PLCD4

phospholipase C delta 4, the group of Phospholipases|C2 domain containing phospholipases|EF-hand domain containing

Basic information

Region (hg38): 2:218607854-218637184

Links

ENSG00000115556 ∙ NCBI:84812 ∙ OMIM:605939 ∙ HGNC:9062 ∙ Uniprot:Q9BRC7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCD4 gene.

• Inborn genetic diseases (34 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCD4 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
missense			31	3		34
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	31	6	0

Variants in PLCD4

This is a list of pathogenic ClinVar variants found in the PLCD4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-218615744-C-T		not specified	Uncertain significance (Jan 16, 2024)
2-218615965-G-T		not specified	Uncertain significance (Oct 17, 2023)
2-218615966-T-C		not specified	Uncertain significance (Feb 07, 2023)
2-218616010-C-T			Likely benign (Nov 01, 2022)
2-218616032-C-T		not specified	Uncertain significance (Nov 09, 2023)
2-218618611-G-T		not specified	Uncertain significance (Jul 19, 2022)
2-218618689-C-T		not specified	Uncertain significance (Jun 28, 2022)
2-218618695-T-G		not specified	Uncertain significance (Jun 02, 2023)
2-218618759-T-C		not specified	Uncertain significance (Aug 30, 2022)
2-218618774-T-C		not specified	Uncertain significance (Jun 12, 2023)
2-218618783-T-C		not specified	Uncertain significance (Oct 05, 2022)
2-218618798-G-A		not specified	Uncertain significance (Dec 27, 2022)
2-218618803-G-C		not specified	Uncertain significance (Jun 24, 2022)
2-218618813-G-A			Likely benign (Nov 01, 2022)
2-218621480-G-A		not specified	Uncertain significance (Oct 27, 2023)
2-218621540-C-T		not specified	Uncertain significance (Jan 03, 2024)
2-218621541-G-A		not specified	Uncertain significance (Mar 06, 2023)
2-218622719-C-T		not specified	Uncertain significance (Nov 07, 2022)
2-218622737-C-A		not specified	Uncertain significance (Nov 09, 2021)
2-218622824-T-C		not specified	Likely benign (Mar 06, 2023)
2-218628127-G-T		not specified	Uncertain significance (Mar 20, 2023)
2-218628139-C-A		not specified	Uncertain significance (Feb 21, 2024)
2-218628173-A-G		not specified	Uncertain significance (Feb 05, 2024)
2-218629529-C-T		not specified	Uncertain significance (Dec 27, 2023)
2-218629530-G-A		not specified	Uncertain significance (Dec 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLCD4	protein_coding	protein_coding	ENST00000450993	15	29420

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.29e-13	0.910	124334	0	323	124657	0.00130

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	361	445	0.810	0.0000259	5033
Missense in Polyphen		148	184.68	0.80137		2038
Synonymous	1.78	138	167	0.825	0.00000887	1435
Loss of Function	2.09	27	41.5	0.651	0.00000212	453

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0130	0.0129
Ashkenazi Jewish	0.000202	0.000199
East Asian	0.00139	0.00139
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000466	0.000460
Middle Eastern	0.00139	0.00139
South Asian	0.000793	0.000785
Other	0.000504	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca(2+) mobilization in the zona pellucida- induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation. {ECO:0000269|PubMed:15140260}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Serotonin and anxiety;Serotonin and anxiety-related events;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Inositol phosphate metabolism;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: 0.116

Intolerance Scores

• loftool: 0.801
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.68

Haploinsufficiency Scores

• pHI: 0.361
• hipred: N
• hipred_score: 0.475
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plcd4
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: acrosome reaction;lipid catabolic process;inositol trisphosphate biosynthetic process;intracellular signal transduction;inositol phosphate metabolic process;phosphatidylinositol metabolic process
• Cellular component: endoplasmic reticulum membrane;cytosol;plasma membrane;nuclear membrane
• Molecular function: phosphatidylinositol phospholipase C activity;calcium ion binding