PLCH2

protein-coding

phospholipase C eta 2, the group of EF-hand domain containing|Phospholipases

Gene summary

PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]

Previous symbols:

PLCL4

MANE transcript

NM_014638.4

Inheritance

—

ClinVar variants

U:268B:40

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:2,425,980-2,505,532

External References & Databases

Ensembl (ENSG00000149527)

Transcript & Mutation Effects

hg38 • Region Span ~79.6 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 PLCH2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 271

not providedTotal: 32

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014638.4. 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			3 clinvar	10 clinvar	8 clinvar	21
missense			261 clinvar	19 clinvar	3 clinvar	283
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	268	29	11	308

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014638.4	RefSeq	NP_055453.2	22	MANE Select
ENST00000378486.8	Ensembl	ENSP00000367747.3	22	MANE Select
NM_001303012.2	RefSeq	NP_001289941.1	22	Standard
NM_001303013.1	RefSeq	NP_001289942.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Proton Pump Inhibitor Pathway, Pharmacodynamics
D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis
Metabolism
phospholipases

Biological Process

biological_process
lipid catabolic process
inositol trisphosphate biosynthetic process
intracellular signal transduction
inositol phosphate metabolic process

Molecular Function

molecular_function
phosphatidylinositol phospholipase C activity
calcium ion binding

Cellular Component

cellular_component
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000449969
Coding exons: 22
Length: 79551
Individuals with no LoFs: 124841
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 124905
p: 0.000256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.23	615	707	0.869	0.0000471	7339
Missense (PolyPhen)		227	303.28	0.74848		3100
Synonymous	-1.50	331	298	1.11	0.0000218	2205
Loss of Function	1.80	35	48.6	0.721	0.00000236	559

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00032	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.0010	0.0010	notable
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00016	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. This phospholipase activity is very sensitive to calcium. May be important for formation and maintenance of the neuronal network in the postnatal brain (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.101

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.394

Gene Damage Prediction

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