GeneBe

PLCH1

protein-coding

phospholipase C eta 1, the group of EF-hand domain containing|Phospholipases|C2 domain containing phospholipases

Gene summary

PLCH1 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Hwang et al., 2005 [PubMed 15702972]).[supplied by OMIM, Jun 2009]

Previous symbols:
  • PLCL3

MANE transcript

NM_014996.4

Inheritance

AR

ClinVar variants

P:2U:227B:25

Top phenotype

Holoprosencephaly 14

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr3:155,375,580-155,745,071

External References & Databases

Ensembl (ENSG00000114805)NCBI Gene (23007)OMIM (612835)HGNC:29185GenCCUniProt (Q4KWH8)AlphaFoldClinVar (PLCH1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~369.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

holoprosencephaly 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030886

Submitter: Labcorp Genetics (formerly Invitae)

holoprosencephaly 14LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030886

Submitter: G2P

holoprosencephaly 14MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030886

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Holoprosencephaly 14AR

Manifestation: Cardiovascular; Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33820834Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLCH1 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 224
not providedTotal: 24
Holoprosencephaly 14Total: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014996.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
16
clinvar
 17
missense
223
clinvar
6
clinvar
3
clinvar
 232
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total20227223254

Highest pathogenic variant AF is 0.0000049570717

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014996.4RefSeqNP_055811.222MANE Select
ENST00000460012.7EnsemblENSP00000417502.222MANE Select
NM_001130960.2RefSeqNP_001124432.123Standard
NM_001130961.2RefSeqNP_001124433.123Standard

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
  • Mesodermal Commitment Pathway
  • GPR40 Pathway
  • D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis

Biological Process

  • lipid catabolic process
  • inositol trisphosphate biosynthetic process
  • inositol phosphate metabolic process
  • phosphatidylinositol-mediated signaling
  • release of sequestered calcium ion into cytosol

Molecular Function

  • phosphatidylinositol phospholipase C activity
  • calcium ion binding
  • calcium-dependent phospholipase C activity

Cellular Component

  • cytoplasm
  • cytosol
  • plasma membrane
  • intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000340059
Coding exons
23
Length
369488
Individuals with no LoFs
125704
Homozygous LoFs
0
Heterozygous LoFs
44
Defined
125748
p
0.000175
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.487779020.8610.000047811177
Missense (PolyPhen)267386.690.690484774
Synonymous1.073093340.9260.00001763262
Loss of Function6.231775.40.2260.00000451897

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000540.000054rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000270.00025rare
South Asian0.000130.00013rare
Other0.000330.00033rare

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 calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}.;

Recessive Scores

pRec
0.0975

Intolerance Scores

LoFtool
0.678
RVIS EVS
-1.07
RVIS percentile EVS
7.34

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.105

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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