PLD1

phospholipase D1, the group of Phospholipases|Pleckstrin homology domain containing

Basic information

Region (hg38): 3:171600403-171810950

Links

ENSG00000075651 ∙ NCBI:5337 ∙ OMIM:602382 ∙ HGNC:9067 ∙ Uniprot:Q13393 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiac valvular defect, developmental (Moderate), mode of inheritance: AR
• cardiac valvular defect, developmental (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiac valvular dysplasia 1	AR	Cardiovascular	Individuals may manifest with cardiac valvular disease, and awareness may allow early diagnosis and medical or surgical management	Cardiovascular	27799408

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLD1 gene.

• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLD1 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				22	9	31
missense		4	103	14	9	130
nonsense	2	3	1			6
start loss						0
frameshift	3	1	1			5
inframe indel						0
splice donor/acceptor (+/-2bp)	1	4	1			6
splice region			2	10	2	14
non coding				11	50	61
Total	6	12	106	47	68

Highest pathogenic variant AF is 0.0000132

Variants in PLD1

This is a list of pathogenic ClinVar variants found in the PLD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-171602816-T-C			Benign (Jun 21, 2021)
3-171603117-C-T			Benign (Jan 31, 2024)
3-171603162-G-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2023)
3-171603178-C-A			Uncertain significance (Feb 18, 2022)
3-171603181-C-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
3-171603208-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
3-171603209-G-A		Cardiac valvular defect, developmental	Likely pathogenic (Jan 29, 2023)
3-171603219-T-C			Benign (Jan 28, 2024)
3-171603221-C-T			Uncertain significance (Jun 22, 2023)
3-171603233-C-T		PLD1-related disorder	Benign (Jan 13, 2024)
3-171603251-C-T			Uncertain significance (Jan 07, 2024)
3-171603267-A-G			Likely benign (Jan 01, 2024)
3-171603294-C-T		PLD1-related disorder	Likely benign (Aug 09, 2023)
3-171603295-C-T		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
3-171603524-T-C			Benign (May 14, 2021)
3-171605084-T-C			Benign (May 14, 2021)
3-171605297-A-T		Cardiac valvular defect, developmental	Uncertain significance (Mar 01, 2023)
3-171605315-G-A		Inborn genetic diseases	Uncertain significance (May 16, 2022)
3-171605321-C-T			Uncertain significance (Mar 22, 2022)
3-171605409-G-A			Uncertain significance (Jan 16, 2022)
3-171605515-T-C			Benign (May 14, 2021)
3-171605603-C-T			Benign (May 15, 2021)
3-171612186-T-C			Benign (May 14, 2021)
3-171612191-T-C			Benign (May 15, 2021)
3-171612277-A-G		Cardiac valvular defect, developmental	Pathogenic (Sep 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLD1	protein_coding	protein_coding	ENST00000351298	26	210546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.78e-21	0.858	125578	0	170	125748	0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.184	602	615	0.979	0.0000341	7120
Missense in Polyphen		224	237.25	0.94417		2763
Synonymous	0.957	200	218	0.918	0.0000128	1956
Loss of Function	2.36	42	62.0	0.677	0.00000327	737

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00121	0.00121
Ashkenazi Jewish	0.00	0.00
East Asian	0.000926	0.000925
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.000905	0.000897
Middle Eastern	0.000926	0.000925
South Asian	0.000478	0.000359
Other	0.000501	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). {ECO:0000250}.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Ether lipid metabolism - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Endocytosis - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Human Thyroid Stimulating Hormone (TSH) signaling pathway;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;One carbon metabolism and related pathways;Ras Signaling;EGF-EGFR Signaling Pathway;Neutrophil degranulation;ras signaling pathway;metabolism of anandamide an endogenous cannabinoid;rac1 cell motility signaling pathway;Metabolism of lipids;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;Metabolism;phospholipases;Phosphatidylinositol phosphate metabolism;Glycerophospholipid metabolism;EGFR1;ErbB1 downstream signaling;Arf6 trafficking events;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PG;Synthesis of PA;mTOR signaling pathway;CDC42 signaling events;IL8- and CXCR1-mediated signaling events;Arf6 downstream pathway;Alpha-synuclein signaling;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.226

Intolerance Scores

• loftool: 0.977
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.36

Haploinsufficiency Scores

• pHI: 0.787
• hipred: Y
• hipred_score: 0.690
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pld1
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: pld1b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: phosphatidic acid biosynthetic process;chemotaxis;small GTPase mediated signal transduction;Ras protein signal transduction;lipid catabolic process;regulation of microvillus assembly;neutrophil degranulation;inositol lipid-mediated signaling;cell motility;regulation of synaptic vesicle cycle
• Cellular component: Golgi membrane;lysosomal membrane;endosome;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;membrane;apical plasma membrane;endocytic vesicle;late endosome membrane;specific granule membrane;perinuclear region of cytoplasm;tertiary granule membrane;cholinergic synapse
• Molecular function: phospholipase D activity;protein binding;phosphatidylinositol binding;N-acylphosphatidylethanolamine-specific phospholipase D activity