PLD6
protein-codingphospholipase D family member 6, the group of Phospholipases
Gene summary
Enables cardiolipin phospholipase D activity and protein homodimerization activity. Involved in mitochondrial fusion and phospholipid biosynthetic process. Acts upstream of or within positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLD6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178836.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 25 | 2 | 27 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 27 | 3 | 1 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_849158.2 | 2 | MANE Select | |
| Ensembl | ENSP00000317177.3 | 2 | MANE Select | |
| Ensembl | ENSP00000797293.1 | 2 | Standard | |
| Ensembl | ENSP00000806527.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Metabolism of lipids
- Metabolism
- phospholipases
- Glycerophospholipid biosynthesis
Biological Process
- phosphatidic acid biosynthetic process
- spermatid development
- mitochondrial fusion
- positive regulation of mitochondrial fusion
- lipid catabolic process
Molecular Function
- endonuclease activity
- protein binding
- cardiolipin hydrolase activity
- protein homodimerization activity
- metal ion binding
Cellular Component
- mitochondrial outer membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000321560
- Coding exons
- 2
- Length
- 5321
- Individuals with no LoFs
- 125166
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125170
- p
- 0.0000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 111 | 146 | 0.761 | 0.00000961 | 1568 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.0997
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.442
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |