PLCD1

Summary

PLCD1 (phospholipase C delta 1, HGNC:9060) is a protein-coding gene on chromosome 3p22.2, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (P51178). The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.

This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5333 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic congenital nail disorder 3 (Strong, GenCC)
• Clinical variants (ClinVar): 248 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_006225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9060
Approved symbol	PLCD1
Name	phospholipase C delta 1
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187091
Ensembl biotype	protein_coding
OMIM	602142
Entrez	5333

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000334661, ENST00000417185, ENST00000461445, ENST00000463876, ENST00000473834, ENST00000479619, ENST00000484829, ENST00000495367, ENST00000495395, ENST00000909332, ENST00000909333, ENST00000909334, ENST00000909335, ENST00000909336, ENST00000937408, ENST00000956063, ENST00000956064, ENST00000956065

RefSeq mRNA: 2 — MANE Select: NM_006225 NM_001130964, NM_006225

CCDS: CCDS2671, CCDS46793

Canonical transcript exons

ENST00000334661 — 15 exons

Exon	Start	End
ENSE00001331513	38029506	38029642
ENSE00002124803	38009904	38010053
ENSE00002127914	38010131	38010275
ENSE00002135583	38008458	38008636
ENSE00003468944	38009042	38009158
ENSE00003501546	38009272	38009431
ENSE00003525186	38008014	38008163
ENSE00003526532	38009653	38009811
ENSE00003584946	38020188	38020352
ENSE00003617509	38016491	38016719
ENSE00003617914	38011544	38011673
ENSE00003621698	38011214	38011445
ENSE00003657302	38010361	38010562
ENSE00003682774	38008235	38008367
ENSE00003902233	38007496	38007858

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2160 / max 233.9033, expressed in 1634 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41705	5.8862	1136
41698	1.7082	58
41702	1.6117	696
41704	1.4667	715
41697	1.1064	58
41703	0.9479	513
41700	0.5411	49
41699	0.5230	51
41701	0.4247	205

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	97.69	silver quality
type B pancreatic cell	CL:0000169	97.11	silver quality
mucosa of transverse colon	UBERON:0004991	96.90	gold quality
tongue squamous epithelium	UBERON:0006919	96.70	gold quality
lower esophagus mucosa	UBERON:0035834	95.85	gold quality
diaphragm	UBERON:0001103	95.55	silver quality
right testis	UBERON:0004534	94.97	gold quality
left testis	UBERON:0004533	94.88	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.71	gold quality
descending thoracic aorta	UBERON:0002345	94.44	gold quality
inferior olivary complex	UBERON:0002127	94.28	gold quality
ascending aorta	UBERON:0001496	93.49	gold quality
thoracic aorta	UBERON:0001515	93.45	gold quality
gingival epithelium	UBERON:0001949	93.45	gold quality
aorta	UBERON:0000947	93.23	gold quality
pharyngeal mucosa	UBERON:0000355	93.19	gold quality
popliteal artery	UBERON:0002250	93.13	gold quality
tibial artery	UBERON:0007610	93.12	gold quality
upper arm skin	UBERON:0004263	92.95	gold quality
testis	UBERON:0000473	92.87	gold quality
cervix squamous epithelium	UBERON:0006922	92.76	silver quality
gingiva	UBERON:0001828	92.57	gold quality
cervix epithelium	UBERON:0004801	92.39	gold quality
mucosa of urinary bladder	UBERON:0001259	92.34	silver quality
tibial nerve	UBERON:0001323	92.32	gold quality
esophagus mucosa	UBERON:0002469	92.24	gold quality
tibia	UBERON:0000979	92.19	gold quality
body of tongue	UBERON:0011876	92.02	gold quality
squamous epithelium	UBERON:0006914	91.76	gold quality
cardia of stomach	UBERON:0001162	91.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	785.58
E-ANND-3	yes	3.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

14 targeting PLCD1, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-191-5P	95.88	67.82	171

Literature-anchored findings (GeneRIF, showing 40)

• Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta (PMID:11960991)
• Pleckstrin homology domains of phospholipases C-beta and -delta confer activation through a common site (PMID:12761218)
• the PLC-delta1 promoter is under the control of NF-kappaB, which mediates the expression of PLC-delta due to Abeta42 (PMID:14550290)
• PLCdelta(1) and PLCdelta(4) are probably differentially regulated in distinct cellular compartments by PI(4,5)P(2) (PMID:15037625)
• results support a model in which PLCbeta2 suppresses the basal catalytic activity of PLCdelta1, which is relieved by binding of Gbetagamma subunits to PLCbeta2 allowing for amplified calcium signals (PMID:15509571)
• Nuclear translocation of phospholipase C-delta1 is linked to the cell cycle and nuclear phosphatidylinositol 4,5-bisphosphate (PMID:15809301)
• the Ral-CaM complex defines a multifaceted regulatory mechanism for PLC-delta1 activation (PMID:15817490)
• In this review, recent findings regarding the molecular machineries and mechanisms of the nucleocytoplasmic shuttling of PLCdelta1 will be discussed. (PMID:16240320)
• These results support the model that activation of selected PLC isoforms at the cleavage furrow controls progression of cytokinesis through regulation of PIP2 levels (PMID:17041247)
• PLC delta 1 plays an important suppressive role in the development and progression of esophageal squamous cell carcinoma (PMID:18006814)
• Human ARHGAP6 protein possessing GTPase stimulating activity for RhoA on the catalytic properties of PLC-delta1, was studied. (PMID:18434237)
• 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)
• PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis. (PMID:19448674)
• After PLC-delta 1 treatment with small interfering RNA, angiotensin II type 1 receptor-stimulated inositol phosphate formation is attenuated. (PMID:20018811)
• Rac1 activates phospholipase Cdelta1 through phospholipase Cbeta2 (PMID:20530480)
• PLCD1 is silenced by promoter methylation in breast cancer. Silencing of PLCD1 is reversed by demethylation which leads to the disruption of cell cycle at G2/M phase in breast cancer, indicating that PLCD1 functions as a tumor suppressor in this tumor. (PMID:20657189)
• these data show that mutations in PLCD1 underlie hereditary leukonychia, revealing a gene involved in molecular control of nail growth. (PMID:21665001)
• Significantly deregulated pathways in colorectal cancer were identified and repression of PLCD1 and PLCE1 expression, was validated. (PMID:21909432)
• Mutations in this gene cause hereditary porcelain nails. Review. (PMID:22078044)
• Increased PLC-delta1 activity causes enhanced coronary vasomotility such as that seen in patients with coronary spastic angina. (PMID:22265909)
• A novel mutation in the PLCD1 gene, which leads to an aberrant splicing event, underlies autosomal recessive leuconychia. (PMID:22458588)
• PLCD1 acts as a functional tumor suppressor and may serve as a biomarker for possible early detection and prognosis of chronic myeloid leukemia. (PMID:22576628)
• Genotyping using microsatellite markers linked the families to the gene PLCD1 on chromosome 3p22.2. Sequence analysis of the gene detected one novel (p.Ser740ArgfsX19) and one previously reported mutation (p.Arg437X). (PMID:23149345)
• Provide evidence for intramolecular interactions in the PLC-delta1 PH domain. (PMID:23388389)
• PLCdelta1 is required for maintenance of homeostasis in skin and metabolic tissues. [review] (PMID:23948486)
• Neuropeptide Y decreased PLCD1 expression in HUVECs. (PMID:24903829)
• PLC-delta1 and TRPV6 are critical actor of Ca(2+) homeostasis in CF human bronchial epithelial cells. (PMID:25477137)
• Ectopic expression of PLCD1 inhibits breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization. (PMID:25655282)
• Both unsaturated and saturated dioleoyl-phosphatidylinositol-(4,5)-bisphosphate successfully recruited PHPLCdelta1 to cell membranes. (PMID:25995263)
• slow phase of Gi/o-mediated TRPC4 activation was diminished by inhibiting RhoA or enhancing PLCdelta function (PMID:26755577)
• High PLC delta expression is associated with breast cancer. (PMID:28112359)
• Phospholipase C delta 1 is both a KLF15-regulated gene and a novel repressor of airway smooth muscle hypertrophy. (PMID:28375666)
• PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of ERK1/2/beta-catenin/MMP7 signalling, at least in part, in breast cancer. (PMID:28423710)
• A loss of epidermal PLCdelta1 impairs epidermal barrier function through dysregulation of Ca2+ and p38 mitogen-activated protein kinase (MAPK) signaling. This study also reveals a possible link among PLCdelta1 downregulation, p38 MAPK hyperactivation, and barrier defects in psoriasis-like skin inflammation. (PMID:28430185)
• The PLCdelta1 negatively regulates autophagy, and PLCdelta1 suppression contributes to the tolerance of CRC cells harboring KRAS mutations to nutrient deprivation and anti-cancer drug treatment. (PMID:28528980)
• Nine of the 32 (28.1%) iCCA patients had gene mutations at chromosome 3p, totaling 11 mutations across five genes. Those included five (15.6%) BAP1 mutations, two each (6.3%) of CACNA2D3 and RASSF1 mutations, and one each (3.1%) of ATG7 and PLCD1 mutations. Six (18.8%) cases had concurrent loss of chromosome 3p and gene mutations. (PMID:29122566)
• For the first time, a hereditary leukonychia case with PLCD1 mutation has been described in Chinese Han pedigree. This finding suggests the PLCD1 mutation maybe involved in hereditary leukonychia. (PMID:30003652)
• tumor-specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in colorectal cancer. (PMID:30618183)
• Epidermal loss of phospholipase C delta 1 attenuates croton oil - induced irritant contact dermatitis. (PMID:30791982)
• PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/beta-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. (PMID:32236884)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcd1b	ENSDARG00000034080
danio_rerio	plcd1a	ENSDARG00000059123
mus_musculus	Plcd1	ENSMUSG00000010660
rattus_norvegicus	Plcd1	ENSRNOG00000032238
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), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 — P51178 (reviewed: P51178)

Alternative names: Phosphoinositide phospholipase C-delta-1, Phospholipase C-III, Phospholipase C-delta-1

All UniProt accessions (2): A0A384MR47, P51178

UniProt curated annotations — full annotation on UniProt →

Function. The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Essential for trophoblast and placental development. Binds phosphatidylinositol 4,5-bisphosphate.

Subunit / interactions. Interacts with TGM2.

Tissue specificity. Strongly expressed in lung, liver and heart. Also expressed at least in pancreas, kidney, skeletal muscle, placenta and brain.

Disease relevance. Nail disorder, non-syndromic congenital, 3 (NDNC3) [MIM:151600] A nail disorder characterized by a white appearance of the nail plate (true leukonychia), the nail bed (pseudoleukonychia), or neither (apparent leukonychia). Leukonychia may involve all of the nail (leukonychia totalis) or only part of the nail (leukonychia partialis), or can appear as one or more transverse bands (leukonychia striata) or white spots (leukonychia punctata). The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51178-1	1	yes
P51178-2	2

RefSeq proteins (2): NP_001124436, NP_006216* (*=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
IPR028391	PLC-delta1_cat	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046975	PLC-delta1_EF	Domain

Pfam: PF00168, PF00387, PF00388, PF09279, PF16457

Enzyme classification (BRENDA):

• EC 3.1.4.11 — phosphoinositide phospholipase C (BRENDA: 69 organisms, 175 substrates, 159 inhibitors, 27 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.006–0.45	8
PHOSPHATIDYLINOSITOL	0.012–100	7
1-PHOSPHATIDYL-1D-MYO-INOSITOL	0.058–18.7	6
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.031–0.182	3
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.031	1

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 (55 total): binding site 24, mutagenesis site 10, domain 6, sequence variant 3, sequence conflict 3, modified residue 2, glycosylation site 2, active site 2, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51178-F1	89.31	0.65

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): 311; 356

Ligand- & substrate-binding residues (24): 153; 155; 157; 159; 164; 189; 191; 193; 195; 200; 312; 341 …

Post-translational modifications (2): 457, 460

Glycosylation sites (2): 191, 193

Mutagenesis-validated functional residues (10):

Position	Phenotype
327	no effect on hydrolysis inositol phospholipids.
338	abolishes hydrolysis inositol phospholipids. no effect on binding to phosphatidylinositol 4,5-bisphosphate.
341	abolishes hydrolysis inositol phospholipids. no effect on binding to phosphatidylinositol 4,5-bisphosphate.
356	abolishes hydrolysis inositol phospholipids. no effect on binding to phosphatidylinositol 4,5-bisphosphate.
381	decreases hydrolysis inositol phospholipids.
388	no effect on hydrolysis inositol phospholipids.
434	decreases on hydrolysis inositol phospholipids.
440	no effect on hydrolysis inositol phospholipids.
441	decreases on hydrolysis inositol phospholipids.
549	decreases on hydrolysis inositol phospholipids.

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: 223 (showing top): AP1_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, TTCCGTT_MIR191, PEREZ_TP63_TARGETS, GOLDRATH_IMMUNE_MEMORY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, AP1_Q4_01, BROWNE_HCMV_INFECTION_14HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, chr3p22, TGANTCA_AP1_C, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (7): phospholipid metabolic process (GO:0006644), lipid catabolic process (GO:0016042), phosphatidylinositol metabolic process (GO:0046488), phospholipase C/protein kinase C signal transduction (GO:0141212), lipid metabolic process (GO:0006629), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556)

GO Molecular Function (14): phosphatidylserine binding (GO:0001786), phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), calcium ion binding (GO:0005509), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), GTPase activating protein binding (GO:0032794), phosphatidic acid binding (GO:0070300), phosphatidylinositol phospholipase C activity (GO:0120548), C-type glycerophospholipase activity (GO:0004629), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), anion binding (GO:0043168), metal ion binding (GO:0046872), phosphatidylinositol phosphate binding (GO:1901981)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

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
phospholipid binding	3
lipid metabolic process	2
intracellular anatomical structure	2
anion binding	2
C-type glycerophospholipase activity	2
organophosphate metabolic process	1
catabolic process	1
phosphorus metabolic process	1
intracellular signaling cassette	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
modified amino acid binding	1
metal ion binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
protein binding	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
ion binding	1
cation binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

1268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCD1	DLC1	Q96QB1	912
PLCD1	PLEK2	Q9NYT0	902
PLCD1	PLEK	P08567	893
PLCD1	DLEC1	Q9Y238	761
PLCD1	STARD8	Q92502	748
PLCD1	A0A0A6YYL4	A0A0A6YYL4	714
PLCD1	RALA	P11233	698
PLCD1	GNAQ	P50148	654
PLCD1	BTK	Q06187	593
PLCD1	CALM1	P02593	590
PLCD1	CALML3	P27482	584
PLCD1	CALML5	Q9NZT1	584
PLCD1	AKT1	P31749	581
PLCD1	CALML6	Q8TD86	577
PLCD1	CALML4	Q96GE6	576

IntAct

64 interactions, top by confidence:

A	B	Type	Score
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
PLCD1	KPNB1	psi-mi:“MI:0915”(physical association)	0.600
PLCD1	KPNB1	psi-mi:“MI:0407”(direct interaction)	0.600
KPNB1	PLCD1	psi-mi:“MI:0407”(direct interaction)	0.600
PLCD1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
HGS	PLCD1	psi-mi:“MI:0915”(physical association)	0.560
RBM24	PPL	psi-mi:“MI:0914”(association)	0.530
GDF5	SERPINB7	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
	PLCD1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCD1	TGM2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCD1	PLEC	psi-mi:“MI:0915”(physical association)	0.400
KIF3A	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
SMARCD1	DPF1	psi-mi:“MI:0914”(association)	0.350
PYHIN1	DUSP14	psi-mi:“MI:0914”(association)	0.350
GPBP1	DUSP14	psi-mi:“MI:0914”(association)	0.350
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
TEX35	SNAPIN	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PNMA2	TARS3	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), PLCD1 (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	160
Likely benign	28
Benign	28

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1074942	NM_006225.4(PLCD1):c.1738C>T (p.Gln580Ter)	Pathogenic
30239	NM_006225.4(PLCD1):c.1246C>T (p.Arg416Ter)	Pathogenic
30240	NM_006225.4(PLCD1):c.1724-5_1728del	Pathogenic
30242	NM_006225.4(PLCD1):c.562T>C (p.Cys188Arg)	Pathogenic
2635865	NM_006225.4(PLCD1):c.1483del (p.Met495fs)	Likely pathogenic
2663335	NM_006225.4(PLCD1):c.992G>A (p.Arg331Gln)	Likely pathogenic
3351246	NM_006225.4(PLCD1):c.1155dup (p.Ile386fs)	Likely pathogenic
4849409	NM_006225.4(PLCD1):c.1597C>T (p.Gln533Ter)	Likely pathogenic

SpliceAI

2384 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38007875:C:CT	acceptor_gain	1.0000
3:38007876:A:T	acceptor_gain	1.0000
3:38008009:CTCA:C	donor_loss	1.0000
3:38008010:TCACC:T	donor_loss	1.0000
3:38008011:CA:C	donor_loss	1.0000
3:38008012:A:AC	donor_gain	1.0000
3:38008012:AC:A	donor_gain	1.0000
3:38008013:C:CT	donor_gain	1.0000
3:38008013:C:G	donor_loss	1.0000
3:38008013:CC:C	donor_gain	1.0000
3:38008013:CCT:C	donor_gain	1.0000
3:38008013:CCTT:C	donor_gain	1.0000
3:38008013:CCTTG:C	donor_gain	1.0000
3:38008090:C:CT	acceptor_gain	1.0000
3:38008091:A:T	acceptor_gain	1.0000
3:38008159:GAAAC:G	acceptor_gain	1.0000
3:38008160:AAAC:A	acceptor_gain	1.0000
3:38008161:AAC:A	acceptor_gain	1.0000
3:38008162:AC:A	acceptor_gain	1.0000
3:38008163:CC:C	acceptor_gain	1.0000
3:38008164:C:CC	acceptor_gain	1.0000
3:38008230:CCTA:C	donor_loss	1.0000
3:38008231:CTAC:C	donor_loss	1.0000
3:38008232:TA:T	donor_loss	1.0000
3:38008233:A:AC	donor_gain	1.0000
3:38008233:A:AT	donor_loss	1.0000
3:38008233:AC:A	donor_gain	1.0000
3:38008234:C:A	donor_loss	1.0000
3:38008234:C:CG	donor_gain	1.0000
3:38008234:CC:C	donor_gain	1.0000

AlphaMissense

4988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38008626:A:C	N578K	1.000
3:38008626:A:T	N578K	1.000
3:38009082:G:C	N561K	0.999
3:38009082:G:T	N561K	0.999
3:38009097:T:A	R556S	0.999
3:38009097:T:G	R556S	0.999
3:38009098:C:G	R556T	0.999
3:38010012:G:C	C393W	0.999
3:38010409:A:G	L315P	0.999
3:38016590:A:G	L110P	0.999
3:38008097:C:G	R701P	0.998
3:38008572:G:C	N596K	0.998
3:38008572:G:T	N596K	0.998
3:38009063:A:G	W568R	0.998
3:38009063:A:T	W568R	0.998
3:38009785:C:A	K438N	0.998
3:38009785:C:G	K438N	0.998
3:38010202:G:C	H356D	0.998
3:38010213:G:T	P352Q	0.998
3:38010417:G:C	N312K	0.998
3:38010417:G:T	N312K	0.998
3:38010418:T:A	N312I	0.998
3:38010420:G:C	H311Q	0.998
3:38010420:G:T	H311Q	0.998
3:38010422:G:C	H311D	0.998
3:38020256:A:G	L44S	0.998
3:38020297:C:A	K30N	0.998
3:38020297:C:G	K30N	0.998
3:38008049:C:T	G717D	0.997
3:38008094:A:G	F702S	0.997

dbSNP variants (sampled 300 via entrez): RS1000019380 (3:38007918 G>A,C,T), RS1000066061 (3:38015715 A>T), RS1000191774 (3:38031508 C>A), RS1000479959 (3:38018467 C>T), RS1000686136 (3:38026998 G>A), RS1000706456 (3:38024707 C>T), RS1000718316 (3:38026837 T>C), RS1000883362 (3:38020334 T>A), RS1000972245 (3:38008876 C>G,T), RS1001067404 (3:38014475 T>C,G), RS1001167534 (3:38016290 C>T), RS1001182011 (3:38017656 G>C,T), RS1001388956 (3:38010874 A>G), RS1001394534 (3:38013998 T>C), RS1001394568 (3:38020078 G>A)

Disease associations

OMIM: gene MIM:602142 | disease phenotypes: MIM:151600

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic congenital nail disorder 3	Strong	Autosomal recessive

Mondo (1): nonsyndromic congenital nail disorder 3 (MONDO:0007900)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000613	Photophobia
HP:0000787	Nephrolithiasis
HP:0001231	Abnormal fingernail morphology
HP:0001595	Abnormal hair morphology
HP:0001598	Concave nail
HP:0001820	Leukonychia
HP:0003577	Congenital onset
HP:0005978	Type II diabetes mellitus
HP:0008388	Abnormal toenail morphology
HP:0009720	Adenoma sebaceum
HP:0011121	Abnormal skin morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537289	Gorlin Bushkell Jensen syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3727 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.60	Kd	250	nM	CHEMBL1916340

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexyl [(2S,3R,5S,6S)-2,6-dihydroxy-3,4,5-triphosphonooxycyclohexyl] hydrogen phosphate	630186: Binding affinity to PLCdelta1 PH domain	kd	0.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
bisphenol S	increases expression, decreases methylation	2
Resveratrol	affects cotreatment, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, affects cotreatment	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, decreases methylation	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
clothianidin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Asbestos	decreases expression	1
Atrazine	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1918087	Binding	Binding affinity to PLCdelta1 PH domain	Design and synthesis of biotinylated inositol 1,3,4,5-tetrakisphosphate targeting Grp1 pleckstrin homology domain. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE26	HAP1 PLCD1 (-) 1	Cancer cell line	Male
CVCL_TE27	HAP1 PLCD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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