PLD3

phospholipase D family member 3, the group of Phospholipases|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:40348456-40389472

Links

ENSG00000105223 ∙ NCBI:23646 ∙ OMIM:615698 ∙ HGNC:17158 ∙ Uniprot:Q8IV08 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia 46 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia 46 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 46	AD	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	Neurologic	8595484; 29053796

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLD3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLD3 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				24	5	29
missense			63	4	3	70
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	7	3	16
non coding			18	20	7	45
Total	0	0	83	48	15

Variants in PLD3

This is a list of pathogenic ClinVar variants found in the PLD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-40366500-T-G			Uncertain significance (Mar 15, 2023)
19-40366506-A-AG			Uncertain significance (Dec 01, 2022)
19-40366513-A-G			Uncertain significance (Jun 20, 2023)
19-40366525-G-T			Likely benign (Feb 10, 2023)
19-40366610-C-G			Uncertain significance (Jul 13, 2023)
19-40366627-G-A		PLD3-related disorder	Likely benign (May 27, 2022)
19-40366632-C-T		not specified	Uncertain significance (May 23, 2023)
19-40366633-C-T			Benign (Jan 11, 2024)
19-40366634-G-A			Uncertain significance (Aug 24, 2023)
19-40366659-T-C			Uncertain significance (Oct 03, 2022)
19-40366661-G-A			Uncertain significance (Feb 27, 2023)
19-40366665-C-T		not specified	Uncertain significance (Oct 12, 2021)
19-40366684-G-A			Uncertain significance (Nov 10, 2023)
19-40366695-T-G			Likely benign (Dec 22, 2023)
19-40366699-CCACCCT-C			Likely benign (Jan 05, 2023)
19-40366755-ACCT-A			Likely benign (Apr 25, 2022)
19-40366762-C-T			Likely benign (May 24, 2022)
19-40366785-G-A		not specified	Uncertain significance (Jan 08, 2024)
19-40366788-C-T			Likely benign (Jul 30, 2023)
19-40366799-C-T			Likely benign (Jan 25, 2024)
19-40366820-C-T			Likely benign (Aug 31, 2022)
19-40366834-C-T		not specified	Uncertain significance (Jun 11, 2021)
19-40366835-T-C			Likely benign (Jan 30, 2023)
19-40366856-C-T			Likely benign (Jun 22, 2023)
19-40366857-G-A		PLD3-related disorder	Benign/Likely benign (Aug 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLD3	protein_coding	protein_coding	ENST00000409587	11	31984

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000175	0.994	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.999	262	312	0.841	0.0000198	3159
Missense in Polyphen		60	76.984	0.77939		814
Synonymous	0.936	119	133	0.897	0.00000852	1016
Loss of Function	2.44	12	25.2	0.476	0.00000121	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.0000713	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in APP processing. {ECO:0000305|PubMed:24336208}.
• Disease: DISEASE: Spinocerebellar ataxia 46 (SCA46) [MIM:617770]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA46 is a slowly progressive, autosomal dominant form with onset in adulthood. {ECO:0000269|PubMed:29053796}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Genetic variants in PLD3 have been suggested to be associated with an increased risk for Alzheimer disease (PubMed:24336208, PubMed:25832409). Further studies, however, did not support PLD3 involvement in this disease (PubMed:25832408, PubMed:25832411, PubMed:25832413, PubMed:25832410, PubMed:26411346). {ECO:0000269|PubMed:24336208, ECO:0000269|PubMed:25832408, ECO:0000269|PubMed:25832409, ECO:0000269|PubMed:25832410, ECO:0000269|PubMed:25832411, ECO:0000269|PubMed:25832413, ECO:0000269|PubMed:26411346}.
• Pathway: Ether lipid metabolism - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);metabolism of anandamide an endogenous cannabinoid;Metabolism of lipids;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;Metabolism;phospholipases;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PG (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.668
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.56

Haploinsufficiency Scores

• pHI: 0.294
• hipred: N
• hipred_score: 0.428
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pld3
• Phenotype: hematopoietic system phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: lipid catabolic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;extracellular exosome
• Molecular function: phospholipase D activity;protein binding;N-acylphosphatidylethanolamine-specific phospholipase D activity