PLCD4

Summary

PLCD4 (phospholipase C delta 4, HGNC:9062) is a protein-coding gene on chromosome 2q35, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (Q9BRC7). 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 delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer.

Source: NCBI Gene 84812 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_032726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9062
Approved symbol	PLCD4
Name	phospholipase C delta 4
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115556
Ensembl biotype	protein_coding
OMIM	605939
Entrez	84812

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 7 retained_intron, 3 nonsense_mediated_decay

ENST00000415854, ENST00000417849, ENST00000432688, ENST00000444453, ENST00000446503, ENST00000450993, ENST00000457773, ENST00000458239, ENST00000459791, ENST00000465713, ENST00000469493, ENST00000473443, ENST00000483685, ENST00000484718, ENST00000497482, ENST00000867504, ENST00000867505, ENST00000944043, ENST00000944044, ENST00000944045

RefSeq mRNA: 1 — MANE Select: NM_032726 NM_032726

CCDS: CCDS46516

Canonical transcript exons

ENST00000450993 — 16 exons

Exon	Start	End
ENSE00001144409	218607899	218608070
ENSE00001703200	218636471	218637175
ENSE00002231854	218633605	218633761
ENSE00003493628	218615904	218616062
ENSE00003502164	218636243	218636392
ENSE00003508834	218634105	218634221
ENSE00003561200	218621470	218621599
ENSE00003570768	218634458	218634630
ENSE00003580339	218632136	218632312
ENSE00003582697	218622647	218622878
ENSE00003606010	218630650	218630802
ENSE00003619943	218628029	218628230
ENSE00003641743	218615707	218615761
ENSE00003646021	218629519	218629663
ENSE00003665233	218635796	218635931
ENSE00003668720	218618579	218618807

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 96.40.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4796 / max 83.0713, expressed in 478 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25361	1.0433	368
25360	0.1495	57
25358	0.1264	42
25362	0.0845	36
25359	0.0760	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.40	gold quality
vastus lateralis	UBERON:0001379	95.50	gold quality
quadriceps femoris	UBERON:0001377	95.15	gold quality
gastrocnemius	UBERON:0001388	94.56	gold quality
skeletal muscle tissue	UBERON:0001134	94.55	gold quality
muscle of leg	UBERON:0001383	94.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.31	gold quality
biceps brachii	UBERON:0001507	93.99	gold quality
deltoid	UBERON:0001476	93.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.83	gold quality
tibialis anterior	UBERON:0001385	91.88	silver quality
mucosa of stomach	UBERON:0001199	91.17	gold quality
muscle tissue	UBERON:0002385	89.06	gold quality
sural nerve	UBERON:0015488	87.25	gold quality
lower esophagus mucosa	UBERON:0035834	86.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.12	gold quality
pituitary gland	UBERON:0000007	80.48	gold quality
lower esophagus	UBERON:0013473	80.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.17	gold quality
adenohypophysis	UBERON:0002196	78.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.78	gold quality
left testis	UBERON:0004533	76.78	gold quality
esophagus	UBERON:0001043	76.40	gold quality
tendon	UBERON:0000043	76.11	gold quality
adult mammalian kidney	UBERON:0000082	75.97	gold quality
right testis	UBERON:0004534	75.63	gold quality
tendon of biceps brachii	UBERON:0008188	75.59	gold quality
cortex of kidney	UBERON:0001225	75.04	gold quality
testis	UBERON:0000473	74.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PLCD4, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-185-5P	99.35	68.60	2497

Literature-anchored findings (GeneRIF, showing 6)

• PLCdelta(1) and PLCdelta(4) are probably differentially regulated in distinct cellular compartments by PI(4,5)P(2) and the PH domain of PLCdelta(4) does not act as a localization signal (PMID:15037625)
• Serial deletion analysis identified the core PLC-delta4 promoter region as being between -402 and -67, in which an E-box and an AP-1 binding site played important roles in the promoter activity. (PMID:17394098)
• Here, the authors report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). (PMID:28463110)
• PLCdelta4 knockdown demonstrated that it is essential for hASC proliferation, without inducing cell death. An increase of cells in G1, and a reduction of cells on interphase and G2/M in knockdown cells were seen. (PMID:29859928)
• PLCD4 functions as a nonreceptor activator of G-proteins. (PMID:30194280)
• PLCE1 activated NF-kappaB [nuclear factor kappa B ] signaling by up-regulating PKCalpha [protein kinase C alpha ], which could promote invasion and migration of esophageal cancer cells. (PMID:30450849)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcd4b	ENSDARG00000040684
danio_rerio	plcd4a	ENSDARG00000057975
mus_musculus	Plcd4	ENSMUSG00000026173
rattus_norvegicus	Plcd4	ENSRNOG00000016361
drosophila_melanogaster	sl	FBGN0003416
drosophila_melanogaster	Plc21C	FBGN0004611
caenorhabditis_elegans		WBGENE00004038
caenorhabditis_elegans		WBGENE00004039
caenorhabditis_elegans		WBGENE00004045

Paralogs (14): PLCB4 (ENSG00000101333), PLCH1 (ENSG00000114805), PLCL1 (ENSG00000115896), PLCG1 (ENSG00000124181), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 — Q9BRC7 (reviewed: Q9BRC7)

Alternative names: Phosphoinositide phospholipase C-delta-4, Phospholipase C-delta-4

All UniProt accessions (6): Q9BRC7, C9JAE4, C9JEA7, F2Z3H8, H7C237, H7C281

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. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca(2+) mobilization in the zona pellucida-induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation. Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3.

Subunit / interactions. Interacts with GRIP1. Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (inactive GDP-bound form); high-affinity interaction. Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (inactive GDP-bound form); low-affinity interaction.

Subcellular location. Membrane. Nucleus. Cytoplasm. Endoplasmic reticulum.

Tissue specificity. Highly expressed in skeletal muscle and kidney tissues, and at moderate level in intestinal tissue. Expressed in corneal epithelial cells.

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

Domain organisation. The PDZ-binding motif mediates the interaction with GRIP1. The C2 domain mediates pre-localization to the membrane prior to Ca(2+) import and non-selective Ca(2+)-mediated targeting to various cellular membranes. The PH domain is not a critical determinant of the membrane localization. The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).

Miscellaneous. Acceptor splice site between exons 4 and 5 is non-canonical but conserved through species for that particular gene. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BRC7-1	1	yes
Q9BRC7-2	2, PLCD4b

RefSeq proteins (1): NP_116115* (*=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
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015359	PLC_EF-hand-like	Domain
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168, PF00169, PF00387, PF00388, PF09279, PF13202

Catalyzed reactions (Rhea), 2 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)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+) (RHEA:43484)

UniProt features (46 total): binding site 24, domain 7, mutagenesis site 3, short sequence motif 2, active site 2, splice variant 2, region of interest 2, chain 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRC7-F1	88.92	0.71

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): 305; 350

Ligand- & substrate-binding residues (24): 147; 149; 151; 153; 158; 183; 185; 187; 189; 194; 306; 335 …

Post-translational modifications (1): 457

Mutagenesis-validated functional residues (3):

Position	Phenotype
224–228	abolishes binding to and activation of gnai3.
227–228	abolishes binding to gnai3.
227	marked but incomplete decrease in gnai3 binding and reduced activation of g-protein signaling.

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: 87 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_SINGLE_FERTILIZATION, GGGTGGRR_PAX4_03, NKX61_01, TGANTCA_AP1_C, GOBP_LIPID_METABOLIC_PROCESS, TGGNNNNNNKCCAR_UNKNOWN, GFI1_01, GOBP_ACROSOME_REACTION, POU3F2_02, GOBP_FERTILIZATION, APPIERTO_RESPONSE_TO_FENRETINIDE_UP, GOBP_LIPID_CATABOLIC_PROCESS, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (6): small GTPase-mediated signal transduction (GO:0007264), acrosome reaction (GO:0007340), lipid catabolic process (GO:0016042), intracellular signal transduction (GO:0035556), lipid metabolic process (GO:0006629), signal transduction (GO:0007165)

GO Molecular Function (9): G-protein alpha-subunit binding (GO:0001965), phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), guanyl-nucleotide exchange factor activity (GO:0005085), calcium ion binding (GO:0005509), phosphatidylinositol phospholipase C activity (GO:0120548), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), 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
cellular anatomical structure	3
intracellular anatomical structure	2
C-type glycerophospholipase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
intracellular signaling cassette	1
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
lipid metabolic process	1
catabolic process	1
signal transduction	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
metal ion binding	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cation binding	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCD4	CIMAP1D	Q3SX64	489
PLCD4	KLHL26	Q53HC5	488
PLCD4	GJD4	Q96KN9	462
PLCD4	ERICH3	Q5RHP9	456
PLCD4	CALHM1	Q8IU99	412
PLCD4	CIB3	Q96Q77	404
PLCD4	CHRNA2	Q15822	398
PLCD4	GDPD2	Q9HCC8	394
PLCD4	PMEPA1	Q969W9	370
PLCD4	PLCD1	P51178	368
PLCD4	GPRIN1	Q7Z2K8	357
PLCD4	PRKAG3	Q9UGI9	340
PLCD4	SLC7A2	P52569	334
PLCD4	PLCXD3	Q63HM9	327
PLCD4	STX2	P32856	323

IntAct

13 interactions, top by confidence:

A	B	Type	Score
MEOX1	PLCD4	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PLCD4	psi-mi:“MI:0915”(physical association)	0.560
TRIM39	PLCD4	psi-mi:“MI:0915”(physical association)	0.550
PLCD4	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	PLCD4	psi-mi:“MI:0915”(physical association)	0.370
IPO11	PLCD4	psi-mi:“MI:0915”(physical association)	0.370
PLCD4	MLLT3	psi-mi:“MI:0914”(association)	0.350
PLCD4	MEOX1	psi-mi:“MI:0915”(physical association)	0.000
PLCD4	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): PLCD4 (Two-hybrid), PLCD4 (Two-hybrid), PLCD4 (Affinity Capture-MS), PLCD4 (Affinity Capture-MS), PLCD4 (Two-hybrid), PLCD4 (Two-hybrid), TCOF1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), HNRNPLL (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), PNMA2 (Affinity Capture-MS), ATAD3C (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), DIEXF (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, B3DLB3, D3ZBP4, F1MH07, O75038, P0C869, P0DPD7, P0DPE1, P10688, P10895, P21671, P21709, P51178, Q0IID2, Q1LWV7, Q2KJ24, Q3U2A8, Q4KM32, Q4R380, Q4R6L3, Q5RET0, Q5RKI3, Q5ST30, Q5TM74, Q60750, Q684M2, Q68DD2, Q6MG21, Q6NVG1, Q6ZSI9, Q767M3, Q86U10, Q86XP0, Q8C9V1, Q8K3R3, Q8NFF5, Q8R3B1, Q8SPR7

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

2 interactions.

A	Effect	B	Mechanism
PLCD4	up-regulates	“1D-myo-inositol 1,4,5-trisphosphate”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2453 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218615758:GACC:G	donor_gain	1.0000
2:218615762:G:GG	donor_gain	1.0000
2:218615812:G:T	donor_gain	1.0000
2:218615896:T:TA	acceptor_gain	1.0000
2:218615900:CTA:C	acceptor_loss	1.0000
2:218615901:TA:T	acceptor_loss	1.0000
2:218615902:A:AG	acceptor_gain	1.0000
2:218615903:G:GG	acceptor_gain	1.0000
2:218615903:GA:G	acceptor_gain	1.0000
2:218615903:GAGCT:G	acceptor_gain	1.0000
2:218616060:GCT:G	donor_gain	1.0000
2:218616063:G:GG	donor_gain	1.0000
2:218618573:T:TA	acceptor_gain	1.0000
2:218618574:G:A	acceptor_gain	1.0000
2:218618577:A:AG	acceptor_gain	1.0000
2:218618577:A:G	acceptor_loss	1.0000
2:218618578:G:A	acceptor_loss	1.0000
2:218618578:G:GT	acceptor_gain	1.0000
2:218618578:GT:G	acceptor_gain	1.0000
2:218618578:GTC:G	acceptor_gain	1.0000
2:218618578:GTCT:G	acceptor_gain	1.0000
2:218618578:GTCTC:G	acceptor_gain	1.0000
2:218618794:G:GT	donor_gain	1.0000
2:218618795:A:T	donor_gain	1.0000
2:218618808:G:GG	donor_gain	1.0000
2:218618818:G:GT	donor_gain	1.0000
2:218618821:G:GT	donor_gain	1.0000
2:218622642:TGCA:T	acceptor_loss	1.0000
2:218622645:A:AG	acceptor_gain	1.0000
2:218622645:A:T	acceptor_loss	1.0000

AlphaMissense

5053 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218629587:T:A	V348D	0.998
2:218634144:G:C	R549P	0.997
2:218634181:C:A	N561K	0.997
2:218634181:C:G	N561K	0.997
2:218634468:T:A	N578K	0.997
2:218634468:T:G	N578K	0.997
2:218629592:C:G	H350D	0.996
2:218634140:A:C	S548R	0.996
2:218634142:C:A	S548R	0.996
2:218634142:C:G	S548R	0.996
2:218628173:A:T	N306I	0.995
2:218628174:C:A	N306K	0.995
2:218628174:C:G	N306K	0.995
2:218628208:A:C	S318R	0.995
2:218628210:C:A	S318R	0.995
2:218628210:C:G	S318R	0.995
2:218630726:T:C	L399P	0.995
2:218634165:G:C	R556T	0.995
2:218634166:G:C	R556S	0.995
2:218634166:G:T	R556S	0.995
2:218636309:G:C	R700P	0.995
2:218636477:G:C	R730P	0.995
2:218628151:T:G	Y299D	0.994
2:218628169:C:G	H305D	0.994
2:218629594:C:A	H350Q	0.994
2:218629594:C:G	H350Q	0.994
2:218634200:T:A	W568R	0.994
2:218634200:T:C	W568R	0.994
2:218628171:T:A	H305Q	0.993
2:218628171:T:G	H305Q	0.993

dbSNP variants (sampled 300 via entrez): RS1000099409 (2:218625129 A>G), RS1000148666 (2:218621604 G>A), RS1000203590 (2:218616227 G>T), RS1000456869 (2:218612272 C>T), RS1000464947 (2:218623162 A>C,T), RS1000472473 (2:218619762 G>A), RS1000522290 (2:218611411 C>T), RS1000573088 (2:218611999 G>T), RS1000641342 (2:218618048 C>G), RS1000653825 (2:218627029 GGATCAC>G), RS1000759344 (2:218611755 C>G), RS1000764863 (2:218626787 A>G), RS1000834514 (2:218610312 G>C,T), RS1000992227 (2:218618253 T>A), RS1000996131 (2:218633849 A>G)

Disease associations

OMIM: gene MIM:605939 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002702_115	Height	2.000000e-10
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST008062_35	Blood urea nitrogen levels	4.000000e-09

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 — Phosphoinositide-specific phospholipase C

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Silver Compounds	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE31	HAP1 PLCD4 (-) 1	Cancer cell line	Male
CVCL_TE32	HAP1 PLCD4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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