PLCZ1

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

Basic information

Region (hg38): 12:18683169-18738100

Links

ENSG00000139151 ∙ NCBI:89869 ∙ OMIM:608075 ∙ HGNC:19218 ∙ Uniprot:Q86YW0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 17 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 17	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	Genitourinary	26721930

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCZ1 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCZ1 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		1	24	2	1	28
nonsense		1	1			2
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	2	25	5	1

Variants in PLCZ1

This is a list of pathogenic ClinVar variants found in the PLCZ1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-18683278-C-T		PLCZ1-related disorder	Likely benign (Jun 18, 2019)
12-18683316-G-A		not specified	Uncertain significance (Oct 25, 2022)
12-18684208-CA-C			Pathogenic (Jul 05, 2022)
12-18684223-C-A		not specified	Uncertain significance (Oct 29, 2021)
12-18688131-T-A		not specified	Uncertain significance (Jul 16, 2024)
12-18688131-T-C		not specified	Uncertain significance (Jun 06, 2023)
12-18688172-T-C		not specified	Uncertain significance (Sep 29, 2023)
12-18688215-T-A		Spermatogenic failure 17 • PLCZ1-related disorder	Likely pathogenic (Sep 19, 2022)
12-18694959-A-C		not specified	Uncertain significance (Mar 25, 2024)
12-18694965-G-A		not specified	Uncertain significance (Oct 07, 2024)
12-18695010-C-T		not specified	Uncertain significance (Mar 25, 2024)
12-18695013-C-T		Spermatogenic failure 17	Pathogenic (Aug 31, 2023)
12-18695061-G-C		not specified	Uncertain significance (Dec 21, 2022)
12-18696161-C-T		not specified	Uncertain significance (Feb 11, 2022)
12-18696167-T-C		Spermatogenic failure 17	Pathogenic (Aug 31, 2023)
12-18696210-T-A		not specified	Uncertain significance (Jun 29, 2023)
12-18699791-T-G		Spermatogenic failure 17	Pathogenic (Aug 31, 2023)
12-18699796-C-T		not specified	Uncertain significance (Aug 16, 2021)
12-18699814-C-T		Spermatogenic failure 17	Uncertain significance (May 05, 2020)
12-18699832-A-G		not specified	Uncertain significance (Jul 25, 2024)
12-18699849-A-G			Likely benign (Nov 01, 2022)
12-18699896-C-G		not specified	Uncertain significance (Sep 27, 2021)
12-18699913-A-G		not specified	Uncertain significance (Oct 25, 2023)
12-18699920-A-G		Spermatogenic failure 17	Pathogenic (Nov 06, 2020)
12-18701502-T-G		not specified	Uncertain significance (May 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLCZ1	protein_coding	protein_coding	ENST00000266505	14	54889

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-12	0.546	125646	0	93	125739	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.608	342	312	1.10	0.0000153	4017
Missense in Polyphen		121	120.16	1.007		1634
Synonymous	-0.756	112	102	1.10	0.00000482	1076
Loss of Function	1.44	23	31.8	0.723	0.00000157	417

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000363	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000603	0.000598
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000525	0.000519
Middle Eastern	0.000603	0.000598
South Asian	0.000230	0.000229
Other	0.000493	0.000489

dbNSFP

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. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)- dependent manner. Triggers intracellular Ca(2+) oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg- activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function. {ECO:0000250|UniProtKB:Q8K4D7, ECO:0000269|PubMed:12416999, ECO:0000269|PubMed:14697805, ECO:0000269|PubMed:15579586, ECO:0000269|PubMed:26721930, ECO:0000305}.
• Disease: DISEASE: Spermatogenic failure 17 (SPGF17) [MIM:617214]: An autosomal recessive infertility disorder due to failure of oocyte activation and fertilization by sperm that otherwise exhibits normal morphology. {ECO:0000269|PubMed:26721930}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Oocyte meiosis - 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;GPR40 Pathway;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;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism (Consensus)

Recessive Scores

• pRec: 0.0925

Intolerance Scores

• loftool: 0.949
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.51

Haploinsufficiency Scores

• pHI: 0.0924
• hipred: N
• hipred_score: 0.458
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.135

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plcz1
• Phenotype: reproductive system phenotype

Gene ontology

• Biological process: calcium ion transport;positive regulation of cytosolic calcium ion concentration;multicellular organism development;egg activation;lipid catabolic process;inositol trisphosphate biosynthetic process;intracellular signal transduction;inositol phosphate metabolic process;positive regulation of cytosolic calcium ion concentration involved in egg activation
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;pronucleus;perinuclear region of cytoplasm;sperm head
• Molecular function: phosphatidylinositol phospholipase C activity;calcium ion binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-5-phosphate binding;phosphatidylinositol-3-phosphate binding