PLCL1

Summary

PLCL1 (phospholipase C like 1 (inactive), HGNC:9063) is a protein-coding gene on chromosome 2q33.1, encoding Inactive phospholipase C-like protein 1 (Q15111). Involved in an inositol phospholipid-based intracellular signaling cascade.

Predicted to enable GABA receptor binding activity and phosphatidylinositol-4,5-bisphosphate phospholipase C activity. Predicted to be involved in several processes, including gamma-aminobutyric acid signaling pathway; negative regulation of cold-induced thermogenesis; and phosphatidylinositol-mediated signaling. Predicted to be located in cytoplasm.

Source: NCBI Gene 5334 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 63 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 147 total
• GTEx eGene: eQTL in 16 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.66 (unconstrained)
• MANE Select transcript: NM_006226
• Notable: 147 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9063
Approved symbol	PLCL1
Name	phospholipase C like 1 (inactive)
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	PLC-L, PLCL, PRIP, PPP1R127
Ensembl gene	ENSG00000115896
Ensembl biotype	protein_coding
OMIM	600597
Entrez	5334

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 nonsense_mediated_decay, 2 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000428675

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 5: 2

ENST00000428675, ENST00000435320, ENST00000472193, ENST00000487695, ENST00000625084, ENST00001019871, ENST00001019872

RefSeq mRNA: 1 — MANE Select: NM_006226 NM_006226

CCDS: CCDS2326

Canonical transcript exons

ENST00000428675 — 6 exons

Exon	Start	End
ENSE00001597184	198146780	198149863
ENSE00003586360	198101285	198101360
ENSE00003606669	198083758	198086232
ENSE00003629993	198103827	198103936
ENSE00003631764	198088858	198089061
ENSE00003847923	197804593	197805339

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 95.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9665 / max 698.3658, expressed in 1001 samples.

Highest expression (Bgee): heart right ventricle, corpus callosum, medial globus pallidus, choroid plexus epithelium, globus pallidus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLCL1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	3.6e-44	-0.41	2:198042419:C:T
Muscle Skeletal	eqtl	5.8e-12	+0.15	2:197931607:T:TAAAC
Thyroid	eqtl	2.2e-10	-0.24	2:198015865:A:G
Cells Cultured fibroblasts	eqtl	4.8e-09	-0.16	2:198048689:A:G
Spleen	eqtl	5.2e-08	-0.45	2:198046702:G:A
Artery Aorta	eqtl	6.7e-07	+0.17	2:197279147:A:G
Lung	eqtl	8.8e-05	+0.18	2:197997876:C:T
Nerve Tibial	eqtl	1.1e-04	+0.18	2:198017006:G:C
Artery Tibial	sqtl	1.7e-04	+0.32	2:197960782:G:C
Brain Hippocampus	sqtl	4.4e-04	+0.59	2:197960782:G:C
Artery Tibial	eqtl	1.8e-03	+0.13	2:198033498:C:A
Adipose Visceral Omentum	eqtl	8.7e-03	-0.13	2:197808655:A:C
Heart Atrial Appendage	eqtl	1.1e-02	-0.19	2:197151291:G:A
Esophagus Mucosa	eqtl	1.4e-02	-0.40	2:198262168:A:G
Brain Hypothalamus	sqtl	1.5e-02	+0.49	2:197946515:A:AT
Esophagus Muscularis	eqtl	1.6e-02	-0.32	2:198250727:T:C
Brain Cerebellum	eqtl	2.1e-02	-0.65	2:198094992:A:G
Brain Caudate basal ganglia	sqtl	2.7e-02	+0.39	2:198087653:CTG:C
Brain Frontal Cortex BA9	eqtl	3.6e-02	+0.32	2:198497257:C:T
Cells EBV-transformed lymphocytes	eqtl	4.4e-02	+0.21	2:197298803:G:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
24491	10.0157	896
24492	2.6899	576
24493	0.9748	374
24494	0.1563	87
24495	0.1298	60

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	95.38	gold quality
corpus callosum	UBERON:0002336	94.79	gold quality
medial globus pallidus	UBERON:0002477	94.33	gold quality
choroid plexus epithelium	UBERON:0003911	93.59	gold quality
globus pallidus	UBERON:0001875	92.73	gold quality
inferior vagus X ganglion	UBERON:0005363	92.14	gold quality
renal medulla	UBERON:0000362	91.99	gold quality
pons	UBERON:0000988	91.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.26	gold quality
secondary oocyte	CL:0000655	90.80	gold quality
nephron tubule	UBERON:0001231	90.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.52	gold quality
blood vessel layer	UBERON:0004797	90.20	gold quality
spinal cord	UBERON:0002240	90.15	gold quality
left ventricle myocardium	UBERON:0006566	90.00	gold quality
subthalamic nucleus	UBERON:0001906	89.77	gold quality
decidua	UBERON:0002450	89.28	gold quality
cardiac ventricle	UBERON:0002082	88.65	gold quality
heart left ventricle	UBERON:0002084	88.57	gold quality
superior vestibular nucleus	UBERON:0007227	87.90	gold quality
kidney epithelium	UBERON:0004819	86.89	gold quality
medulla oblongata	UBERON:0001896	86.85	gold quality
myocardium	UBERON:0002349	86.74	gold quality
endothelial cell	CL:0000115	86.66	silver quality
heart	UBERON:0000948	86.54	gold quality
cortical plate	UBERON:0005343	85.97	gold quality
orbitofrontal cortex	UBERON:0004167	85.76	gold quality
biceps brachii	UBERON:0001507	85.68	gold quality
vastus lateralis	UBERON:0001379	85.62	gold quality
oocyte	CL:0000023	85.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.90	gold quality
midbrain	UBERON:0001891	84.77	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.67	gold quality
substantia nigra	UBERON:0002038	84.56	gold quality
postcentral gyrus	UBERON:0002581	84.53	gold quality
Ammon’s horn	UBERON:0001954	84.11	gold quality
quadriceps femoris	UBERON:0001377	83.99	gold quality
parietal lobe	UBERON:0001872	83.96	gold quality
kidney	UBERON:0002113	83.96	gold quality
right coronary artery	UBERON:0001625	83.93	gold quality
skeletal muscle tissue	UBERON:0001134	83.90	gold quality
cardiac atrium	UBERON:0002081	83.63	gold quality
right atrium auricular region	UBERON:0006631	83.54	gold quality
cauda epididymis	UBERON:0004360	83.47	gold quality
adult mammalian kidney	UBERON:0000082	83.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.39	gold quality
ventral tegmental area	UBERON:0002691	83.34	gold quality
muscle tissue	UBERON:0002385	83.32	gold quality
metanephric glomerulus	UBERON:0004736	83.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	83.23	gold quality
prefrontal cortex	UBERON:0000451	83.14	gold quality
renal glomerulus	UBERON:0000074	83.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.03	gold quality
muscle organ	UBERON:0001630	82.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.89	gold quality
lower esophagus	UBERON:0013473	82.80	gold quality
calcaneal tendon	UBERON:0003701	82.67	gold quality
muscle of leg	UBERON:0001383	82.36	gold quality
descending thoracic aorta	UBERON:0002345	82.36	gold quality
lateral globus pallidus	UBERON:0002476	81.85	gold quality
gastrocnemius	UBERON:0001388	81.50	gold quality
seminal vesicle	UBERON:0000998	81.26	gold quality
hypothalamus	UBERON:0001898	81.23	gold quality
putamen	UBERON:0001874	81.22	gold quality
left coronary artery	UBERON:0001626	81.04	gold quality
amygdala	UBERON:0001876	81.04	gold quality
superior frontal gyrus	UBERON:0002661	81.03	gold quality
occipital lobe	UBERON:0002021	80.90	gold quality
coronary artery	UBERON:0001621	80.89	gold quality
buccal mucosa cell	CL:0002336	80.80	silver quality
primary visual cortex	UBERON:0002436	80.52	gold quality
cerebral cortex	UBERON:0000956	80.24	gold quality
telencephalon	UBERON:0001893	80.18	gold quality
popliteal artery	UBERON:0002250	80.12	gold quality
temporal lobe	UBERON:0001871	80.08	gold quality
tibial artery	UBERON:0007610	80.07	gold quality
cortex of kidney	UBERON:0001225	80.04	gold quality
frontal cortex	UBERON:0001870	79.99	gold quality
aorta	UBERON:0000947	79.98	gold quality
myometrium	UBERON:0001296	79.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.83	gold quality
thoracic aorta	UBERON:0001515	79.82	gold quality
middle temporal gyrus	UBERON:0002771	79.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.66	gold quality
metanephros	UBERON:0000081	79.64	gold quality
substantia nigra pars compacta	UBERON:0001965	79.62	gold quality
ascending aorta	UBERON:0001496	79.58	gold quality
urethra	UBERON:0000057	79.45	gold quality
apex of heart	UBERON:0002098	79.34	gold quality
neocortex	UBERON:0001950	79.28	gold quality
pigmented layer of retina	UBERON:0001782	79.19	gold quality
cranial nerve II	UBERON:0000941	78.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.71	gold quality
entorhinal cortex	UBERON:0002728	78.59	gold quality
inferior olivary complex	UBERON:0002127	78.25	silver quality
parietal pleura	UBERON:0002400	78.22	gold quality
forebrain	UBERON:0001890	78.14	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	77.99	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2726.68
E-HCAD-35	yes	110.70
E-HCAD-25	yes	55.11
E-CURD-119	yes	39.28
E-ANND-3	no	5.09

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	120.8
Medulla oblongata	tissue	64.4
Midbrain	tissue	57.2
Substantia nigra	tissue	56.6
Superior colliculi	tissue	50.9
Spinal cord	tissue	50.3
Putamen	tissue	48.4
Thalamus	tissue	48.2
Periaqueductal gray	tissue	48.1
Locus coeruleus	tissue	47.7
Pons	tissue	46.8
Nucleus accumbens	tissue	45.4
Ventral forebrain	tissue	41.7
Hypothalamus	tissue	41.4
Tongue	tissue	38.1
Hippocampal formation	tissue	34.7
Hippocampus	tissue	32.4	medium
Postcentral gyrus	tissue	31.6
Choroid plexus	tissue	31.4
Septum	tissue	31.1
Heart muscle	tissue	30.4	high
Kidney	tissue	29.4	high
Skeletal muscle	tissue	28.9	low
Cerebral cortex	tissue	28.6	medium
Somatosensory cortex	tissue	28.6
Occipital cortex	tissue	27.1
Retrosplenial cortex	tissue	26.4
Motor cortex	tissue	25.5
Insular cortex	tissue	23.5
Retrosplenial and cingulate cortex	tissue	23.4
Prefrontal cortex	tissue	23.0
Entorhinal cortex	tissue	22.6
Temporal cortex	tissue	21.4
Amygdala	tissue	20.1
Thymus	tissue	16.0
Basal ganglia	tissue	15.7	medium
Olfactory bulb	tissue	15.1
Parathyroid gland	tissue	13.9	medium
Caudate putamen	tissue	13.4
Prostate	tissue	9.8	medium
Frontal cortex	tissue	9.7
Cerebellum	tissue	8.3	medium
Ovary	tissue	7.7	high
Placenta	tissue	7.4	medium
Seminal vesicle	tissue	6.7	medium
Smooth muscle	tissue	5.6	medium
Endometrium 1	tissue	5.2	medium
Cervix	tissue	4.2	medium
Adrenal gland	tissue	3.9	high
Retina	tissue	3.7
Adipose tissue	tissue	3.7	low
Esophagus	tissue	3.4	medium
Lymph node	tissue	3.2	medium
Thyroid gland	tissue	3.1	medium
Fallopian tube	tissue	3.1	medium
Lung	tissue	3.0	medium
Epididymis	tissue	2.9	low
Urinary bladder	tissue	2.8	medium
Gallbladder	tissue	2.8	high
Appendix	tissue	2.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (142.7), Cerebellar white matter (125.0), White matter (120.8), Temporal white matter (120.0), Corpus callosum, genu (white matter) (115.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PLCL1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 147 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165

Functional genomics

gnomAD constraint: pLI 8.03e-05, LOEUF 0.663, missense Z 1.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000428675 — one region, missense o/e 0.88.

Literature-anchored findings (GeneRIF, showing 10)

• PRIP-1 plays an important role in type A receptor signaling for gamma-aminobutyric acid in the brain (PMID:16952428)
• PLCL1 is a novel gene associated with variation in hip bone size, which has a role in the pathogenesis of hip fractures (PMID:18776929)
• In postmenopausal women, our results suggest that the PLCL1 rs7595412 polymorphism has no obvious effect on hip bone size and bone mineral density but may be associated with increased proportion of vertebral fracture and increased levels of osteocalcin (PMID:20030815)
• effect of DZP on PRIP-1 knockout mice was reduced (PMID:22128345)
• PRIP interacts with the catalytic subunits of PP1 and PP2A and the interactions are regulated by phosphorylation. [review] (PMID:23911386)
• susceptibility gene for dermatomyositis in Chinese patients with idiopathic inflammatory myopathies (PMID:26603167)
• Identification of novel pleiotropic gene for bone mineral density and lean mass using the cFDR method. (PMID:34115876)
• PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis. (PMID:35820936)
• PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma. (PMID:37801481)
• DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1. (PMID:39456056)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcl1	ENSDARG00000067676
mus_musculus	Plcl1	ENSMUSG00000038349
rattus_norvegicus	Plcl1	ENSRNOG00000032659
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), PLCG1 (ENSG00000124181), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3036262) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased susceptibility to xenobiotic induced morbidity/mortality	2
epidermal hyperplasia	1
abnormal motor coordination/balance	1
seizures	1
abnormal nervous system electrophysiology	1
increased susceptibility to pharmacologically induced seizures	1
increased tumor growth/size	1
increased incidence of tumors by chemical induction	1
impaired behavioral response to xenobiotic	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RET0	98.4%	Diamond
Bos taurus	P10894	97.1%	Diamond
Xenopus tropicalis	B1WAZ6	95.2%	Diamond
Xenopus laevis	Q7T0T9	95.2%	Diamond
Macaca fascicularis	Q4R6L3	91.4%	Diamond
Sus scrofa	Q8SPR7	85.8%	Diamond
Gallus gallus	Q2VRL0	59.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01923	ncRNA	101927619
BOLL	protein-coding	66037
MARS2	protein-coding	92935
RFTN2	protein-coding	130132

Protein

Protein identifiers

Inactive phospholipase C-like protein 1 — Q15111 (reviewed: Q15111)

Alternative names: Phospholipase C-deleted in lung carcinoma, Phospholipase C-related but catalytically inactive protein

All UniProt accessions (3): F8WAR2, H3BUD4, Q15111

UniProt curated annotations — full annotation on UniProt →

Function. Involved in an inositol phospholipid-based intracellular signaling cascade. Shows no PLC activity to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol. Component in the phospho-dependent endocytosis process of GABA A receptor. Regulates the turnover of receptors and thus contributes to the maintenance of GABA-mediated synaptic inhibition. Its aberrant expression could contribute to the genesis and progression of lung carcinoma. Acts as an inhibitor of PPP1C.

Subunit / interactions. Interacts with PPP2CA. Interacts with Ins(1,4,5)P3, Ins(1,4,5,6)P4, GABARAP, GABA receptor beta subunits, GABA receptor gamma-2 subunits and PPP1C. May form a ternary complex with GABA receptor beta subunit and GABARAP. The formation of a ternary complex with GABA receptor beta subunit and GABARAP could be the key step for facilitating the association of GABARAP with the GABA receptor gamma-2 subunit and to allow it to be transported at the right destination.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in a variety of fetal and adult organs including brain, lung and kidney. Its expression was greatly reduced in small and non-small cell lung carcinoma. Isoform 1 is predominantly expressed in brain.

Post-translational modifications. Phosphorylated by the catalytic subunit of PKA. Phosphorylation of Thr-93 resulted in dissociation of PPP1C from PRIP1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15111-1	1	yes
Q15111-2	2

RefSeq proteins (1): NP_006217* (*=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
IPR015359	PLC_EF-hand-like	Domain
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168, PF00387, PF00388, PF09279, PF16457

Enzyme classification (BRENDA)

• EC 2.7.11.10 — IkappaB kinase (BRENDA: 7 organisms, 122 substrates, 335 inhibitors, 1 Km, 0 kcat entries)

UniProt features (29 total): modified residue 7, sequence variant 6, domain 4, region of interest 4, coiled-coil region 2, compositionally biased region 2, sequence conflict 2, chain 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15111-F1	82.49	0.59

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7)

Type	Positions
Phosphoserine	47, 77, 95, 569, 1079
Phosphothreonine	93, 556

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 237 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, ZHAN_MULTIPLE_MYELOMA_PR_DN, BROWNE_HCMV_INFECTION_8HR_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MCLACHLAN_DENTAL_CARIES_DN, GOBP_MAINTENANCE_OF_LOCATION

GO Biological Process (10): gamma-aminobutyric acid signaling pathway (GO:0007214), regulation of synaptic transmission, GABAergic (GO:0032228), intracellular signal transduction (GO:0035556), phosphatidylinositol metabolic process (GO:0046488), phosphatidylinositol-mediated signaling (GO:0048015), release of sequestered calcium ion into cytosol (GO:0051209), negative regulation of cold-induced thermogenesis (GO:0120163), lipid metabolic process (GO:0006629), signal transduction (GO:0007165), lipid catabolic process (GO:0016042)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), C-type glycerophospholipase activity (GO:0004629), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

26 GO namespaces:

Category	Terms
intracellular anatomical structure	2
cell-cell signaling	1
GABA receptor activity	1
modulation of chemical synaptic transmission	1
synaptic transmission, GABAergic	1
signal transduction	1
glycerophospholipid metabolic process	1
intracellular signal transduction	1
calcium ion transmembrane import into cytosol	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
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
C-type glycerophospholipase activity	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 764 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCL1	CBL	P22681	470
PLCL1	RFTN2	Q52LD8	441
PLCL1	INO80E	Q8NBZ0	408
PLCL1	BOLL	Q8N9W6	385
PLCL1	LCP2	Q13094	370
PLCL1	ARHGEF7	Q14155	370
PLCL1	ROPN1L	Q96C74	367
PLCL1	RNF17	Q9BXT8	363
PLCL1	NDUFB11	Q9NX14	358
PLCL1	COX7C	P15954	358
PLCL1	PLN	P26678	357
PLCL1	DMRT1	Q9Y5R6	339
PLCL1	ARHGEF6	Q15052	324
PLCL1	PRUNE2	Q8WUY3	321
PLCL1	BLK	P51451	310

IntAct

Human interaction partners of PLCL1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
HSPA5	physical association	0.400	1
KIN	physical association	0.400	1

BioGRID (12 interactions; top human partners by supporting records): DCAF10 (Proximity Label-MS), HSPA5 (Cross-Linking-MS (XL-MS)), KIN (Cross-Linking-MS (XL-MS)), PARP12 (Proximity Label-MS), PARP9 (Proximity Label-MS), PDIA3 (Cross-Linking-MS (XL-MS)), PLCD4 (Negative Genetic), PLCZ1 (Negative Genetic), PRNP (Affinity Capture-MS), TIPARP (Proximity Label-MS), TOPBP1 (Proximity Label-MS), UBE2H (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PLCL1: 147 ClinVar records (0 pathogenic / likely pathogenic); 63 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	134
Likely benign	3
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,384):

Position(s)	Effect	Δscore	Sites
2:197805340–197805341	donor_loss	1.0000	3
2:198083757	acceptor_loss	1.0000	2
2:198101274	acceptor_gain	1.0000
2:198101281	acceptor_gain	1.0000
2:198101283–198101284	acceptor_loss	1.0000	4
2:198101361–198101362	donor_loss	1.0000	5
2:198103825	acceptor_gain	1.0000
2:198103826	acceptor_loss	1.0000
2:198103937–198103938	donor_loss	1.0000	6
2:198146771	acceptor_gain	1.0000

AlphaMissense

2,602 missense substitutions predicted likely pathogenic (of 7,306 scored), across 680 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M115	9	0.918	0.998
M400	9	0.879	0.969
D800	8	0.994	0.998
F96	8	0.989	1.000
D806	8	0.982	0.997
D760	8	0.976	0.994
D202	8	0.974	0.993
D650	8	0.974	0.994
D801	8	0.970	0.995
N688	8	0.968	0.996
N670	8	0.964	0.998
N1030	8	0.963	0.997
F338	8	0.961	0.998
N653	8	0.961	0.999
F685	8	0.956	0.997
F248	8	0.955	0.998
D679	8	0.949	0.985
D802	8	0.949	0.990
F303	8	0.945	0.999
D375	8	0.945	0.985

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.54e-09
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000272
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000295

Disease associations

OMIM: gene MIM:600597 | disease phenotypes:

GWAS associations

showing 30 of 63 associations:

Study	Trait	p-value
GCST010701_19	Cortical surface area (MOSTest)	2e-37
GCST007565_185	Morning person	4e-31
GCST007576_409	Chronotype	4e-31
GCST007565_65	Morning person	1e-27
GCST90011900_166	Serum alkaline phosphatase levels	9e-24
GCST003989_12	Chin dimples	7e-20
GCST90000025_784	Appendicular lean mass	6e-19
GCST006409_12	Allergic rhinitis	4e-14
GCST006803_15	Schizophrenia	4e-13
GCST000880_39	Menarche (age at onset)	6e-13
GCST005038_83	Allergic disease (asthma, hay fever or eczema)	5e-12
GCST009600_46	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1e-11
GCST010702_115	Subcortical volume (MOSTest)	1e-11
GCST010703_247	Brain morphology (MOSTest)	1e-11
GCST002539_26	Schizophrenia	2e-11
GCST010988_476	Adult body size	2e-11
GCST004521_281	Autism spectrum disorder or schizophrenia	3e-11
GCST010796_250	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-11
GCST007293_132	Body fat distribution (arm fat ratio)	8e-11
GCST003429_34	Morning vs. evening chronotype	1e-10
GCST003470_1	Coronary artery disease	2e-10
GCST003990_16	Allergy	2e-10
GCST010700_25	Cortical thickness (MOSTest)	2e-10
GCST010043_127	Asthma	4e-10
GCST002083_13	Self-reported allergy	6e-10
GCST012226_101	Waist circumference adjusted for body mass index	8e-10
GCST003993_39	Menarche (age at onset)	1e-9
GCST010699_54	Brain morphology (min-P)	1e-9
GCST012226_100	Waist circumference adjusted for body mass index	2e-9
GCST007294_2	Body fat distribution (trunk fat ratio)	3e-9

EFO canonical traits (from GWAS)

18 canonical traits:

EFO ID	Trait name
EFO:0006913	prefrontal cortex cytoarchtiectural measurement
EFO:0004703	age at menarche
EFO:0004833	neutrophil count
EFO:0004784	self reported educational attainment
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0008475	mood instability measurement
EFO:0009282	sodium measurement
EFO:0010554	retinal vasculature measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004327	electrocardiography
EFO:0010729	sun exposure measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Aflatoxin B1	affects expression, decreases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
clothianidin	decreases expression	1
bisphenol S	increases methylation	1
Arsenic Trioxide	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Air Pollutants	increases expression, increases abundance	1
Hexachlorocyclohexane	increases expression	1
Fluoxetine	increases expression	1
Folic Acid	decreases expression	1
Ozone	increases abundance, increases expression	1
Prednisolone	increases expression	1
Smoke	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Asbestos, Amphibole	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Sirolimus	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders