PLCH1

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

Basic information

Region (hg38): 3:155375580-155745071

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
• holoprosencephaly 14 (Limited), 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.

• not_specified (198 variants)
• not_provided (17 variants)
• Holoprosencephaly_14 (2 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. These statistics are base on transcript: NM_000014996.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	1	7
missense			196	4	3	203
nonsense	1					1
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)						0
Total	2	0	196	10	4

Highest pathogenic variant AF is 0.00000495707

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