PLCL1

protein-coding

phospholipase C like 1 (inactive), the group of Protein phosphatase 1 regulatory subunits|C2 domain containing phospholipases

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

PLCE

MANE transcript

NM_006226.4

Inheritance

—

ClinVar variants

U:138B:5

Top phenotype

Autism spectrum disorder

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr2:197,804,593-198,572,581

External References & Databases

Ensembl (ENSG00000115896)

Transcript & Mutation Effects

hg38 • Region Span ~768.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLCL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 10

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006226.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar	2 clinvar	7
missense			134 clinvar	2 clinvar		136
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	138	3	2	143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006226.4	RefSeq	NP_006217.3	6	MANE Select
ENST00000428675.6	Ensembl	ENSP00000402861.1	6	MANE Select
ENST00000435320.1	Ensembl	ENSP00000410488.1	2	Standard
ENST00000487695.6	Ensembl	ENSP00000457588.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GABAergic synapse - Homo sapiens (human)
Proton Pump Inhibitor Pathway, Pharmacodynamics
GPR40 Pathway

Biological Process

lipid metabolic process
gamma-aminobutyric acid signaling pathway
regulation of synaptic transmission, GABAergic
inositol trisphosphate biosynthetic process
regulation of peptidyl-serine phosphorylation

Molecular Function

phosphatidylinositol phospholipase C activity
phospholipase C activity
inositol 1,4,5 trisphosphate binding

Cellular Component

cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428675
Coding exons: 6
Length: 767880
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125742
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.86	437	561	0.779	0.0000302	7257
Missense (PolyPhen)		109	207.98	0.52409		2550
Synonymous	-0.698	213	200	1.06	0.0000112	2074
Loss of Function	4.09	11	38.3	0.287	0.00000230	477

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:17254016}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.683
RVIS EVS: -0.24
RVIS percentile EVS: 36.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.418

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High