BPGM

Summary

BPGM (bisphosphoglycerate mutase, HGNC:1093) is a protein-coding gene on chromosome 7q33, encoding Bisphosphoglycerate mutase (P07738). Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG).

2,3-diphosphoglycerate (2,3-DPG) is a small molecule found at high concentrations in red blood cells where it binds to and decreases the oxygen affinity of hemoglobin. This gene encodes a multifunctional enzyme that catalyzes 2,3-DPG synthesis via its synthetase activity, and 2,3-DPG degradation via its phosphatase activity. The enzyme also has phosphoglycerate phosphomutase activity. Deficiency of this enzyme increases the affinity of cells for oxygen. Mutations in this gene result in hemolytic anemia. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 669 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic anemia due to diphosphoglycerate mutase deficiency (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 61 total — 5 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_001724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1093
Approved symbol	BPGM
Name	bisphosphoglycerate mutase
Location	7q33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172331
Ensembl biotype	protein_coding
OMIM	613896
Entrez	669

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000344924, ENST00000393132, ENST00000418040, ENST00000443095, ENST00000904928, ENST00000904929, ENST00000904930, ENST00000919676, ENST00000919677, ENST00000919678, ENST00000950393, ENST00000950394

RefSeq mRNA: 3 — MANE Select: NM_001724 NM_001293085, NM_001724, NM_199186

CCDS: CCDS5833

Canonical transcript exons

ENST00000344924 — 3 exons

Exon	Start	End
ENSE00001242893	134661447	134662108
ENSE00001853980	134646853	134646937
ENSE00003843419	134678853	134679816

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.3251 / max 2700.5355, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81265	22.1657	1642
81264	11.0309	1756
81266	0.1286	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.54	gold quality
oocyte	CL:0000023	99.49	gold quality
amniotic fluid	UBERON:0000173	97.65	gold quality
trabecular bone tissue	UBERON:0002483	96.36	gold quality
placenta	UBERON:0001987	94.06	gold quality
monocyte	CL:0000576	93.83	gold quality
bone marrow	UBERON:0002371	93.70	gold quality
stromal cell of endometrium	CL:0002255	93.49	gold quality
mononuclear cell	CL:0000842	93.32	gold quality
leukocyte	CL:0000738	92.63	gold quality
bone marrow cell	CL:0002092	92.33	gold quality
ganglionic eminence	UBERON:0004023	90.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.93	gold quality
blood	UBERON:0000178	89.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.74	gold quality
islet of Langerhans	UBERON:0000006	87.73	gold quality
sperm	CL:0000019	87.72	gold quality
gingiva	UBERON:0001828	87.35	gold quality
spinal cord	UBERON:0002240	87.33	gold quality
muscle of leg	UBERON:0001383	87.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.02	gold quality
cortical plate	UBERON:0005343	86.85	gold quality
cingulate cortex	UBERON:0003027	86.80	gold quality
anterior cingulate cortex	UBERON:0009835	86.76	gold quality
tibial nerve	UBERON:0001323	86.74	gold quality
prefrontal cortex	UBERON:0000451	86.72	gold quality
gastrocnemius	UBERON:0001388	86.69	gold quality
metanephros cortex	UBERON:0010533	86.69	gold quality
adenohypophysis	UBERON:0002196	86.00	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	1164.16
E-MTAB-9221	yes	784.70
E-MTAB-10042	yes	300.51
E-CURD-112	yes	48.73
E-MTAB-9388	yes	8.60
E-HCAD-9	yes	8.33
E-HCAD-10	yes	7.39
E-MTAB-9067	yes	6.76
E-MTAB-9467	yes	4.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting BPGM, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-876-3P	98.76	68.23	945

Literature-anchored findings (GeneRIF, showing 5)

• bisphosphoglycerate mutase crystallographic structure (PMID:15258155)
• analysis of histidine phosphorylation in human bisphosphoglycerate mutase (PMID:17052986)
• 1.94 A resolution X-ray structure of bisphosphoglycerate mutase is presented, focusing on the dynamic nature of key ligand-binding residues and their interaction with the inhibitor citrate (PMID:21045285)
• Dysregulation of bisphosphoglycerate mutase during in vitro maturation of oocytes. (PMID:34052998)
• Heterozygosity for bisphosphoglycerate mutase deficiency expressing clinically as congenital erythrocytosis: A case series and literature review. (PMID:36177683)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bpgm	ENSDARG00000070826
mus_musculus	Bpgm	ENSMUSG00000038871
rattus_norvegicus	Bpgm	ENSRNOG00000010133
drosophila_melanogaster	CG7059	FBGN0038957

Paralogs (3): PGAM2 (ENSG00000164708), PGAM1 (ENSG00000171314), PGAM4 (ENSG00000226784)

Protein

Protein identifiers

Bisphosphoglycerate mutase — P07738 (reviewed: P07738)

Alternative names: 2,3-bisphosphoglycerate mutase, erythrocyte, 2,3-bisphosphoglycerate synthase, 2,3-diphosphoglycerate mutase, BPG-dependent PGAM

All UniProt accessions (3): P07738, A0A024R782, C9JH23

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.11) activity.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed in red blood cells. Expressed in non-erythroid cells of the placenta; present in the syncytiotrophoblast layer of the placental villi at the feto-maternal interface (at protein level).

Post-translational modifications. Glycation of Lys-159 in diabetic patients inactivates the enzyme.

Disease relevance. Erythrocytosis, familial, 8 (ECYT8) [MIM:222800] An autosomal recessive disorder characterized by elevated serum hemoglobin and hematocrit, and biphosphoglycerate mutase deficiency. ECYT8 affected individuals manifest hemolytic anemia and splenomegaly. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. At alkaline pH BPGM favors the synthase reaction; however, at lower pH the phosphatase reaction is dominant. Inhibited by citrate.

Similarity. Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.

RefSeq proteins (3): NP_001280014, NP_001715, NP_954655 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001345	PG/BPGM_mutase_AS	Active_site
IPR005952	Phosphogly_mut1	Family
IPR013078	His_Pase_superF_clade-1	Family
IPR029033	His_PPase_superfam	Homologous_superfamily

Pfam: PF00300

Enzyme classification (BRENDA):

• EC 5.4.2.4 — Bisphosphoglycerate mutase (BRENDA: 5 organisms, 11 substrates, 17 inhibitors, 22 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2,3-DIPHOSPHOGLYCERATE	0.0024–0.583	10
1,3-DIPHOSPHOGLYCERATE	0.0005–0.0036	5
2,3-BISPHOSPHO-D-GLYCERATE	0.042–0.2253	5

Catalyzed reactions (Rhea), 2 shown:

• (2R)-2-phosphoglycerate = (2R)-3-phosphoglycerate (RHEA:15901)
• (2R)-3-phospho-glyceroyl phosphate = (2R)-2,3-bisphosphoglycerate + H(+) (RHEA:17765)

UniProt features (55 total): helix 15, site 10, strand 9, binding site 7, glycosylation site 6, active site 2, modified residue 2, sequence variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
7THI	X-RAY DIFFRACTION	1.33
2HHJ	X-RAY DIFFRACTION	1.5
9SD0	X-RAY DIFFRACTION	1.65
2H4X	X-RAY DIFFRACTION	1.85
8X2S	X-RAY DIFFRACTION	1.9
9SCV	X-RAY DIFFRACTION	1.9
3NFY	X-RAY DIFFRACTION	1.94
2A9J	X-RAY DIFFRACTION	2
2F90	X-RAY DIFFRACTION	2
2H4Z	X-RAY DIFFRACTION	2
2H52	X-RAY DIFFRACTION	2
9SCY	X-RAY DIFFRACTION	2
7N3R	X-RAY DIFFRACTION	2.25
9SCX	X-RAY DIFFRACTION	2.35
7N3S	X-RAY DIFFRACTION	2.48
1T8P	X-RAY DIFFRACTION	2.5
9SD1	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07738-F1	95.81	0.94

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 (12): 29 (not glycated); 46 (not glycated); 143 (not glycated); 181 (not glycated); 188 (transition state stabilizer); 246 (not glycated); 247 (not glycated); 253 (not glycated); 258 (not glycated); 11 (tele-phosphohistidine intermediate); 259 (not glycated); 89 (proton donor/acceptor)

Ligand- & substrate-binding residues (7): 189–190; 10–17; 23–24; 62; 89–92; 100; 116–117

Post-translational modifications (2): 2, 122

Glycosylation sites (6): 3, 5, 18, 43, 159, 197

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70171	Glycolysis

MSigDB gene sets: 240 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, TSENG_IRS1_TARGETS_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP

GO Biological Process (11): carbohydrate metabolic process (GO:0005975), glycolytic process (GO:0006096), respiratory gaseous exchange by respiratory system (GO:0007585), oxygen transport (GO:0015671), cellular response to stress (GO:0033554), defense response to protozoan (GO:0042832), erythrocyte development (GO:0048821), establishment of blood-brain barrier (GO:0060856), neuroinflammatory response (GO:0150076), carbohydrate derivative catabolic process (GO:1901136), nucleoside phosphate metabolic process (GO:0006753)

GO Molecular Function (7): bisphosphoglycerate mutase activity (GO:0004082), phosphoglycerate mutase activity (GO:0004619), hydrolase activity (GO:0016787), catalytic activity (GO:0003824), protein binding (GO:0005515), isomerase activity (GO:0016853), intramolecular phosphotransferase activity (GO:0016868)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intramolecular phosphotransferase activity	2
catalytic activity	2
primary metabolic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
multicellular organismal process	1
gas transport	1
response to stress	1
cellular response to stimulus	1
response to protozoan	1
defense response to other organism	1
erythrocyte differentiation	1
myeloid cell development	1
central nervous system development	1
cell development	1
inflammatory response	1
catabolic process	1
carbohydrate derivative metabolic process	1
organophosphate metabolic process	1
nucleobase-containing small molecule metabolic process	1
molecular_function	1
binding	1
intramolecular transferase activity	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1802 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPGM	GYPB	P06028	548
BPGM	TPI1	P00938	527
BPGM	ENO3	P13929	523
BPGM	J3KPS3	J3KPS3	516
BPGM	FECH	P22830	511
BPGM	ALDOA	P04075	507
BPGM	PGK1	P00558	501
BPGM	ENO1	P06733	498
BPGM	HBB	P02023	484
BPGM	GYPA	P02724	481
BPGM	GALM	Q96C23	477
BPGM	HMGXB4	Q9UGU5	475
BPGM	HBA1	P01922	472
BPGM	EPB42	P16452	470
BPGM	PFKL	P17858	464

IntAct

34 interactions, top by confidence:

A	B	Type	Score
PGAM2	BPGM	psi-mi:“MI:0914”(association)	0.740
BPGM	PGAM2	psi-mi:“MI:0915”(physical association)	0.740
BPGM	FLYWCH2	psi-mi:“MI:0914”(association)	0.530
NCF2	BPGM	psi-mi:“MI:0914”(association)	0.530
Zap70	BPGM	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
BPGM	ATP4B	psi-mi:“MI:0915”(physical association)	0.370
BPGM	CEL	psi-mi:“MI:0915”(physical association)	0.370
EGR2	BPGM	psi-mi:“MI:0915”(physical association)	0.370
NEK3	BPGM	psi-mi:“MI:0915”(physical association)	0.370
BPGM	ATF6	psi-mi:“MI:0915”(physical association)	0.370
BPGM	EHD2	psi-mi:“MI:0915”(physical association)	0.370
CTNNBIP1	TK2	psi-mi:“MI:0914”(association)	0.350
NCF2	TBC1D4	psi-mi:“MI:0914”(association)	0.350
IQCF1	TBC1D4	psi-mi:“MI:0914”(association)	0.350
PPM1B	BPGM	psi-mi:“MI:0914”(association)	0.350
BOD1	BPGM	psi-mi:“MI:0914”(association)	0.350
CHPT1	BPGM	psi-mi:“MI:0914”(association)	0.350
SPANXN5	USP1	psi-mi:“MI:0914”(association)	0.350
SPANXB1	PAPSS2	psi-mi:“MI:0914”(association)	0.350
BOD1L2	BPGM	psi-mi:“MI:0914”(association)	0.350
ARHGEF4	BPGM	psi-mi:“MI:0914”(association)	0.350
BPGM	PGAM1	psi-mi:“MI:0914”(association)	0.350
BPGM	GRB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): BPGM (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), HDLBP (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), NRBP1 (Affinity Capture-MS), MRGBP (Affinity Capture-MS), KLF16 (Affinity Capture-MS), BPGM (Affinity Capture-MS), KLF16 (Affinity Capture-MS), BPGM (Affinity Capture-MS), BPGM (Affinity Capture-MS), BPGM (Affinity Capture-MS), NRBP1 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), BPGM (Affinity Capture-MS)

ESM2 similar proteins: A0RE96, A1BE55, A1R083, A6L9K8, A6LUA1, A7GPN5, A7I8A7, A9KN01, A9VFW9, B0K4E2, B0KBW9, B2RHB7, B3DZZ7, B3EFK8, B4RIY7, B4SEI0, B4U616, B5EC38, B5Y7Q7, B7H7P4, B7HS46, B7IX37, B7J2L3, B7JPK2, B9J102, C1EUQ5, C3LIE5, C3PAW8, O51602, P07738, P07952, Q2FTH0, Q2Y9Z7, Q39V40, Q3JBA8, Q4R6L7, Q5F7C0, Q5LAT7, Q63B92, Q64R85

Diamond homologs: A1K9B9, A1R083, A1TTW5, A1UZX9, A1VKR6, A1WBJ3, A2S625, A3MQ23, A3N5B0, A3NR09, A4JI45, A4SDM0, A6T6I3, A6VLV0, A9BUZ3, A9IFJ0, A9KN01, B0K4E2, B0KBW9, B0RQR7, B0U2F2, B1GZZ1, B1JZ61, B1Y3R5, B1YNA6, B2AGP7, B2I4U0, B2JC95, B2S101, B2SRM8, B2SX15, B2VBS6, B3DZZ7, B3EN99, B3QPN8, B3QVL0, B4EA64, B4RZM6, B4S616, B4SEI0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	34
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
12091	NM_001724.5(BPGM):c.268C>T (p.Arg90Cys)	Pathogenic
12092	NM_001724.5(BPGM):c.61del (p.Arg21fs)	Pathogenic
685463	GRCh37/hg19 7q33(chr7:134341813-134366849)x1	Pathogenic
973177	NM_001724.5(BPGM):c.185G>A (p.Arg62Gln)	Pathogenic
973178	NM_001724.5(BPGM):c.269G>A (p.Arg90His)	Pathogenic

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
7:134646934:GCAG:G	donor_gain	1.0000
7:134646935:CAGGT:C	donor_loss	1.0000
7:134646936:AGGT:A	donor_loss	1.0000
7:134646937:GGTG:G	donor_loss	1.0000
7:134661446:GAT:G	acceptor_gain	1.0000
7:134677399:T:G	donor_gain	1.0000
7:134678843:T:A	acceptor_gain	1.0000
7:134678848:A:AG	acceptor_gain	1.0000
7:134678850:CAGG:C	acceptor_loss	1.0000
7:134678851:A:AG	acceptor_gain	1.0000
7:134678851:A:T	acceptor_loss	1.0000
7:134678852:G:GA	acceptor_gain	1.0000
7:134678852:GGT:G	acceptor_gain	1.0000
7:134646933:TGCAG:T	donor_gain	0.9900
7:134646934:GCAGG:G	donor_gain	0.9900
7:134646935:CAG:C	donor_gain	0.9900
7:134646936:AG:A	donor_gain	0.9900
7:134646937:GG:G	donor_gain	0.9900
7:134646938:G:GG	donor_gain	0.9900
7:134661102:GAC:G	donor_gain	0.9900
7:134661441:TTCTA:T	acceptor_loss	0.9900
7:134661442:TCTA:T	acceptor_loss	0.9900
7:134661443:CTA:C	acceptor_loss	0.9900
7:134661444:TAGAT:T	acceptor_loss	0.9900
7:134661445:A:AG	acceptor_gain	0.9900
7:134661445:A:AT	acceptor_loss	0.9900
7:134661446:G:GG	acceptor_gain	0.9900
7:134661446:GATGT:G	acceptor_gain	0.9900
7:134661985:G:GT	donor_gain	0.9900
7:134662033:G:GT	donor_gain	0.9900

AlphaMissense

1707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:134661571:T:C	F22L	0.998
7:134661573:T:A	F22L	0.998
7:134661573:T:G	F22L	0.998
7:134661773:A:T	E89V	0.998
7:134661577:A:C	S24R	0.997
7:134661579:C:A	S24R	0.997
7:134661579:C:G	S24R	0.997
7:134661580:T:A	W25R	0.997
7:134661580:T:C	W25R	0.997
7:134661760:T:A	W85R	0.996
7:134661760:T:C	W85R	0.996
7:134661785:G:A	G93E	0.996
7:134661785:G:T	G93V	0.996
7:134662078:A:C	S191R	0.996
7:134662080:C:A	S191R	0.996
7:134662080:C:G	S191R	0.996
7:134661572:T:C	F22S	0.995
7:134661582:G:C	W25C	0.995
7:134661582:G:T	W25C	0.995
7:134661784:G:T	G93W	0.995
7:134661850:T:A	W115R	0.995
7:134661850:T:C	W115R	0.995
7:134661695:C:T	S63F	0.994
7:134661774:G:C	E89D	0.994
7:134661774:G:T	E89D	0.994
7:134662077:T:A	N190K	0.994
7:134662077:T:G	N190K	0.994
7:134661578:G:T	S24I	0.993
7:134661680:C:T	S58F	0.993
7:134661854:G:C	R116T	0.993

dbSNP variants (sampled 300 via entrez): RS1000046485 (7:134660947 G>C), RS1000314010 (7:134668663 T>C,G), RS1000349065 (7:134676447 A>G), RS1000407549 (7:134675071 G>T), RS1000712343 (7:134677461 A>C), RS1000743289 (7:134676971 C>A), RS1000869545 (7:134670316 A>T), RS1000920952 (7:134670195 C>T), RS1001018939 (7:134656207 C>G,T), RS1001117219 (7:134663404 G>A,C), RS1001137489 (7:134675840 T>A,C), RS1001148164 (7:134663105 A>C,G), RS1001189728 (7:134675391 T>C), RS1001261924 (7:134662649 C>T), RS1001327976 (7:134649190 T>C)

Disease associations

OMIM: gene MIM:613896 | disease phenotypes: MIM:222800

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic anemia due to diphosphoglycerate mutase deficiency	Strong	Autosomal recessive

Mondo (1): hemolytic anemia due to diphosphoglycerate mutase deficiency (MONDO:0009113)

Orphanet (1): Hemolytic anemia due to diphosphoglycerate mutase deficiency (Orphanet:714)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001744	Splenomegaly
HP:0001899	Increased hematocrit
HP:0001900	Increased circulating hemoglobin concentration
HP:0001901	Polycythemia
HP:0003581	Adult onset
HP:6000557	Reduced erythrocyte bisphosphoglycerate mutase activity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2685	Blood protein levels	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169112 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.72	IC50	19	nM	CHEMBL5205844
7.68	IC50	21	nM	CHEMBL5208793
7.30	IC50	50	nM	CHEMBL5189697
7.04	IC50	92	nM	CHEMBL5195133
6.86	IC50	138	nM	CHEMBL5170142
6.80	IC50	159	nM	CHEMBL5183929

PubChem BioAssay actives

6 with measured affinity, of 6 total; 6 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
1-[[5-[6-(4,7-difluoro-2H-benzotriazol-5-yl)-2-pyridinyl]-4-methyl-1,3-thiazol-2-yl]methoxy]-2-methylpropan-2-ol	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.0190	uM
5-[6-(4,7-difluoro-2H-benzotriazol-5-yl)-2-pyridinyl]-4-methyl-2-[(5-methylpyrimidin-2-yl)oxymethyl]-1,3-thiazole	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.0210	uM
methyl N-[[5-[2-(4,7-difluoro-2H-benzotriazol-5-yl)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]methyl]carbamate	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.0500	uM
5-[2-(7-fluoro-2H-benzotriazol-5-yl)-1,3-thiazol-4-yl]-4-methyl-2-(pyridazin-3-yloxymethyl)-1,3-thiazole	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.0920	uM
3-[4-[6-[4-methyl-2-(pyrimidin-2-yloxymethyl)-1,3-thiazol-5-yl]-2-pyridinyl]phenyl]-4H-1,2,4-oxadiazol-5-one	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.1380	uM
2,3,6-trifluoro-4-[4-[4-methyl-2-(pyrimidin-2-yloxymethyl)-1,3-thiazol-5-yl]-1,3-thiazol-2-yl]phenol	1880697: Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	ic50	0.1590	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Valproic Acid	affects cotreatment, increases expression, affects expression	3
bisphenol A	decreases expression, increases methylation	2
Air Pollutants	increases abundance, decreases expression	2
Okadaic Acid	increases expression	2
dicrotophos	decreases expression	1
daidzein	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
decabromobiphenyl ether	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
alpha-naphthoflavone	decreases expression, decreases reaction, increases expression	1
daidzin	affects cotreatment, affects expression	1
arsenite	affects binding, increases reaction	1
zinc chromate	increases abundance, increases expression	1
genistin	affects cotreatment, affects expression	1
epigallocatechin gallate	decreases expression	1
dinophysistoxin 1	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
glycitein	affects expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
glycitin	affects expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction, increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	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
CHEMBL5136393	Binding	Inhibition of human Bis-phosphoglycerate mutase using 3-PG, GAP and NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 100 mins in presence of GAPDH by resazurin reagent based fluorescence analysis	Novel Bis-phosphoglycerate Mutase Modulators for Treating Sickle Cell Disease. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SF44	HAP1 BPGM (-) 1	Cancer cell line	Male
CVCL_XM07	HAP1 BPGM (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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