PLPP1

Summary

PLPP1 (phospholipid phosphatase 1, HGNC:9228) is a protein-coding gene on chromosome 5q11.2, encoding Phospholipid phosphatase 1 (O14494). Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate….

The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in synthesis of glycerolipids and in phospholipase D-mediated signal transduction. This enzyme is an integral membrane glycoprotein that plays a role in the hydrolysis and uptake of lipids from extracellular space. Alternate splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 8611 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_003711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9228
Approved symbol	PLPP1
Name	phospholipid phosphatase 1
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PAP-2a, LPP1
Ensembl gene	ENSG00000067113
Ensembl biotype	protein_coding
OMIM	607124
Entrez	8611

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000264775, ENST00000307259, ENST00000502907, ENST00000509667, ENST00000515132, ENST00000520263, ENST00000908450, ENST00000908451, ENST00000962875, ENST00000962876, ENST00000962877, ENST00000962878, ENST00000962879, ENST00000962880

RefSeq mRNA: 2 — MANE Select: NM_003711 NM_003711, NM_176895

CCDS: CCDS34159, CCDS34160

Canonical transcript exons

ENST00000307259 — 6 exons

Exon	Start	End
ENSE00001006521	55425863	55426039
ENSE00001345520	55534572	55534964
ENSE00001345535	55441851	55441908
ENSE00002051082	55424854	55425334
ENSE00003644375	55467869	55468149
ENSE00003689402	55475299	55475450

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.6406 / max 578.2797, expressed in 1694 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61701	10.0708	1345
61700	8.5246	1300
61702	5.4444	1543
61704	1.9559	1142
61703	1.5640	1044
61699	1.0537	361
61696	0.0112	2
61695	0.0090	4
61697	0.0069	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.05	gold quality
gall bladder	UBERON:0002110	98.90	gold quality
prostate gland	UBERON:0002367	98.87	gold quality
renal glomerulus	UBERON:0000074	98.84	gold quality
metanephric glomerulus	UBERON:0004736	98.80	gold quality
left coronary artery	UBERON:0001626	98.49	gold quality
right coronary artery	UBERON:0001625	98.43	gold quality
coronary artery	UBERON:0001621	98.42	gold quality
mucosa of urinary bladder	UBERON:0001259	98.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.33	gold quality
omental fat pad	UBERON:0010414	98.32	gold quality
peritoneum	UBERON:0002358	98.30	gold quality
pericardium	UBERON:0002407	98.27	gold quality
saphenous vein	UBERON:0007318	98.26	gold quality
tibial artery	UBERON:0007610	98.26	gold quality
popliteal artery	UBERON:0002250	98.25	gold quality
aorta	UBERON:0000947	98.20	gold quality
adipose tissue	UBERON:0001013	98.17	gold quality
thoracic aorta	UBERON:0001515	98.15	gold quality
ascending aorta	UBERON:0001496	98.14	gold quality
dorsal root ganglion	UBERON:0000044	98.00	gold quality
skin of hip	UBERON:0001554	98.00	gold quality
synovial joint	UBERON:0002217	97.97	gold quality
descending thoracic aorta	UBERON:0002345	97.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.88	gold quality
metanephros	UBERON:0000081	97.86	gold quality
connective tissue	UBERON:0002384	97.78	gold quality
smooth muscle tissue	UBERON:0001135	97.77	gold quality
vena cava	UBERON:0004087	97.75	gold quality
germinal epithelium of ovary	UBERON:0001304	97.74	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	11420.77
E-GEOD-131882	yes	7170.23
E-CURD-119	yes	6077.89
E-MTAB-11268	yes	4382.04
E-CURD-88	yes	3587.21
E-GEOD-135922	yes	766.79
E-MTAB-6701	yes	143.93
E-MTAB-10287	yes	108.51
E-MTAB-6678	yes	28.79
E-CURD-46	yes	26.12
E-HCAD-9	yes	14.18
E-HCAD-1	yes	11.27
E-MTAB-9543	yes	9.57
E-MTAB-10553	yes	7.62
E-GEOD-99795	no	1017.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARX, EBF3, EGR1, ETS2, PPARA, PPARG, TP73

miRNA regulators (miRDB)

32 targeting PLPP1, 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-8485	100.00	77.57	4731
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-648	98.64	66.13	553

Literature-anchored findings (GeneRIF, showing 9)

• this enzyme regulates interleukin-4-mediated STAT6 signaling. (PMID:12426308)
• This protein and phosphoprotein SET regulate androgen production by P450c17. (PMID:12444089)
• lipid phosphate phosphatase-1 has a role in regulating accumulation of lysophosphatidic acid in ovarian cancer (PMID:14506139)
• Lipopolysaccharide-induced up-regulation of cyclooxygenase-2 depends on the activity of the Mg(+2)-dependent phosphatidic acid phosphohydrolase 1 (PAP-1) (PMID:16950767)
• LPP1 and LPP3 are distributed in distinct lipid rafts that may provide unique microenvironments defining their non-redundant physiological functions. (PMID:17005594)
• These results suggest that the expression of PAP2a is directly regulated by p73. (PMID:17169329)
• These results suggest that LPP1a is important for the determination of plasma FTY720-P levels. (PMID:18755152)
• Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association (PMID:23426360)
• the first of the two transmembrane regions in human SAC1 (TM1) functions in Golgi localization (PMID:23936490)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	plpp1a	ENSDARG00000053381
danio_rerio	PLPP1	ENSDARG00000079790
mus_musculus	Plpp1	ENSMUSG00000021759
rattus_norvegicus	Plpp1	ENSRNOG00000009980
drosophila_melanogaster	wun	FBGN0016078
drosophila_melanogaster	laza	FBGN0037163
drosophila_melanogaster	CG11438	FBGN0037164
drosophila_melanogaster	CG11437	FBGN0037165
drosophila_melanogaster	CG11426	FBGN0037166
drosophila_melanogaster	CG11425	FBGN0037167
drosophila_melanogaster	CG12746	FBGN0037341
drosophila_melanogaster	wun2	FBGN0041087
caenorhabditis_elegans		WBGENE00018756

Paralogs (9): PLPPR2 (ENSG00000105520), PLPPR5 (ENSG00000117598), PLPPR4 (ENSG00000117600), PLPPR3 (ENSG00000129951), PLPP2 (ENSG00000141934), PLPP5 (ENSG00000147535), PLPPR1 (ENSG00000148123), PLPP3 (ENSG00000162407), PLPP4 (ENSG00000203805)

Protein

Protein identifiers

Phospholipid phosphatase 1 — O14494 (reviewed: O14494)

Alternative names: Lipid phosphate phosphohydrolase 1, PAP2-alpha, Phosphatidate phosphohydrolase type 2a, Phosphatidic acid phosphatase 2a

All UniProt accessions (2): O14494, D6REC3

UniProt curated annotations — full annotation on UniProt →

Function. Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes. It is for instance essential for the extracellular hydrolysis of S1P and subsequent conversion into intracellular S1P. Involved in the regulation of inflammation, platelets activation, cell proliferation and migration among other processes. May also have an intracellular activity to regulate phospholipid-mediated signaling pathways.

Subunit / interactions. Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity. Can also form heterooligomers with PLPP2 and PLPP3.

Subcellular location. Cell membrane. Apical cell membrane. Membrane raft. Membrane. Caveola.

Tissue specificity. Widely expressed with highest expression found in prostate. Found to be down-regulated in colon adenocarcinomas. Predominant in kidney, lung, placenta and liver. Predominant in heart and pancreas.

Post-translational modifications. N-glycosylated. N-linked sugars are of the complex type. N-glycosylation is not required for the phosphatase activity.

Activity regulation. Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide. Inhibited by sphingosine, zinc ions and modestly by propanolol. Inhibited by vanadate.

Induction. By androgens.

Pathway. Lipid metabolism; phospholipid metabolism.

Similarity. Belongs to the PA-phosphatase related phosphoesterase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14494-1	1, Alpha-1, hLPP1, PAP2-a1	yes
O14494-2	2, Alpha-2, hLPP1-a, PAP2-a2

RefSeq proteins (2): NP_003702, NP_795714 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR036938	PAP2/HPO_sf	Homologous_superfamily
IPR043216	PAP-like	Family

Pfam: PF01569

Catalyzed reactions (Rhea), 12 shown:

• a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate (RHEA:27429)
• a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacyl-sn-glycero-3-phosphate + phosphate + H(+) (RHEA:27449)
• sphing-4-enine 1-phosphate + H2O = sphing-4-enine + phosphate (RHEA:27518)
• a 1-acyl-sn-glycero-3-phosphate + H2O = a 1-acyl-sn-glycerol + phosphate (RHEA:33155)
• an N-acylsphing-4-enine 1-phosphate + H2O = an N-acylsphing-4-enine + phosphate (RHEA:33743)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:39835)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:41255)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-dihexadecanoyl-sn-glycerol + phosphate (RHEA:43236)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:43244)
• a monoacyl-sn-glycero-3-phosphate + H2O = a monoacylglycerol + phosphate (RHEA:46736)
• (9Z)-octadecenoyl-sn-glycero-3-phosphate + H2O = (9Z-octadecenoyl)-glycerol + phosphate (RHEA:50884)
• N-(octanoyl)-sphing-4-enine-1-phosphate + H2O = N-octanoylsphing-4-enine + phosphate (RHEA:62040)

UniProt features (31 total): topological domain 7, transmembrane region 6, sequence conflict 5, region of interest 4, active site 2, chain 1, short sequence motif 1, compositionally biased region 1, site 1, glycosylation site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9L0U	ELECTRON MICROSCOPY	2.28
9L0S	ELECTRON MICROSCOPY	2.47
9L0I	ELECTRON MICROSCOPY	2.61
9VL3	ELECTRON MICROSCOPY	2.82
9L0O	ELECTRON MICROSCOPY	2.83

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14494-F1	87.11	0.70

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): 171 (proton donors); 223 (nucleophile); 227 (stabilizes the active site histidine for nucleophilic attack)

Glycosylation sites (1): 142

Mutagenesis-validated functional residues (1):

Position	Phenotype
217	decreased lipid phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9845614	Sphingolipid catabolism

MSigDB gene sets: 305 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOZGIT_ESR1_TARGETS_DN, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CROONQUIST_NRAS_SIGNALING_UP, CHX10_01, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, LUND_SILENCED_BY_METHYLATION, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP

GO Biological Process (12): phospholipid metabolic process (GO:0006644), sphingosine metabolic process (GO:0006670), ceramide metabolic process (GO:0006672), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), negative regulation of cell population proliferation (GO:0008285), regulation of lipid metabolic process (GO:0019216), sphingolipid catabolic process (GO:0030149), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), androgen receptor signaling pathway (GO:0030521), phospholipid dephosphorylation (GO:0046839), lipid metabolic process (GO:0006629)

GO Molecular Function (8): diacylglycerol diphosphate phosphatase activity (GO:0000810), phosphatidate phosphatase activity (GO:0008195), sphingosine-1-phosphate phosphatase activity (GO:0042392), lipid phosphatase activity (GO:0042577), lysophosphatidic acid phosphatase activity (GO:0052642), ceramide-1-phosphate phosphatase activity (GO:0106235), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): plasma membrane (GO:0005886), caveola (GO:0005901), membrane (GO:0016020), apical plasma membrane (GO:0016324), membrane raft (GO:0045121), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid phosphatase activity	3
lipid metabolic process	2
sphingolipid metabolic process	2
phosphatase activity	2
organophosphate metabolic process	1
diol metabolic process	1
sphingoid metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of primary metabolic process	1
lipid catabolic process	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
nuclear receptor-mediated steroid hormone signaling pathway	1
dephosphorylation	1
lipid modification	1
primary metabolic process	1
pyrophosphatase activity	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
plasma membrane raft	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
membrane microdomain	1
extracellular vesicle	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPP1	PLPP6	Q8IY26	942
PLPP1	GPLD1	P80108	745
PLPP1	EPHX2	P34913	728
PLPP1	DGAT2	Q96PD7	569
PLPP1	DGAT1	O75907	561
PLPP1	LPIN1	Q14693	550
PLPP1	RALYL	Q86SE5	495
PLPP1	LPIN2	Q92539	485
PLPP1	ENPP2	Q13822	480
PLPP1	SGPP2	Q8IWX5	480
PLPP1	PTPN7	P35236	472
PLPP1	LPIN3	Q9BQK8	471
PLPP1	CIDEC	Q96AQ7	460
PLPP1	SGPP1	Q9BX95	454
PLPP1	PTPRA	P18433	452

IntAct

43 interactions, top by confidence:

A	B	Type	Score
PLPP1	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	CASP1	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	PSEN1	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	TGIF1	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	APP	psi-mi:“MI:0915”(physical association)	0.560
PLPP1	TRIM68	psi-mi:“MI:0915”(physical association)	0.400
PLPP1	CREB3	psi-mi:“MI:0915”(physical association)	0.370
PLPP1	FAHD1	psi-mi:“MI:0915”(physical association)	0.370
ARRDC5	PLPP1	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
PLPP2	PLPP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): PPAP2A (Two-hybrid), PPAP2A (Affinity Capture-Western), PPAP2B (Affinity Capture-Western), PPAP2C (Affinity Capture-Western), PPAP2A (Affinity Capture-Western), PPAP2A (Affinity Capture-Western), TRIM68 (Affinity Capture-MS), PPAP2A (Affinity Capture-RNA), GPR42 (Two-hybrid), SSMEM1 (Two-hybrid), PPAP2A (Proximity Label-MS), PPAP2A (Proximity Label-MS), PPAP2A (Proximity Label-MS), PPAP2A (Proximity Label-MS), PPAP2A (Affinity Capture-MS)

ESM2 similar proteins: A2AKQ0, A2VE55, A5GFZ5, B8B7Q4, F4JN00, O14494, O42602, O60762, O70152, O75352, O88956, P0CK96, P60588, Q15B89, Q1JQ93, Q28HF8, Q2M3R5, Q3ZCD7, Q4L208, Q4R8V4, Q52KD1, Q5PT50, Q5PT53, Q5RDC9, Q5XF09, Q5ZJ75, Q5ZJH8, Q64232, Q6DBP3, Q6DHK8, Q6NMB6, Q6ZL17, Q762D5, Q76EJ3, Q7T0V6, Q8C811, Q8GUJ1, Q8IVW8, Q8R4D1, Q8RXL8

Diamond homologs: O08564, O14494, O14495, O43688, O88956, P60588, P97544, Q04396, Q0VBU9, Q0WNG6, Q10022, Q2HJ61, Q3SZE3, Q3UMZ3, Q5VZY2, Q61469, Q6GQ62, Q6IQH6, Q86AF0, Q8K593, Q8LFD1, Q8NEB5, Q99JY8, Q9DAX2, Q9V576, Q9XI60, B0CM95, B0KWE9, B1MTH4, Q86YN1, Q9ZU49, Q29RT8, Q54PR7, Q6GM05, Q6WAY2, Q7Z2D5, Q8BFZ2, Q8TBJ4, B2KI79, Q32ZL2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1725 predictions. Top by Δscore:

Variant	Effect	Δscore
5:55425861:A:AC	donor_gain	1.0000
5:55425862:C:CC	donor_gain	1.0000
5:55425862:CA:C	donor_gain	1.0000
5:55425862:CAA:C	donor_gain	1.0000
5:55425885:C:CA	donor_gain	1.0000
5:55426035:TAAAG:T	acceptor_gain	1.0000
5:55426040:C:CC	acceptor_gain	1.0000
5:55441849:A:AC	donor_gain	1.0000
5:55441849:ACTG:A	donor_gain	1.0000
5:55441850:C:CC	donor_gain	1.0000
5:55441850:CTG:C	donor_gain	1.0000
5:55441850:CTGC:C	donor_gain	1.0000
5:55467864:CTCA:C	donor_loss	1.0000
5:55467866:CA:C	donor_loss	1.0000
5:55467867:A:AC	donor_gain	1.0000
5:55467867:A:T	donor_loss	1.0000
5:55467868:C:A	donor_loss	1.0000
5:55467868:C:CC	donor_gain	1.0000
5:55467868:CCTG:C	donor_gain	1.0000
5:55468146:TAAT:T	acceptor_gain	1.0000
5:55468150:C:CC	acceptor_gain	1.0000
5:55475293:A:C	donor_gain	1.0000
5:55475297:A:AC	donor_gain	1.0000
5:55475298:C:CC	donor_gain	1.0000
5:55475298:CAA:C	donor_gain	1.0000
5:55475447:CCAG:C	acceptor_gain	1.0000
5:55475448:CAGC:C	acceptor_gain	1.0000
5:55475451:C:CC	acceptor_gain	1.0000
5:55475455:C:CT	acceptor_gain	1.0000
5:55475456:A:T	acceptor_gain	1.0000

AlphaMissense

1838 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:55425885:C:T	G235E	0.999
5:55425886:C:G	G235R	0.999
5:55425886:C:T	G235R	0.999
5:55425897:C:T	G231E	0.999
5:55425898:C:G	G231R	0.999
5:55425898:C:T	G231R	0.999
5:55425909:T:A	D227V	0.999
5:55441899:G:C	F167L	0.999
5:55441899:G:T	F167L	0.999
5:55441901:A:G	F167L	0.999
5:55467959:C:G	C134S	0.999
5:55467959:C:T	C134Y	0.999
5:55467960:A:G	C134R	0.999
5:55467960:A:T	C134S	0.999
5:55468000:C:A	K120N	0.999
5:55468000:C:G	K120N	0.999
5:55468037:C:T	G108D	0.999
5:55425897:C:A	G231V	0.998
5:55425909:T:C	D227G	0.998
5:55425909:T:G	D227A	0.998
5:55425910:C:G	D227H	0.998
5:55425920:G:C	H223Q	0.998
5:55425920:G:T	H223Q	0.998
5:55425922:G:C	H223D	0.998
5:55425939:C:G	R217P	0.998
5:55425949:C:G	G214R	0.998
5:55441882:G:C	S173W	0.998
5:55441885:G:A	S172F	0.998
5:55441885:G:T	S172Y	0.998
5:55441887:G:C	H171Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000073884 (5:55478302 G>A,T), RS1000075842 (5:55436288 T>C), RS1000129336 (5:55485134 CAG>C), RS1000131458 (5:55524265 A>C,G,T), RS1000153638 (5:55534329 C>G), RS1000189854 (5:55530338 G>A,C,T), RS1000264864 (5:55517624 A>G), RS1000285735 (5:55438850 G>A), RS1000312090 (5:55464717 A>ACAT), RS1000324454 (5:55445411 C>A,T), RS1000341305 (5:55491363 A>G), RS1000364990 (5:55536402 A>G), RS1000377439 (5:55456298 T>A), RS1000405332 (5:55478622 G>A), RS1000422296 (5:55536061 G>T)

Disease associations

OMIM: gene MIM:607124 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006288_215	Heel bone mineral density	5.000000e-08
GCST006288_534	Heel bone mineral density	1.000000e-11
GCST006979_101	Heel bone mineral density	8.000000e-17
GCST006979_775	Heel bone mineral density	1.000000e-21
GCST008399_7	Cocaine dependence	8.000000e-06
GCST008839_362	Height	3.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lipid phosphate phosphatases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
ginger extract	increases abundance, increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
acyline	decreases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Irinotecan	decreases response to substance	1
Rosiglitazone	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Azacitidine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Hydrogen Peroxide	affects expression	1
Iron	increases expression	1
Isoflavones	decreases expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Oils, Volatile	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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