PLCD3

Summary

PLCD3 (phospholipase C delta 3, HGNC:9061) is a protein-coding gene on chromosome 17q21.31, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (Q8N3E9). Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).

This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate the second messengers diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diacylglycerol and IP3 mediate a variety of cellular responses to extracellular stimuli by inducing protein kinase C and increasing cytosolic Ca(2+) concentrations. This enzyme localizes to the plasma membrane and requires calcium for activation. Its activity is inhibited by spermine, sphingosine, and several phospholipids.

Source: NCBI Gene 113026 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 117 total
• MANE Select transcript: NM_133373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9061
Approved symbol	PLCD3
Name	phospholipase C delta 3
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000161714
Ensembl biotype	protein_coding
OMIM	608795
Entrez	113026

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000538093, ENST00000538988, ENST00000539433, ENST00000542173, ENST00000543623, ENST00000544446, ENST00000546350, ENST00000590644, ENST00000611986, ENST00000615898, ENST00000618022, ENST00000619929, ENST00000864955, ENST00000864956, ENST00000864957, ENST00000864958, ENST00000864959, ENST00000864960, ENST00000939188, ENST00000945489, ENST00000945490, ENST00000945491

RefSeq mRNA: 1 — MANE Select: NM_133373 NM_133373

CCDS: CCDS74077

Canonical transcript exons

ENST00000619929 — 15 exons

Exon	Start	End
ENSE00003522050	45121211	45121372
ENSE00003596677	45120902	45121130
ENSE00003629668	45113122	45113257
ENSE00003712672	45117994	45118138
ENSE00003714791	45114250	45114366
ENSE00003715446	45113439	45113605
ENSE00003721627	45108959	45112704
ENSE00003723685	45118291	45118492
ENSE00003726020	45116632	45116784
ENSE00003727218	45115344	45115490
ENSE00003727980	45118815	45119043
ENSE00003728651	45112863	45113012
ENSE00003730817	45120325	45120454
ENSE00003743122	45115094	45115244
ENSE00003753541	45132248	45132515

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7001 / max 301.4402, expressed in 1661 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166502	25.3246	1645
166503	1.7738	1050
166501	0.2313	111
166500	0.2166	117
166504	0.1538	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.17	gold quality
apex of heart	UBERON:0002098	97.58	gold quality
mucosa of stomach	UBERON:0001199	97.18	gold quality
descending thoracic aorta	UBERON:0002345	96.57	gold quality
right coronary artery	UBERON:0001625	96.54	gold quality
buccal mucosa cell	CL:0002336	96.41	gold quality
left adrenal gland cortex	UBERON:0035825	96.32	gold quality
left adrenal gland	UBERON:0001234	96.17	gold quality
thoracic aorta	UBERON:0001515	96.06	gold quality
ascending aorta	UBERON:0001496	95.97	gold quality
gastrocnemius	UBERON:0001388	95.94	gold quality
muscle of leg	UBERON:0001383	95.92	gold quality
transverse colon	UBERON:0001157	95.91	gold quality
right adrenal gland	UBERON:0001233	95.70	gold quality
right adrenal gland cortex	UBERON:0035827	95.40	gold quality
adrenal cortex	UBERON:0001235	95.39	gold quality
stromal cell of endometrium	CL:0002255	95.03	gold quality
rectum	UBERON:0001052	94.67	gold quality
heart left ventricle	UBERON:0002084	94.52	gold quality
aorta	UBERON:0000947	94.31	gold quality
cardiac ventricle	UBERON:0002082	94.26	gold quality
amygdala	UBERON:0001876	93.98	gold quality
sural nerve	UBERON:0015488	93.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.74	gold quality
substantia nigra	UBERON:0002038	93.71	gold quality
adrenal gland	UBERON:0002369	93.53	gold quality
tendon of biceps brachii	UBERON:0008188	93.51	gold quality
spinal cord	UBERON:0002240	93.41	gold quality
upper arm skin	UBERON:0004263	93.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting PLCD3, 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-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1909-3P	99.03	66.56	1662

Literature-anchored findings (GeneRIF, showing 9)

• Data are consistent with the idea that phospholipase C d1 and d3 isoforms support the growth and migration of normal and neoplastic mammary epithelial cells in vitro. (PMID:19344632)
• In mouse, Plcd1 and Plcd3 may act together in murine hair follicles. (PMID:22723964)
• PLCdelta3 regulates microvilli formation in enterocytes and the radial migration of neurons in the cerebral cortex of the developing brain. [review] (PMID:23948486)
• Results identified an interaction between PLCD3 and FLOT2. Inhibition of PLCD3 expression impaired the malignant potential of nasopharyngeal carcinoma (NPC) cells, by restraining its growth, proliferation, mobility and migration. This study demonstrated that PLCD3 may be an oncogenic protein in NPC and that it plays an important role in the progression of NPC partially by interacting with Flot2. (PMID:29115528)
• Noteworthy prognostic value of phospholipase C delta genes in early stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy and potential molecular mechanisms. (PMID:31808619)
• Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway. (PMID:33674820)
• CircMAP3K4 protects human lens epithelial cells from H2O2-induced dysfunction by targeting miR-193a-3p/PLCD3 axis in age-related cataract. (PMID:36071682)
• Circ_0003747 promotes thyroid cancer progression by sponging miR-338-3p to upregulate PLCD3 expression. (PMID:37166441)
• PLCD3 promotes malignant cell behaviors in esophageal squamous cell carcinoma via the PI3K/AKT/P21 signaling. (PMID:37773107)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcd3a	ENSDARG00000052957
danio_rerio	plcd3b	ENSDARG00000079572
mus_musculus	Plcd3	ENSMUSG00000020937
rattus_norvegicus	Plcd3	ENSRNOG00000003033
drosophila_melanogaster	sl	FBGN0003416
drosophila_melanogaster	Plc21C	FBGN0004611
caenorhabditis_elegans		WBGENE00004038
caenorhabditis_elegans		WBGENE00004039
caenorhabditis_elegans		WBGENE00004045

Paralogs (14): PLCB4 (ENSG00000101333), PLCH1 (ENSG00000114805), PLCD4 (ENSG00000115556), PLCL1 (ENSG00000115896), PLCG1 (ENSG00000124181), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 — Q8N3E9 (reviewed: Q8N3E9)

Alternative names: Phosphoinositide phospholipase C-delta-3, Phospholipase C-delta-3

All UniProt accessions (4): Q8N3E9, F5GXC1, H0YGF8, K7EQF2

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Essential for trophoblast and placental development. May participate in cytokinesis by hydrolyzing PIP2 at the cleavage furrow. Regulates neurite outgrowth through the inhibition of RhoA/Rho kinase signaling.

Subcellular location. Membrane. Cytoplasm. Cleavage furrow.

Tissue specificity. Present in corneal epithelial cells (at protein level).

Activity regulation. Strongly activated by phosphatidic acid. Inhibited by phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), sphingomyelin and phosphatidylserine (PtdSer).

Cofactor. Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.

Domain organisation. The C2 domain is a Ca(2+)-dependent membrane-targeting module. The PH domain mediates interaction with the surface membrane by binding to PIP2.

Induction. Down-regulated by Ca(2+) and cAMP.

RefSeq proteins (1): NP_588614* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000909	PLipase_C_PInositol-sp_X_dom	Domain
IPR001192	PI-PLC_fam	Family
IPR001711	PLipase_C_Pinositol-sp_Y	Domain
IPR001849	PH_domain	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039504	PLC-delta3_EF-hand	Domain

Pfam: PF00168, PF00387, PF00388, PF14788

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H(+) (RHEA:33179)

UniProt features (43 total): binding site 24, domain 7, modified residue 3, compositionally biased region 2, active site 2, region of interest 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3E9-F1	85.51	0.64

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 (2): 352; 397

Ligand- & substrate-binding residues (24): 195; 197; 199; 201; 206; 231; 233; 235; 237; 242; 353; 382 …

Post-translational modifications (3): 105, 496, 573

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol

MSigDB gene sets: 106 (showing top): ATF_B, RNGTGGGC_UNKNOWN, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, TERAMOTO_OPN_TARGETS_CLUSTER_1, GOBP_PLACENTA_BLOOD_VESSEL_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_LABYRINTHINE_LAYER_BLOOD_VESSEL_DEVELOPMENT, HEN1_01, GOBP_BLOOD_VESSEL_MORPHOGENESIS, ATF3_Q6, GOBP_LIPID_METABOLIC_PROCESS, CREB_Q3, GOBP_EMBRYO_DEVELOPMENT

GO Biological Process (7): angiogenesis (GO:0001525), lipid catabolic process (GO:0016042), intracellular signal transduction (GO:0035556), regulation of cell population proliferation (GO:0042127), labyrinthine layer blood vessel development (GO:0060716), lipid metabolic process (GO:0006629), signal transduction (GO:0007165)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), metal ion binding (GO:0046872), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cleavage furrow (GO:0032154), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Inositol phosphate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
regulation of cellular process	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
lipid metabolic process	1
catabolic process	1
signal transduction	1
cell population proliferation	1
embryonic organ development	1
placenta blood vessel development	1
labyrinthine layer development	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
C-type glycerophospholipase activity	1
cation binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
membrane	1
cell periphery	1
cell division site	1
plasma membrane region	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCD3	CABCOCO1	Q8IVU9	669
PLCD3	ZNF652	Q9Y2D9	576
PLCD3	DOCK10	Q96BY6	484
PLCD3	RAPGEF4	Q8WZA2	463
PLCD3	PLEK2	Q9NYT0	462
PLCD3	ULK4	Q96C45	445
PLCD3	CAMK2A	Q9UQM7	434
PLCD3	ATP2B1	P20020	432
PLCD3	PLEK	P08567	430
PLCD3	PLEKHA7	Q6IQ23	419
PLCD3	DCAKD	Q8WVC6	400
PLCD3	PRODH	O43272	391
PLCD3	C22orf39	Q6P5X5	388
PLCD3	PRODH	O43272	383
PLCD3	CYP17A1	P05093	379

IntAct

99 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
PIP4K2A	AHCYL1	psi-mi:“MI:0914”(association)	0.730
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NFKBIB	CHUK	psi-mi:“MI:0914”(association)	0.670
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
KANK4	TRAPPC3	psi-mi:“MI:0914”(association)	0.640
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
FBXL19	MED19	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	TUBG1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	METTL18	psi-mi:“MI:0914”(association)	0.530
ABHD14A	TMEM259	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530

BioGRID (137): PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS)

ESM2 similar proteins: A1L134, A3KN46, A5A779, A6QR40, A8MTL0, A8MYZ5, A9ULG4, B1H1N7, O15554, O89109, P0C7M6, P62295, P70606, Q05AA6, Q08602, Q13474, Q148G5, Q149M9, Q15051, Q1HAQ0, Q1LWG4, Q2M2U5, Q2TBP5, Q32KU4, Q3SYS7, Q5EA80, Q5NVK5, Q643R3, Q6NVG1, Q6P1Q0, Q86VI3, Q8BP00, Q8IXL9, Q8K2J0, Q8N3E9, Q8N6M8, Q8NF37, Q921Q3, Q924L1, Q92696

Diamond homologs: A2AP18, A3KGF7, A5D6R3, G5EBH0, G5EFI8, O75038, O89040, P10687, P10688, P10894, P10895, P21671, P25455, P51178, P51432, Q00722, Q01970, Q07722, Q15111, Q15147, Q1RML2, Q2VRL0, Q32NH8, Q3USB7, Q4KWH5, Q4KWH8, Q4R6L3, Q5FX52, Q5RET0, Q62688, Q62711, Q6NMA7, Q7YRU3, Q86YW0, Q8K2J0, Q8K394, Q8K3R3, Q8K4D7, Q8K4S1, Q8L706

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Respiratory Syncytial Virus Infection Pathway	5	15.2×	3e-03
RSV-host interactions	5	12.0×	4e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	11.9×	2e-04
Constitutive Signaling by Aberrant PI3K in Cancer	6	11.7×	3e-03
PIP3 activates AKT signaling	7	7.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2626 predictions. Top by Δscore:

Variant	Effect	Δscore
17:45112859:CAAC:C	donor_loss	1.0000
17:45112860:AACCT:A	donor_loss	1.0000
17:45112861:ACC:A	donor_loss	1.0000
17:45112862:CCTTG:C	donor_gain	1.0000
17:45113010:AGC:A	acceptor_gain	1.0000
17:45113010:AGCC:A	acceptor_loss	1.0000
17:45113011:GCCTA:G	acceptor_loss	1.0000
17:45113013:C:CA	acceptor_loss	1.0000
17:45113013:C:CC	acceptor_gain	1.0000
17:45113014:T:G	acceptor_loss	1.0000
17:45113103:T:TA	donor_gain	1.0000
17:45113117:CCCAC:C	donor_loss	1.0000
17:45113119:CACCA:C	donor_loss	1.0000
17:45113120:A:AC	donor_gain	1.0000
17:45113120:A:T	donor_loss	1.0000
17:45113121:C:A	donor_loss	1.0000
17:45113121:C:CC	donor_gain	1.0000
17:45113253:AGCAC:A	acceptor_gain	1.0000
17:45113254:GCAC:G	acceptor_gain	1.0000
17:45113255:CAC:C	acceptor_gain	1.0000
17:45113255:CACC:C	acceptor_gain	1.0000
17:45113258:C:CC	acceptor_gain	1.0000
17:45113258:C:CG	acceptor_loss	1.0000
17:45113437:A:AT	donor_loss	1.0000
17:45113438:C:CG	donor_loss	1.0000
17:45113601:GGCCA:G	acceptor_gain	1.0000
17:45113602:GCCA:G	acceptor_gain	1.0000
17:45113603:CCA:C	acceptor_gain	1.0000
17:45113603:CCAC:C	acceptor_gain	1.0000
17:45113604:CA:C	acceptor_gain	1.0000

AlphaMissense

5123 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:45113595:G:C	N613K	0.999
17:45113595:G:T	N613K	0.999
17:45113550:G:C	F628L	0.998
17:45113550:G:T	F628L	0.998
17:45113552:A:G	F628L	0.998
17:45114271:A:G	W603R	0.998
17:45114271:A:T	W603R	0.998
17:45114290:G:C	N596K	0.998
17:45114290:G:T	N596K	0.998
17:45118347:G:C	N353K	0.998
17:45118347:G:T	N353K	0.998
17:45118065:G:C	H397D	0.997
17:45118348:T:A	N353I	0.997
17:45121034:A:T	I141N	0.997
17:45112946:C:G	R733P	0.996
17:45113551:A:G	F628S	0.996
17:45114269:C:A	W603C	0.996
17:45114269:C:G	W603C	0.996
17:45118063:A:C	H397Q	0.996
17:45118063:A:T	H397Q	0.996
17:45118339:A:G	L356P	0.996
17:45112949:A:T	V732D	0.995
17:45118034:A:G	F407S	0.995
17:45118298:A:C	Y370D	0.995
17:45118311:G:C	S365R	0.995
17:45118311:G:T	S365R	0.995
17:45118313:T:G	S365R	0.995
17:45118343:A:G	Y355H	0.995
17:45118352:G:C	H352D	0.995
17:45120969:A:G	W163R	0.995

dbSNP variants (sampled 300 via entrez): RS1000037052 (17:45132545 G>C,T), RS1000499129 (17:45130704 C>T), RS1000544875 (17:45109476 T>C), RS1000555930 (17:45126303 C>T), RS1000576053 (17:45111717 C>T), RS1000909821 (17:45109776 G>A), RS1000920141 (17:45126230 T>C), RS1000953776 (17:45125812 A>T), RS1001063151 (17:45132259 A>G), RS1001256658 (17:45119987 C>A,T), RS1001298427 (17:45129909 G>A), RS1001436131 (17:45119347 C>G), RS1001535212 (17:45131920 C>T), RS1001689970 (17:45111440 A>C), RS1001723271 (17:45125885 A>G)

Disease associations

OMIM: gene MIM:608795 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000395_1	Systolic blood pressure	1.000000e-08
GCST004412_12	Craniofacial microsomia	9.000000e-06
GCST006021_38	Systolic blood pressure	2.000000e-06
GCST006258_54	Diastolic blood pressure	7.000000e-06
GCST006259_13	Systolic blood pressure	5.000000e-10
GCST006661_255	Male-pattern baldness	2.000000e-22
GCST007096_183	Pulse pressure	3.000000e-10
GCST007099_238	Systolic blood pressure	1.000000e-09
GCST008916_39	Asthma	8.000000e-12
GCST009685_49	Hypertension	1.000000e-18
GCST010244_178	Triglyceride levels	2.000000e-08
GCST010703_91	Brain morphology (MOSTest)	2.000000e-65
GCST90020026_438	Hip index	4.000000e-16
GCST90020028_1371	Hip circumference adjusted for BMI	2.000000e-12
GCST90020028_1373	Hip circumference adjusted for BMI	1.000000e-16
GCST90020028_1374	Hip circumference adjusted for BMI	2.000000e-08
GCST90020028_1375	Hip circumference adjusted for BMI	7.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12946454	Efficacy	3	diltiazem	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12946454	ACBD4, PLCD3	3	3.00	1	diltiazem

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphoinositide-specific phospholipase C

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	increases phosphorylation	1
clothianidin	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Microplastics	increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1
Caffeine	increases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TE28	HAP1 PLCD3 (-) 1	Cancer cell line	Male
CVCL_TE29	HAP1 PLCD3 (-) 2	Cancer cell line	Male
CVCL_TE30	HAP1 PLCD3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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