PLCH1

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

Basic information

Region (hg38): 3:155375579-155745071

Previous symbols: [ "PLCL3" ]

Links

ENSG00000114805 ∙ NCBI:23007 ∙ OMIM:612835 ∙ HGNC:29185 ∙ Uniprot:Q4KWH8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• holoprosencephaly 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Holoprosencephaly 14	AR	General	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	Cardiovascular; Craniofacial; Neurologic	33820834

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCH1 gene.

• Inborn genetic diseases (65 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCH1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	3	6
missense			64	2	3	69
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	64	5	6

Variants in PLCH1

This is a list of pathogenic ClinVar variants found in the PLCH1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-155481050-T-C		not specified	Uncertain significance (Sep 26, 2023)
3-155481065-T-A		not specified	Uncertain significance (Feb 13, 2024)
3-155481104-C-A		not specified	Uncertain significance (Jan 26, 2022)
3-155481120-C-T		not specified	Uncertain significance (Feb 13, 2024)
3-155481125-G-A		not specified	Uncertain significance (Sep 17, 2021)
3-155481144-C-A		not specified	Uncertain significance (Dec 27, 2022)
3-155481144-C-T		not specified	Uncertain significance (Nov 17, 2022)
3-155481145-G-C		not specified	Uncertain significance (May 10, 2022)
3-155481156-C-T		not specified	Uncertain significance (Feb 12, 2024)
3-155481195-G-T			Benign (May 24, 2018)
3-155481290-C-T		not specified	Uncertain significance (Feb 15, 2023)
3-155481293-A-G		not specified	Uncertain significance (May 22, 2023)
3-155481335-C-T		not specified	Uncertain significance (Jul 21, 2021)
3-155481366-A-G		not specified	Uncertain significance (Sep 12, 2023)
3-155481410-C-T		not specified	Uncertain significance (Dec 28, 2022)
3-155481459-C-T		not specified	Uncertain significance (Sep 20, 2023)
3-155481486-C-T		not specified	Uncertain significance (Oct 14, 2021)
3-155481653-T-G		not specified	Uncertain significance (Dec 30, 2023)
3-155481665-T-G		not specified	Uncertain significance (Nov 20, 2023)
3-155481685-G-C		not specified	Uncertain significance (Jul 11, 2023)
3-155481702-A-C		not specified	Uncertain significance (Apr 12, 2022)
3-155481774-C-G		not specified	Uncertain significance (Jun 21, 2023)
3-155481807-G-A		not specified	Uncertain significance (Oct 13, 2023)
3-155481810-G-A		not specified	Uncertain significance (Mar 27, 2023)
3-155481944-A-G		not specified	Uncertain significance (May 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLCH1	protein_coding	protein_coding	ENST00000340059	23	369488

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.396	0.604	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	777	902	0.861	0.0000478	11177
Missense in Polyphen		267	386.69	0.69048		4774
Synonymous	1.07	309	334	0.926	0.0000176	3262
Loss of Function	6.23	17	75.4	0.226	0.00000451	897

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000213
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000267	0.000255
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000334	0.000326

dbNSFP

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}.
• Pathway: 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;Metabolism;phospholipases;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism (Consensus)

Recessive Scores

• pRec: 0.0975

Intolerance Scores

• loftool: 0.678
• rvis_EVS: -1.07
• rvis_percentile_EVS: 7.34

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.463
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.105

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plch1

Gene ontology

• Biological process: lipid catabolic process;inositol trisphosphate biosynthetic process;inositol phosphate metabolic process;phosphatidylinositol-mediated signaling;release of sequestered calcium ion into cytosol
• Cellular component: cytoplasm;cytosol;plasma membrane;intracellular membrane-bounded organelle
• Molecular function: phosphatidylinositol phospholipase C activity;calcium ion binding;calcium-dependent phospholipase C activity