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.

not_provided (126 variants)
not_specified (65 variants)
Spinocerebellar_ataxia_46 (7 variants)
PLD3-related_disorder (7 variants)
Alzheimer_disease_19 (1 variants)

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. These statistics are base on transcript: NM_000012268.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	27 clinvar	5 clinvar	35
missense			101 clinvar	11 clinvar	2 clinvar	114
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	106	38	7

Loading clinvar variants...

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