APOH

Summary

APOH (apolipoprotein H, HGNC:616) is a protein-coding gene on chromosome 17q24.2, encoding Beta-2-glycoprotein 1 (P02749). Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate.

Apolipoprotein H, also known as beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a required cofactor for anionic phospholipid binding by the antiphospholipid autoantibodies found in sera of many patients with lupus and primary antiphospholipid syndrome (APS). The anti-beta (2) glycoprotein I antibodies from APS patients, mediate inhibition of activated protein C which has anticoagulant properties. Because beta-2-GPI is the main autoantigen in patients with APS, the disruption of this pathway by autoantibodies may be an important mechanism for thrombosis in patients with APS.

Source: NCBI Gene 350 — RefSeq curated summary.

At a glance

• GWAS associations: 37
• Clinical variants (ClinVar): 47 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_000042

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:616
Approved symbol	APOH
Name	apolipoprotein H
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	BG
Ensembl gene	ENSG00000091583
Ensembl biotype	protein_coding
OMIM	138700
Entrez	350

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 23 protein_coding

ENST00000205948, ENST00000577982, ENST00000581797, ENST00000585162, ENST00000879109, ENST00000879110, ENST00000879111, ENST00000879112, ENST00000879113, ENST00000879114, ENST00000879115, ENST00000879116, ENST00000879117, ENST00000879118, ENST00000879119, ENST00000879120, ENST00000879121, ENST00000879122, ENST00000879123, ENST00000879124, ENST00000879125, ENST00000879126, ENST00000879127

RefSeq mRNA: 1 — MANE Select: NM_000042 NM_000042

CCDS: CCDS11663

Canonical transcript exons

ENST00000205948 — 8 exons

Exon	Start	End
ENSE00000584156	66216788	66216967
ENSE00000742648	66214453	66214650
ENSE00000742652	66220554	66220742
ENSE00000742663	66223698	66223774
ENSE00000742665	66226028	66226124
ENSE00000837173	66212033	66212188
ENSE00002728335	66229316	66229415
ENSE00003463428	66228020	66228196

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 99.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 42.3816 / max 16217.2390, expressed in 67 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167666	42.0088	64
167661	0.1472	13
167663	0.0665	10
167658	0.0649	11
167662	0.0366	10
167664	0.0315	10
167665	0.0261	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	99.92	gold quality
right lobe of liver	UBERON:0001114	99.90	gold quality
nephron tubule	UBERON:0001231	93.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.00	gold quality
islet of Langerhans	UBERON:0000006	89.99	gold quality
kidney epithelium	UBERON:0004819	88.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.31	gold quality
renal glomerulus	UBERON:0000074	86.47	gold quality
metanephric glomerulus	UBERON:0004736	85.58	gold quality
epithelial cell of pancreas	CL:0000083	84.09	gold quality
pancreas	UBERON:0001264	82.01	gold quality
body of pancreas	UBERON:0001150	79.94	gold quality
type B pancreatic cell	CL:0000169	77.86	gold quality
kidney	UBERON:0002113	76.46	gold quality
adult mammalian kidney	UBERON:0000082	76.04	gold quality
cortex of kidney	UBERON:0001225	74.05	gold quality
pancreatic ductal cell	CL:0002079	72.81	silver quality
diaphragm	UBERON:0001103	71.68	gold quality
adrenal tissue	UBERON:0018303	71.53	gold quality
metanephros	UBERON:0000081	70.94	gold quality
duodenum	UBERON:0002114	69.05	gold quality
gall bladder	UBERON:0002110	69.01	gold quality
colonic epithelium	UBERON:0000397	68.74	silver quality
jejunal mucosa	UBERON:0000399	68.67	gold quality
lower lobe of lung	UBERON:0008949	68.30	silver quality
fundus of stomach	UBERON:0001160	67.84	gold quality
body of stomach	UBERON:0001161	67.23	gold quality
olfactory bulb	UBERON:0002264	67.10	gold quality
stomach	UBERON:0000945	65.97	gold quality
lung	UBERON:0002048	65.29	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	10580.36
E-CURD-98	yes	9706.36
E-HCAD-9	yes	6059.45
E-GEOD-81547	yes	27.99
E-GEOD-81608	yes	17.98
E-ENAD-27	yes	8.58
E-GEOD-83139	yes	3.86
E-CURD-10	no	41.19
E-MTAB-5061	no	3.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A

miRNA regulators (miRDB)

9 targeting APOH, 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-5010-3P	99.83	70.60	2357
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-147A	98.33	66.40	795

Literature-anchored findings (GeneRIF, showing 40)

• The flexible loop region of the protein’s distinctly folded fifth domain is the binding site for hydrophobic compounds. The mechanism of action resembles that observed between protein folding intermediates and hydrophobic ligands. (PMID:11434778)
• Oxidation of beta2-glycoprotein I (beta2GPI) by the hydroxyl radical alters phospholipid binding and modulates recognition by anti-beta2GPI autoantibodies. (PMID:11686326)
• The phagocytosis of platelets opsonised by anti-beta2GPI antibodies determined the release of TNF-alpha and IL-1beta by dendritic cells and macrophages. (PMID:11816715)
• serum specimens from APS (antiphospholipid syndrome) patients showed characteristic immunofluorescent pattern (PMID:11953211)
• Prevalence and clinical significance of anticardiolipin and anti-beta2-glycoprotein-I antibodies in patients with non-Hodgkin’s lymphoma. (PMID:12038453)
• on neutral lipid layer ApoH has an upright orientation, which is not sensitive to the phase state of the lipid layer, but on acidic lipid layer, ApoH may have two forms of orientation (PMID:12124280)
• Solution structure of human and bovine beta(2)-glycoprotein I revealed by small-angle X-ray scattering (PMID:12139935)
• omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL (PMID:12235181)
• Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids. (PMID:12362233)
• NFkappaB response to anti-beta(2)GP1 antibodies is indirect, and is an essential intermediate in the activation of endothelial cells by anti-beta(2)GP1 antibodies (PMID:12428105)
• Protein hydrophobic exposure was studied in this protein to characterize membrane insertion. (PMID:12440522)
• conformational changes of the fifth domain of human beta(2)-glycoprotein I upon binding to GroEL (PMID:12441378)
• Binding of beta-2-glycoprotein I autoantibodies purified from sera of patients with antiphospholipid syndrome is significantly affected by a number of single point mutations in domain I of B2GI, particularly by mutations in the region of residues 40-43. (PMID:12471146)
• Both the presence of beta2-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. The beta2-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis. (PMID:12562869)
• VV genotype at position 247 of the beta(2)GPI gene may play a role in the generation of anti-beta(2)GPI antibodies and perhaps in the expression of arterial thrombosis in primary antiphospholipid syndrome. (PMID:12571857)
• the multimeric structure is not affected by the presence of mutations in the phospholipid-binding domain (PMID:12590955)
• dimeric beta 2GPI induces increased platelet adhesion and thrombus formation, which depends on activation via apoER2’ (PMID:12807892)
• Behcet’s disease with vascular complications involves higher levels of anticardiolipin antibodies. (PMID:12918732)
• The binding of beta(2)GPI to HBsAg suggests that beta(2)GPI may be a carrier of HBV and that beta(2)GPI may play important roles in HBV infection. (PMID:12970918)
• A high degree of simultaneous reactivity against several beta2GPI-peptides was found in patients with the antiphospholipid syndrome (PMID:14601646)
• antibodies provide additional information in in patients with thrombosis in conjunction with lupus anticoagulant or anticardiolipin antibody. (PMID:14644075)
• the G341A (Ser88Asn) polymorphism might be associated with increased risk of primary cerebral hemorrhage in a Chinese population (PMID:14707422)
• Women with high serum aCLbeta2GPI titers experienced severe maternal-fetal complications. (PMID:14719180)
• beta(2)-GPI/plasmin-nicked beta(2)-GPI ratio controls extrinsic fibrinolysis via a negative feedback pathway loop. (PMID:14726399)
• autoantibodies against beta2-glycoprotein I/oxidized low density lipoprotein complexes are etiologically important in the development of atherosclerosis in antiphospholipid syndrome (PMID:14768953)
• Data suggest that high levels of beta(2)-GPI may be involved in protective mechanisms operating during the atherosclerosis process. (PMID:15025925)
• plasma beta2-GPI levels were lower in the patients with liver cirrhosis and correlated with Child classification (PMID:15094940)
• Presentation of a disease-relevant cryptic T-cell determinant in beta 2-glycoprotein I (beta 2GPI) is induced as a direct consequence of antigen processing from beta 2GPI bound to anionic phospholipids. (PMID:15486070)
• The study provides first demonstration of the occurrence of anti-phospholipid and anti-beta2-GPI activities separately on heavy and light chains of an autoantibody. (PMID:15488942)
• Beta 2 glycoprotein I has roles in blood coagulation and antiphospholipid syndrome [review] (PMID:15507263)
• Beta2-glycoprotein I has roles in antiphospholipid syndrome and T-cell reactivity [review] (PMID:15507264)
• positively charged residues Lys284, Lys286, and Lys287 in DV are essential for the interaction of beta2GPI with FXI/FXIa (PMID:15522884)
• beta(2)-GPI may be important in the prevention of apoptosis in vascular cells (PMID:15534879)
• Val(247) beta(2)allele associated with higher anti-beta2-glycoprotein I (GPI) antibodies and stronger reactivity with anti-beta(2)GPI antibodies compared with Leu(247) beta(2)GPI allele. May be genetic risk factor for antiphospholipid syndrome. (PMID:15641049)
• No significant differences in the distribution of apoH phenotypes was observed among control subjects and patients with apoH-dependent/lupus anticoagulant activity-positive autoantibodies. (PMID:15653437)
• presence of anti-beta(2)-GP1 increases the risk of thrombosis (PMID:15821830)
• Beta-2-glycoprotein I might act to prevent blood clotting on the placental surfaces and also prevents disseminated intravascular coagulation in the microcirculation and maternal plasma just after delivery (PMID:15916797)
• beta2-glycoprotein I causes antibodies to form which trigger coagulation subsequent to a priming proinflammatory factor, which is mediated by terminal C complex (PMID:15956288)
• associations between beta2GPI mutations and both antiphospholipid antibodies (aPL) and their associated clinical manifestations in a pediatric and adolescent cohort (PMID:16038107)
• APOH: major gene effect influencing LDL-peak particle diameter and a positive association with a positional candidate gene located on chromosome 17q (PMID:16159595)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apoh	ENSMUSG00000000049
rattus_norvegicus	Apoh	ENSRNOG00000003566

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Beta-2-glycoprotein 1 — P02749 (reviewed: P02749)

Alternative names: APC inhibitor, Activated protein C-binding protein, Anticardiolipin cofactor, Apolipoprotein H, Beta-2-glycoprotein I

All UniProt accessions (5): P02749, A0A384NKM6, J3KS17, J3QLI0, J3QRN2

UniProt curated annotations — full annotation on UniProt →

Function. Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Post-translational modifications. N- and O-glycosylated. PubMed:6587378 also reports glycosylation on ‘Asn-188’ for their allele.

RefSeq proteins (1): NP_000033* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR015104	Sushi_2	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily

Pfam: PF00084, PF09014

UniProt features (71 total): strand 34, disulfide bond 11, glycosylation site 6, sequence variant 6, domain 4, turn 3, sequence conflict 2, helix 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
3OP8	X-RAY DIFFRACTION	1.9
6V06	X-RAY DIFFRACTION	2.4
6XSD	X-RAY DIFFRACTION	2.54
6V08	X-RAY DIFFRACTION	2.58
7JIK	X-RAY DIFFRACTION	2.69
1QUB	X-RAY DIFFRACTION	2.7
1C1Z	X-RAY DIFFRACTION	2.87
6XST	X-RAY DIFFRACTION	2.92
6V09	X-RAY DIFFRACTION	2.99
4JHS	X-RAY DIFFRACTION	3
7KG4	X-RAY DIFFRACTION	3.3
1G4F	SOLUTION NMR
1G4G	SOLUTION NMR
2KRI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02749-F1	93.16	0.90

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 (11): 23–66, 51–79, 84–124, 110–137, 142–188, 174–200, 205–248, 234–260, 264–315, 300–325, 307–345

Glycosylation sites (6): 183, 193, 253, 33, 149, 162

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 195 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, MODULE_52, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MODULE_64, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOCC_CELL_SURFACE, MODULE_478

GO Biological Process (16): negative regulation of endothelial cell proliferation (GO:0001937), blood coagulation, intrinsic pathway (GO:0007597), negative regulation of endothelial cell migration (GO:0010596), negative regulation of angiogenesis (GO:0016525), positive regulation of blood coagulation (GO:0030194), negative regulation of blood coagulation (GO:0030195), plasminogen activation (GO:0031639), negative regulation of myeloid cell apoptotic process (GO:0033033), triglyceride transport (GO:0034197), chylomicron remodeling (GO:0034371), very-low-density lipoprotein particle remodeling (GO:0034372), negative regulation of smooth muscle cell apoptotic process (GO:0034392), regulation of fibrinolysis (GO:0051917), negative regulation of fibrinolysis (GO:0051918), positive regulation of triglyceride metabolic process (GO:0090208), regulation of blood coagulation (GO:0030193)

GO Molecular Function (7): phospholipid binding (GO:0005543), heparin binding (GO:0008201), lipid binding (GO:0008289), lipase binding (GO:0035473), identical protein binding (GO:0042802), lipoprotein lipase activator activity (GO:0060230), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cell surface (GO:0009986), platelet dense granule lumen (GO:0031089), very-low-density lipoprotein particle (GO:0034361), high-density lipoprotein particle (GO:0034364), chylomicron (GO:0042627), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood coagulation	3
regulation of blood coagulation	3
triglyceride-rich lipoprotein particle remodeling	2
fibrinolysis	2
binding	2
cellular anatomical structure	2
plasma lipoprotein particle	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
protein activation cascade	1
blood coagulation, fibrin clot formation	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
zymogen activation	1
myeloid cell apoptotic process	1
regulation of myeloid cell apoptotic process	1
negative regulation of apoptotic process	1
acylglycerol transport	1
negative regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
regulation of smooth muscle cell apoptotic process	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
negative regulation of biological process	1
regulation of fibrinolysis	1
triglyceride metabolic process	1
positive regulation of lipid metabolic process	1
regulation of triglyceride metabolic process	1
regulation of response to external stimulus	1

Protein interactions and networks

STRING

1809 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOH	ANXA2	P07355	922
APOH	F2	P00734	913
APOH	LRP8	Q14114	908
APOH	TLR4	O00206	842
APOH	TLR2	O60603	836
APOH	APOD	P05090	800
APOH	APOC3	P02656	796
APOH	PLG	P00747	782
APOH	APOA2	P02652	776
APOH	APOA1	P02647	768
APOH	APOA4	P06727	766
APOH	APOF	Q13790	765
APOH	APOB	P04114	760
APOH	APOC2	P02655	751
APOH	CRP	P02741	744

IntAct

48 interactions, top by confidence:

A	B	Type	Score
LDLR	APOH	psi-mi:“MI:0407”(direct interaction)	0.620
LPA	APOH	psi-mi:“MI:0915”(physical association)	0.590
LPA	APOH	psi-mi:“MI:0407”(direct interaction)	0.590
APOH	LPA	psi-mi:“MI:0915”(physical association)	0.590
APOH	Lrp8	psi-mi:“MI:0407”(direct interaction)	0.560
APOH	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
APOH	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
APOH	APOH	psi-mi:“MI:0407”(direct interaction)	0.560
APOH	PF4	psi-mi:“MI:0914”(association)	0.500
APOH	PF4	psi-mi:“MI:0915”(physical association)	0.500
APOH	MBL2	psi-mi:“MI:0407”(direct interaction)	0.490
APOH	MBL2	psi-mi:“MI:0403”(colocalization)	0.490
PLG	APOH	psi-mi:“MI:0407”(direct interaction)	0.440
APOH	PLG	psi-mi:“MI:0407”(direct interaction)	0.440
APOH	FLNA	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
SAV1	APOH	psi-mi:“MI:0915”(physical association)	0.370
	APOH	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (29): FLNA (Affinity Capture-MS), LRP8 (Affinity Capture-Western), APOH (Affinity Capture-MS), LRP2 (Reconstituted Complex), APOH (Reconstituted Complex), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), APOH (Reconstituted Complex), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), APOH (Affinity Capture-MS), EPB41 (Co-fractionation)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P08607, P14151, P15529, P16109, P17690, P19070, P20023, P26644, P27113, P30836, P42201, P49457, P70105, P79138, P98107, P98109, P98131, Q01102, Q03472, Q07968, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735

Diamond homologs: A0A1D5NSM8, A2AVA0, O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P08607, P0C6B8, P15529, P17927, P19070, P20023, P20851, P68638, P68639, P70105, P79138, Q01016, Q03472, Q09101, Q22328, Q2HRD4, Q2VPA4, Q4LDE5, Q501P1, Q53RD9, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735, Q6VE48, Q8HYX8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLG	“down-regulates activity”	APOH	cleavage
APOH	“down-regulates quantity by destabilization”	cardiolipin	binding
F10	“down-regulates activity”	APOH	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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.

GO biological processes:

GO term	Partners	Fold	FDR
cytokine-mediated signaling pathway	5	18.1×	2e-03
negative regulation of gene expression	5	9.6×	9e-03
protein stabilization	5	9.3×	9e-03
positive regulation of gene expression	7	7.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	30
Likely benign	1
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
152211	GRCh38/hg38 17q24.1-24.2(chr17:64634771-67686888)x1	Pathogenic
96713	NM_000042.3(APOH):c.112A>G (p.Lys38Glu)	Likely pathogenic

SpliceAI

1053 predictions. Top by Δscore:

Variant	Effect	Δscore
17:66214451:AC:A	donor_gain	1.0000
17:66214452:CC:C	donor_gain	1.0000
17:66214651:C:CC	acceptor_gain	1.0000
17:66223696:A:AC	donor_gain	1.0000
17:66223697:C:CC	donor_gain	1.0000
17:66223697:CGAG:C	donor_gain	1.0000
17:66226121:CTGG:C	acceptor_gain	1.0000
17:66226125:C:CC	acceptor_gain	1.0000
17:66228014:A:AC	donor_gain	1.0000
17:66228015:C:CC	donor_gain	1.0000
17:66228015:CTTA:C	donor_gain	1.0000
17:66228016:TTACG:T	donor_loss	1.0000
17:66228017:TAC:T	donor_loss	1.0000
17:66228018:A:AC	donor_gain	1.0000
17:66228018:ACGT:A	donor_loss	1.0000
17:66228019:C:CC	donor_gain	1.0000
17:66228019:CGTGT:C	donor_gain	1.0000
17:66228193:CAGG:C	acceptor_gain	1.0000
17:66228194:AGG:A	acceptor_gain	1.0000
17:66228195:GG:G	acceptor_gain	1.0000
17:66228197:C:CC	acceptor_gain	1.0000
17:66228197:CTGAA:C	acceptor_loss	1.0000
17:66228198:T:C	acceptor_loss	1.0000
17:66214551:TTATC:T	donor_gain	0.9900
17:66214646:AGATG:A	acceptor_gain	0.9900
17:66214647:GATG:G	acceptor_gain	0.9900
17:66214648:ATG:A	acceptor_gain	0.9900
17:66214649:TG:T	acceptor_gain	0.9900
17:66214651:C:A	acceptor_loss	0.9900
17:66216963:TACTT:T	acceptor_gain	0.9900

AlphaMissense

2260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:66220576:C:A	W194C	0.999
17:66220576:C:G	W194C	0.999
17:66223723:C:A	W130C	0.999
17:66223723:C:G	W130C	0.999
17:66228045:C:A	W72C	0.999
17:66228045:C:G	W72C	0.999
17:66214491:C:G	C315S	0.998
17:66214492:A:T	C315S	0.998
17:66214536:C:G	C300S	0.998
17:66214537:A:T	C300S	0.998
17:66216810:C:A	W254C	0.998
17:66216810:C:G	W254C	0.998
17:66223742:C:G	C124S	0.998
17:66223743:A:T	C124S	0.998
17:66214492:A:G	C315R	0.997
17:66216829:C:G	C248S	0.997
17:66216830:A:T	C248S	0.997
17:66220559:C:G	C200S	0.997
17:66220560:A:T	C200S	0.997
17:66220637:C:G	C174S	0.997
17:66220638:A:T	C174S	0.997
17:66223725:A:G	W130R	0.997
17:66223725:A:T	W130R	0.997
17:66228025:C:G	C79S	0.997
17:66228026:A:T	C79S	0.997
17:66228047:A:G	W72R	0.997
17:66228047:A:T	W72R	0.997
17:66216871:C:G	C234S	0.996
17:66216872:A:T	C234S	0.996
17:66220595:C:G	C188S	0.996

dbSNP variants (sampled 300 via entrez): RS1000014274 (17:66217446 G>A), RS1000204351 (17:66218043 A>C), RS1000355881 (17:66228720 G>A), RS1000424502 (17:66221420 G>GAAGGAAGGAAGGAAAGC,GAAGGAAGGAAGGA,GAAGGAAGGAAGGAAGGA,GAAGGAAGGAAGGAAGGAAGGA), RS1000427296 (17:66221138 A>C), RS1000601388 (17:66222623 G>A), RS1000656044 (17:66217130 C>T), RS1000710727 (17:66222831 A>G), RS1000724040 (17:66215791 T>G), RS1001437702 (17:66212596 G>A), RS1001586986 (17:66221216 A>C), RS1001742171 (17:66215018 C>T), RS1001747858 (17:66227149 G>A), RS1002214073 (17:66215265 C>T), RS1002426157 (17:66223850 C>T)

Disease associations

OMIM: gene MIM:138700 | 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
GCST001800_5	β2-Glycoprotein I (β2-GPI) plasma levels	1.000000e-06
GCST002222_20	LDL cholesterol	1.000000e-11
GCST002252_10	Blood pressure measurement (high sodium and potassium intervention)	3.000000e-07
GCST002252_4	Blood pressure measurement (high sodium and potassium intervention)	3.000000e-07
GCST003563_1	Presence of antiphospholipid antibodies	1.000000e-11
GCST003563_2	Presence of antiphospholipid antibodies	1.000000e-11
GCST004603_184	Platelet count	2.000000e-17
GCST004607_78	Plateletcrit	7.000000e-27
GCST005196_224	Coronary artery disease	8.000000e-06
GCST006014_26	Creatine kinase levels	1.000000e-33
GCST006018_5	Activated partial thromboplastin time	5.000000e-13
GCST006101_9	Cardiometabolic and hematological traits	4.000000e-19
GCST006612_27	LDL cholesterol	2.000000e-30
GCST006613_81	Triglycerides	6.000000e-23
GCST006628_7	Systolic blood pressure	3.000000e-09
GCST008077_29	LDL cholesterol levels	6.000000e-06
GCST008077_77	LDL cholesterol levels	8.000000e-08
GCST008078_103	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-14
GCST008078_14	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-13
GCST008079_151	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-15
GCST008079_22	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-13
GCST008086_65	LDL cholesterol levels in current drinkers	1.000000e-09
GCST008086_97	LDL cholesterol levels in current drinkers	6.000000e-08
GCST010173_23	Triglyceride levels	2.000000e-20
GCST010204_99	Low density lipoprotein cholesterol levels	1.000000e-30
GCST010243_196	Apolipoprotein B levels	9.000000e-27
GCST010244_67	Triglyceride levels	2.000000e-30
GCST010245_133	LDL cholesterol levels	2.000000e-24
GCST010653_52	Thyroid stimulating hormone levels	3.000000e-11
GCST010703_202	Brain morphology (MOSTest)	1.000000e-11

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004555	glycoprotein measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005401	response to high sodium diet
EFO:0005403	response to dietary potassium supplementation
EFO:0006340	mean arterial pressure
EFO:0006336	diastolic blood pressure
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004534	creatine kinase measurement
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0004329	alcohol drinking
EFO:0004615	apolipoprotein B measurement
EFO:0004346	neuroimaging measurement
EFO:0006925	lipoprotein A measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1801689	APOH		0.00	0
rs1801690	APOH		0.00	0
rs8178822	APOH		0.00	0
rs52797880	APOH		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	4
sodium arsenite	decreases expression, increases methylation	2
Acetaminophen	decreases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cordycepin	affects expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Olanzapine	affects phosphorylation	1
Gemcitabine	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Chenodeoxycholic Acid	decreases expression	1
Cisplatin	affects cotreatment, increases expression, decreases expression	1
Copper	affects binding	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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