PLCXD2

Summary

PLCXD2 (phosphatidylinositol specific phospholipase C X domain containing 2, HGNC:26462) is a protein-coding gene on chromosome 3q13.2, encoding PI-PLC X domain-containing protein 2 (Q0VAA5). Catalyzes the hydrolysis of inositol from phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI).

Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus.

Source: NCBI Gene 257068 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001413064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26462
Approved symbol	PLCXD2
Name	phosphatidylinositol specific phospholipase C X domain containing 2
Location	3q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31579
Ensembl gene	ENSG00000240891
Ensembl biotype	protein_coding
OMIM	617015
Entrez	257068

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000393934, ENST00000468174, ENST00000474484, ENST00000477665, ENST00000636933

RefSeq mRNA: 1 — MANE Select: NM_001413064 NM_001413064

Canonical transcript exons

ENST00000636933 — 4 exons

Exon	Start	End
ENSE00001581142	111713887	111714128
ENSE00001585070	111707926	111708386
ENSE00001900737	111674676	111675408
ENSE00003797720	111720723	111727007

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 91.64.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9573 / max 190.5686, expressed in 591 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37875	1.0846	477
37879	0.7699	149
37877	0.0696	32
37878	0.0332	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	91.64	gold quality
islet of Langerhans	UBERON:0000006	91.25	gold quality
metanephros cortex	UBERON:0010533	90.48	gold quality
endothelial cell	CL:0000115	89.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.03	gold quality
amniotic fluid	UBERON:0000173	85.13	gold quality
adult mammalian kidney	UBERON:0000082	85.10	gold quality
cortical plate	UBERON:0005343	84.76	gold quality
pancreas	UBERON:0001264	83.87	gold quality
substantia nigra pars compacta	UBERON:0001965	83.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.17	gold quality
body of pancreas	UBERON:0001150	82.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.48	gold quality
ileal mucosa	UBERON:0000331	80.32	gold quality
jejunal mucosa	UBERON:0000399	79.57	gold quality
primary visual cortex	UBERON:0002436	78.17	gold quality
superior frontal gyrus	UBERON:0002661	78.07	gold quality
secondary oocyte	CL:0000655	78.03	gold quality
postcentral gyrus	UBERON:0002581	77.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.63	gold quality
pigmented layer of retina	UBERON:0001782	77.61	gold quality
cortex of kidney	UBERON:0001225	77.56	gold quality
ganglionic eminence	UBERON:0004023	77.49	gold quality
liver	UBERON:0002107	76.51	gold quality
upper lobe of left lung	UBERON:0008952	75.73	gold quality
body of stomach	UBERON:0001161	75.72	gold quality
entorhinal cortex	UBERON:0002728	75.44	gold quality
parietal lobe	UBERON:0001872	75.04	gold quality
kidney	UBERON:0002113	74.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.36
E-MTAB-6058	no	371.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting PLCXD2, 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-5193	100.00	67.26	1744
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-4511	98.32	67.97	1500

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcxd2	ENSDARG00000058200
mus_musculus	Plcxd2	ENSMUSG00000087141
rattus_norvegicus	Plcxd2	ENSRNOG00000042289
drosophila_melanogaster	CG10747	FBGN0032845
caenorhabditis_elegans		WBGENE00018184

Paralogs (2): PLCXD1 (ENSG00000182378), PLCXD3 (ENSG00000182836)

Protein

Protein identifiers

PI-PLC X domain-containing protein 2 — Q0VAA5 (reviewed: Q0VAA5)

Alternative names: Phospholipase C X-domain containing protein 2

All UniProt accessions (2): A0A1B0GW80, Q0VAA5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of inositol from phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI). Could also hydrolyze various multi-phosphorylated derivatives of PI, such as phosphatidylinositol-4,5 bisphosphate (PIP2), releasing inositol-1,4,5-trisphosphate (IP3) and the protein kinase C activator diacylglycerol (DAG), therefore mediating cell signaling.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q0VAA5-1	1	yes
Q0VAA5-2	2

RefSeq proteins (1): NP_001399993* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000909	PLipase_C_PInositol-sp_X_dom	Domain
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR042158	PLCXD1/2/3	Family
IPR051057	PI-PLC_domain	Family

Catalyzed reactions (Rhea), 1 shown:

• 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 (5 total): active site 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0VAA5-F1	80.31	0.56

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): 57; 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): PEREZ_TP63_TARGETS, GOZGIT_ESR1_TARGETS_DN, TGACCTY_ERR1_Q2, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, GATA1_04, GOBP_LIPID_METABOLIC_PROCESS, PEREZ_TP53_AND_TP63_TARGETS, TGGNNNNNNKCCAR_UNKNOWN, GOBP_LIPID_CATABOLIC_PROCESS, LEE_RECENT_THYMIC_EMIGRANT, RNCTGNYNRNCTGNY_UNKNOWN, GOMF_PHOSPHORIC_DIESTER_HYDROLASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY

GO Biological Process (3): signal transduction (GO:0007165), lipid catabolic process (GO:0016042), lipid metabolic process (GO:0006629)

GO Molecular Function (2): phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid metabolic process	1
catabolic process	1
primary metabolic process	1
phosphoric ester hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCXD2	ARMC6	Q6NXE6	547
PLCXD2	PI15	O43692	405
PLCXD2	NSMAF	Q92636	397
PLCXD2	TANC1	Q9C0D5	387
PLCXD2	SBK1	Q52WX2	386
PLCXD2	CPLX3	Q8WVH0	380
PLCXD2	RGS7BP	Q6MZT1	379
PLCXD2	RBM28	Q9NW13	378
PLCXD2	SYT6	Q5T7P8	371
PLCXD2	C21orf58	P58505	369
PLCXD2	TRMT44	Q8IYL2	362
PLCXD2	LRRC10B	A6NIK2	357
PLCXD2	ASMTL	O95671	351
PLCXD2	RASGRF2	O14827	350
PLCXD2	YPEL2	Q96QA6	349

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PLCXD2	HRAS	psi-mi:“MI:0915”(physical association)	0.400
PLCXD2	KIF26A	psi-mi:“MI:0915”(physical association)	0.400
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): HRAS (Affinity Capture-MS), PLCXD2 (Affinity Capture-MS), PLCXD2 (Affinity Capture-MS), PLCXD2 (Affinity Capture-MS), KIF26A (Affinity Capture-MS)

ESM2 similar proteins: A0A0D4WTV1, A0AVT1, A3KMX8, A5PN38, A6H630, A6QNU9, B2RXA1, B8ZXI1, C0JB40, D3YUE4, O15886, O22585, O45228, O64407, O65015, P09194, P10538, P37830, P49221, P49915, Q0VAA5, Q1RML2, Q27Q54, Q29LW1, Q2KHV5, Q2VRL0, Q3THK7, Q4V7C6, Q567I4, Q58EK3, Q58EM4, Q5FX52, Q5R998, Q5RA96, Q63HM9, Q64319, Q6AXB1, Q6AYT5, Q6DJA3, Q6UXP7

Diamond homologs: A6QNU9, B2RXA1, P34024, Q0VAA5, Q567I4, Q58EK3, Q63HM9, Q8BLJ3, Q8CHS4, Q9NUJ7, Q55DH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2101 predictions. Top by Δscore:

Variant	Effect	Δscore
3:111708346:A:T	donor_gain	1.0000
3:111708383:CCAGG:C	donor_loss	1.0000
3:111708384:CAGGT:C	donor_loss	1.0000
3:111708385:AGG:A	donor_loss	1.0000
3:111708386:GGT:G	donor_loss	1.0000
3:111708387:G:T	donor_loss	1.0000
3:111708388:T:G	donor_loss	1.0000
3:111720856:G:GT	donor_gain	1.0000
3:111720866:C:G	donor_gain	1.0000
3:111720872:C:G	donor_gain	1.0000
3:111674722:G:GT	donor_gain	0.9900
3:111707924:A:AG	acceptor_gain	0.9900
3:111707925:G:GG	acceptor_gain	0.9900
3:111708395:G:T	donor_gain	0.9900
3:111713918:A:G	acceptor_gain	0.9900
3:111720830:TCATC:T	donor_gain	0.9900
3:111720838:T:G	donor_gain	0.9900
3:111720859:G:GT	donor_gain	0.9900
3:111720871:GC:G	donor_gain	0.9900
3:111720879:C:G	donor_gain	0.9900
3:111774960:GGA:G	donor_gain	0.9900
3:111774961:GAG:G	donor_gain	0.9900
3:111802331:G:T	donor_gain	0.9900
3:111802346:G:T	donor_gain	0.9900
3:111674759:GGGGA:G	donor_gain	0.9800
3:111674760:GGGAG:G	donor_gain	0.9800
3:111674764:G:GG	donor_gain	0.9800
3:111707920:GTACA:G	acceptor_loss	0.9800
3:111707921:TACAG:T	acceptor_loss	0.9800
3:111707923:CAGGC:C	acceptor_loss	0.9800

AlphaMissense

2237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:111708087:G:T	G109W	1.000
3:111713990:T:C	L243P	1.000
3:111675348:T:A	W35R	0.999
3:111675348:T:C	W35R	0.999
3:111675350:G:C	W35C	0.999
3:111675350:G:T	W35C	0.999
3:111675408:G:C	G55R	0.999
3:111707926:G:A	G55D	0.999
3:111707928:T:C	S56P	0.999
3:111707931:C:G	H57D	0.999
3:111707933:T:A	H57Q	0.999
3:111707933:T:G	H57Q	0.999
3:111708042:T:A	W94R	0.999
3:111708042:T:C	W94R	0.999
3:111708056:G:C	Q98H	0.999
3:111708056:G:T	Q98H	0.999
3:111708076:A:C	Q105P	0.999
3:111708079:T:C	L106P	0.999
3:111708088:G:A	G109E	0.999
3:111708088:G:T	G109V	0.999
3:111708093:C:A	R111S	0.999
3:111708094:G:C	R111P	0.999
3:111708103:A:C	D114A	0.999
3:111708103:A:G	D114G	0.999
3:111708103:A:T	D114V	0.999
3:111708104:C:A	D114E	0.999
3:111708104:C:G	D114E	0.999
3:111708106:T:C	L115P	0.999
3:111708190:T:C	L143P	0.999
3:111708207:T:C	F149L	0.999

dbSNP variants (sampled 300 via entrez): RS1000026746 (3:111840439 T>G), RS1000027355 (3:111810073 G>A), RS1000049064 (3:111721398 T>A,C), RS1000066133 (3:111818607 C>G), RS1000083114 (3:111715528 T>C), RS1000090435 (3:111673518 C>T), RS1000096100 (3:111763073 G>C), RS1000098480 (3:111768472 C>T), RS1000111320 (3:111740307 A>G), RS1000114212 (3:111722680 T>C), RS1000138904 (3:111796365 C>T), RS1000146364 (3:111811488 G>A), RS1000186108 (3:111704761 C>T), RS1000215296 (3:111821162 C>T), RS1000232946 (3:111693833 C>A)

Disease associations

OMIM: gene MIM:617015 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000579_15	Cognitive performance	5.000000e-06
GCST002916_4	Cannabis use (initiation)	1.000000e-06
GCST006414_80	Atrial fibrillation	2.000000e-15
GCST006627_7	Diastolic blood pressure	8.000000e-11
GCST010796_5187	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_5188	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST012489_83	Heel bone mineral density x serum urate levels interaction	6.000000e-09
GCST90014033_24	Haemorrhoidal disease	1.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0007586	Cannabis use initiation
EFO:0006336	diastolic blood pressure
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	decreases methylation, increases expression	3
GSK-J4	increases expression	1
urushiol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Irinotecan	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Benzo(a)pyrene	increases expression	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methotrexate	decreases expression	1

Clinical trials (associated diseases)

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