PLCXD3

Summary

PLCXD3 (phosphatidylinositol specific phospholipase C X domain containing 3, HGNC:31822) is a protein-coding gene on chromosome 5p13.1, encoding PI-PLC X domain-containing protein 3 (Q63HM9).

Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in cytoplasm. Predicted to be active in glutamatergic synapse.

Source: NCBI Gene 345557 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_001005473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31822
Approved symbol	PLCXD3
Name	phosphatidylinositol specific phospholipase C X domain containing 3
Location	5p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182836
Ensembl biotype	protein_coding
OMIM	617016
Entrez	345557

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377801

RefSeq mRNA: 1 — MANE Select: NM_001005473 NM_001005473

CCDS: CCDS34150

Canonical transcript exons

ENST00000377801 — 3 exons

Exon	Start	End
ENSE00001312584	41381826	41382534
ENSE00001475151	41306952	41313770
ENSE00002040229	41510424	41510601

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 97.62.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5091 / max 228.4630, expressed in 392 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61471	2.1195	374
61473	0.1365	76
61472	0.1340	67
61474	0.1190	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	97.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.44	gold quality
myocardium	UBERON:0002349	96.89	gold quality
islet of Langerhans	UBERON:0000006	93.67	gold quality
heart right ventricle	UBERON:0002080	93.43	gold quality
cardiac ventricle	UBERON:0002082	90.05	gold quality
heart left ventricle	UBERON:0002084	89.99	gold quality
cardiac atrium	UBERON:0002081	89.27	gold quality
right atrium auricular region	UBERON:0006631	88.82	gold quality
heart	UBERON:0000948	88.71	gold quality
cerebellar vermis	UBERON:0004720	87.27	gold quality
left ovary	UBERON:0002119	87.24	gold quality
right ovary	UBERON:0002118	86.81	gold quality
cerebellum	UBERON:0002037	86.24	gold quality
cerebellar cortex	UBERON:0002129	85.88	gold quality
cerebellar hemisphere	UBERON:0002245	85.73	gold quality
kidney epithelium	UBERON:0004819	85.71	silver quality
apex of heart	UBERON:0002098	85.46	gold quality
ovary	UBERON:0000992	83.88	gold quality
superior vestibular nucleus	UBERON:0007227	83.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.23	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.64	gold quality
entorhinal cortex	UBERON:0002728	81.58	gold quality
left coronary artery	UBERON:0001626	79.80	gold quality
pons	UBERON:0000988	79.70	gold quality
postcentral gyrus	UBERON:0002581	79.67	gold quality
coronary artery	UBERON:0001621	79.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.98	gold quality
endothelial cell	CL:0000115	78.80	silver quality
substantia nigra pars compacta	UBERON:0001965	78.36	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	24.57
E-MTAB-5061	yes	16.44
E-ENAD-27	yes	12.83
E-GEOD-83139	yes	10.24
E-ANND-3	yes	7.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

336 targeting PLCXD3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Literature-anchored findings (GeneRIF, showing 3)

• We found no supportive evidence that PLCXD3 variants are associated with sporadic Creutzfeldt-Jakob disease. (PMID:27055460)
• One potential miRNA-target gene pair, miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), was identified in patients with severe oligozoospermia. (PMID:27486773)
• Genetic Variants of the PLCXD3 Gene Are Associated with Risk of Metabolic Syndrome in the Emirati Population. (PMID:32570874)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcxd3	ENSDARG00000054794
mus_musculus	Plcxd3	ENSMUSG00000049148
rattus_norvegicus	Plcxd3	ENSRNOG00000014550
drosophila_melanogaster	CG10747	FBGN0032845
caenorhabditis_elegans		WBGENE00018184

Paralogs (2): PLCXD1 (ENSG00000182378), PLCXD2 (ENSG00000240891)

Protein

Protein identifiers

PI-PLC X domain-containing protein 3 — Q63HM9 (reviewed: Q63HM9)

All UniProt accessions (1): Q63HM9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at highest levels in heart. Also detected in kidney, lung, small intestine and colon. Expressed at very low levels, if any, in leukocytes, thymus and skeletal muscle.

RefSeq proteins (1): NP_001005473* (*=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

Pfam: PF00388

UniProt features (5 total): active site 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q63HM9-F1	89.40	0.69

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): 37; 114

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): AATGGAG_MIR136, GTGCCTT_MIR506, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_LIPID_METABOLIC_PROCESS, LU_TUMOR_VASCULATURE_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_LIPID_CATABOLIC_PROCESS, TGCCTTA_MIR124A, GOCC_SYNAPSE, GOMF_PHOSPHORIC_DIESTER_HYDROLASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_IPS_ICP_WITH_H3K4ME3_AND_H327ME3

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

GO Molecular Function (3): phosphoric diester hydrolase activity (GO:0008081), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), synapse (GO:0045202)

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
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCXD3	ASMTL	O95671	459
PLCXD3	TSACC	Q96A04	412
PLCXD3	WDR64	B1ANS9	399
PLCXD3	CIB4	A0PJX0	360
PLCXD3	WDR38	Q5JTN6	356
PLCXD3	TMCO5A	Q8N6Q1	344
PLCXD3	NUP210L	Q5VU65	332
PLCXD3	PLCH1	Q4KWH8	328
PLCXD3	PLCD4	Q9BRC7	327
PLCXD3	DIP2C	Q9Y2E4	323
PLCXD3	ANKRD34A	Q69YU3	307
PLCXD3	AK8	Q96MA6	298
PLCXD3	SMOC1	Q9H4F8	296
PLCXD3	PLCH2	O75038	294
PLCXD3	GRID1	Q9ULK0	289
PLCXD3	ARHGAP25	P42331	289

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MAGEA11	PLCXD3	psi-mi:“MI:0915”(physical association)	0.560
P4HB	PLCXD3	psi-mi:“MI:0915”(physical association)	0.560
CD109	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PLCXD3	MAGEA11	psi-mi:“MI:0915”(physical association)	0.000
PLCXD3	P4HB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): MAGEA11 (Two-hybrid), P4HB (Two-hybrid), PLCXD3 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1240 predictions. Top by Δscore:

Variant	Effect	Δscore
5:41313769:CT:C	acceptor_gain	1.0000
5:41381824:A:AC	donor_gain	1.0000
5:41381825:C:CC	donor_gain	1.0000
5:41382533:CC:C	acceptor_gain	1.0000
5:41382534:CC:C	acceptor_gain	1.0000
5:41382535:C:CC	acceptor_gain	1.0000
5:41481509:T:TA	donor_gain	1.0000
5:41510419:CCTA:C	donor_loss	1.0000
5:41510420:CTAC:C	donor_loss	1.0000
5:41510421:TACC:T	donor_loss	1.0000
5:41510422:A:T	donor_loss	1.0000
5:41510423:C:CA	donor_loss	1.0000
5:41313604:C:CA	donor_gain	0.9900
5:41313770:TCTGA:T	acceptor_gain	0.9900
5:41313771:C:CC	acceptor_gain	0.9900
5:41313771:C:G	acceptor_gain	0.9900
5:41381821:CTTA:C	donor_loss	0.9900
5:41381822:TTAC:T	donor_loss	0.9900
5:41381823:TACCT:T	donor_loss	0.9900
5:41381825:CCTTT:C	donor_gain	0.9900
5:41382531:GACC:G	acceptor_gain	0.9900
5:41382532:ACC:A	acceptor_gain	0.9900
5:41382533:CCC:C	acceptor_gain	0.9900
5:41382536:T:G	acceptor_loss	0.9900
5:41387262:AG:A	donor_gain	0.9900
5:41510465:T:A	donor_gain	0.9900
5:41313677:G:C	donor_gain	0.9800
5:41313766:GAGCT:G	acceptor_gain	0.9800
5:41313768:GCT:G	acceptor_gain	0.9800
5:41313769:CTC:C	acceptor_gain	0.9800

AlphaMissense

2142 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:41313692:A:C	F297L	1.000
5:41313692:A:T	F297L	1.000
5:41313694:A:G	F297L	1.000
5:41313696:T:A	D296V	1.000
5:41313697:C:G	D296H	1.000
5:41313710:A:C	N291K	1.000
5:41313710:A:T	N291K	1.000
5:41313748:A:G	W279R	1.000
5:41313748:A:T	W279R	1.000
5:41381886:G:T	P251H	1.000
5:41381964:A:G	L225P	1.000
5:41381992:A:G	W216R	1.000
5:41381992:A:T	W216R	1.000
5:41382019:A:G	W207R	1.000
5:41382019:A:T	W207R	1.000
5:41382298:G:C	H114D	1.000
5:41382348:A:G	L97P	1.000
5:41382351:T:A	D96V	1.000
5:41382361:G:T	R93S	1.000
5:41382366:C:T	G91E	1.000
5:41382398:C:A	Q80H	1.000
5:41382398:C:G	Q80H	1.000
5:41382412:A:G	W76R	1.000
5:41382412:A:T	W76R	1.000
5:41382515:G:C	S41R	1.000
5:41382515:G:T	S41R	1.000
5:41382517:T:G	S41R	1.000
5:41382522:G:A	S39F	1.000
5:41382527:A:C	H37Q	1.000
5:41382527:A:T	H37Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000048819 (5:41320996 T>C), RS1000049801 (5:41343132 T>C), RS1000054698 (5:41487453 T>C), RS1000068085 (5:41423026 G>A), RS1000072783 (5:41406576 T>C), RS1000084159 (5:41471392 G>A,C,T), RS1000088390 (5:41487781 G>A,C), RS1000097841 (5:41499738 C>T), RS1000126780 (5:41448175 A>G), RS1000147317 (5:41317387 G>C), RS1000157176 (5:41317054 C>A,T), RS1000178772 (5:41351278 C>T), RS1000180893 (5:41360495 G>A), RS1000191230 (5:41369627 G>A), RS1000196012 (5:41450091 C>T)

Disease associations

OMIM: gene MIM:617016 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003805_1	Diastolic blood pressure response to hydrochlorothiazide in hypertension	7.000000e-06
GCST009391_1038	Metabolite levels	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement
EFO:0009775	threonine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
arsenite	affects binding, decreases reaction, increases methylation	2
Copper	affects binding, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Poly(amidoamine)	increases expression	1
NSC 689534	affects binding, decreases expression	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Chelating Agents	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Phthalic Acids	decreases methylation	1
Fenofibrate	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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