PHGDH

Summary

PHGDH (phosphoglycerate dehydrogenase, HGNC:8923) is a protein-coding gene on chromosome 1p12, encoding D-3-phosphoglycerate dehydrogenase (O43175). Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway.

This gene encodes the enzyme which is involved in the early steps of L-serine synthesis in animal cells. L-serine is required for D-serine and other amino acid synthesis. The enzyme requires NAD/NADH as a cofactor and forms homotetramers for activity. Mutations in this gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. Multiple alternatively spliced transcript variants have been found, however the full-length nature of most are not known.

Source: NCBI Gene 26227 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurometabolic disorder due to serine deficiency (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 24
• Clinical variants (ClinVar): 959 total — 50 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 112
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8923
Approved symbol	PHGDH
Name	phosphoglycerate dehydrogenase
Location	1p12
Locus type	gene with protein product
Status	Approved
Aliases	SERA, PGDH, PDG
Ensembl gene	ENSG00000092621
Ensembl biotype	protein_coding
OMIM	606879
Entrez	26227

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 14 protein_coding, 11 nonsense_mediated_decay, 7 retained_intron, 6 protein_coding_CDS_not_defined

ENST00000369407, ENST00000369409, ENST00000462324, ENST00000469443, ENST00000482968, ENST00000493622, ENST00000496756, ENST00000641023, ENST00000641074, ENST00000641115, ENST00000641213, ENST00000641247, ENST00000641272, ENST00000641314, ENST00000641371, ENST00000641375, ENST00000641455, ENST00000641491, ENST00000641513, ENST00000641570, ENST00000641573, ENST00000641587, ENST00000641597, ENST00000641711, ENST00000641720, ENST00000641756, ENST00000641811, ENST00000641847, ENST00000641891, ENST00000641927, ENST00000641939, ENST00000641947, ENST00000642021, ENST00000642041, ENST00000858460, ENST00000936416, ENST00000936417, ENST00000936419

RefSeq mRNA: 1 — MANE Select: NM_006623 NM_006623

CCDS: CCDS904

Canonical transcript exons

ENST00000641023 — 12 exons

Exon	Start	End
ENSE00000785270	119740386	119740518
ENSE00000957946	119734634	119734766
ENSE00000957948	119737114	119737266
ENSE00001888153	119743886	119744215
ENSE00002723217	119735295	119735443
ENSE00003469615	119742807	119743044
ENSE00003494365	119741767	119741897
ENSE00003520458	119721170	119721321
ENSE00003537955	119726851	119726905
ENSE00003556711	119723376	119723441
ENSE00003622630	119727004	119727102
ENSE00003812999	119711934	119712160

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.1633 / max 1154.9011, expressed in 1647 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4928	100.1379	1647
4929	0.0167	3
201636	0.0087	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.26	gold quality
ganglionic eminence	UBERON:0004023	97.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.59	gold quality
amygdala	UBERON:0001876	97.21	gold quality
nucleus accumbens	UBERON:0001882	97.06	gold quality
embryo	UBERON:0000922	97.04	gold quality
spinal cord	UBERON:0002240	97.04	gold quality
caudate nucleus	UBERON:0001873	96.98	gold quality
right lobe of liver	UBERON:0001114	96.83	gold quality
body of pancreas	UBERON:0001150	96.79	gold quality
putamen	UBERON:0001874	96.79	gold quality
stromal cell of endometrium	CL:0002255	96.51	gold quality
corpus callosum	UBERON:0002336	96.09	gold quality
minor salivary gland	UBERON:0001830	96.04	gold quality
saliva-secreting gland	UBERON:0001044	95.95	gold quality
skin of abdomen	UBERON:0001416	95.88	gold quality
right frontal lobe	UBERON:0002810	95.76	gold quality
hypothalamus	UBERON:0001898	95.74	gold quality
skin of leg	UBERON:0001511	95.52	gold quality
right uterine tube	UBERON:0001302	95.46	gold quality
cingulate cortex	UBERON:0003027	95.25	gold quality
anterior cingulate cortex	UBERON:0009835	95.23	gold quality
popliteal artery	UBERON:0002250	95.20	gold quality
substantia nigra	UBERON:0002038	95.18	gold quality
tibial artery	UBERON:0007610	95.17	gold quality
lateral globus pallidus	UBERON:0002476	94.73	gold quality
midbrain	UBERON:0001891	94.72	gold quality
zone of skin	UBERON:0000014	94.56	gold quality
left testis	UBERON:0004533	94.55	gold quality
ectocervix	UBERON:0012249	94.54	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	258.74
E-HCAD-5	yes	52.57
E-CURD-112	yes	39.97
E-HCAD-10	yes	29.71
E-GEOD-93593	yes	12.85
E-HCAD-1	yes	12.78
E-MTAB-9388	yes	11.59
E-ENAD-27	yes	6.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HOXA10, NFYA, NFYB, NFYC, SP1

miRNA regulators (miRDB)

12 targeting PHGDH, 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-6499-3P	99.90	66.38	1212
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-8056	97.15	64.49	769
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-759	96.16	66.77	873

Literature-anchored findings (GeneRIF, showing 40)

• we conclude that this mutation impairs the folding and/or assembly of PHGDH but has minimal effects on the activity or stability of that portion of the V490M mutant that reaches a mature conformation (PMID:11751922)
• The crystal structure of Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase has been solved with bound effector, 1-serine, and substrate, hydroxypyruvic acid phosphate. The human enzyme was also examined. (PMID:18627175)
• These data suggest that missense mutations associated with 3-PGDH deficiency either primarily affect substrate binding or result in very low residual enzymatic activity. (PMID:19235232)
• Studies in bacteria showed that addition of substrate at the active site is ordered, with HPAP binding before NADH. Also, NADH can compete with the substrate for binding to the allosteric site and thereby eliminate the substrate inhibition. (PMID:19388702)
• a coding PHGDH SNP (rs543703) was weakly associated with the development of schizophrenia in Korean population (PMID:19404161)
• The frequency of antibodies to Phgdh is much higher in patients with autoimmune hepatitis than in patients with other types of hepatitis or normal controls. (PMID:19497206)
• PHGDH is expressed in cytoplasm of stromal and glandular cells in endometrium; expression is relatively high in proliferative phase and lower in secretory phase. Data suggest expression of PHGDH in endometrium is regulated by HOXA10. (PMID:19778996)
• results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets (PMID:21760589)
• in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase. (PMID:21804546)
• The potential mechanisms by which PHGDH promotes cancer are discussed. (PMID:21981974)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• PHGDH overexpression is found in cervical cancer, in particular, in bigger tumors and with advanced stages. Its expression is positively correlated with squamous cell carcinoma antigen level (PMID:24247658)
• We report on the identification of homozygous mutations in PHGDH and serine deficiency in individuals with Neu-Laxova syndrome. This disorder thus seems to be an extremely severe expression of PHGDH deficiency. (PMID:24836451)
• Phosphoglycerate Dehydrogenase deficiency is associated with Neu-Laxova syndrome. (PMID:25152457)
• p53-mediated repression of PHGDH enhances the apoptotic response upon serine starvation in melanoma cells. (PMID:25404730)
• Overexpression of Phgdh may be generally associated with CK5 cells, and oncogenic function may be determined by isoform expression. (PMID:26026368)
• High expression of PHGDH is associated with Colon Cancer. (PMID:26439504)
• High PHGDH expression is associated with idiopathic pulmonary fibrosis. (PMID:27836973)
• This report present 6 individuals from 3 unrelated families with infantile serine biosynthesis defect due to PGDH deficiency. (PMID:28135894)
• Study provides evidence that a unique metabolic program is activated in a lung adenocarcinoma subset, described by PHGDH, which confers cell growth. (PMID:28614715)
• Therefore, we show for the first time that the nuclear localization of Cat L and its substrate Cux1can be positively regulated by Snail NLS and importin beta1, suggesting that Snail, Cat L and Cux1 all utilize importin beta1 for nuclear import. (PMID:28698143)
• These findings highlight the role of epigenetic regulation of the PHGDH gene in triglyceride metabolism, providing novel insights on putative intervention targets. (PMID:28894120)
• Data show there was a significant negative correlation between PHGDH copy-number alteration and EPAS1 (HIF2A) expression. (PMID:28951458)
• Data indicate that the expression of PHGDH is increased in pancreatic cancer and is an independent molecular prognostic factor for pancreatic cancer patients. In addition, PHGDH controls cell proliferation, migration and invasion abilities. (PMID:29128633)
• PHGDH expression is regulated by PlncRNA-1 in breast cancer. (PMID:29626321)
• Authors find that PHGDH(high) breast cancer cell lines are exquisitely sensitive to inhibition of the NAD(+) salvage pathway. Further, authors find that PHGDH protein levels and those of the rate-limiting enzyme of NAD(+) salvage, NAMPT, correlate in ER-negative, basal-like breast cancers. (PMID:30157431)
• this study identifies a clinically-relevant role for PHGDH in the regulation of stemness-differentiation axis within cancer stem-like cells . (PMID:30250195)
• major fluxes affected upon PHGDH inhibition that alter nucleotide metabolism are related to central carbon metabolism, and not the serine synthesis pathway (PMID:30575741)
• Besides catalyzing serine synthesis, PHGDH promotes pancreatic cancer development through enhancing the translation initiations by interacting with eIF4A1 and eIF4E. (PMID:30744688)
• Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting. (PMID:30905671)
• These data suggest increased PHGDH expression impacts normal melanocyte biology, but PHGDH expression alone is not sufficient to cause cancer. (PMID:31331318)
• phosphoglycerate dehydrogenase (PHGDH), the first committed enzyme in the serine synthesis pathway (SSP), is a critical driver for Sorafenib (and other tyrosine kinase inhibitors ) resistance in hepatocellular carcinoma. (PMID:31615983)
• Reduced Phgdh expression and serine levels are closely associated with the development of Fatty Liver Disease. (PMID:31678070)
• This study is the first description of PHGDH and PSAT1 mutations in Chinese Neu-Laxova syndrome patients, which strongly implicates them in the pathogenesis of Neu-Laxova syndrome. (PMID:31903955)
• Clinical, molecular, and pathological findings in a Neu-Laxova syndrome stillborn: A Brazilian case report. (PMID:32196970)
• Serine-dependent redox homeostasis regulates glioblastoma cell survival. (PMID:32203214)
• Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation. (PMID:32386122)
• High Phosphoglycerate Dehydrogenase Expression Induces Stemness and Aggressiveness in Thyroid Cancer. (PMID:32438862)
• Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression. (PMID:32478681)
• Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders. (PMID:32579715)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phgdh	ENSDARG00000001873
mus_musculus	Phgdh	ENSMUSG00000053398
rattus_norvegicus	Phgdh	ENSRNOG00000019328
drosophila_melanogaster	CG6287	FBGN0032350
caenorhabditis_elegans		WBGENE00007836

Paralogs (3): GRHPR (ENSG00000137106), CTBP1 (ENSG00000159692), CTBP2 (ENSG00000175029)

Protein

Protein identifiers

D-3-phosphoglycerate dehydrogenase — O43175 (reviewed: O43175)

Alternative names: 2-oxoglutarate reductase, Malate dehydrogenase

All UniProt accessions (15): O43175, A0A286YER3, A0A286YEZ0, A0A286YF22, A0A286YF34, A0A286YF78, A0A286YFA2, A0A286YFB2, A0A286YFC8, A0A286YFE1, A0A286YFF3, A0A286YFK5, A0A286YFL2, A0A286YFM8, A0A2C9F2M7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate.

Subunit / interactions. Homotetramer.

Disease relevance. Phosphoglycerate dehydrogenase deficiency (PHGDHD) [MIM:601815] An autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures. The disease is caused by variants affecting the gene represented in this entry. Neu-Laxova syndrome 1 (NLS1) [MIM:256520] A lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies including lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears. The disease is caused by variants affecting the gene represented in this entry.

Induction. Induced by 17-beta-estradiol (estrogenic ligand) and 4-hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by the transcription factors SP1 and NF-Y.

Pathway. Amino-acid biosynthesis; L-serine biosynthesis; L-serine from 3-phospho-D-glycerate: step 1/3.

Similarity. Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.

RefSeq proteins (1): NP_006614* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006139	D-isomer_2_OHA_DH_cat_dom	Domain
IPR006140	D-isomer_DH_NAD-bd	Domain
IPR006236	PGDH	Family
IPR029009	ASB_dom_sf	Homologous_superfamily
IPR029752	D-isomer_DH_CS1	Conserved_site
IPR029753	D-isomer_DH_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR045626	PGDH_ASB_dom	Domain

Pfam: PF00389, PF02826, PF19304

Enzyme classification (BRENDA):

• EC 1.1.1.95 — phosphoglycerate dehydrogenase (BRENDA: 40 organisms, 64 substrates, 191 inhibitors, 190 Km, 125 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-PHOSPHO-D-GLYCERATE	0.003–320	76
NAD+	0.0053–0.551	24
NADH	0.0005–12	22
3-PHOSPHOHYDROXYPYRUVATE	0.0001–40.2	19
3-PHOSPHOOXYPYRUVATE	0.0032–0.17	11
2-OXOGLUTARATE	0.088–53.1	9
ALPHA-KETOGLUTARATE	0.038–0.088	4
D-3-PHOSPHOGLYCERATE	0.15–1.1	4
OXALOACETATE	3.9–14.1	4
NADPH	0.02–0.15	3
3-ACETYLPYRIDINE-NAD+	0.0003–0.0054	2
3-ACETYLPYRIDINE-NADH	0.0002	1
3-PHOSPHOGLYCERATE	0.212	1
ACETYLPYRIDINE	0.0393	1
D-2-HYDROXYGLUTARATE	0.4	1

Catalyzed reactions (Rhea), 3 shown:

• (2R)-3-phosphoglycerate + NAD(+) = 3-phosphooxypyruvate + NADH + H(+) (RHEA:12641)
• (S)-malate + NAD(+) = oxaloacetate + NADH + H(+) (RHEA:21432)
• (R)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + NADH + H(+) (RHEA:49612)

UniProt features (64 total): strand 17, helix 16, sequence variant 8, binding site 7, modified residue 5, active site 3, turn 3, cross-link 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
5NZO	X-RAY DIFFRACTION	1.29
5NZP	X-RAY DIFFRACTION	1.3
6RJ3	X-RAY DIFFRACTION	1.42
5N53	X-RAY DIFFRACTION	1.48
5NZQ	X-RAY DIFFRACTION	1.5
5OFM	X-RAY DIFFRACTION	1.5
5OFV	X-RAY DIFFRACTION	1.5
5OFW	X-RAY DIFFRACTION	1.5
2G76	X-RAY DIFFRACTION	1.7
6PLF	X-RAY DIFFRACTION	1.7
7DKM	X-RAY DIFFRACTION	1.7
7VA1	X-RAY DIFFRACTION	1.74
6CWA	X-RAY DIFFRACTION	1.77
6RJ5	X-RAY DIFFRACTION	1.89
6RJ6	X-RAY DIFFRACTION	1.98
6RJ2	X-RAY DIFFRACTION	2
6RIH	X-RAY DIFFRACTION	2.15
5N6C	X-RAY DIFFRACTION	2.3
7CVP	X-RAY DIFFRACTION	2.5
6PLG	X-RAY DIFFRACTION	2.93
7EWH	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43175-F1	93.06	0.83

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): 236; 265; 283 (proton donor)

Ligand- & substrate-binding residues (7): 260; 283–286; 78; 155–156; 175; 207; 234–236

Post-translational modifications (7): 2, 14, 21, 58, 78, 21, 21

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-977347	Serine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 575 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_SERINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GLIAL_CELL_DEVELOPMENT, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MCBRYAN_TERMINAL_END_BUD_DN, GOBP_NEUROGENESIS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (16): L-glutamine metabolic process (GO:0006541), glycine metabolic process (GO:0006544), L-serine biosynthetic process (GO:0006564), L-threonine metabolic process (GO:0006566), brain development (GO:0007420), obsolete GABA metabolic process (GO:0009448), regulation of gene expression (GO:0010468), taurine metabolic process (GO:0019530), spinal cord development (GO:0021510), glial cell development (GO:0021782), neural tube development (GO:0021915), neuron projection development (GO:0031175), G1 to G0 transition (GO:0070314), L-serine metabolic process (GO:0006563), amino acid biosynthetic process (GO:0008652), neurogenesis (GO:0022008)

GO Molecular Function (7): phosphoglycerate dehydrogenase activity (GO:0004617), electron transfer activity (GO:0009055), L-malate dehydrogenase (NAD+) activity (GO:0030060), NAD binding (GO:0051287), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (2): cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteinogenic amino acid metabolic process	4
L-amino acid metabolic process	3
central nervous system development	2
nervous system development	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
L-serine metabolic process	1
serine family amino acid biosynthetic process	1
L-amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
animal organ development	1
head development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
alkanesulfonate metabolic process	1
anatomical structure development	1
glial cell differentiation	1
cell development	1
tube development	1
chordate embryonic development	1
epithelium development	1
neuron development	1
plasma membrane bounded cell projection organization	1
cell cycle process	1
amino acid metabolic process	1
biosynthetic process	1
cell differentiation	1
molecular_function	1
malate dehydrogenase activity	1
adenyl nucleotide binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

5692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHGDH	TNPO1	Q92973	913
PHGDH	PSAT1	Q9Y617	893
PHGDH	PSPH	P78330	858
PHGDH	LGALS4	P56470	857
PHGDH	KPNA4	O00629	849
PHGDH	KPNA2	P52292	824
PHGDH	GAPDH	P00354	816
PHGDH	KPNA1	P52294	796
PHGDH	KPNA3	O00505	790
PHGDH	XPO1	O14980	781
PHGDH	SHMT2	P34897	775
PHGDH	MYC	P01106	742
PHGDH	SHMT1	P34896	741
PHGDH	TP53	P04637	717
PHGDH	KPNB1	Q14974	700

IntAct

154 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EPN1	PHGDH	psi-mi:“MI:0914”(association)	0.710
PHGDH	EPN1	psi-mi:“MI:0915”(physical association)	0.710
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
SLCO4C1	CLGN	psi-mi:“MI:0914”(association)	0.530
Cdk1	PHGDH	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
Ddb1	PHGDH	psi-mi:“MI:0915”(physical association)	0.400
Tubb4b	MGST3	psi-mi:“MI:0915”(physical association)	0.400
Bles03		psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
PHGDH	CHMP2B	psi-mi:“MI:0915”(physical association)	0.370
PHGDH	RHOB	psi-mi:“MI:0915”(physical association)	0.370
PIAS4	PHGDH	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	PHGDH	psi-mi:“MI:0915”(physical association)	0.370
STK4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
KIF20A	NEURL4	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (474): PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), PHGDH (Affinity Capture-MS), ADH5 (Co-fractionation), ASNS (Co-fractionation), ASS1 (Co-fractionation), CCDC25 (Co-fractionation)

ESM2 similar proteins: A1L1F0, A4IFG2, A5A6P1, A5GFY8, C3K0A7, D9IVE5, O43175, P10688, P10895, P18407, P25335, Q01415, Q02JZ8, Q09913, Q0V9A9, Q1ED21, Q2KIG4, Q32NH8, Q3B8C3, Q3KFK9, Q3TV70, Q48KS4, Q4K8H3, Q4R964, Q4ZVG8, Q58DU8, Q5EAD2, Q5PQR3, Q5R6J8, Q5R7M2, Q61753, Q640T1, Q68FH4, Q6AYP0, Q6DGA6, Q6LPX9, Q86WQ0, Q87YX4, Q8BIP0, Q8C726

Diamond homologs: A0A348AXY0, A1RYE4, A4TGN1, A5A6P1, A5GFY8, A6TFG7, A7FPA2, A9R4G6, B1JH01, B1L765, B2K7F1, B2VCD1, B5XMZ4, B6YWH0, C0CMQ8, C5A1V0, D2RJU7, G9EZR6, J7SHB8, O04130, O08651, O27051, O29445, O33116, O43175, O46036, O49485, O58320, O83080, O88712, O94574, P0A545, P17584, P26297, P26298, P30799, P30901, P35136, P43885, P44501

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
HOXA10	“down-regulates quantity by repression”	PHGDH	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
NFYB	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
PHGDH	“up-regulates activity”	3-phosphonato-D-glycerate(3-)	“chemical modification”
PHGDH	“up-regulates activity”	3-phosphonatooxypyruvate(3-)	“chemical modification”
PRKN	“down-regulates quantity by destabilization”	PHGDH	ubiquitination
PHGDH	“up-regulates activity”	(R)-2-hydroxyglutarate(2-)	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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
Signalling to RAS	5	34.3×	7e-05
FCERI mediated MAPK activation	5	17.7×	2e-04
Selective autophagy	6	17.1×	8e-05
Aggrephagy	5	12.7×	7e-04
Macroautophagy	9	10.6×	7e-05
Signaling by BRAF and RAF1 fusions	6	10.4×	4e-04
Kinesins	5	9.1×	2e-03
Autophagy	6	9.1×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	7	19.2×	8e-05
positive regulation of fibroblast proliferation	7	16.2×	1e-04
intrinsic apoptotic signaling pathway	5	14.0×	5e-03
endocytosis	9	6.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	30
Uncertain significance	314
Likely benign	463
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070698	NM_006623.4(PHGDH):c.1075C>T (p.Gln359Ter)	Pathogenic
1075820	NM_006623.4(PHGDH):c.1186del (p.Leu396fs)	Pathogenic
1076466	NC_000001.10:g.(?120277247)(120277399_?)del	Pathogenic
1298474	GRCh37/hg19 1p12(chr1:120254646-120254783)x0	Pathogenic
1358340	NM_006623.4(PHGDH):c.1222dup (p.His408fs)	Pathogenic
1384387	NM_006623.4(PHGDH):c.363del (p.Gln123fs)	Pathogenic
1410064	NM_006623.4(PHGDH):c.118G>T (p.Glu40Ter)	Pathogenic
1451879	NM_006623.4(PHGDH):c.996G>A (p.Trp332Ter)	Pathogenic
1454660	NM_006623.4(PHGDH):c.117_118delinsCT (p.Glu39_Glu40delinsAspTer)	Pathogenic
1455226	NM_006623.4(PHGDH):c.271_274del (p.Lys91fs)	Pathogenic
1455475	NM_006623.4(PHGDH):c.670C>T (p.Gln224Ter)	Pathogenic
1455703	NM_006623.4(PHGDH):c.919del (p.Met306_Val307insTer)	Pathogenic
1456214	NC_000001.10:g.(?120254636)(120286673_?)del	Pathogenic
1456712	NM_006623.4(PHGDH):c.709G>T (p.Gly237Ter)	Pathogenic
1458004	NM_006623.4(PHGDH):c.1228_1232dup (p.Ala412fs)	Pathogenic
156360	NM_006623.4(PHGDH):c.793G>A (p.Glu265Lys)	Pathogenic
1964515	NM_006623.4(PHGDH):c.398G>A (p.Trp133Ter)	Pathogenic
2000405	NM_006623.4(PHGDH):c.775del (p.Leu259fs)	Pathogenic
2008171	NM_006623.4(PHGDH):c.1258del (p.Glu420fs)	Pathogenic
2031299	NM_006623.4(PHGDH):c.1499del (p.Val500fs)	Pathogenic
2087437	NM_006623.4(PHGDH):c.859del (p.Ser287fs)	Pathogenic
2113696	NM_006623.4(PHGDH):c.358C>T (p.Gln120Ter)	Pathogenic
2200542	NM_006623.4(PHGDH):c.1485C>G (p.Tyr495Ter)	Pathogenic
2202834	NM_006623.4(PHGDH):c.1297C>T (p.Gln433Ter)	Pathogenic
2579118	NM_006623.4(PHGDH):c.765del (p.Ala257fs)	Pathogenic
2696662	NM_006623.4(PHGDH):c.889del (p.Glu297fs)	Pathogenic
2703194	NM_006623.4(PHGDH):c.483dup (p.Thr162fs)	Pathogenic
2733973	NM_006623.4(PHGDH):c.1429dup (p.Met477fs)	Pathogenic
2763482	NM_006623.4(PHGDH):c.578del (p.Leu193fs)	Pathogenic
2813247	NM_006623.4(PHGDH):c.1089del (p.Lys364fs)	Pathogenic

SpliceAI

2420 predictions. Top by Δscore:

Variant	Effect	Δscore
1:119712157:GCAG:G	donor_gain	1.0000
1:119712161:G:GA	donor_loss	1.0000
1:119712161:G:GG	donor_gain	1.0000
1:119712162:T:G	donor_loss	1.0000
1:119721301:G:GT	donor_gain	1.0000
1:119721302:A:T	donor_gain	1.0000
1:119721315:TTATG:T	donor_gain	1.0000
1:119721319:G:GT	donor_gain	1.0000
1:119721319:GAA:G	donor_gain	1.0000
1:119721320:AA:A	donor_gain	1.0000
1:119721320:AAG:A	donor_loss	1.0000
1:119721321:AG:A	donor_loss	1.0000
1:119721322:G:GG	donor_gain	1.0000
1:119721322:GTAA:G	donor_loss	1.0000
1:119721323:TAA:T	donor_loss	1.0000
1:119723370:CTTTA:C	acceptor_loss	1.0000
1:119723374:A:AG	acceptor_gain	1.0000
1:119723374:A:C	acceptor_loss	1.0000
1:119723375:G:GG	acceptor_gain	1.0000
1:119723375:GC:G	acceptor_gain	1.0000
1:119726845:TTGCA:T	acceptor_loss	1.0000
1:119726846:TGCA:T	acceptor_loss	1.0000
1:119726847:GCA:G	acceptor_loss	1.0000
1:119726848:CAGGC:C	acceptor_loss	1.0000
1:119726849:A:AG	acceptor_gain	1.0000
1:119726849:A:AT	acceptor_loss	1.0000
1:119726850:G:GC	acceptor_loss	1.0000
1:119726850:G:GG	acceptor_gain	1.0000
1:119726850:GGC:G	acceptor_gain	1.0000
1:119726850:GGCA:G	acceptor_gain	1.0000

AlphaMissense

3445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:119721189:T:A	V53D	0.999
1:119723398:A:C	S105R	0.999
1:119723400:T:A	S105R	0.999
1:119723400:T:G	S105R	0.999
1:119726891:T:A	W133R	0.999
1:119726891:T:C	W133R	0.999
1:119726893:G:C	W133C	0.999
1:119726893:G:T	W133C	0.999
1:119727053:G:A	G154D	0.999
1:119727061:G:T	G157W	0.999
1:119727062:G:A	G157E	0.999
1:119735350:C:A	N233K	0.999
1:119735350:C:G	N233K	0.999
1:119737168:C:G	H283D	0.999
1:119721256:G:C	R75S	0.998
1:119721256:G:T	R75S	0.998
1:119721315:T:A	V95D	0.998
1:119723391:C:A	N102K	0.998
1:119723391:C:G	N102K	0.998
1:119723404:G:C	A107P	0.998
1:119723441:G:C	R119T	0.998
1:119727047:G:A	G152D	0.998
1:119727062:G:T	G157V	0.998
1:119727073:G:C	A161P	0.998
1:119727080:G:C	R163P	0.998
1:119734641:G:A	G173E	0.998
1:119734739:C:G	H206D	0.998
1:119735353:T:G	C234W	0.998
1:119735355:C:A	A235D	0.998
1:119737170:C:A	H283Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000123066 (1:119723774 G>A), RS1000155412 (1:119710333 C>T), RS1000288987 (1:119744153 G>T), RS1000365816 (1:119732228 C>G), RS1000712015 (1:119730668 A>G), RS1000816103 (1:119736594 G>A), RS1001033012 (1:119734890 T>C), RS1001074222 (1:119729087 T>C), RS1001086747 (1:119735124 C>A), RS1001256337 (1:119731573 T>C), RS1001328772 (1:119740708 T>C), RS1001449162 (1:119717100 T>C), RS1001531439 (1:119742997 T>C), RS1001697657 (1:119740303 A>G), RS1001707639 (1:119737296 A>C,G)

Disease associations

OMIM: gene MIM:606879 | disease phenotypes: MIM:601815, MIM:256520

GenCC curated gene-disease

Disease	Classification	Inheritance
PHGDH deficiency	Definitive	Autosomal recessive
neurometabolic disorder due to serine deficiency	Strong	Autosomal recessive
Neu-Laxova syndrome 1	Moderate	Autosomal recessive
Neu-Laxova syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurometabolic disorder due to serine deficiency	Definitive	AR

Mondo (4): PHGDH deficiency (MONDO:0011152), Neu-Laxova syndrome 1 (MONDO:0009736), neurometabolic disorder due to serine deficiency (MONDO:0018162), Neu-Laxova syndrome (MONDO:0000179)

Orphanet (4): 3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form (Orphanet:79351), Neu-Laxova syndrome (Orphanet:2671), Neu-Laxova syndrome due to 3-phosphoglycerate dehydrogenase deficiency (Orphanet:583607), Neurometabolic disorder due to serine deficiency (Orphanet:35705)

HPO phenotypes

112 total (30 of 112 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000104	Renal agenesis
HP:0000135	Hypogonadism
HP:0000136	Bifid uterus
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000204	Cleft upper lip
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000520	Proptosis
HP:0000561	Absent eyelashes
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0001059	Pterygium
HP:0001181	Adducted thumb

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001217_24	Metabolic traits	3.000000e-14
GCST001852_2	Metabolite levels	2.000000e-14
GCST002647_12	Height	2.000000e-09
GCST004171_1	Macular telangiectasia type 2	2.000000e-14
GCST004198_1	Severe gingival inflammation	1.000000e-06
GCST004250_11	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	4.000000e-07
GCST004601_4	Red blood cell count	2.000000e-09
GCST005531_29	Multiple sclerosis	6.000000e-12
GCST006614_46	Total cholesterol levels	2.000000e-08
GCST006631_3	Nicotine dependence and major depression (severity of comorbidity)	3.000000e-06
GCST007638_50	Glycine levels	8.000000e-14
GCST007836_2	Glycine levels	3.000000e-10
GCST007837_1	Glycine levels	2.000000e-06
GCST009597_126	Multiple sclerosis	2.000000e-06
GCST009597_39	Multiple sclerosis	1.000000e-17
GCST010083_327	Hemoglobin levels	1.000000e-10
GCST012020_236	Serum metabolite levels	3.000000e-20
GCST012251_10	Macular telangiectasia type 2	1.000000e-20
GCST012252_1	Macular telangiectasia type 2	8.000000e-22
GCST90002383_331	Hematocrit	2.000000e-12
GCST90002384_5	Hemoglobin	3.000000e-11
GCST90002390_15	Mean corpuscular hemoglobin	2.000000e-09
GCST90002397_771	Mean spheric corpuscular volume	7.000000e-11
GCST90002403_18	Red blood cell count	3.000000e-22

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0004471	insulin sensitivity measurement
EFO:1002009	macular telangiectasia type 2
EFO:0007965	response to combination chemotherapy
EFO:0004305	erythrocyte count
EFO:0004574	total cholesterol measurement
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0009767	glycine measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536405	Neu Laxova syndrome (supp.)
C566618	Phosphoglycerate Dehydrogenase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2311243 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,611 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL964	DISULFIRAM	4	38,611

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

Binding affinities (BindingDB)

3 measured of 12 human assays (12 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-{4-[(1R)-1-{[3-(1H-indol-7-yl)-1-methyl-1H-pyrazol-5- yl]formamido}ethyl]benzenesulfonyl}acetic acid	IC50	53 nM	US-11304929: Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors
methyl 2-{4-[(1R)-1-{[3-(1H-indol-7-yl)-1-methyl-1H-pyrazol-5- yl]formamido}ethyl]benzenesulfonyl}acetate	IC50	1270 nM	US-11304929: Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors
ethyl 2-{4-[(1R)-1-{[3-(1H-indol-7-yl)-1-methyl-1H-pyrazol-5- yl]formamido}ethyl]benzenesulfonyl}acetate	IC50	3000 nM	US-11304929: Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors

ChEMBL bioactivities

762 potent at pChembl≥5 of 1011 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL4541133
9.10	IC50	0.8	nM	CHEMBL4536737
8.80	IC50	1.6	nM	CHEMBL4584313
8.70	IC50	2	nM	CHEMBL4436264
8.54	IC50	2.9	nM	CHEMBL4518579
8.52	IC50	3	nM	CHEMBL4467246
8.52	IC50	3	nM	CHEMBL4520837
8.52	IC50	3	nM	CHEMBL4515492
8.52	IC50	3	nM	CHEMBL4527607
8.48	IC50	3.3	nM	CHEMBL4579388
8.43	IC50	3.7	nM	CHEMBL4540875
8.41	IC50	3.9	nM	CHEMBL4521661
8.40	IC50	4	nM	CHEMBL4436264
8.40	IC50	4	nM	CHEMBL4542437
8.40	IC50	4	nM	CHEMBL4515492
8.40	IC50	4	nM	CHEMBL4520837
8.30	IC50	5	nM	CHEMBL4548014
8.30	IC50	5	nM	CHEMBL4483622
8.30	IC50	5	nM	CHEMBL4587306
8.30	IC50	5	nM	CHEMBL4527607
8.30	IC50	5	nM	CHEMBL4541457
8.22	IC50	6	nM	CHEMBL4547034
8.22	IC50	6	nM	CHEMBL4533417
8.22	IC50	6	nM	CHEMBL4483483
8.22	IC50	6	nM	CHEMBL4542437
8.15	IC50	7	nM	CHEMBL4560976
8.15	IC50	7	nM	CHEMBL4548203
8.15	IC50	7	nM	CHEMBL4548014
8.15	IC50	7	nM	CHEMBL4483622
8.15	IC50	7	nM	CHEMBL4526788
8.14	IC50	7.3	nM	CHEMBL4522256
8.10	IC50	8	nM	CHEMBL4467246
8.10	IC50	8	nM	CHEMBL4585012
8.10	IC50	8	nM	CHEMBL4517873
8.10	IC50	8	nM	CHEMBL4580665
8.10	IC50	8	nM	CHEMBL4536020
8.08	IC50	8.3	nM	CHEMBL4545772
8.05	IC50	9	nM	CHEMBL4518612
8.05	IC50	9	nM	CHEMBL4560976
8.05	IC50	9	nM	CHEMBL4587306
8.05	IC50	9	nM	CHEMBL4436264
8.03	Kd	9.445	nM	CHEMBL3752910
8.03	ED50	9.445	nM	CHEMBL3752910
8.00	IC50	10	nM	CHEMBL4539932
8.00	IC50	10	nM	CHEMBL4513843
8.00	IC50	10	nM	CHEMBL4592933
8.00	IC50	10	nM	CHEMBL4536556
8.00	IC50	10.1	nM	CHEMBL4522032
7.96	IC50	11	nM	CHEMBL4547905
7.96	IC50	11	nM	CHEMBL4517506

PubChem BioAssay actives

176 with measured affinity, of 665 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[4-[(1R)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]ethyl]phenyl]sulfonylacetic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0020	uM
2-[4-[(1S)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetic acid	1576916: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 250 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0030	uM
2-[4-[(1R)-1-[(4-chloro-1,6-dimethylindole-2-carbonyl)amino]ethyl]phenyl]sulfonylacetic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0030	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148996: Binding affinity to human PHGDH incubated for 45 mins by Kinobead based pull down assay	kd	0.0094	uM
2-[1-(acetylsulfamoyl)-4-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]piperidin-3-yl]acetic acid	1576911: Inhibition of His6-tagged PHGDH (unknown origin) expressed in Escherichia coli BL21 assessed as effect on NADH fluorescence incubated for 60 mins using 3-PG as substrate in presence of 500 uM NAD+ and PSAT1 by diaphorase and resazurin dye based fluorescence assay	ic50	0.0100	uM
4-[(1R)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0140	uM
2-[4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]phenyl]-2-pyridin-3-ylacetic acid	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.0150	uM
2-[4-[(1R)-1-[(1-methyl-3-phenylpyrazole-5-carbonyl)amino]ethyl]phenyl]sulfonylacetic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0250	uM
3-[4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]phenyl]-3-pyridin-3-ylpropanoic acid	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.0250	uM
4-[(1R)-1-[(3,5-dimethylbenzo[e]indole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0280	uM
4-[(1R)-1-[(4-chloro-1,6-dimethylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0280	uM
ethyl 2-[4-[(1S)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetate	1576924: Inhibition of PHGDH in human MDA-MB-468 cells assessed as reduction in [13C]-serine incubated for 1 hr using [13C]glucose as substrate by LC-MS/MS analysis	ic50	0.0290	uM
2-[4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]phenyl]acetic acid	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.0300	uM
4-[(1R)-1-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0300	uM
4-[(1R)-1-[(4-chloro-6-ethyl-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0300	uM
2-[4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]-2-fluorophenyl]acetic acid	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.0340	uM
4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]-2-fluorobenzoic acid	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.0370	uM
4-[(1R)-1-[(5-chloro-1,6-dimethylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0510	uM
4-[(1R)-1-[(3-methylbenzo[e]indole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0580	uM
4-[(1R)-1-[(6-bromo-5-chloro-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0610	uM
N-[1-[4-(acetylsulfamoyl)phenyl]ethyl]-1-methyl-3-phenylpyrazole-5-carboxamide	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0700	uM
4-[(1R)-1-[(5-chloro-7-methoxy-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0720	uM
4-[(1R)-1-[[4-chloro-6-(difluoromethyl)-1-methylindole-2-carbonyl]amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.0810	uM
N-[(1R)-1-[4-(acetylsulfamoyl)phenyl]ethyl]-1-methyl-3-phenylpyrazole-5-carboxamide	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.1000	uM
(2S)-1-[4-[(1R)-1-[(1-methyl-3-phenylpyrazole-5-carbonyl)amino]ethyl]phenyl]-5-oxopyrrolidine-2-carboxylic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.1000	uM
2-[4-[(1S)-1-[(4-chloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetic acid	1965764: Inhibition of wild type PHGDH (unknown origin) preincubated for 30 mins followed by substrate addition and measured after 5 mins	ic50	0.1000	uM
4-[(1R)-1-[(4-chloro-5-fluoro-7-methoxy-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.1230	uM
4-[3-[(4,5-dichloro-1-methylindole-2-carbonyl)amino]oxetan-3-yl]benzoic acid	1552728: Inhibition of PHGDH (unknown origin) using 140 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.1530	uM
methyl 2-[4-[(1S)-1-[(4-chloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetate	1965734: Inhibition of PHGDH (unknown origin) preincubated for 30 mins followed by substrate addition and measured after 5 mins	ic50	0.1620	uM
(4-methylpiperazine-1-carbothioyl)sulfanyl 4-methylpiperazine-1-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.1700	uM
4-[(1S)-1-[[5-chloro-6-[2-(2-hydroxyethylamino)-2-oxoethoxy]-1H-indole-2-carbonyl]amino]-2-hydroxyethyl]benzoic acid	1426914: Binding affinity to PHGDH (unknown origin) by SPR assay	kd	0.1800	uM
morpholine-4-carbothioylsulfanyl morpholine-4-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.2100	uM
4-[(1S)-1-[[5-chloro-6-[[(5S)-2-oxo-1,3-oxazolidin-5-yl]methoxy]-1H-indole-2-carbonyl]amino]-2-hydroxyethyl]benzoic acid	1552740: Mixed type inhibition of PHGDH (unknown origin) using 3-PG as substrate incubated for 20 mins in presence of , PSAT1, PSPH and varying NAD+ by diaphorase and resazurin dye based fluorescence assay	ki	0.2140	uM
4-[(1R)-1-[(5-chloro-6-methoxy-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1552728: Inhibition of PHGDH (unknown origin) using 140 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.2350	uM
4-[1-[(5-chloro-6-methoxy-1-methylindole-2-carbonyl)amino]-2-hydroxyethyl]benzoic acid	1552728: Inhibition of PHGDH (unknown origin) using 140 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.2350	uM
4-[(1R)-1-[(5-chloro-1-methylindole-2-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.2540	uM
4,5-dichloro-N-[3-[4-[2-(methoxyamino)-2-oxoethyl]phenyl]oxetan-3-yl]-1-methylindole-2-carboxamide	1552728: Inhibition of PHGDH (unknown origin) using 140 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.2870	uM
1-methyl-N-[(1R)-1-[4-(methylsulfonylcarbamoyl)phenyl]ethyl]-3-phenylpyrazole-5-carboxamide	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.3000	uM
thiomorpholine-4-carbothioylsulfanyl thiomorpholine-4-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.3400	uM
phenylcarbamothioylsulfanyl N-phenylcarbamodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.3600	uM
4,5-dichloro-N-[3-[4-[(R)-hydroxy(pyridin-3-yl)methyl]phenyl]oxetan-3-yl]-1-methylindole-2-carboxamide	1552728: Inhibition of PHGDH (unknown origin) using 140 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.3700	uM
3,4-dihydro-1H-isoquinoline-2-carbothioylsulfanyl 3,4-dihydro-1H-isoquinoline-2-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.3800	uM
4-[(1R)-1-[(1-methyl-3-phenylpyrazole-5-carbonyl)amino]ethyl]benzoic acid	1576915: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay	ic50	0.4000	uM
(4-phenylpiperazine-1-carbothioyl)sulfanyl 4-phenylpiperazine-1-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.4100	uM
(2,5-dimethylpyrrolidine-1-carbothioyl)sulfanyl 2,5-dimethylpyrrolidine-1-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.4200	uM
[methyl(phenyl)carbamothioyl]sulfanyl N-methyl-N-phenylcarbamodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.4200	uM
4,5-dichloro-N-[3-[4-[2-(methanesulfonamido)-2-oxoethyl]phenyl]oxetan-3-yl]-1-methylindole-2-carboxamide	1552730: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay	ic50	0.4390	uM
piperidine-1-carbothioylsulfanyl piperidine-1-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.5100	uM
2,4-dihydroxy-N-[(E)-(2-hydroxy-5-nitrophenyl)methylideneamino]benzamide	1802335: PHGDH SPR Assay from Article 10.1016/j.chembiol.2016.11.013: “Rational Design of Selective Allosteric Inhibitors of PHGDH and Serine Synthesis with Anti-tumor Activity.”	ic50	0.5600	uM
(4-cyclohexylpiperazine-1-carbothioyl)sulfanyl 4-cyclohexylpiperazine-1-carbodithioate	1929050: Inhibition of human PHGDH by fluorescence based analysis	ic50	0.5700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, affects cotreatment, increases expression	6
Cyclosporine	affects expression, increases expression	6
bisphenol A	decreases expression, increases expression	5
Aflatoxin B1	affects expression, decreases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cadmium Chloride	decreases reaction, increases abundance, increases expression, affects expression, affects binding (+4 more)	4
deoxynivalenol	decreases expression	3
perfluorooctane sulfonic acid	increases expression	3
Cadmium	decreases reaction, increases abundance, increases palmitoylation, affects reaction, affects binding (+3 more)	3
Cisplatin	decreases expression, increases reaction, increases expression	3
Tunicamycin	affects reaction, increases expression, decreases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
ochratoxin A	decreases expression, increases expression	2
nivalenol	decreases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Arsenic	increases expression, increases ubiquitination, increases abundance	2
Chelating Agents	affects binding, increases expression	2
Copper	affects binding, increases expression	2
Doxorubicin	decreases expression, affects expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
Rotenone	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
beta-Naphthoflavone	increases expression	2
aristolochic acid I	decreases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1

ChEMBL screening assays

118 unique, capped per target: 118 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2318052	Binding	Binding affinity to 3-PGDH in human HEI-193 cells harboring NF2 mutant at 100 uM after 30 mins by SDS-PAGE analysis	Binding partners for curcumin in human schwannoma cells: biologic implications. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1UZ	ICC10-6	Cancer cell line	Male
CVCL_A1VA	ICC10-8	Cancer cell line	Male
CVCL_A1VB	ICC10	Cancer cell line	Male
CVCL_D1YB	Abcam A-549 PHGDH KO	Cancer cell line	Male
CVCL_D2NW	Abcam THP-1 PHGDH KO	Cancer cell line	Male
CVCL_E0K3	Ubigene HeLa PHGDH KO	Cancer cell line	Female
CVCL_E4KQ	ICC11	Cancer cell line	Male
CVCL_TD23	HAP1 PHGDH (-) 1	Cancer cell line	Male
CVCL_TD24	HAP1 PHGDH (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening