PLPP6

Summary

PLPP6 (phospholipid phosphatase 6, HGNC:23682) is a protein-coding gene on chromosome 9p24.1, encoding Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 (Q8IY26). Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates.

Enables isoprenoid diphosphate phosphatase activity and phosphatase activity. Involved in several processes, including phospholipid dephosphorylation; phospholipid metabolic process; and positive regulation of neutrophil activation. Located in endoplasmic reticulum membrane and nuclear membrane.

Source: NCBI Gene 403313 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pyruvate dehydrogenase phosphatase deficiency (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 241 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 22
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_203453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23682
Approved symbol	PLPP6
Name	phospholipid phosphatase 6
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90191, FLJ46512, PDP1
Ensembl gene	ENSG00000205808
Ensembl biotype	protein_coding
OMIM	611666
Entrez	403313

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381883

RefSeq mRNA: 1 — MANE Select: NM_203453 NM_203453

CCDS: CCDS34981

Canonical transcript exons

ENST00000381883 — 1 exons

Exon	Start	End
ENSE00001490142	4662294	4665258

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 93.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5934 / max 50.0734, expressed in 1568 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95903	3.5934	1568

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.41	gold quality
oocyte	CL:0000023	91.47	gold quality
ileal mucosa	UBERON:0000331	90.94	gold quality
corpus epididymis	UBERON:0004359	85.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.59	gold quality
epithelial cell of pancreas	CL:0000083	85.35	gold quality
body of pancreas	UBERON:0001150	84.90	gold quality
pancreatic ductal cell	CL:0002079	84.29	silver quality
islet of Langerhans	UBERON:0000006	83.72	gold quality
pancreas	UBERON:0001264	83.62	gold quality
jejunal mucosa	UBERON:0000399	83.10	gold quality
right lobe of liver	UBERON:0001114	81.93	gold quality
upper arm skin	UBERON:0004263	81.37	silver quality
rectum	UBERON:0001052	81.34	gold quality
parotid gland	UBERON:0001831	81.34	gold quality
liver	UBERON:0002107	81.25	gold quality
placenta	UBERON:0001987	81.06	gold quality
mucosa of transverse colon	UBERON:0004991	80.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.50	gold quality
gingival epithelium	UBERON:0001949	80.14	gold quality
esophagus squamous epithelium	UBERON:0006920	80.12	gold quality
body of stomach	UBERON:0001161	80.03	gold quality
upper leg skin	UBERON:0004262	79.91	gold quality
cortical plate	UBERON:0005343	79.76	gold quality
cartilage tissue	UBERON:0002418	79.42	gold quality
epithelium of nasopharynx	UBERON:0001951	79.31	gold quality
duodenum	UBERON:0002114	79.14	gold quality
prostate gland	UBERON:0002367	79.12	gold quality
colonic mucosa	UBERON:0000317	78.93	gold quality
right adrenal gland cortex	UBERON:0035827	78.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	1080.52
E-ANND-3	no	3.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting PLPP6, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
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-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 4)

• findings indicate that PPAPDC2 in human PMN is the first lipid phosphate phosphohydrolase identified for PSDP; regulation of this activity of the enzyme may have important roles for PMN activation in innate immunity (PMID:16464866)
• PDP1 can serve as a new checkpoint for polyisoprenyl phosphate remodeling during cell activation.[PDP1] (PMID:19220020)
• PDP1/PPAPDC2 is a functional isoprenoid diphosphate phosphatase. (PMID:20110354)
• Data indicate that polyisoprenyl diphosphate phosphatase 1 (PDP1) serves an integral signaling role in neutrophil proinflammatory responses and as a target for counter-regulatory mediators. (PMID:23568778)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plpp6	ENSDARG00000043527
mus_musculus	Plpp6	ENSMUSG00000040105
rattus_norvegicus	Plpp6	ENSRNOG00000015268
drosophila_melanogaster	CG31717	FBGN0051717
caenorhabditis_elegans		WBGENE00020486

Paralogs (3): SGPP1 (ENSG00000126821), PLPP7 (ENSG00000160539), SGPP2 (ENSG00000163082)

Protein

Protein identifiers

Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 — Q8IY26 (reviewed: Q8IY26)

Alternative names: Lipid phosphatase-related protein-B, PA-PSP, Phosphatidic acid phosphatase type 2 domain-containing protein 2, Phospholipid phosphatase 6, Presqualene diphosphate phosphatase, Type 1 polyisoprenoid diphosphate phosphatase

All UniProt accessions (1): Q8IY26

UniProt curated annotations — full annotation on UniProt →

Function. Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates. Functions in the innate immune response through the dephosphorylation of presqualene diphosphate which acts as a potent inhibitor of the signaling pathways contributing to polymorphonuclear neutrophils activation. May regulate the biosynthesis of cholesterol and related sterols by dephosphorylating presqualene and farnesyl diphosphate, two key intermediates in this biosynthetic pathway. May also play a role in protein prenylation by acting on farnesyl diphosphate and its derivative geranylgeranyl diphosphate, two precursors for the addition of isoprenoid anchors to membrane proteins. Has a lower activity towards phosphatidic acid (PA), but through phosphatidic acid dephosphorylation may participate in the biosynthesis of phospholipids and triacylglycerols. May also act on ceramide-1-P, lysophosphatidic acid (LPA) and sphing-4-enine 1-phosphate/sphingosine-1-phosphate.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope. Nucleus inner membrane.

Tissue specificity. Widely expressed. Expressed in most organs, in particular gastrointestinal organs, spleen, placenta, kidney, thymus and brain.

Post-translational modifications. Phosphorylation by PKC activates the phosphatase activity towards presqualene diphosphate.

Activity regulation. Inhibited by propranolol. Not inhibited by N-ethylmaleimide or bromoenolactome.

Similarity. Belongs to the PA-phosphatase related phosphoesterase family.

RefSeq proteins (1): NP_982278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR036938	PAP2/HPO_sf	Homologous_superfamily

Pfam: PF01569

Catalyzed reactions (Rhea), 9 shown:

• 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-dihexadecanoyl-sn-glycerol + phosphate (RHEA:43236)
• (2E)-geranyl diphosphate + H2O = (2E)-geranyl phosphate + phosphate + H(+) (RHEA:47944)
• (2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-farnesyl phosphate + phosphate + H(+) (RHEA:48128)
• (2E,6E)-farnesyl phosphate + H2O = (2E,6E)-farnesol + phosphate (RHEA:48132)
• presqualene diphosphate + H2O = presqualene phosphate + phosphate + H(+) (RHEA:67968)
• (2E,6E,10E)-geranylgeranyl diphosphate + H2O = (2E,6E,10E)-geranylgeranyl phosphate + phosphate + H(+) (RHEA:68008)
• (2E,6E,10E)-geranylgeranyl phosphate + H2O = (2E,6E,10E)-geranylgeraniol + phosphate (RHEA:68016)
• (2E)-geranyl phosphate + H2O = (2E)-geraniol + phosphate (RHEA:68020)
• presqualene phosphate + H2O = presqualene alcohol + phosphate (RHEA:68024)

UniProt features (28 total): topological domain 5, region of interest 5, transmembrane region 4, modified residue 3, sequence variant 3, mutagenesis site 3, active site 2, chain 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY26-F1	73.75	0.46

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): 214 (proton donors); 256 (nucleophile); 260 (stabilizes the active site histidine for nucleophilic attack)

Post-translational modifications (3): 26, 36, 70

Mutagenesis-validated functional residues (3):

Position	Phenotype
184	loss of polyisoprenoid diphosphate phosphatase activity.
212	loss of polyisoprenoid diphosphate phosphatase activity.
256	loss of polyisoprenoid diphosphate phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 470 (showing top): ATF_B, AHRARNT_01, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, ACTACCT_MIR196A_MIR196B, GOBP_STEROL_HOMEOSTASIS, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS

GO Biological Process (11): cholesterol biosynthetic process (GO:0006695), isoprenoid metabolic process (GO:0006720), protein prenylation (GO:0018342), geranyl diphosphate metabolic process (GO:0033383), innate immune response (GO:0045087), farnesyl diphosphate catabolic process (GO:0045339), phospholipid dephosphorylation (GO:0046839), geranylgeranyl diphosphate catabolic process (GO:1902247), positive regulation of neutrophil activation (GO:1902565), immune system process (GO:0002376), lipid metabolic process (GO:0006629)

GO Molecular Function (9): phosphatidate phosphatase activity (GO:0008195), hydrolase activity (GO:0016787), lyase activity (GO:0016829), sphingosine-1-phosphate phosphatase activity (GO:0042392), lipid phosphatase activity (GO:0042577), lysophosphatidic acid phosphatase activity (GO:0052642), isoprenoid diphosphate phosphatase activity (GO:0106405), farnesyl diphosphatase activity (GO:0120557), protein binding (GO:0005515)

GO Cellular Component (8): nuclear inner membrane (GO:0005637), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear membrane (GO:0031965), nucleus (GO:0005634), nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cholesterol biosynthesis	1
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid catabolic process	2
terpenoid catabolic process	2
lipid phosphatase activity	2
catalytic activity	2
phosphatase activity	2
organelle membrane	2
nucleus	2
intracellular membrane-bounded organelle	2
endomembrane system	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
lipid metabolic process	1
protein modification process	1
prenylation	1
phospholipid metabolic process	1
terpenoid metabolic process	1
immune response	1
defense response to symbiont	1
farnesyl diphosphate metabolic process	1
dephosphorylation	1
lipid modification	1
geranylgeranyl diphosphate metabolic process	1
positive regulation of leukocyte activation	1
neutrophil activation	1
regulation of neutrophil activation	1
biological_process	1
primary metabolic process	1
pyrophosphatase activity	1
polyprenyl diphosphate phosphatase activity	1
binding	1
organelle inner membrane	1
nuclear membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
nuclear envelope	1
organelle envelope	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPP6	PLPP1	O14494	942
PLPP6	EPHX2	P34913	808
PLPP6	PIGC	Q92535	542
PLPP6	PLPP5	Q8NEB5	538
PLPP6	PLPP4	Q5VZY2	512
PLPP6	PRRC2C	Q9Y520	507
PLPP6	PLPP2	O43688	490
PLPP6	MTMR9	Q96QG7	470
PLPP6	VAMP4	O75379	462
PLPP6	METTL13	Q8N6R0	462
PLPP6	ACKR5	O15218	455
PLPP6	PUDP	Q08623	445
PLPP6	PDXP	Q96GD0	431
PLPP6	LRRC72	A6NJI9	430
PLPP6	NT5DC2	Q9H857	430

IntAct

190 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PLPP6	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	PRLR	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	BTNL9	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	VSIR	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	RETREG3	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	SMAGP	psi-mi:“MI:0915”(physical association)	0.560
STX1A	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	KASH5	psi-mi:“MI:0915”(physical association)	0.560
LDLRAD1	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	CLDN15	psi-mi:“MI:0915”(physical association)	0.560
CLN5	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
COMT	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
PDGFRA	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	GKN1	psi-mi:“MI:0915”(physical association)	0.560
BTNL9	PLPP6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (81): PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid), PPAPDC2 (Two-hybrid)

ESM2 similar proteins: A2XWN6, A5PJS2, A7MBC7, B8B6G5, C7T2J9, D2HBV9, F1NXU8, O70536, O75908, O77759, O88908, P0C8N6, P18405, P24008, P43428, Q0P4J9, Q28891, Q3TD49, Q49LS8, Q4V7R2, Q58DI5, Q5BJF2, Q5GH72, Q5HZE5, Q5I7T1, Q5ND56, Q5PQL3, Q5RJM1, Q60457, Q61263, Q66H88, Q68FF9, Q6J4K2, Q7F0Q2, Q7G7C7, Q7TQM4, Q7XUH5, Q8AVI9, Q8BMD6, Q8CB65

Diamond homologs: O34349, Q58DI5, Q5TZ07, Q66H88, Q6P0E8, Q8IY26, Q8NBV4, Q9D4F2, A0R627, P9WI52, P9WI53, B2RLI7, Q1MA49, Q2K2U9, Q57819, Q5FVJ3, Q91WB2, P80143, Q9SUW4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	137
Likely benign	78
Benign	4

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2427439	NC_000008.10:g.(?94767143)(94935901_?)del	Pathogenic
4663	NM_018444.4(PDP1):c.851_853del (p.Leu284del)	Pathogenic
4664	NM_018444.4(PDP1):c.277G>T (p.Glu93Ter)	Pathogenic
3596009	NM_018444.4(PDP1):c.48dup (p.Leu17fs)	Likely pathogenic
391847	NM_018444.4(PDP1):c.1263G>A (p.Trp421Ter)	Likely pathogenic
422914	NM_018444.4(PDP1):c.467_547delinsCT (p.Ser156fs)	Likely pathogenic
982568	NM_018444.4(PDP1):c.500dup (p.Leu167fs)	Likely pathogenic

SpliceAI

930 predictions. Top by Δscore:

Variant	Effect	Δscore
8:93917836:A:AG	acceptor_gain	0.9900
8:93917836:AAT:A	acceptor_gain	0.9900
8:93917836:AATG:A	acceptor_gain	0.9900
8:93917836:AATGG:A	acceptor_gain	0.9900
8:93917838:T:TA	acceptor_gain	0.9900
8:93917839:G:A	acceptor_gain	0.9900
8:93918800:GATAT:G	donor_gain	0.9900
8:93919087:A:AG	acceptor_gain	0.9900
8:93921371:A:T	donor_gain	0.9900
8:93917837:A:G	acceptor_gain	0.9800
8:93917837:AT:A	acceptor_gain	0.9700
8:93917838:T:G	acceptor_gain	0.9700
8:93917843:C:A	acceptor_gain	0.9700
8:93917946:GTA:G	donor_loss	0.9700
8:93916886:G:GT	donor_gain	0.9600
8:93917837:ATG:A	acceptor_gain	0.9600
8:93917946:G:GG	donor_gain	0.9600
8:93917947:T:G	donor_loss	0.9600
8:93918751:T:G	donor_gain	0.9600
9:4663449:CATAT:C	acceptor_gain	0.9600
8:93917050:G:GT	donor_gain	0.9500
8:93916886:G:T	donor_gain	0.9400
9:4663524:CAA:C	acceptor_gain	0.9400
8:93917050:G:T	donor_gain	0.9300
8:93921383:G:GT	donor_gain	0.9300
9:4663450:A:C	acceptor_gain	0.9300
9:4663453:T:TC	acceptor_gain	0.9300
8:93918760:AG:A	donor_gain	0.9200
8:93921828:G:GT	donor_gain	0.9200
9:4663527:C:CC	acceptor_gain	0.9200

AlphaMissense

1888 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:4662704:A:C	D110A	0.999
9:4662716:C:T	S114F	0.999
9:4663007:C:A	P211H	0.999
9:4662704:A:T	D110V	0.998
9:4662926:A:T	K184I	0.998
9:4662927:A:C	K184N	0.998
9:4662927:A:T	K184N	0.998
9:4663003:T:C	F210L	0.998
9:4663005:C:A	F210L	0.998
9:4663005:C:G	F210L	0.998
9:4663006:C:T	P211S	0.998
9:4663099:T:A	W242R	0.998
9:4663099:T:C	W242R	0.998
9:4663153:G:C	D260H	0.998
9:4663154:A:T	D260V	0.998
9:4663165:G:C	G264R	0.998
9:4663166:G:A	G264D	0.998
9:4663177:G:C	G268R	0.998
9:4663178:G:A	G268D	0.998
9:4662811:T:A	W146R	0.997
9:4662811:T:C	W146R	0.997
9:4662879:C:A	N168K	0.997
9:4662879:C:G	N168K	0.997
9:4662941:G:T	R189M	0.997
9:4662942:G:C	R189S	0.997
9:4662942:G:T	R189S	0.997
9:4663001:C:T	S209F	0.997
9:4663046:T:C	F224S	0.997
9:4663124:G:T	R250M	0.997
9:4663148:T:A	V258D	0.997

dbSNP variants (sampled 300 via entrez): RS1000112166 (9:4661002 T>A,C,G), RS1000441433 (9:4660851 A>G), RS1000956267 (9:4661112 A>C,G), RS1001437537 (9:4664736 G>A), RS1001537336 (9:4660688 C>A), RS1001612229 (9:4660796 G>A,C), RS1001785308 (9:4664454 A>T), RS1002384837 (9:4663342 C>T), RS1002867348 (9:4663591 G>A), RS1002893224 (9:4660315 G>T), RS1003042662 (9:4662169 C>T), RS1003848793 (9:4664461 A>G), RS1004261065 (9:4662885 C>T), RS1004687557 (9:4661509 T>A), RS1004737511 (9:4661303 A>C)

Disease associations

OMIM: gene MIM:611666 | disease phenotypes: MIM:608782, MIM:213300, MIM:249000

GenCC curated gene-disease

Disease	Classification	Inheritance
pyruvate dehydrogenase phosphatase deficiency	Strong	Autosomal recessive
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (4): pyruvate dehydrogenase phosphatase deficiency (MONDO:0012120), Joubert syndrome (MONDO:0018772), Meckel syndrome (MONDO:0018921), Tourette syndrome (MONDO:0007661)

Orphanet (3): Pyruvate dehydrogenase phosphatase deficiency (Orphanet:79246), Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001319	Neonatal hypotonia
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002151	Increased circulating lactate concentration
HP:0002928	Decreased activity of the pyruvate dehydrogenase complex
HP:0003128	Lactic acidosis
HP:0003348	Hyperalaninemia
HP:0003623	Neonatal onset
HP:0003648	Lacticaciduria
HP:0008358	Hyperprolinemia
HP:0008936	Axial hypotonia
HP:0011342	Mild global developmental delay
HP:0011968	Feeding difficulties
HP:0040328	Focal hyperintensity of cerebral white matter on MRI
HP:0410263	Brain imaging abnormality

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850
C536258	Pyruvate dehydrogenase phosphatase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
resorcinol	increases expression	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
bisphenol S	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Phosphatidylcholines	increases chemical synthesis, increases reaction	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome