (24 total): sequence variant 9, splice variant 4, sequence conflict 4, domain 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9IGO	X-RAY DIFFRACTION	1.5
9IGP	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6Q3-F1	85.67	0.68

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): 408

Glycosylation sites (1): 189

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140875
R-HSA-109582	Hemostasis
R-HSA-140877
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 159 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_REGULATION_OF_SUPEROXIDE_ANION_GENERATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELL_CELL_ADHESION, GOBP_CELLULAR_EXTRAVASATION, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (13): cell adhesion (GO:0007155), leukocyte cell-cell adhesion (GO:0007159), regulation of endocytosis (GO:0030100), positive regulation of superoxide anion generation (GO:0032930), protein localization to cell surface (GO:0034394), positive regulation of neutrophil degranulation (GO:0043315), innate immune response (GO:0045087), cell-cell junction maintenance (GO:0045217), neutrophil extravasation (GO:0072672), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), neutrophil migration (GO:1990266), regulation of integrin-mediated signaling pathway (GO:2001044), immune system process (GO:0002376)

GO Molecular Function (4): protease binding (GO:0002020), integrin binding (GO:0005178), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (12): plasma membrane (GO:0005886), lamellipodium (GO:0030027), secretory granule membrane (GO:0030667), specific granule membrane (GO:0035579), plasma membrane raft (GO:0044853), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), side of membrane (GO:0098552), extracellular region (GO:0005576), membrane (GO:0016020), cell projection (GO:0042995), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Hemostasis	1
Innate Immune System	1
Coagulation pathway	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
secretory granule membrane	2
cellular process	1
cell-cell adhesion	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
intracellular protein localization	1
positive regulation of myeloid leukocyte mediated immunity	1
positive regulation of leukocyte degranulation	1
neutrophil degranulation	1
regulation of neutrophil degranulation	1
positive regulation of immune response	1
immune response	1
defense response to symbiont	1
cell junction maintenance	1
cell-cell junction organization	1
cellular extravasation	1
neutrophil migration	1
granulocyte migration	1
integrin-mediated signaling pathway	1
regulation of signal transduction	1
biological_process	1
enzyme binding	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
calcium ion binding	1
protein binding	1
binding	1
cell periphery	1
cell leading edge	1
plasma membrane bounded cell projection	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

1100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD177	PECAM1	P16284	986
CD177	PRTN3	P15637	916
CD177	CNTN5	O94779	910
CD177	CNTN6	Q9UQ52	843
CD177	PLAUR	Q03405	750
CD177	ITGAM	P11215	740
CD177	FCGR3B	O75015	658
CD177	COL18A1	P39060	645
CD177	FCGR3A	P08637	621
CD177	CEACAM8	P31997	614
CD177	CSF3	P09919	599
CD177	OLFM4	Q6UX06	542
CD177	SERPINC1	P01008	497
CD177	F11R	Q9Y624	484
CD177	CD38	P28907	483
CD177	CD47	Q08722	483

IntAct

17 interactions, top by confidence:

A	B	Type	Score
KCNIP3	CD177	psi-mi:“MI:0915”(physical association)	0.780
CD177	KCNIP3	psi-mi:“MI:0915”(physical association)	0.780
CD177	PECAM1	psi-mi:“MI:0407”(direct interaction)	0.440
CD177	ITGB2	psi-mi:“MI:0914”(association)	0.430
ITGB2	CD177	psi-mi:“MI:0403”(colocalization)	0.430
ITGAM	CD177	psi-mi:“MI:0403”(colocalization)	0.430
EWSR1	CD177	psi-mi:“MI:0915”(physical association)	0.370
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
CD177	KCNIP3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): CD177 (Two-hybrid), CD177 (Two-hybrid), CD177 (Two-hybrid), CD177 (Affinity Capture-MS), CD177 (Two-hybrid), CD177 (Protein-peptide), CD177 (Two-hybrid)

ESM2 similar proteins: A6NCL2, D3ZTT2, O19131, O46655, O70280, P01177, P01178, P01179, P01180, P01183, P01185, P01186, P03973, P13389, P19438, P22298, P22934, P25118, P35454, P35455, P50555, P58658, P58659, Q02509, Q14AE4, Q32LD3, Q3URS3, Q5T700, Q68US5, Q6UWE3, Q6UWL2, Q6V9X0, Q6WN34, Q76LW6, Q86Y78, Q8BPP5, Q8BVP6, Q8N6Q3, Q8VEA6, Q8WXA2

Diamond homologs: Q32LD3, Q6UWN0, Q8BVP6, Q8N6Q3, Q7TQN2, Q8R2S8, Q924B5, Q9BY14, Q9JMI7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1035 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43353989:GAGCG:G	donor_gain	1.0000
19:43353991:GCG:G	donor_gain	1.0000
19:43354199:C:CA	acceptor_gain	1.0000
19:43354332:G:GT	donor_gain	1.0000
19:43354354:T:G	donor_gain	1.0000
19:43355987:T:A	acceptor_gain	1.0000
19:43355987:TGCAG:T	acceptor_loss	1.0000
19:43355988:GCA:G	acceptor_loss	1.0000
19:43355989:CAG:C	acceptor_loss	1.0000
19:43355990:A:AG	acceptor_gain	1.0000
19:43355990:AG:A	acceptor_gain	1.0000
19:43355990:AGG:A	acceptor_loss	1.0000
19:43355990:AGGAG:A	acceptor_gain	1.0000
19:43355991:G:GC	acceptor_gain	1.0000
19:43355991:GG:G	acceptor_gain	1.0000
19:43355991:GGA:G	acceptor_gain	1.0000
19:43355991:GGAGG:G	acceptor_gain	1.0000
19:43356106:AAGGT:A	donor_loss	1.0000
19:43356107:AGG:A	donor_loss	1.0000
19:43356109:G:GG	donor_gain	1.0000
19:43362083:TCTAG:T	acceptor_loss	1.0000
19:43362084:CTAGG:C	acceptor_loss	1.0000
19:43362086:AGGT:A	acceptor_gain	1.0000
19:43362087:GGTG:G	acceptor_gain	1.0000
19:43353765:AGGT:A	donor_loss	0.9900
19:43353766:GGTG:G	donor_loss	0.9900
19:43353767:G:A	donor_loss	0.9900
19:43353768:T:A	donor_loss	0.9900
19:43353848:TCCA:T	acceptor_loss	0.9900
19:43353849:CCA:C	acceptor_loss	0.9900

AlphaMissense

2823 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000207945 (19:43354142 G>A,C), RS1000336340 (19:43352947 C>A,T), RS1000383035 (19:43361832 G>A,C,T), RS1000678785 (19:43353164 A>C), RS1001220105 (19:43362242 C>A,T), RS1001278746 (19:43362029 G>A,T), RS1002186384 (19:43353644 C>T), RS1002216282 (19:43360972 C>A), RS1002268551 (19:43360668 C>G,T), RS1002386475 (19:43366030 G>A), RS1002740968 (19:43366284 G>A), RS1002891136 (19:43362998 AAT>A), RS1003049513 (19:43352197 G>C), RS1003347863 (19:43354840 T>C), RS1003408517 (19:43354627 C>T)

Disease associations

OMIM: gene MIM:162860 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1640	Blood protein levels	1.000000e-63

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, increases abundance	2
Smoke	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
abrine	increases expression	1
Arsenic Trioxide	increases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lipopolysaccharides	increases expression	1
Methamphetamine	increases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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