PGP

Summary

PGP (phosphoglycolate phosphatase, HGNC:8909) is a protein-coding gene on chromosome 16p13.3, encoding Glycerol-3-phosphate phosphatase (A6NDG6). Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. It is a selective cancer dependency (DepMap: 10.8% of cell lines).

Enables glycerol-3-phosphatase activity and phosphoglycolate phosphatase activity. Involved in glycerol biosynthetic process; glycerophospholipid metabolic process; and negative regulation of gluconeogenesis. Predicted to be active in cytoplasm.

Source: NCBI Gene 283871 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• MANE Select transcript: NM_001042371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8909
Approved symbol	PGP
Name	phosphoglycolate phosphatase
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	AUM, G3PP
Ensembl gene	ENSG00000184207
Ensembl biotype	protein_coding
OMIM	172280
Entrez	283871

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000333503, ENST00000562001

RefSeq mRNA: 1 — MANE Select: NM_001042371 NM_001042371

CCDS: CCDS42104

Canonical transcript exons

ENST00000333503 — 2 exons

Exon	Start	End
ENSE00001304476	2214138	2214840
ENSE00001539854	2211593	2214053

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 96.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7022 / max 95.5856, expressed in 1789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155915	13.1376	1787
155913	0.4306	165
155914	0.1340	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	96.47	gold quality
left ventricle myocardium	UBERON:0006566	95.38	gold quality
pons	UBERON:0000988	95.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.76	gold quality
cerebellar vermis	UBERON:0004720	94.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.55	gold quality
cerebellar cortex	UBERON:0002129	94.25	gold quality
cerebellar hemisphere	UBERON:0002245	94.24	gold quality
cerebellum	UBERON:0002037	93.91	gold quality
body of tongue	UBERON:0011876	93.30	gold quality
apex of heart	UBERON:0002098	93.27	gold quality
parietal lobe	UBERON:0001872	92.80	gold quality
postcentral gyrus	UBERON:0002581	92.64	gold quality
right testis	UBERON:0004534	91.96	gold quality
left testis	UBERON:0004533	91.88	gold quality
quadriceps femoris	UBERON:0001377	91.73	gold quality
right frontal lobe	UBERON:0002810	91.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.39	gold quality
superior frontal gyrus	UBERON:0002661	91.06	gold quality
vastus lateralis	UBERON:0001379	90.98	gold quality
dorsal root ganglion	UBERON:0000044	90.73	gold quality
adult organism	UBERON:0007023	90.51	gold quality
deltoid	UBERON:0001476	90.42	gold quality
sperm	CL:0000019	90.40	gold quality
biceps brachii	UBERON:0001507	90.34	gold quality
tongue	UBERON:0001723	90.33	gold quality
frontal cortex	UBERON:0001870	90.22	gold quality
testis	UBERON:0000473	90.21	gold quality
skeletal muscle tissue	UBERON:0001134	90.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	6.20
E-ANND-3	yes	5.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, TP53

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• “The available data indicate that St. John’s wort is a potent induced of CYP 3A4 and P-glycoprotein (PgP), although it may inhibit or induce other CYPs…” See page 262. (PMID:15260917)
• cerp-gp confers resistance to ceramide-induced apoptosis, with modulation of the ceramide-glucosylceramide pathway GCS making a marked contribution to this resistance (PMID:15661399)
• the PI3K/Akt pathway is involved in MDR in lymphoma cell lines and PI3K/Akt inhibition correlates down-regulation of NF-kappaB activity and inhibition Pgp function. (PMID:18640717)
• expressed in skin lesions from groins and axilla in patients with hidradenitis suppurativa (PMID:20091410)
• acute myeloid leukemia patients with co-expression of PGP and Ly showed better overall survival compared with PGP(+) patients without Ly expression (PMID:21861206)
• Data indicate that Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) overcomes multidrug resistance (MDR) via utilization of lysosomal P-glycoprotein (Pgp) transport activity. (PMID:25720491)
• Phosphoglycolate phosphatase rescues central carbon metabolism from toxic secondary metabolites in humans and yeast. (PMID:27544441)
• data explain how PGP exerts control over EGF-induced cellular protein tyrosine phosphorylation, and reveal an unexpected influence of triacylglycerol turnover on growth factor signaling. (PMID:29524543)
• Exome-Wide Association Study Identifies FN3KRP and PGP as New Candidate Longevity Genes. (PMID:33491046)
• Exploring the dynamics of the ABCB1 membrane transporter P-glycoprotein in the presence of ATP and active/non-active compounds through molecular dynamics simulations. (PMID:38272384)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgp	ENSDARG00000029695
mus_musculus	Pgp	ENSMUSG00000043445
rattus_norvegicus	Pgp	ENSRNOG00000009536
drosophila_melanogaster	CG2680	FBGN0024995
drosophila_melanogaster	CG15739	FBGN0030347
drosophila_melanogaster	CG10352	FBGN0030348
drosophila_melanogaster	CG11291	FBGN0034713
drosophila_melanogaster	CG5577	FBGN0036759
drosophila_melanogaster	CG5567	FBGN0036760
drosophila_melanogaster	CG32487	FBGN0052487
drosophila_melanogaster	CG32488	FBGN0052488
caenorhabditis_elegans		WBGENE00016664
caenorhabditis_elegans		WBGENE00016892
caenorhabditis_elegans		WBGENE00018424
caenorhabditis_elegans		WBGENE00019604

Paralogs (3): LHPP (ENSG00000107902), HDHD2 (ENSG00000167220), PDXP (ENSG00000241360)

Protein

Protein identifiers

Glycerol-3-phosphate phosphatase — A6NDG6 (reviewed: A6NDG6)

Alternative names: Aspartate-based ubiquitous Mg(2+)-dependent phosphatase, Phosphoglycolate phosphatase

All UniProt accessions (2): A6NDG6, H3BV17

UniProt curated annotations — full annotation on UniProt →

Function. Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism. Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear. In vitro, also has a phosphatase activity toward ADP, ATP, GDP and GTP.

Subunit / interactions. Homodimer.

Tissue specificity. Detected in all tissues including red cells, lymphocytes and cultured fibroblasts (at protein level). The highest activities occur in skeletal muscle and cardiac muscle.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the HAD-like hydrolase superfamily. CbbY/CbbZ/Gph/YieH family.

RefSeq proteins (1): NP_001035830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006349	PGP_euk	Family
IPR006357	HAD-SF_hydro_IIA	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF13242, PF13344

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• sn-glycerol 1-phosphate + H2O = glycerol + phosphate (RHEA:46084)
• sn-glycerol 3-phosphate + H2O = glycerol + phosphate (RHEA:66372)

UniProt features (7 total): binding site 3, active site 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NDG6-F1	94.02	0.90

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): 34 (nucleophile); 36 (proton donor); 204 (important for substrate specificity)

Ligand- & substrate-binding residues (3): 34; 36; 260

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483206	Glycerophospholipid biosynthesis

MSigDB gene sets: 182 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POLYOL_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLUCOSE_METABOLIC_PROCESS, GOBP_GLUCOSE_METABOLIC_PROCESS

GO Biological Process (3): glycerol biosynthetic process (GO:0006114), glycerophospholipid metabolic process (GO:0006650), negative regulation of gluconeogenesis (GO:0045721)

GO Molecular Function (10): sn-glycerol 1-phosphatase activity (GO:0000121), magnesium ion binding (GO:0000287), protein tyrosine phosphatase activity (GO:0004725), phosphoglycolate phosphatase activity (GO:0008967), sn-glycerol 3-phosphatase activity (GO:0043136), ADP phosphatase activity (GO:0043262), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phospholipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatase activity	4
cellular anatomical structure	2
glycerol metabolic process	1
alditol biosynthetic process	1
phospholipid metabolic process	1
glycerolipid metabolic process	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
metal ion binding	1
phosphoprotein phosphatase activity	1
nucleoside diphosphate phosphatase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
phosphoric ester hydrolase activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGP	HAGH	Q16775	734
PGP	HP	P00737	634
PGP	PGK1	P00558	522
PGP	GPT	P24298	518
PGP	XYLB	O75191	501
PGP	HBA1	P01922	497
PGP	CYS1	Q717R9	493
PGP	GAPDH	P00354	489
PGP	FN3KRP	Q9HA64	452
PGP	GK2	Q14410	448
PGP	TALDO1	P37837	442
PGP	GK	P32189	442
PGP	BCHE	P06276	440
PGP	PPCDC	Q96CD2	438
PGP	PRKD1	Q15139	436

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
PGP	GORASP2	psi-mi:“MI:0915”(physical association)	0.400
LRRK2		psi-mi:“MI:0914”(association)	0.350
RGS20	PGP	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TCL1A	PGP	psi-mi:“MI:0914”(association)	0.350
MT1M	PGP	psi-mi:“MI:0914”(association)	0.350
PARD3B	PGP	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): PGP (Co-fractionation), PGP (Co-fractionation), GORASP2 (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Proximity Label-MS), PGP (Positive Genetic), PGP (Affinity Capture-RNA), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS), PGP (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A4FV42, A4FV98, A6NDG6, D3YWP0, D3ZVU9, O15315, O35719, O70277, O75382, O94759, P21964, P57775, P81799, Q2TBS1, Q3UGX3, Q4R3I0, Q5E9V4, Q5H879, Q5RJL2, Q5SUV1, Q6DC64, Q7Z624, Q86WI3, Q86XA0, Q8BNV1, Q8C436, Q8CIW5, Q8IZ69, Q8N8L6, Q8N9F0, Q8VCX6, Q8WXB1, Q96AZ1, Q96FB5, Q96RR1, Q9BQD7, Q9BRQ3, Q9BUU2, Q9CQL0

Diamond homologs: A6NDG6, D3ZDK7, P0AF24, P0AF25, P0DKC3, P0DKC4, P19881, P34492, P46351, P60487, P94512, Q00472, Q2FIE5, Q2FZX0, Q2T9S4, Q2YWR1, Q3ZBF9, Q5F4B1, Q5HHF6, Q6GAZ7, Q6GIF9, Q6ZT62, Q7A1D4, Q7A6K4, Q8CHP8, Q8GWU0, Q8VD52, Q96GD0, Q99VE8, O33194, A4QFW4, O32125, Q5HQN3, Q8CPW3, Q8ENK3, Q9K6Y7, P94526, F6NVH9, O55125, O55126

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2052 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2213915:T:A	D260V	1.000
16:2214574:G:C	N68K	1.000
16:2214574:G:T	N68K	1.000
16:2213899:G:C	D265E	0.999
16:2213899:G:T	D265E	0.999
16:2213900:T:A	D265V	0.999
16:2213900:T:C	D265G	0.999
16:2213900:T:G	D265A	0.999
16:2213901:C:A	D265Y	0.999
16:2213901:C:G	D265H	0.999
16:2213914:G:C	D260E	0.999
16:2213914:G:T	D260E	0.999
16:2213915:T:C	D260G	0.999
16:2213915:T:G	D260A	0.999
16:2213916:C:G	D260H	0.999
16:2213918:C:A	G259V	0.999
16:2213918:C:T	G259E	0.999
16:2213993:C:T	G234E	0.999
16:2214176:T:A	D201V	0.999
16:2214177:C:G	D201H	0.999
16:2214181:G:C	N199K	0.999
16:2214181:G:T	N199K	0.999
16:2214575:T:A	N68I	0.999
16:2214578:G:A	T67I	0.999
16:2214671:T:A	D36V	0.999
16:2214676:G:C	D34E	0.999
16:2214676:G:T	D34E	0.999
16:2214677:T:A	D34V	0.999
16:2213780:G:T	P305H	0.998
16:2213849:C:T	G282E	0.998

dbSNP variants (sampled 300 via entrez): RS1000209221 (16:2215300 C>G,T), RS1000468861 (16:2215053 C>G), RS1000631882 (16:2213071 C>A,G,T), RS1001624743 (16:2215302 T>G), RS1002317461 (16:2214490 C>A,T), RS1002578573 (16:2216162 G>A,C), RS1002731996 (16:2211153 G>A,T), RS1003215184 (16:2211320 C>G,T), RS1003262465 (16:2215856 C>A,G,T), RS1003813865 (16:2212202 C>A,G), RS1003979338 (16:2213977 G>A), RS1004145341 (16:2212061 C>G,T), RS1004913365 (16:2215321 G>A), RS1005252164 (16:2214795 C>A,G,T), RS1005989026 (16:2216703 G>C)

Disease associations

OMIM: gene MIM:172280 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066480 (SINGLE PROTEIN)

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
sodium arsenite	decreases expression, increases expression	3
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
MT19c compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5516948	Binding	Inhibition of PGP (unknown origin)	Discovery of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor for the Treatment of Heart Failure. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TD03	HAP1 PGP (-) 1	Cancer cell line	Male
CVCL_TD04	HAP1 PGP (-) 2	Cancer cell line	Male
CVCL_TD05	HAP1 PGP (-) 3	Cancer cell line	Male
CVCL_TD06	HAP1 PGP (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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