PLD6

Summary

PLD6 (phospholipase D family member 6, HGNC:30447) is a protein-coding gene on chromosome 17p11.2, encoding Mitochondrial cardiolipin hydrolase (Q8N2A8). Presents phospholipase and nuclease activities, depending on the different physiological conditions.

Enables cardiolipin hydrolase activity and protein homodimerization activity. Involved in mitochondrial fusion. Acts upstream of or within positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane.

Source: NCBI Gene 201164 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total — 1 likely-pathogenic
• MANE Select transcript: NM_178836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30447
Approved symbol	PLD6
Name	phospholipase D family member 6
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	Zuc
Ensembl gene	ENSG00000179598
Ensembl biotype	protein_coding
OMIM	614960
Entrez	201164

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000321560

RefSeq mRNA: 1 — MANE Select: NM_178836 NM_178836

CCDS: CCDS11182

Canonical transcript exons

ENST00000321560 — 2 exons

Exon	Start	End
ENSE00001262626	17200995	17203098
ENSE00001262633	17205860	17206333

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6919 / max 190.8531, expressed in 1098 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164751	3.6919	1098

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	95.35	gold quality
tibialis anterior	UBERON:0001385	89.39	silver quality
right hemisphere of cerebellum	UBERON:0014890	85.88	gold quality
cerebellar hemisphere	UBERON:0002245	84.84	gold quality
right testis	UBERON:0004534	84.71	gold quality
cerebellar cortex	UBERON:0002129	84.60	gold quality
left testis	UBERON:0004533	84.53	gold quality
testis	UBERON:0000473	84.51	gold quality
cerebellum	UBERON:0002037	83.63	gold quality
adult organism	UBERON:0007023	83.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.42	gold quality
sperm	CL:0000019	82.59	silver quality
ileal mucosa	UBERON:0000331	81.44	gold quality
pancreatic ductal cell	CL:0002079	80.83	silver quality
medial globus pallidus	UBERON:0002477	80.68	silver quality
secondary oocyte	CL:0000655	80.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.47	gold quality
fallopian tube	UBERON:0003889	79.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.48	gold quality
hypothalamus	UBERON:0001898	78.05	gold quality
globus pallidus	UBERON:0001875	78.00	silver quality
caudate nucleus	UBERON:0001873	77.85	gold quality
nucleus accumbens	UBERON:0001882	77.85	gold quality
middle temporal gyrus	UBERON:0002771	77.45	silver quality
right uterine tube	UBERON:0001302	77.42	gold quality
amniotic fluid	UBERON:0000173	77.40	gold quality
bronchial epithelial cell	CL:0002328	77.27	gold quality
right frontal lobe	UBERON:0002810	77.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.03	gold quality
primary visual cortex	UBERON:0002436	76.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting PLD6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-762	99.58	66.61	1994

Literature-anchored findings (GeneRIF, showing 6)

• PLD6, aka MitoPLD, encodes an N-terminal mitochondrial localization sequence, localizes to the outer mitochondrial surface, generates phosphatidic acid, a signaling lipid, and triggers trans-mitochondrial association; involved in mitochondrial fusion. (PMID:17028579)
• Data suggest that mitochondrial-surface phosphatidic acid generated by MitoPLD/Zuc recruits or activates nuage components critical for piRNA production. (PMID:21397848)
• MitoPLD performs a critical function in a pathway that creates a specialized form of RNAi required by developing spermatocytes to suppress transposon mobilization during meiosis. (PMID:22281006)
• Propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. (PMID:26711011)
• Decreased piRNAs in Infertile Semen Are Related to Downregulation of Sperm MitoPLD Expression. (PMID:34326815)
• NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering. (PMID:37584589)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pld6	ENSDARG00000059951
mus_musculus	Pld6	ENSMUSG00000043648
rattus_norvegicus	Pld6	ENSRNOG00000021657
drosophila_melanogaster	zuc	FBGN0261266

Protein

Protein identifiers

Mitochondrial cardiolipin hydrolase — Q8N2A8 (reviewed: Q8N2A8)

Alternative names: Choline phosphatase 6, Mitochondrial phospholipase, Phosphatidylcholine-hydrolyzing phospholipase D6, Phospholipase D6, Protein zucchini homolog

All UniProt accessions (1): Q8N2A8

UniProt curated annotations — full annotation on UniProt →

Function. Presents phospholipase and nuclease activities, depending on the different physiological conditions. Interaction with Mitoguardin (MIGA1 or MIGA2) affects the dimer conformation, facilitating the lipase activity over the nuclease activity. Plays a key role in mitochondrial fusion and fission via its phospholipase activity. In its phospholipase role, it uses the mitochondrial lipid cardiolipin as substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-phosphate), a second messenger signaling lipid. Production of PA facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by the Lipin family of phosphatases produces diacylgycerol (DAG) which promotes mitochondrial fission. Both Lipin and DAG regulate mitochondrial dynamics and membrane fusion/fission, important processes for adapting mitochondrial metabolism to changes in cell physiology. Mitochondrial fusion enables cells to cope with the increased nucleotide demand during DNA synthesis. Mitochondrial function and dynamics are closely associated with biological processes such as cell growth, proliferation, and differentiation. Mediator of MYC activity, promotes mitochondrial fusion and activates AMPK which in turn inhibits YAP/TAZ, thereby inducing cell growth and proliferation. The endonuclease activity plays a critical role in PIWI-interacting RNA (piRNA) biogenesis during spermatogenesis. Implicated in spermatogenesis and sperm fertility in testicular germ cells, its single strand-specific nuclease activity is critical for the biogenesis/maturation of PIWI-interacting RNA (piRNA). MOV10L1 selectively binds to piRNA precursors and funnels them to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins. Cleaves either DNA or RNA substrates with similar affinity, producing a 5’ phosphate end, in this way it participates in the processing of primary piRNA transcripts. piRNAs provide essential protection against the activity of mobile genetic elements. 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. PA may act as signaling molecule in the recognition/transport of the precursor RNAs of primary piRNAs. Interacts with tesmin in testes, suggesting a role in spermatogenesis via association with its interacting partner.

Subunit / interactions. Homodimer. Interacts with MOV10L1. Interacts with MIGA1 and MIGA2; possibly facilitating homodimer formation. Interacts with GK2. Interacts with TRABD.

Subcellular location. Mitochondrion outer membrane. Golgi apparatus.

Tissue specificity. Predominantly expressed in testis and ovary, but not limited to gonads (at protein level). It is also found in brain, heart, pituitary gland, prostate, pancreas, thyroid, bone marrow, lung and muscle.

Activity regulation. MYC stimulates its phospholipase activity. MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity. Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+).

Domain organisation. In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site.

Similarity. Belongs to the phospholipase D family. MitoPLD/Zucchini subfamily.

RefSeq proteins (1): NP_849158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001736	PLipase_D/transphosphatidylase	Domain
IPR025202	PLD-like_dom	Domain
IPR051406	PLD_domain	Family

Pfam: PF13091

Catalyzed reactions (Rhea), 1 shown:

• a cardiolipin + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) + a 1,2-diacyl-sn-glycero-3-phosphate + H(+) (RHEA:44884)

UniProt features (13 total): active site 3, topological domain 2, sequence variant 2, chain 1, mutagenesis site 1, transmembrane region 1, domain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9LKX	ELECTRON MICROSCOPY	3.76
9LKY	ELECTRON MICROSCOPY	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2A8-F1	84.22	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 156; 158; 163

Mutagenesis-validated functional residues (1):

Position	Phenotype
156	mitochondrial fragmentation. no apoptosis, no alterations of cell homeostasis.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1483148	Synthesis of PG
R-HSA-1483166	Synthesis of PA
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis

MSigDB gene sets: 134 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_AXIS_SPECIFICATION, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOMF_NUCLEASE_ACTIVITY, GOBP_OOGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOMF_RNA_ENDONUCLEASE_ACTIVITY

GO Biological Process (11): spermatid development (GO:0007286), mitochondrial fusion (GO:0008053), phospholipid biosynthetic process (GO:0008654), positive regulation of mitochondrial fusion (GO:0010636), lipid catabolic process (GO:0016042), P granule organization (GO:0030719), piRNA processing (GO:0034587), meiotic cell cycle (GO:0051321), lipid metabolic process (GO:0006629), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (13): zinc ion binding (GO:0008270), RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism (GO:0016891), cardiolipin phospholipase D activity (GO:0035755), protein homodimerization activity (GO:0042803), catalytic activity (GO:0003824), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), glycerophospholipase activity (GO:0004620), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	2
Gene Silencing by RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
germ cell development	1
spermatid differentiation	1
mitochondrion organization	1
organelle fusion	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
mitochondrial fusion	1
regulation of mitochondrial fusion	1
positive regulation of organelle organization	1
positive regulation of developmental process	1
lipid metabolic process	1
catabolic process	1
organelle organization	1
pole plasm assembly	1
regulatory ncRNA processing	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
primary metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
transition metal ion binding	1
RNA endonuclease activity	1
hydrolase activity, acting on ester bonds	1
D-type glycerophospholipase activity	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
phospholipase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
protein binding	1

Protein interactions and networks

STRING

1320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLD6	MOV10L1	Q9BXT6	827
PLD6	TDRD9	Q8NDG6	807
PLD6	PIWIL4	Q7Z3Z4	797
PLD6	PIWIL1	Q96J94	770
PLD6	TDRKH	Q9Y2W6	769
PLD6	ASZ1	Q8WWH4	732
PLD6	HENMT1	Q5T8I9	732
PLD6	PNLDC1	Q8NA58	731
PLD6	PIWIL2	Q8TC59	716
PLD6	AGO3	Q9H9G7	715
PLD6	PLD5	Q8N7P1	712
PLD6	PLD4	Q96BZ4	710
PLD6	PLD2	O14939	705
PLD6	PLD3	Q8IV08	701
PLD6	TDRD1	Q9BXT4	672

IntAct

43 interactions, top by confidence:

A	B	Type	Score
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SFN	YWHAQ	psi-mi:“MI:0914”(association)	0.530
KCNC4	GXYLT2	psi-mi:“MI:0914”(association)	0.350
IL27RA	NRP1	psi-mi:“MI:0914”(association)	0.350
SFN	YWHAQ	psi-mi:“MI:0914”(association)	0.350
MAGEE2	PLD6	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LRP3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
DGCR2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
SPPL2B	GPR89A	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (177): PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), PLD6 (Proximity Label-MS)

ESM2 similar proteins: A1L1C2, A3KNW0, A6H603, A6NFQ2, A6QLU7, A9ULG4, B1H1N7, E1BE10, E2RD63, O35405, O55230, O60294, O60906, O75771, O95479, P21709, P51839, P56201, Q0V8L6, Q149M9, Q1JPJ9, Q28DT3, Q2KJJ8, Q2TBP8, Q4R583, Q5FVH2, Q5R4Y7, Q5XIA3, Q60750, Q643R3, Q6NVG1, Q6QHF9, Q80XS7, Q865R1, Q8BG07, Q8BYR1, Q8C0L6, Q8CFX1, Q8IV08, Q8N0W3

Diamond homologs: A1L1C2, A3KNW0, A8IW99, E1BE10, E2RD63, Q28DT3, Q5SWZ9, Q8N2A8, Q9VKD7, Q92G53, Q1RK58, Q4UJZ1, Q68VT0, Q9ZCD8, Q9D7I8, P56117, Q9ZMP2, Q4K3D9, Q4ZL66, Q87TY7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neuronal System	6	7.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

24 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	16
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3024494	NM_178836.4(PLD6):c.469del (p.His157fs)	Likely pathogenic

SpliceAI

472 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17203094:GATCC:G	acceptor_gain	1.0000
17:17203095:ATCC:A	acceptor_gain	1.0000
17:17203096:TCC:T	acceptor_gain	1.0000
17:17203097:CC:C	acceptor_gain	1.0000
17:17203097:CCC:C	acceptor_gain	1.0000
17:17203098:CC:C	acceptor_gain	1.0000
17:17203099:C:CC	acceptor_gain	1.0000
17:17203102:C:CT	acceptor_gain	1.0000
17:17203103:A:T	acceptor_gain	0.9900
17:17205855:CCTA:C	donor_loss	0.9900
17:17205856:CTACC:C	donor_loss	0.9900
17:17203099:C:T	acceptor_gain	0.9800
17:17205857:TA:T	donor_loss	0.9700
17:17205859:C:CA	donor_loss	0.9700
17:17203632:T:TA	donor_gain	0.9500
17:17205860:C:G	donor_loss	0.9500
17:17205859:CCTG:C	donor_gain	0.9400
17:17204962:AG:A	donor_gain	0.9300
17:17205858:A:AC	donor_gain	0.9200
17:17205859:C:CC	donor_gain	0.9200
17:17204539:T:TA	donor_gain	0.9100
17:17204077:C:G	acceptor_gain	0.9000
17:17205008:C:CT	donor_gain	0.9000
17:17205427:C:A	donor_gain	0.9000
17:17205862:G:A	donor_gain	0.9000
17:17205858:ACCTG:A	donor_gain	0.8900
17:17205859:CCTGC:C	donor_gain	0.8900
17:17205875:G:T	donor_gain	0.8900
17:17204975:C:A	donor_gain	0.8800
17:17203095:ATCCC:A	acceptor_gain	0.8700

AlphaMissense

1606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17203007:G:C	N173K	0.999
17:17203007:G:T	N173K	0.999
17:17203006:A:G	W174R	0.998
17:17203006:A:T	W174R	0.998
17:17203002:G:A	T175I	0.997
17:17203049:A:C	F159L	0.997
17:17203049:A:T	F159L	0.997
17:17203051:A:G	F159L	0.997
17:17203052:C:A	K158N	0.997
17:17203052:C:G	K158N	0.997
17:17203053:T:A	K158M	0.997
17:17202908:C:A	W206C	0.996
17:17202908:C:G	W206C	0.996
17:17202975:T:A	E184V	0.996
17:17203047:G:T	A160D	0.996
17:17203054:T:C	K158E	0.996
17:17205922:A:T	V122D	0.996
17:17205996:G:C	C97W	0.996
17:17202920:A:C	F202L	0.995
17:17202920:A:T	F202L	0.995
17:17202922:A:G	F202L	0.995
17:17202971:A:C	N185K	0.995
17:17202971:A:T	N185K	0.995
17:17205990:G:C	F99L	0.995
17:17205990:G:T	F99L	0.995
17:17205992:A:G	F99L	0.995
17:17203050:A:G	F159S	0.994
17:17203060:G:C	H156D	0.994
17:17203004:C:A	W174C	0.993
17:17203004:C:G	W174C	0.993

dbSNP variants (sampled 300 via entrez): RS1000032971 (17:17202051 T>C), RS1000122328 (17:17203205 A>G), RS1000136455 (17:17207069 C>T), RS1000540053 (17:17204595 C>A), RS1001226432 (17:17201757 A>G), RS1001337276 (17:17206486 C>A,G,T), RS1001716604 (17:17206650 G>A), RS1002845631 (17:17200767 C>T), RS1002990188 (17:17206345 G>A,C), RS1003285096 (17:17206896 G>A,T), RS1003395803 (17:17204246 G>A), RS1004161065 (17:17205371 C>T), RS1004173095 (17:17202578 G>A), RS1004639077 (17:17205097 T>C), RS1004779606 (17:17204009 C>T)

Disease associations

OMIM: gene MIM:614960 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Leflunomide	increases expression	2
Acetaminophen	increases expression	2
Cisplatin	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
dicrotophos	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentabromodiphenyl ether	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Silicon Dioxide	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3E1	Abcam HEK293T PLD6 KO	Transformed cell line	Female
CVCL_TE51	HAP1 PLD6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

125 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia