PLD6

phospholipase D family member 6, the group of Phospholipases

Basic information

Region (hg38): 17:17200995-17206333

Links

ENSG00000179598 ∙ NCBI:201164 ∙ OMIM:614960 ∙ HGNC:30447 ∙ Uniprot:Q8N2A8 ∙ 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 PLD6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLD6 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				1	1	2
missense			16	2		18
nonsense						0
start loss			1			1
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	17	3	1

Variants in PLD6

This is a list of pathogenic ClinVar variants found in the PLD6 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-17202772-T-C		not specified	Uncertain significance (Jul 09, 2024)
17-17202834-G-A		not specified	Likely benign (Oct 12, 2022)
17-17202867-T-C		not specified	Uncertain significance (Jan 10, 2023)
17-17202904-G-C		not specified	Likely benign (Sep 18, 2024)
17-17202912-A-G		not specified	Uncertain significance (Feb 12, 2024)
17-17202965-G-A			Benign (Apr 16, 2018)
17-17203014-G-A		not specified	Uncertain significance (Mar 12, 2024)
17-17203014-G-C		not specified	Uncertain significance (Feb 13, 2025)
17-17203031-C-G		not specified	Uncertain significance (Jul 25, 2023)
17-17203042-C-T		not specified	Uncertain significance (Dec 06, 2022)
17-17203056-TG-T		Male infertility	Likely pathogenic (Feb 27, 2023)
17-17205891-G-C		not specified	Uncertain significance (Sep 05, 2024)
17-17205909-G-A			Likely benign (Jul 01, 2022)
17-17205954-C-A		not specified	Uncertain significance (Sep 26, 2023)
17-17205994-A-C		not specified	Uncertain significance (Jun 28, 2024)
17-17206004-C-A		not specified	Uncertain significance (Feb 06, 2024)
17-17206013-C-G		not specified	Uncertain significance (May 30, 2024)
17-17206019-C-G		not specified	Uncertain significance (Feb 27, 2023)
17-17206022-C-T		not specified	Uncertain significance (Mar 22, 2023)
17-17206106-C-G		not specified	Uncertain significance (Feb 15, 2023)
17-17206147-T-C		not specified	Uncertain significance (May 15, 2024)
17-17206193-A-G		not specified	Uncertain significance (Jun 23, 2021)
17-17206286-T-A		Male infertility	Uncertain significance (Feb 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLD6	protein_coding	protein_coding	ENST00000321560	2	5321

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00230	0.547	125166	0	4	125170	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	111	146	0.761	0.00000961	1568
Missense in Polyphen		32	36.591	0.87454		405
Synonymous	1.08	55	66.2	0.831	0.00000476	544
Loss of Function	0.243	4	4.56	0.877	2.36e-7	48

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000179	0.0000178
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endonuclease that plays a critical role in PIWI- interacting RNA (piRNA) biogenesis during spermatogenesis. piRNAs provide essential protection against the activity of mobile genetic elements (By similarity). piRNA-mediated transposon silencing is thus critical for maintaining genome stability, in particular in germline cells when transposons are mobilized as a consequence of wide-spread genomic demethylation (By similarity). Has been proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at mitochondrial surface (By similarity). Although it cannot be excluded that it can act as a phospholipase in some circumstances, it should be noted that cardiolipin hydrolase activity is either undetectable in vitro, or very low (PubMed:21397848). In addition, cardiolipin is almost exclusively found on the inner mitochondrial membrane, while PLD6 localizes to the outer mitochondrial membrane, facing the cytosol (PubMed:21397848). Has been shown to be a backbone-non-specific, single strand-specific nuclease, cleaving either RNA or DNA substrates with similar affinity. Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts (By similarity). Also acts as a regulator of mitochondrial shape through facilitating mitochondrial fusion (PubMed:17028579, PubMed:26711011). {ECO:0000250|UniProtKB:Q5SWZ9, ECO:0000269|PubMed:17028579, ECO:0000269|PubMed:21397848, ECO:0000269|PubMed:26711011}.
• Pathway: Gene expression (Transcription);Metabolism of lipids;Metabolism;phospholipases;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PG;Synthesis of PA;PIWI-interacting RNA (piRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.0997

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.273
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.442

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pld6
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: phosphatidic acid biosynthetic process;spermatid development;mitochondrial fusion;positive regulation of mitochondrial fusion;lipid catabolic process;P granule organization;piRNA metabolic process;DNA methylation involved in gamete generation;meiotic cell cycle;nucleic acid phosphodiester bond hydrolysis
• Cellular component: mitochondrial outer membrane;integral component of membrane
• Molecular function: endonuclease activity;protein binding;cardiolipin hydrolase activity;protein homodimerization activity;metal ion binding