PHGDH (phosphoglycerate dehydrogenase)

Gene

• Entrez ID: 26227
• Gene name: Phosphoglycerate dehydrogenase
• Gene symbol: PHGDH
• Synonyms (NCBI Gene): 3-PGDH, 3PGDH, HEL-S-113, NLS, NLS1, PDG, PGAD, PGD, PGDH, PHGDHD, SERA
• Chromosome: 1
• Chromosome location: 1p12
• Summary: 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. Mut

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121907987	G>A	Pathogenic	Missense variant, coding sequence variant
rs121907988	G>A	Pathogenic	Missense variant, coding sequence variant
rs267606947	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs267606948	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs587777774	G>A	Pathogenic	Coding sequence variant, missense variant
rs587777775	G>C	Pathogenic	Coding sequence variant, missense variant
rs730882181	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs769256568	C>T	Pathogenic	Stop gained, coding sequence variant
rs775936961	C>T	Pathogenic	Coding sequence variant, missense variant
rs886041874	T>C	Pathogenic, likely-pathogenic	Splice donor variant
rs1553238760	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1571013274	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020945	hsa-miR-155-5p	Proteomics	18668040
MIRT030040	hsa-miR-26b-5p	Microarray	19088304
MIRT048300	hsa-miR-107	CLASH	23622248
MIRT043507	hsa-miR-331-3p	CLASH	23622248
MIRT039728	hsa-miR-615-3p	CLASH	23622248
MIRT038390	hsa-miR-296-3p	CLASH	23622248
MIRT036377	hsa-miR-1229-3p	CLASH	23622248
MIRT265758	hsa-miR-4519	PAR-CLIP	20371350
MIRT367150	hsa-miR-1178-5p	PAR-CLIP	20371350
MIRT571070	hsa-miR-6847-5p	PAR-CLIP	20371350
MIRT571069	hsa-miR-4257	PAR-CLIP	20371350
MIRT265756	hsa-miR-759	PAR-CLIP	20371350
MIRT332444	hsa-miR-6733-3p	PAR-CLIP	20371350
MIRT265759	hsa-miR-6499-3p	PAR-CLIP	20371350
MIRT367151	hsa-miR-6801-5p	PAR-CLIP	20371350
MIRT265755	hsa-miR-143-5p	PAR-CLIP	20371350
MIRT265760	hsa-miR-6792-5p	PAR-CLIP	20371350
MIRT265758	hsa-miR-4519	PAR-CLIP	20371350
MIRT367150	hsa-miR-1178-5p	PAR-CLIP	20371350
MIRT571070	hsa-miR-6847-5p	PAR-CLIP	20371350
MIRT571069	hsa-miR-4257	PAR-CLIP	20371350
MIRT265756	hsa-miR-759	PAR-CLIP	20371350
MIRT332444	hsa-miR-6733-3p	PAR-CLIP	20371350
MIRT265759	hsa-miR-6499-3p	PAR-CLIP	20371350
MIRT367151	hsa-miR-6801-5p	PAR-CLIP	20371350
MIRT265755	hsa-miR-143-5p	PAR-CLIP	20371350
MIRT265760	hsa-miR-6792-5p	PAR-CLIP	20371350
MIRT1231364	hsa-miR-128	CLIP-seq
MIRT1231365	hsa-miR-1293	CLIP-seq
MIRT1231366	hsa-miR-137	CLIP-seq
MIRT1231367	hsa-miR-27a	CLIP-seq
MIRT1231368	hsa-miR-27b	CLIP-seq
MIRT1231369	hsa-miR-4483	CLIP-seq
MIRT1231370	hsa-miR-4659a-3p	CLIP-seq
MIRT1231371	hsa-miR-4659b-3p	CLIP-seq
MIRT1231372	hsa-miR-4718	CLIP-seq
MIRT1231373	hsa-miR-483-5p	CLIP-seq
MIRT1231374	hsa-miR-629	CLIP-seq
MIRT1231366	hsa-miR-137	CLIP-seq
MIRT2295349	hsa-miR-1471	CLIP-seq
MIRT2295350	hsa-miR-3157-5p	CLIP-seq
MIRT2295351	hsa-miR-4690-3p	CLIP-seq
MIRT1231372	hsa-miR-4718	CLIP-seq
MIRT2295352	hsa-miR-4747-3p	CLIP-seq
MIRT1231373	hsa-miR-483-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HOXA10	Repression	19778996
SP1	Activation	18378410

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004617	Function	Phosphoglycerate dehydrogenase activity	IBA
GO:0004617	Function	Phosphoglycerate dehydrogenase activity	IEA
GO:0004617	Function	Phosphoglycerate dehydrogenase activity	TAS	8758134
GO:0005515	Function	Protein binding	IPI	25036637, 33961781, 35271311
GO:0005829	Component	Cytosol	TAS
GO:0006541	Process	Glutamine metabolic process	IEA
GO:0006544	Process	Glycine metabolic process	IEA
GO:0006563	Process	L-serine metabolic process	IEA
GO:0006564	Process	L-serine biosynthetic process	IEA
GO:0006566	Process	Threonine metabolic process	IEA
GO:0007420	Process	Brain development	TAS	8758134
GO:0008652	Process	Amino acid biosynthetic process	IEA
GO:0009055	Function	Electron transfer activity	TAS	8758134
GO:0009448	Process	Gamma-aminobutyric acid metabolic process	IEA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016616	Function	Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA
GO:0019530	Process	Taurine metabolic process	IEA
GO:0021510	Process	Spinal cord development	IEA
GO:0021782	Process	Glial cell development	IEA
GO:0021915	Process	Neural tube development	IEA
GO:0022008	Process	Neurogenesis	IEA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IEA
GO:0031175	Process	Neuron projection development	IEA
GO:0051287	Function	NAD binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 19199708, 20458337, 23533145
GO:0070314	Process	G1 to G0 transition	IEA

Other IDs

• MIM: 606879
• HGNC: 8923
• e!Ensembl: ENSG00000092621

Protein

• UniProt ID: O43175
• Protein name: D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37)
• Protein 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 re
• PDB: 2G76, 5N53, 5N6C, 5NZO, 5NZP, 5NZQ, 5OFM, 5OFV, 5OFW, 6CWA, 6PLF, 6PLG, 6RIH, 6RJ2, 6RJ3, 6RJ5, 6RJ6, 7CVP, 7DKM, 7EWH, 7VA1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00389	2-Hacid_dh	9 → 317	D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain	Domain
  PF02826	2-Hacid_dh_C	111 → 285	D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain	Domain

• Sequence:

  MAFANLRKVLISDSLDPCCRKILQDGGLQVVEKQNLSKEELIAELQDCEGLIVRSATKVT
  ADVINAAEKLQVVGRAGTGVDNVDLEAATRKGILVMNTPNGNSLSAAELTCGMIMCLARQ
  IPQATASMKDGKWERKKFMGTELNGKTLGILGLGRIGREVATRMQSFGMKTIGYDPIISP
  EVSASFGVQQLPLEEIWPLCDFITVHTPLLPSTTGLLNDNTFAQCKKGVRVVNCARGGIV
  DEGALLRALQSGQCAGAALDVFTEEPPRDRALVDHENVISCPHLGASTKEAQSRCGEEIA
  VQFVDMVKGKSLTGVVNAQALTSAFSPHTKPWIGLAEALGTLMRAWAGSPKGTIQVITQG
  TSLKNAGNCLSPAVIVGLLKEASKQADVNLVNAKLLVKEAGLNVTTSHSPAAPGEQGFGE
  CLLAVALAGAPYQAVGLVQGTTPVLQGLNGAVFRPEVPLRRDLPLLLFRTQTSDPAMLPT
  MIGLLAEAGVRLLSYQTSLVSDGETWHVMGISSLLPSLEAWKQHVTEAFQFHF

• Sequence length: 533

Pathways

KEGG:

Glycine, serine and threonine metabolism
Cysteine and methionine metabolism
Metabolic pathways
Carbon metabolism
Biosynthesis of amino acids

Reactome:

Serine biosynthesis

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Epileptic encephalopathy	Likely pathogenic; Pathogenic	rs886041874	RCV000415201
Neu-Laxova syndrome 1	Likely pathogenic; Pathogenic	rs2101221217, rs766427173, rs951372478, rs1331155296, rs749134845, rs587777774, rs121907987, rs267606949, rs267606948, rs149128100, rs2464204681, rs886041874, rs2464160831, rs2464159619, rs2464187735, rs769256568, rs1571013274, rs1224279673, rs1652276195, rs1651455730	RCV005014544 RCV001420191 RCV003339747 RCV005006219 RCV005016804 RCV000144444 RCV002482824 RCV000675113 RCV000850583 RCV003882739 RCV005008776 RCV003340589 RCV003338496 RCV003327315 RCV005014824 RCV005013104 RCV000625901 RCV003338892 RCV002497363 RCV004798890 RCV003339553
PHGDH deficiency	Likely pathogenic; Pathogenic	rs2101195348, rs2101225889, rs979237677, rs1652150288, rs2101221217, rs1652224758, rs766427173, rs951372478, rs781273456, rs1418800829, rs1331155296, rs758517215, rs2101205361, rs1302054606, rs1651264976, rs1650717188, rs2101220673, rs2101160478, rs1217925678, rs1650721954, rs2101216259, rs2101136632, rs750368565, rs1341545186, rs1489498331, rs2101224520, rs2101155246, rs2101198087, rs2101160151, rs1215699403, rs749134845, rs779159301, rs121907987, rs730882181, rs267606949, rs267606948, rs1652276791, rs2464209193, rs2464112148, rs2464161009, rs2464203249, rs2464209283, rs149128100, rs2464080054, rs1557978852, rs2464204681, rs2464111708, rs886041874, rs2464170715, rs2464114660, rs2464205035, rs2464155152, rs2464079458, rs2464159619, rs2464195486, rs2464112014, rs587615037, rs1433746199, rs2464203420, rs2464115103, rs2464034378, rs2464187735, rs1651455730, rs1650721119, rs1651447610, rs2464114425, rs1282624852, rs2464092239, rs775936961, rs769256568, rs1571013274, rs1398758559, rs1224279673, rs1652276195, rs1650723432, rs1651881638	RCV001377803 RCV001379151 RCV001383227 RCV001382946 RCV001388882 RCV001389517 RCV002554083 RCV001806759 RCV001895959 RCV001928342 RCV001930502 RCV001995115 RCV001950791 RCV001998760 RCV002008301 RCV001898184 RCV002048610 RCV002002351 RCV002038316 RCV001916252 RCV002007439 RCV001939555 RCV001941620 RCV001951277 RCV001951038 RCV001878603 RCV001939702 RCV001958615 RCV002033034 RCV001972772 RCV001915700 RCV002015813 RCV003072758 RCV000004071 RCV000004073 RCV000004074 RCV000004075 RCV003093173 RCV002648196 RCV002644156 RCV002721411 RCV002824507 RCV002833671 RCV002867105 RCV002895129 RCV002947840 RCV003000029 RCV003012523 RCV003038907 RCV001197384 RCV003502859 RCV003503530 RCV003504503 RCV003503307 RCV003609358 RCV003609409 RCV003610170 RCV003610312 RCV003610330 RCV003610451 RCV003608906 RCV003608933 RCV003608841 RCV003609037 RCV003610518 RCV003610567 RCV003610730 RCV003826176 RCV003882749 RCV003989165 RCV000625821 RCV000798475 RCV001380452 RCV001052239 RCV001037635 RCV001172237 RCV001172238 RCV001245690 RCV001239074
PHGDH-related disorder	Likely pathogenic; Pathogenic	rs121907987	RCV004757095
See cases	Likely pathogenic; Pathogenic	rs121907987	RCV002251869
Seizure	Likely pathogenic; Pathogenic	rs886041874	RCV000415201

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign; Likely benign	rs146953046, rs371736796	RCV005901141 RCV005910745
Cervical cancer	Benign; Likely benign; Conflicting classifications of pathogenicity	rs146953046, rs139063843, rs139827025	RCV005901144 RCV005901740 RCV005911686
Cholangiocarcinoma	Benign; Likely benign	rs146953046	RCV005901153
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	rs139063843	RCV005901741
Colon adenocarcinoma	Conflicting classifications of pathogenicity	rs147866831	RCV005891478
Familial cancer of breast	Benign; Likely benign	rs146953046, rs371736796	RCV005901140 RCV005910744
Gastric cancer	Benign; Likely benign	rs146953046	RCV005901148
Hepatocellular carcinoma	Benign	rs1557967706	RCV005871343
Lung cancer	Benign; Likely benign; Conflicting classifications of pathogenicity	rs146953046, rs139827025	RCV005901154 RCV005911688
Lymphoma	Benign; Likely benign	rs146953046	RCV005901149
Malignant tumor of esophagus	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	rs143217390, rs146953046, rs139063843	RCV005924218 RCV005901142 RCV005901739
Neurometabolic disorder due to serine deficiency	Conflicting classifications of pathogenicity	rs121907988	RCV005632162
Nonpapillary renal cell carcinoma	Benign; Likely benign	rs146953046, rs543703	RCV005901143 RCV005905933
Ovarian cancer	Benign; Likely benign	rs146953046	RCV005901145
Ovarian serous cystadenocarcinoma	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	rs146953046, rs139827025	RCV005925702 RCV005901150 RCV005911687
Sarcoma	Benign; Likely benign	rs146953046	RCV005901147
Thymoma	Benign; Likely benign	rs146953046	RCV005901152
Thyroid cancer, nonmedullary, 1	Uncertain significance	rs146398308	RCV005925470
Uterine carcinosarcoma	Benign; Likely benign	rs146953046	RCV005901151
Uterine corpus endometrial carcinoma	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	rs146953046, rs139827025, rs371736796	RCV005925703 RCV005901155 RCV005911689 RCV005910746
Uveal melanoma	Benign; Likely benign	rs146953046	RCV005901146

Associations from Text Mining
Disease Name	Relationship Type	References
AA amyloidosis	Associate	30662332
Acidosis	Associate	39900217
Adenocarcinoma Follicular	Associate	27277113
Altitude Sickness	Associate	35668171
Alzheimer Disease	Stimulate	32220323
Alzheimer Disease	Associate	35508106
Amyotrophic lateral sclerosis 1	Associate	33311513
Aneurysm Ruptured	Stimulate	32589050
Brain Neoplasms	Associate	30250195
Breast Neoplasms	Associate	18703606, 21437235, 24979213, 25406093, 25496516, 30250195, 33112838, 36782224, 36925195, 8955125
Breast Neoplasms	Stimulate	21804546
Carcinogenesis	Associate	21804546, 36314841, 37327589
Carcinoma	Associate	27277113
Carcinoma Ductal	Associate	25053597
Carcinoma Embryonal	Associate	30250195
Carcinoma Hepatocellular	Associate	30176945, 31615983, 36314841
Carcinoma Lobular	Associate	25053597
Carcinoma Medullary	Associate	27277113
Carcinoma Pancreatic Ductal	Associate	36951402
Cardiomyopathy Dilated	Associate	35728000
Chromosome 1 monosomy 1p	Associate	30726924
Cognition Disorders	Associate	32220323
Colitis Ulcerative	Associate	39596612
Colorectal Neoplasms	Associate	34720086, 36707056, 37544925, 39670663, 39900217
Colorectal Neoplasms	Stimulate	38317509
Corneal Dystrophy Crystalline of Schnyder	Associate	16163269
Drug Related Side Effects and Adverse Reactions	Associate	36144843
Endometrial Neoplasms	Associate	32894095, 36803157, 39326337
Essential Hypertension	Associate	40118787
Genetic Diseases Inborn	Associate	32077105, 37812589
Glioblastoma	Associate	32203214, 37823569, 38098117
Glioma	Associate	30726924
Glucosephosphate Dehydrogenase Deficiency	Associate	30017355
Gonadal Dysgenesis 46 XY	Associate	19513096
Gonadoblastoma	Associate	19513096
Growth Disorders	Associate	37812589
Hypertension	Associate	40118787
Hypoxia	Associate	30867055
Hypoxia	Stimulate	32203214, 37823569
Idiopathic Pulmonary Fibrosis	Stimulate	27836973
Immunologic Deficiency Syndromes	Inhibit	37650587
Insulin Resistance	Associate	36782224
Intellectual Disability	Associate	37812589
Leukemia Myeloid Acute	Associate	35143932
Liver Neoplasms	Associate	30176945
Lung Neoplasms	Associate	29569651
Lupus Erythematosus Systemic	Inhibit	36053251
Lymphoma	Associate	35316216
Lymphoma Mantle Cell	Associate	27277113
Lymphoma Mantle Cell	Stimulate	27277113
Malignant mesenchymal tumor	Stimulate	37192160
Melanoma	Associate	21804546, 25404730, 25406093, 28500236, 33099398
Metabolic Syndrome	Associate	34887389
Mitochondrial Diseases	Associate	30017355, 30662332
Multiple Acyl Coenzyme A Dehydrogenase Deficiency	Associate	34066864
Myocardial Infarction	Associate	33413638
Neoplasm Metastasis	Associate	36951402
Neoplasms	Inhibit	15740626, 35931688
Neoplasms	Associate	21804546, 25053597, 25406093, 26026368, 29569651, 29925909, 30250195, 32420915, 32620753, 33503424, 34971423, 36314841, 36615660, 36707056, 36803157, 37192160, 37299011, 37327589, 38317509
Neoplasms	Stimulate	24247658, 36144843
Neoplasms Adipose Tissue	Associate	26110892
Neu Laxova syndrome	Associate	25152457, 30348640, 32077105, 37650587
Neuroblastoma	Associate	34192988, 36319669
Obesity	Associate	33413638
Ophthalmoplegia painful	Associate	38233749
Osler rendu weber syndrome 2	Associate	28250457
Osteoarthritis	Associate	37723556
Osteosarcoma	Associate	33503424
Ovarian Diseases	Associate	37533289
Pancreatic Neoplasms	Associate	31706267
Parkinson Disease	Associate	32420915
Phosphoglycerate Dehydrogenase Deficiency	Inhibit	30017355
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	37280363
Primary hyperoxaluria type 1	Associate	32077105, 34066864, 37812589
Retinal Diseases	Associate	33758422
Sarcoma Ewing	Associate	28720588
Scleroderma Systemic	Inhibit	36053251
Stomach Neoplasms	Associate	36144843, 37192160
Thyroid Cancer Papillary	Stimulate	27277113
Thyroid Cancer Papillary	Associate	27277113
Thyroid Neoplasms	Associate	27277113
Triple Negative Breast Neoplasms	Associate	24390667
Triple Negative Breast Neoplasms	Stimulate	26026368
Urinary Bladder Neoplasms	Associate	34418989, 36147463
Uterine Cervical Neoplasms	Associate	24247658