PLA1A

Summary

PLA1A (phospholipase A1 member A, HGNC:17661) is a protein-coding gene on chromosome 3q13.33, encoding Phospholipase A1 member A (Q53H76). Hydrolyzes the ester bond of the acyl group attached at the sn-1 position of phosphatidylserines (phospholipase A1 activity) and 1-acyl-2-lysophosphatidylserines (lysophospholipase activity) in the pathway of phosphatidylserines acyl chain remodeling.

The protein encoded by this gene is a phospholipase that hydrolyzes fatty acids at the sn-1 position of phosphatidylserine and 1-acyl-2-lysophosphatidylserine. This secreted protein hydrolyzes phosphatidylserine in liposomes. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51365 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 80 total — 1 pathogenic
• MANE Select transcript: NM_015900

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17661
Approved symbol	PLA1A
Name	phospholipase A1 member A
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	ps-PLA1
Ensembl gene	ENSG00000144837
Ensembl biotype	protein_coding
OMIM	607460
Entrez	51365

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000273371, ENST00000472126, ENST00000475963, ENST00000488919, ENST00000494440, ENST00000495992, ENST00000874104, ENST00000874105, ENST00000874106, ENST00000874107, ENST00000874108

RefSeq mRNA: 4 — MANE Select: NM_015900 NM_001206960, NM_001206961, NM_001293225, NM_015900

CCDS: CCDS2991, CCDS56268, CCDS56269, CCDS77795

Canonical transcript exons

ENST00000273371 — 11 exons

Exon	Start	End
ENSE00000967430	119606774	119606975
ENSE00001012136	119625124	119625232
ENSE00001012145	119619563	119619652
ENSE00001074151	119613017	119613118
ENSE00001074161	119616012	119616101
ENSE00001074170	119628701	119628865
ENSE00001137956	119629384	119629811
ENSE00001150084	119618019	119618186
ENSE00001857724	119597885	119597986
ENSE00003566071	119608770	119608947
ENSE00003597043	119609468	119609576

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 97.86.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6821 / max 406.3268, expressed in 389 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38132	4.5855	386
38131	0.0965	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	97.86	gold quality
seminal vesicle	UBERON:0000998	96.25	gold quality
caput epididymis	UBERON:0004358	94.87	gold quality
choroid plexus epithelium	UBERON:0003911	91.82	gold quality
right lung	UBERON:0002167	90.09	gold quality
cauda epididymis	UBERON:0004360	89.52	gold quality
upper lobe of left lung	UBERON:0008952	87.51	gold quality
right lobe of liver	UBERON:0001114	87.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.00	gold quality
upper lobe of lung	UBERON:0008948	86.79	gold quality
liver	UBERON:0002107	86.29	gold quality
pigmented layer of retina	UBERON:0001782	86.17	gold quality
retina	UBERON:0000966	86.15	gold quality
gastrocnemius	UBERON:0001388	82.98	gold quality
lymph node	UBERON:0000029	82.32	gold quality
decidua	UBERON:0002450	81.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.51	gold quality
muscle of leg	UBERON:0001383	79.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.85	gold quality
lung	UBERON:0002048	79.66	gold quality
metanephros cortex	UBERON:0010533	79.53	gold quality
spinal cord	UBERON:0002240	77.05	gold quality
adult mammalian kidney	UBERON:0000082	76.71	gold quality
lower lobe of lung	UBERON:0008949	76.67	silver quality
left lobe of thyroid gland	UBERON:0001120	76.32	gold quality
buccal mucosa cell	CL:0002336	75.90	silver quality
apex of heart	UBERON:0002098	75.65	gold quality
prostate gland	UBERON:0002367	75.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.25	gold quality
mucosa of stomach	UBERON:0001199	75.03	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PLA1A, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-148B-5P	97.29	66.30	992

Literature-anchored findings (GeneRIF, showing 17)

• polymorphisms in the gene encoding phosphatidylserine-specific phospholipase A1 (PMID:12436198)
• Data show that iPLA(1)gamma is a novel membrane transport factor that contributes to a specific Golgi-to-ER retrograde pathway distinct from presently characterized COPI- and Rab6-dependent pathways. (PMID:19632984)
• These results suggest that the expression of PS-PLA(1) mRNA in THP-1-derived macrophages is activated via TLR4. (PMID:20573295)
• Overall, our study shed the light on new structural features of the phospholipase activity of pancreatic lipase family members. (PMID:24368210)
• PLA1A2 polymorphism is associated with mortality in participants whose hemoglobin A1c ranges from 5.5% to 6.5%. (PMID:24886443)
• These data suggest that PLA1A plays an important role in bridging the membrane-associated NS2-E2 complex and the NS5A-associated replication complex via its interaction with hepatitis C virus E2, NS2, and NS5A. (PMID:25505071)
• PS-PLA1 expression in colorectal cancer is associated with tumor invasion and metastasis. (PMID:25750298)
• the LysoPA levels might be determined largely by LysoPC and LysoPI (possible precursors) and the PS-PLA1-mediated pathway might be involved in the production of LysoPS in gastric cancer. (PMID:28143894)
• Serum PS-PLA1 levels were significantly higher in the melanoma subjects and associated with the clinical stages. (PMID:29500864)
• this report identified PLA1A as a host factor that modulates the TBK1 activation during antiviral innate immune response (PMID:30016790)
• PLA1A interacts with hepatitis C virus E2, NS2 and NS5A via multiple interaction sites, which is important for HCV assembly (PMID:31161554)
• Serum PS-PLA1 is associated with disease activity of systemic lupus erythematosus, indicating its possible use as a biomarker for monitoring SLE disease activity. (PMID:31468739)
• Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism. (PMID:31978406)
• Possible involvement of PS-PLA1 and lysophosphatidylserine receptor (LPS1) in hepatocellular carcinoma. (PMID:32060356)
• PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer. (PMID:33723350)
• Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis. (PMID:34884486)
• Phosphatidylserine-Specific Phospholipase A1 Limits Aggressiveness of Lung Adenocarcinoma by Lysophosphatidylserine and Protein Kinase A-Dependent Pathway. (PMID:35358472)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla1a	ENSDARG00000102176
mus_musculus	Pla1a	ENSMUSG00000002847
rattus_norvegicus	Pla1a	ENSRNOG00000057153
drosophila_melanogaster	CG5162	FBGN0030828
drosophila_melanogaster	CG6675	FBGN0032973
drosophila_melanogaster	CG6472	FBGN0034166
drosophila_melanogaster	CG5665	FBGN0036977
drosophila_melanogaster	sxe2	FBGN0038398
drosophila_melanogaster	CG4582	FBGN0039344
drosophila_melanogaster	CG6296	FBGN0039470
drosophila_melanogaster	CG6295	FBGN0039471
drosophila_melanogaster	CG17192	FBGN0039472
drosophila_melanogaster	CG17191	FBGN0039473
drosophila_melanogaster	CG6283	FBGN0039474
drosophila_melanogaster	CG6277	FBGN0039475
drosophila_melanogaster	CG6271	FBGN0039476
drosophila_melanogaster	CG4267	FBGN0264979
drosophila_melanogaster	CG18258	FBGN0265267

Paralogs (9): LIPG (ENSG00000101670), LIPH (ENSG00000163898), LIPC (ENSG00000166035), LPL (ENSG00000175445), PNLIP (ENSG00000175535), PNLIPRP1 (ENSG00000187021), LIPI (ENSG00000188992), PNLIPRP3 (ENSG00000203837), PNLIPRP2 (ENSG00000266200)

Protein

Protein identifiers

Phospholipase A1 member A — Q53H76 (reviewed: Q53H76)

Alternative names: Phosphatidylserine-specific phospholipase A1

All UniProt accessions (3): Q53H76, G5E9W0, H7C4H1

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the ester bond of the acyl group attached at the sn-1 position of phosphatidylserines (phospholipase A1 activity) and 1-acyl-2-lysophosphatidylserines (lysophospholipase activity) in the pathway of phosphatidylserines acyl chain remodeling. Cleaves phosphatidylserines exposed on the outer leaflet of the plasma membrane of apoptotic cells producing 2-acyl-1-lysophosphatidylserines, which in turn enhance mast cell activation and histamine production. Has no activity toward other glycerophospholipids including phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids or phosphatidylinositols, or glycerolipids such as triolein. Hydrolyzes lyso-PS but not PS.

Subcellular location. Secreted.

Tissue specificity. Widely expressed. Expressed in placenta, prostate and liver. Weakly or not expressed in skin, leukocytes, platelets, colon, spleen, lung, muscle and kidney.

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q53H76-1	1	yes
Q53H76-2	2, DeltaC
Q53H76-3	3
Q53H76-4	4

RefSeq proteins (4): NP_001193889, NP_001193890, NP_001280154, NP_056984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000734	TAG_lipase	Family
IPR013818	Lipase	Domain
IPR016272	Lipase_LIPH	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033906	Lipase_N	Domain

Pfam: PF00151

Enzyme classification (BRENDA):

• EC 3.1.1.111 — phosphatidylserine sn-1 acylhydrolase (BRENDA: 3 organisms, 14 substrates, 2 inhibitors, 0 Km, 0 kcat entries)
• EC 3.1.1.32 — phospholipase A1 (BRENDA: 55 organisms, 221 substrates, 99 inhibitors, 14 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATIDYLCHOLINE	0.11–4	4
1-PALMITOYL-2-ARACHIDONOYLGLYCEROPHOSPHOCHOLINE	0.5	1
DIACYL-SN-GLYCERO-3-PHOSPHORYLCHOLINE	0.6	1
DIACYL-SN-GLYCERO-3-PHOSPHORYLETHANOLAMINE	0.92	1
DIACYL-SN-GLYCERO-3-PHOSPHORYLSERINE	1.19	1
PHOSPHATIDIC ACID	2.38	1
PHOSPHATIDYLGLYCEROL	0.0003	1
SOYBEAN LECITHIN	18.53	1
TRIACYLGLYCEROL	1.53	1
HIGH-DENSITY LIPOPROTEIN	—	0

Catalyzed reactions (Rhea), 5 shown:

• a 1-acyl-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + a fatty acid + H(+) (RHEA:32979)
• 1,2-di-(9Z)-octadecenoyl-sn-glycero-3-phospho-L-serine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+) (RHEA:40491)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+) (RHEA:40499)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-L-serine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-L-serine + hexadecanoate + H(+) (RHEA:41187)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine + H2O = a 2-acyl-sn-glycero-3-phospho-L-serine + a fatty acid + H(+) (RHEA:42212)

UniProt features (19 total): splice variant 4, disulfide bond 3, sequence variant 3, active site 3, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53H76-F1	89.55	0.78

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 (3): 166 (nucleophile); 190 (charge relay system); 260 (charge relay system)

Disulfide bonds (3): 296–304, 245–258, 282–293

Glycosylation sites (2): 79, 365

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1482801	Acyl chain remodelling of PS

MSigDB gene sets: 158 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_PHOSPHATIDYLSERINE_ACYL_CHAIN_REMODELING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, NFKB_Q6, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, NFKB_C, JAZAG_TGFB1_SIGNALING_DN, RGTTAMWNATT_HNF1_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, RYTTCCTG_ETS2_B

GO Biological Process (4): lipid metabolic process (GO:0006629), phosphatidylserine metabolic process (GO:0006658), lipid catabolic process (GO:0016042), phosphatidylserine acyl-chain remodeling (GO:0036150)

GO Molecular Function (6): glycerophospholipid phospholipase A1 activity (GO:0008970), phosphatidylserine lysophospholipase A1 activity (GO:0120560), lipase activity (GO:0016298), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (3): acrosomal membrane (GO:0002080), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydrolase activity, acting on ester bonds	2
primary metabolic process	1
modified amino acid metabolic process	1
glycerophospholipid metabolic process	1
lipid metabolic process	1
catabolic process	1
phosphatidylserine metabolic process	1
A1-type glycerophospholipase activity	1
lysophospholipase A1 activity	1
catalytic activity	1
cation binding	1
acrosomal vesicle	1
secretory granule membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA1A	POU2F3	Q9UKI9	918
PLA1A	LPAR3	Q9UBY5	755
PLA1A	LPAR6	P43657	693
PLA1A	ABHD16A	O95870	519
PLA1A	GPR174	Q9BXC1	511
PLA1A	P2RY10	O00398	455
PLA1A	HSPA13	P48723	439
PLA1A	ENPP2	Q13822	436
PLA1A	PLA2G4C	Q9UP65	431
PLA1A	DDHD1	Q8NEL9	419
PLA1A	ABHD12	Q8N2K0	409
PLA1A	CFAP91	Q7Z4T9	401
PLA1A	MAVS	Q7Z434	390
PLA1A	GPR34	Q9UPC5	382
PLA1A	KAAG1	Q9UBP8	362

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PLA1A	DNLZ	psi-mi:“MI:0915”(physical association)	0.400
ARRB1		psi-mi:“MI:0914”(association)	0.350
PLA1A	RAB29	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), CNPY3 (Affinity Capture-MS), CCDC47 (Affinity Capture-MS), RAB29 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A1A547, A6QPN6, D2GZV9, E1BPW0, O18956, O75356, O75594, O93295, P10852, P15396, P22413, P49961, P55772, P57110, P70665, P82450, P97535, P97687, Q0V8L2, Q0VB07, Q53H76, Q58CQ9, Q5E9H0, Q5R5M5, Q5RBQ5, Q5RFU0, Q67BJ4, Q6P6S9, Q6YGZ1, Q71RP1, Q794F9, Q8K0L2, Q8TE60, Q8VI78, Q95194, Q96LB8, Q96LB9, Q99JP7, Q99MZ4, Q9HAT2

Diamond homologs: A2VBC4, A5PK46, C0HLL3, D7EZN2, J3RZ81, O46559, O46647, O88354, P00591, P06857, P06858, P0CH47, P0CH86, P11150, P11151, P11152, P11153, P11602, P16233, P17892, P27656, P27657, P29183, P49060, P49923, P50903, P51528, P53357, P54315, P54316, P54317, P54318, P55031, P81139, P83629, P97535, Q02157, Q06000, Q06478, Q17RR3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4082121	NM_015900.4(PLA1A):c.1361C>G (p.Ala454Gly)	Pathogenic

SpliceAI

1538 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119613011:TCACA:T	acceptor_loss	1.0000
3:119613012:CACAG:C	acceptor_loss	1.0000
3:119613013:ACAGG:A	acceptor_loss	1.0000
3:119613014:CAGGC:C	acceptor_loss	1.0000
3:119613015:A:AG	acceptor_gain	1.0000
3:119613015:AG:A	acceptor_gain	1.0000
3:119613015:AGGC:A	acceptor_loss	1.0000
3:119613016:G:GT	acceptor_gain	1.0000
3:119613016:GG:G	acceptor_gain	1.0000
3:119613016:GGC:G	acceptor_gain	1.0000
3:119613016:GGCC:G	acceptor_gain	1.0000
3:119613016:GGCCT:G	acceptor_gain	1.0000
3:119613094:G:GT	donor_gain	1.0000
3:119613115:GACA:G	donor_gain	1.0000
3:119613119:G:GG	donor_gain	1.0000
3:119613148:GGAA:G	donor_gain	1.0000
3:119618015:TCA:T	acceptor_loss	1.0000
3:119618017:A:AG	acceptor_gain	1.0000
3:119618017:A:C	acceptor_loss	1.0000
3:119618018:G:GG	acceptor_gain	1.0000
3:119618182:GA:G	donor_gain	1.0000
3:119619607:G:GT	donor_gain	1.0000
3:119619650:GCA:G	donor_gain	1.0000
3:119619653:GTGA:G	donor_gain	1.0000
3:119625233:GTAC:G	donor_gain	1.0000
3:119625237:G:GG	donor_gain	1.0000
3:119628696:TGCA:T	acceptor_loss	1.0000
3:119628698:CAGA:C	acceptor_loss	1.0000
3:119628699:A:AC	acceptor_loss	1.0000
3:119628699:A:AG	acceptor_gain	1.0000

AlphaMissense

2991 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119609510:A:C	S166R	0.995
3:119609512:C:A	S166R	0.995
3:119609512:C:G	S166R	0.995
3:119613068:T:C	L205S	0.993
3:119616080:T:A	C245S	0.993
3:119616081:G:C	C245S	0.993
3:119606971:T:C	F91L	0.992
3:119606973:C:A	F91L	0.992
3:119606973:C:G	F91L	0.992
3:119608794:G:C	W100C	0.992
3:119608794:G:T	W100C	0.992
3:119613103:C:G	H217D	0.992
3:119618036:T:A	C258S	0.992
3:119618037:G:C	C258S	0.992
3:119608792:T:A	W100R	0.990
3:119608792:T:C	W100R	0.990
3:119609516:G:T	G168W	0.990
3:119618037:G:A	C258Y	0.990
3:119609511:G:T	S166I	0.989
3:119613023:A:G	D190G	0.989
3:119608855:T:A	W121R	0.988
3:119608855:T:C	W121R	0.988
3:119613107:C:T	T218I	0.988
3:119616044:G:C	D233H	0.988
3:119608857:G:C	W121C	0.987
3:119608857:G:T	W121C	0.987
3:119613020:T:C	L189P	0.987
3:119613023:A:T	D190V	0.987
3:119616080:T:C	C245R	0.987
3:119613107:C:A	T218K	0.986

dbSNP variants (sampled 300 via entrez): RS1000072687 (3:119606239 A>C,G), RS1000120197 (3:119608346 A>G,T), RS1000262172 (3:119626263 T>C), RS1000378734 (3:119596209 T>C), RS1000476254 (3:119612646 G>A), RS1000819296 (3:119621349 G>A), RS1000877147 (3:119596444 C>A,T), RS1000887063 (3:119600577 A>T), RS1000951271 (3:119618650 C>A), RS1000980031 (3:119600867 A>T), RS1001063175 (3:119611325 T>A), RS1001109396 (3:119621097 G>A), RS1001173841 (3:119600975 T>A), RS1001268295 (3:119615345 T>C), RS1001305652 (3:119605286 T>C)

Disease associations

OMIM: gene MIM:607460 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): familial hypercholesterolemia (MONDO:0005439)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases methylation	4
Benzo(a)pyrene	affects methylation, decreases methylation	2
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance, affects cotreatment	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
arsenite	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
CGP 52608	increases reaction, affects binding	1
GW 7647	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Beclomethasone	decreases reaction, increases expression	1
Bilirubin	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Demecolcine	increases expression	1
Dexamethasone	decreases reaction, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methotrexate	decreases reaction, increases expression	1
Methylprednisolone	decreases reaction, increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Prednisolone	decreases reaction, increases expression	1
Fenofibrate	increases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT02048410	PHASE1/PHASE2	COMPLETED	Efficacy of a New Symbiotic Formulation in Children With Familial Hypercholesterolemia
NCT02100839	PHASE1/PHASE2	COMPLETED	Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results