MPI

Summary

MPI (mannose phosphate isomerase, HGNC:7216) is a protein-coding gene on chromosome 15q24.1, encoding Mannose-6-phosphate isomerase (P34949). Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions.

Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4351 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MPI-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 20
• Clinical variants (ClinVar): 621 total — 37 pathogenic, 85 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 42 tissues, sQTL in 39 (q < 0.05)
• Phenotypes (HPO): 38
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_002435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7216
Approved symbol	MPI
Name	mannose phosphate isomerase
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178802
Ensembl biotype	protein_coding
OMIM	154550
Entrez	4351

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 26 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000352410

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 7, TSL 3: 5, TSL 4: 5, TSL 5: 2

ENST00000352410, ENST00000323744, ENST00000535694, ENST00000561470, ENST00000562606, ENST00000562800, ENST00000563422, ENST00000563786, ENST00000564003, ENST00000564633, ENST00000564692, ENST00000565576, ENST00000566377, ENST00000566556, ENST00000567116, ENST00000567132, ENST00000567177, ENST00000567570, ENST00000568303, ENST00000568828, ENST00000568840, ENST00000568907, ENST00000569233, ENST00000569931, ENST00000897793, ENST00000940246, ENST00000967445, ENST00000976484, ENST00000976485, ENST00000976486, ENST00001031366, ENST00001031367, ENST00001031368, ENST00001077751, ENST00001077752, ENST00001091307, ENST00001136676

RefSeq mRNA: 5 — MANE Select: NM_002435 NM_001289155, NM_001289156, NM_001289157, NM_001330372, NM_002435

CCDS: CCDS10272, CCDS73756, CCDS73757, CCDS73758, CCDS81908

Canonical transcript exons

ENST00000352410 — 8 exons

Exon	Start	End
ENSE00001245539	74897011	74897219
ENSE00001245546	74896152	74896325
ENSE00003468114	74892661	74892802
ENSE00003476529	74890527	74890654
ENSE00003507946	74890042	74890089
ENSE00003620329	74891379	74891579
ENSE00003622704	74893138	74893320
ENSE00004789231	74897512	74902219

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 95.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6045 / max 112.2348, expressed in 1782 samples.

Highest expression (Bgee): apex of heart, mucosa of transverse colon, adrenal gland, adrenal gland cortex, hindlimb stylopod muscle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MPI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 39 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 81 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	4.2e-48	+0.36	15:74873410:G:T
Nerve Tibial	eqtl	8.4e-25	+0.26	15:74872189:G:A
Whole Blood	eqtl	4.6e-24	+0.18	15:74892117:G:C
Cells EBV-transformed lymphocytes	sqtl	3.4e-22	+1.76	15:74897328:G:A
Nerve Tibial	sqtl	2.6e-21	+1.44	15:74935347:T:G
Cells Cultured fibroblasts	sqtl	5.1e-21	+1.33	15:74897328:G:A
Brain Caudate basal ganglia	eqtl	5.7e-21	+0.38	15:74916208:T:C
Brain Nucleus accumbens basal ganglia	eqtl	6.5e-21	+0.40	15:74899881:T:G
Cells EBV-transformed lymphocytes	eqtl	6.6e-21	+0.34	15:74892117:G:C
Brain Cortex	eqtl	2.8e-17	+0.45	15:74878050:CG:C
Brain Frontal Cortex BA9	eqtl	2.8e-17	+0.40	15:74888780:A:G
Esophagus Mucosa	eqtl	3.4e-17	+0.22	15:74868657:G:C
Skin Sun Exposed Lower leg	eqtl	4.8e-17	+0.20	15:74882685:A:G
Thyroid	eqtl	2.8e-16	+0.24	15:74943986:ACT:A
Testis	sqtl	4.2e-16	+1.74	15:74897328:G:A
Brain Putamen basal ganglia	eqtl	1.4e-15	+0.37	15:74867092:A:G
Lung	eqtl	2.2e-15	+0.16	15:74892117:G:C
Testis	eqtl	1.2e-14	+0.24	15:74916208:T:C
Brain Anterior cingulate cortex BA24	eqtl	9.7e-14	+0.42	15:74873410:G:T
Brain Hippocampus	eqtl	2.5e-13	+0.30	15:74873410:G:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
147742	22.6045	1782

Top tissues by expression

showing 100 of 283 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.26	gold quality
mucosa of transverse colon	UBERON:0004991	95.12	gold quality
right adrenal gland	UBERON:0001233	95.02	gold quality
right adrenal gland cortex	UBERON:0035827	94.49	gold quality
left adrenal gland	UBERON:0001234	94.09	gold quality
left adrenal gland cortex	UBERON:0035825	93.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.38	gold quality
prefrontal cortex	UBERON:0000451	93.22	gold quality
right frontal lobe	UBERON:0002810	93.20	gold quality
cingulate cortex	UBERON:0003027	92.91	gold quality
anterior cingulate cortex	UBERON:0009835	92.87	gold quality
adrenal gland	UBERON:0002369	92.58	gold quality
ventricular zone	UBERON:0003053	92.42	gold quality
rectum	UBERON:0001052	92.33	gold quality
colonic epithelium	UBERON:0000397	92.24	gold quality
right atrium auricular region	UBERON:0006631	92.22	gold quality
adrenal tissue	UBERON:0018303	92.04	gold quality
gastrocnemius	UBERON:0001388	91.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.90	gold quality
adrenal cortex	UBERON:0001235	91.78	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.74	gold quality
muscle of leg	UBERON:0001383	91.63	gold quality
heart left ventricle	UBERON:0002084	91.52	gold quality
gall bladder	UBERON:0002110	91.45	gold quality
transverse colon	UBERON:0001157	91.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.33	gold quality
cardiac ventricle	UBERON:0002082	90.85	gold quality
right lobe of liver	UBERON:0001114	90.80	gold quality
right ovary	UBERON:0002118	90.80	gold quality
right uterine tube	UBERON:0001302	90.72	gold quality
islet of Langerhans	UBERON:0000006	90.67	gold quality
nucleus accumbens	UBERON:0001882	90.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.52	gold quality
left ovary	UBERON:0002119	90.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.46	gold quality
body of pancreas	UBERON:0001150	90.39	gold quality
middle frontal gyrus	UBERON:0002702	90.32	gold quality
caudate nucleus	UBERON:0001873	90.28	gold quality
smooth muscle tissue	UBERON:0001135	90.07	gold quality
amygdala	UBERON:0001876	90.02	gold quality
ganglionic eminence	UBERON:0004023	89.65	gold quality
right lobe of thyroid gland	UBERON:0001119	89.57	gold quality
adenohypophysis	UBERON:0002196	89.48	gold quality
cerebellar hemisphere	UBERON:0002245	89.43	gold quality
ectocervix	UBERON:0012249	89.37	gold quality
cortical plate	UBERON:0005343	89.35	gold quality
endocervix	UBERON:0000458	89.34	gold quality
heart	UBERON:0000948	89.33	gold quality
cardiac atrium	UBERON:0002081	89.33	gold quality
cerebellar cortex	UBERON:0002129	89.33	gold quality
putamen	UBERON:0001874	89.25	gold quality
small intestine	UBERON:0002108	89.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.19	gold quality
spinal cord	UBERON:0002240	89.17	gold quality
body of uterus	UBERON:0009853	89.11	gold quality
neocortex	UBERON:0001950	89.10	gold quality
tibial nerve	UBERON:0001323	89.05	gold quality
stromal cell of endometrium	CL:0002255	88.89	gold quality
granulocyte	CL:0000094	88.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.71	gold quality
left uterine tube	UBERON:0001303	88.70	gold quality
lower esophagus	UBERON:0013473	88.70	gold quality
left testis	UBERON:0004533	88.63	gold quality
left lobe of thyroid gland	UBERON:0001120	88.55	gold quality
esophagus	UBERON:0001043	88.54	gold quality
pancreas	UBERON:0001264	88.54	gold quality
frontal cortex	UBERON:0001870	88.54	gold quality
esophagus mucosa	UBERON:0002469	88.54	gold quality
frontal pole	UBERON:0002795	88.46	gold quality
hypothalamus	UBERON:0001898	88.41	gold quality
left coronary artery	UBERON:0001626	88.29	gold quality
right testis	UBERON:0004534	88.29	gold quality
body of stomach	UBERON:0001161	88.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.05	gold quality
right coronary artery	UBERON:0001625	87.91	gold quality
metanephros cortex	UBERON:0010533	87.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.59	gold quality
paraflocculus	UBERON:0005351	87.53	gold quality
muscle organ	UBERON:0001630	87.52	gold quality
minor salivary gland	UBERON:0001830	87.34	gold quality
thoracic aorta	UBERON:0001515	87.29	gold quality
ascending aorta	UBERON:0001496	87.27	gold quality
mucosa of stomach	UBERON:0001199	87.24	gold quality
thyroid gland	UBERON:0002046	87.23	gold quality
cerebellum	UBERON:0002037	87.18	gold quality
pituitary gland	UBERON:0000007	87.17	gold quality
popliteal artery	UBERON:0002250	87.13	gold quality
tibial artery	UBERON:0007610	87.11	gold quality
aorta	UBERON:0000947	87.05	gold quality
coronary artery	UBERON:0001621	86.88	gold quality
descending thoracic aorta	UBERON:0002345	86.84	gold quality
telencephalon	UBERON:0001893	86.78	gold quality
stomach	UBERON:0000945	86.76	gold quality
forebrain	UBERON:0001890	86.72	gold quality
intestine	UBERON:0000160	86.71	gold quality
cerebral cortex	UBERON:0000956	86.65	gold quality
lymph node	UBERON:0000029	86.57	gold quality
lower esophagus mucosa	UBERON:0035834	86.51	gold quality
ovary	UBERON:0000992	86.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.89

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	66.1
Frontal cortex	tissue	58.3
Skeletal muscle	tissue	49.0	low
Locus coeruleus	tissue	46.1
Duodenum	tissue	42.8	medium
Caudate putamen	tissue	41.1
Postcentral gyrus	tissue	39.6
Heart muscle	tissue	38.7	low
Nucleus accumbens	tissue	38.0
Pons	tissue	37.0
Hippocampus	tissue	35.6	medium
Epididymis	tissue	33.3	medium
Retina	tissue	31.2
Small intestine	tissue	31.1	low
Choroid plexus	tissue	30.9
Colon	tissue	29.8	low
Cerebral cortex	tissue	29.6	medium
Substantia nigra	tissue	29.6
Somatosensory cortex	tissue	29.6
Rectum	tissue	29.5	low
Parathyroid gland	tissue	29.2	not detected
Thalamus	tissue	29.2
Kidney	tissue	29.1	medium
Adrenal gland	tissue	28.0	high
Superior colliculi	tissue	27.8
Hippocampal formation	tissue	27.7
Liver	tissue	27.3	medium
Ovary	tissue	26.7	low
Hypothalamus	tissue	26.4
Fallopian tube	tissue	26.1	medium
Occipital cortex	tissue	25.9
Prostate	tissue	25.8	medium
Motor cortex	tissue	25.6
Medulla oblongata	tissue	25.6
Basal ganglia	tissue	25.5	medium
Prefrontal cortex	tissue	25.3
Midbrain	tissue	25.1
Temporal cortex	tissue	24.9
Retrosplenial and cingulate cortex	tissue	24.8
Putamen	tissue	24.4
Entorhinal cortex	tissue	23.8
Spinal cord	tissue	23.5
Pancreas	tissue	23.2	high
Ventral forebrain	tissue	23.1
Septum	tissue	23.1
Periaqueductal gray	tissue	22.8
Tonsil	tissue	22.7	medium
Testis	tissue	22.4	high
Salivary gland	tissue	22.3	high
Insular cortex	tissue	22.1
Pituitary gland	tissue	21.7
Thyroid gland	tissue	21.7	medium
Seminal vesicle	tissue	21.6
Thymus	tissue	21.6
Retrosplenial cortex	tissue	21.4
Esophagus	tissue	21.0
Smooth muscle	tissue	21.0	not detected
Cervix	tissue	20.1	medium
Amygdala	tissue	20.0
Lymph node	tissue	19.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Pontine nuclei (62.1), Nuclei of the trapezoid body (62.0), Nucleus raphe magnus (60.6), Spinal trigeminal nucleus, interpolar (56.5), Principal sensory trigeminal nucleus (56.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MPI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 76 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-24-3P	99.59	69.97	1934

Functional genomics

gnomAD constraint: pLI 9.34e-10, LOEUF 1.04, missense Z 0.592 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000352410 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 6)

• The mannose-6-phosphate-enzyme complex is developed and the key residues involved in the ligand binding are determined. Our results suggest a hydride transfer mechanism of alpha-hydrogen between the C1 and C2 positions. (PMID:16488169)
• Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts (PMID:21949237)
• This work provides mechanistic evidence by which mannose phosphate isomerase loss induces p53, and identifies mannose phosphate isomerase as a novel regulator of p53 and Warburg metabolism. (PMID:28644127)
• MPI loss is a driver of liver fibrosis and suggest that modulating mannose metabolism pathways could reduce hepatic stellate cell activation and improve hepatic fibrosis. (PMID:31016744)
• MPI-based bioinformatic analysis and co-inhibitory therapy with mannose for oral squamous cell carcinoma. (PMID:34313879)
• Selective Immobilization of His-Tagged Phosphomannose Isomerase on Ni Chelated Nanoparticles with Good Reusability and Activity. (PMID:34958513)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpi	ENSDARG00000030786
mus_musculus	Mpi	ENSMUSG00000032306
rattus_norvegicus	Mpi	ENSRNOG00000018898
drosophila_melanogaster	Mpi	FBGN0286506
caenorhabditis_elegans		WBGENE00014013
caenorhabditis_elegans		WBGENE00015464

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97075) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vascular development	1
abnormal angiogenesis	1
abnormal cell proliferation	1
abnormal placenta morphology	1
abnormal placenta labyrinth morphology	1
absent vitelline blood vessels	1
abnormal chorioallantoic fusion	1
abnormal bone mineralization	1
abnormal vitelline vasculature morphology	1
embryonic growth retardation	1
caudal body truncation	1
delayed embryo turning	1
abnormal spongiotrophoblast layer morphology	1
abnormal trophoblast layer morphology	1
abnormal cell physiology	1
increased prepulse inhibition	1
embryonic lethality during organogenesis, complete penetrance	1
increased embryonic tissue cell apoptosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	A5A6K3	99.5%	Diamond
Escherichia coli K-12	P00946	99.5%	Diamond
Shigella flexneri	Q83KZ1	99.5%	Diamond
Macaca fascicularis	Q8HXX2	97.4%	Diamond
Bos taurus	Q3SZI0	91.3%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P25081	86.4%	Diamond
Aspergillus nidulans FGSC A4	P29951	81.5%	Diamond
Aspergillus fumigatus Af293	Q66WM4	81.5%	Diamond
Saccharomyces cerevisiae S288C	P29952	72.7%	Diamond
Eremothecium gossypii ATCC 10895	Q75AB5	72.7%	Diamond
Nakaseomyces glabratus CBS 138	Q76IQ2	68.5%	Diamond
Candida albicans SC5314	P34948	63.2%	Diamond
Arabidopsis thaliana	Q9FZH5	62.3%	Diamond
Neurospora crassa OR74A	Q870Y1	61.1%	Diamond
Ogataea parapolymorpha DL-1	Q8J093	59.3%	Diamond
Schizosaccharomyces pombe 972h-	O43014	45.9%	Diamond
Cryptococcus deneoformans JEC21	Q9HFU4	44.6%	Diamond
Echinococcus multilocularis	Q9GP38	43.2%	Diamond
Dictyostelium discoideum	Q54PA0	40.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6882	ncRNA	102465531
ULK3	protein-coding	25989
FAM219B	protein-coding	57184
CPLX3	protein-coding	594855
COX5A	protein-coding	9377
SCAMP2	protein-coding	10066
LMAN1L	protein-coding	79748
RPP25	protein-coding	54913
SCAMP5	protein-coding	192683
PPCDC	protein-coding	60490

Protein

Protein identifiers

Mannose-6-phosphate isomerase — P34949 (reviewed: P34949)

Alternative names: Phosphohexomutase, Phosphomannose isomerase

All UniProt accessions (18): B4DYB8, F5GX71, H3BM77, H3BMZ9, H3BN01, H3BNY8, H3BP57, H3BPB8, H3BPM5, H3BPP3, H3BPU7, H3BQX0, H3BT46, H3BT48, H3BU66, H3BUG1, H3BUZ9, P34949

UniProt curated annotations — full annotation on UniProt →

Function. Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in all tissues, but more abundant in heart, brain and skeletal muscle.

Disease relevance. Congenital disorder of glycosylation 1B (CDG1B) [MIM:602579] A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1B is clinically characterized by protein-losing enteropathy. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Pathway. Nucleotide-sugar biosynthesis; GDP-alpha-D-mannose biosynthesis; alpha-D-mannose 1-phosphate from D-fructose 6-phosphate: step 1/2.

Similarity. Belongs to the mannose-6-phosphate isomerase type 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P34949-1	1	yes
P34949-2	2

RefSeq proteins (5): NP_001276084, NP_001276085, NP_001276086, NP_001317301, NP_002426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001250	Man6P_Isoase-1	Family
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR014710	PpnP-like_jellyroll	Homologous_superfamily
IPR016305	Mannose-6-P_Isomerase	Family
IPR018050	Pmannose_isomerase-type1_CS	Conserved_site
IPR046456	PMI_typeI_C	Domain
IPR046457	PMI_typeI_cat	Domain
IPR046458	PMI_typeI_hel	Domain

Pfam: PF01238, PF20511, PF20512

Enzyme classification (BRENDA)

• EC 5.3.1.8 — mannose-6-phosphate isomerase (BRENDA: 57 organisms, 79 substrates, 92 inhibitors, 78 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MANNOSE 6-PHOSPHATE	0.0413–243	36
MANNOSE 6-PHOSPHATE	0.17–4	15
D-FRUCTOSE 6-PHOSPHATE	0.06–0.44	7
L-RIBULOSE	136–308	7
BETA-D-MANNOSE 6-PHOSPHATE	0.0004–0.33	3
D-GLUCOSE 6-PHOSPHATE	0.72–3.5	2
D-LYXOSE	433	1
D-MANNOSE	946	1
D-RIBOSE	110	1
D-TALOSE	469	1
L-ALLOSE	312	1
L-RIBOSE	998	1

Catalyzed reactions (Rhea)

• D-mannose 6-phosphate = D-fructose 6-phosphate (RHEA:12356)

UniProt features (24 total): sequence variant 13, binding site 4, modified residue 3, initiator methionine 1, chain 1, splice variant 1, active site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34949-F1	96.50	0.97

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of glycan/glycoprotein metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH approved · IF approved

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 (1)

Position	Role
295

Ligand- & substrate-binding residues (4)

Position	Role
110	Zn(2+)
112	Zn(2+)
137	Zn(2+)
276	Zn(2+)

Post-translational modifications (3)

Type	Positions
N-acetylalanine	2
Phosphoserine	102, 108

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 11; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-4043916	Defective MPI causes MPI-CDG ⚕	curated
R-HSA-446205	Synthesis of GDP-mannose	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5609975	Diseases associated with glycosylation precursor biosynthesis ⚕	—
R-HSA-3781865	Diseases of glycosylation ⚕	—
R-HSA-5668914	Diseases of metabolism ⚕	—
R-HSA-446203	Asparagine N-linked glycosylation	—
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis	—

MSigDB gene sets: 225 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, AACYNNNNTTCCS_UNKNOWN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, BROWNE_HCMV_INFECTION_14HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, WINTER_HYPOXIA_METAGENE, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (3): GDP-mannose biosynthetic process (GO:0009298), mannose to fructose-6-phosphate catabolic process (GO:0061611), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (5): mannose-6-phosphate isomerase activity (GO:0004476), zinc ion binding (GO:0008270), protein binding (GO:0005515), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Diseases associated with glycosylation precursor biosynthesis	1
Synthesis of substrates in N-glycan biosythesis	1
Diseases of metabolism	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Diseases of glycosylation	1
Disease	1
Metabolism of proteins	1

GO top-level categories

17 GO namespaces:

Category	Terms
cellular anatomical structure	2
phosphomannomutase activity	1
nucleotide-sugar biosynthetic process	1
GDP-mannose metabolic process	1
mannose-6-phosphate isomerase activity	1
fructose 6-phosphate metabolic process	1
mannokinase activity	1
mannose catabolic process	1
primary metabolic process	1
intramolecular oxidoreductase activity, interconverting aldoses and ketoses	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
mannose to fructose-6-phosphate catabolic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
mannose-6-phosphate isomerase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 982 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPI	PMM2	O15305	951
MPI	GPI	P06744	929
MPI	LEMD3	Q9Y2U8	846
MPI	SRD5A3	Q9H8P0	843
MPI	PMM1	Q92871	841
MPI	PGD	P52209	768
MPI	GUSB	P08236	755
MPI	ALG12	Q9BV10	694
MPI	H6PD	O95479	691
MPI	GALE	Q14376	690
MPI	G6PD	P11413	649
MPI	SERPINC1	P01008	631
MPI	PKM	P14618	602
MPI	GMPPB	Q9Y5P6	584
MPI	GDPGP1	Q6ZNW5	555

IntAct

Human interaction partners of MPI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
CPNE8	physical association	0.400	1
BDKRB2	physical association	0.370	1
CFTR	physical association	0.370	1
NP	physical association	0.370	1
ADA	association	0.350	1
SERPINA3	association	0.350	1

BioGRID (65 interactions; top human partners by supporting records): TGM1 (Affinity Capture-MS; 3 records), HSPE1 (Co-fractionation; 2 records), IVL (Affinity Capture-MS; 2 records), SERBP1 (Affinity Capture-MS; 2 records), SERPINA3 (Affinity Capture-MS; 2 records), SERPINB4 (Affinity Capture-MS; 2 records), ADA (Affinity Capture-MS), ANLN (Affinity Capture-MS), APP (Reconstituted Complex), BDKRB2 (Two-hybrid), CAPN9 (Co-fractionation), CC2D1A (Affinity Capture-MS), CCDC113 (Affinity Capture-MS), CCNF (Proximity Label-MS), CFTR (PCA)

Disease & clinical

Genetic variants

Variant evidence for MPI: 621 ClinVar records (122 pathogenic / likely pathogenic); 20 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	85
Uncertain significance	146
Likely benign	280
Benign	8

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 122 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
14345	NM_002435.3(MPI):c.656G>A (p.Arg219Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
188967	NM_002435.3(MPI):c.166dup (p.Arg56fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
370410	NM_002435.3(MPI):c.120del (p.Ile40fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
553083	NM_002435.3(MPI):c.845-2del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
554263	NM_002435.3(MPI):c.844+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1339719	NM_002435.3(MPI):c.497_498del (p.Glu166fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
834890	NM_002435.3(MPI):c.845-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1066765	NM_002435.3(MPI):c.145-1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2676655	NM_002435.3(MPI):c.1017_1024delinsACCCCTT (p.Asp339fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3239735	NM_002435.3(MPI):c.16+2T>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3577714	NM_002435.3(MPI):c.488-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
218094	NM_002435.3(MPI):c.1205A>G (p.Glu402Gly)	Pathogenic	criteria provided, single submitter	1
1071838	NM_002435.3(MPI):c.1034dup (p.Thr346fs)	Pathogenic	criteria provided, single submitter	1
1366385	NM_002435.3(MPI):c.820dup (p.Val274fs)	Pathogenic	criteria provided, single submitter	1
1367639	NM_002435.3(MPI):c.335_338del (p.His112fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore MPI’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 939):

Position(s)	Effect	Δscore	Sites
15:74890655–74890656	donor_loss	1.0000	5
15:74892647–74892648	acceptor_gain	1.0000	2
15:74892653	acceptor_gain	1.0000
15:74892659–74892660	acceptor_loss	1.0000	4
15:74892776	donor_gain	1.0000
15:74893331	donor_gain	1.0000
15:74892658	acceptor_gain	0.9900
15:74892659	acceptor_loss	0.9900
15:74892803–74892804	donor_loss	0.9900	5
15:74893136–74893137	acceptor_loss	0.9900	6

AlphaMissense

876 missense substitutions predicted likely pathogenic (of 2,776 scored), across 222 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M287	9	0.890	0.978
H112	8	0.982	0.998
H276	8	0.980	0.996
F151	8	0.960	0.995
D248	8	0.959	0.986
F345	8	0.951	0.996
N292	8	0.946	0.996
D131	8	0.942	0.975
F145	8	0.931	0.987
D291	8	0.927	0.981
D304	8	0.922	0.960
H54	8	0.909	0.990
H134	8	0.871	0.959
F252	8	0.846	0.971
D344	8	0.794	0.942
F98	8	0.726	0.936
W18	7	0.983	0.997
E285	7	0.981	0.993
W50	7	0.977	0.995
K135	7	0.976	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.09e-07
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.00055
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.00082

Disease associations

OMIM: gene MIM:154550 | disease phenotypes: MIM:602579

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
MPI-congenital disorder of glycosylation	Definitive	Autosomal recessive	6

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
MPI-congenital disorder of glycosylation	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
Cholestasis	green
Congenital disorders of glycosylation	green
DDG2P	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Neonatal cholestasis	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): MPI-congenital disorder of glycosylation (MONDO:0011257)

Orphanet (1): MPI-CDG (Orphanet:79319)

HPO phenotypes

38 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000107	Renal cyst
HP:0000114	Proximal tubulopathy
HP:0000707	Abnormality of the nervous system
HP:0000821	Hypothyroidism
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000969	Edema
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001508	Failure to thrive
HP:0001892	Abnormal bleeding
HP:0001929	Reduced factor XI activity
HP:0001976	Reduced antithrombin III activity
HP:0001977	Abnormal thrombosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002243	Protein-losing enteropathy
HP:0002570	Steatorrhea
HP:0003073	Hypoalbuminemia
HP:0003256	Abnormality of the coagulation cascade
HP:0003593	Infantile onset
HP:0003642	Type I transferrin isoform profile
HP:0003819	Death in childhood
HP:0004855	Reduced protein S activity
HP:0005543	Reduced protein C activity
HP:0011473	Villous atrophy
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0031842	Lymphangiectasis
HP:0040246	Reduced antithrombin antigen
HP:6000782	Reduced tissue phosphomannose isomerase activity

GWAS associations

20 associations:

Study	Trait	p-value
GCST006193_47	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3e-27
GCST006190_89	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7e-25
GCST006193_58	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2e-24
GCST006193_37	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4e-24
GCST006190_78	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	1e-21
GCST006190_2	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	8e-21
GCST006195_6	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4e-20
GCST006193_69	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1e-18
GCST006192_5	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2e-18
GCST006195_85	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1e-16
GCST006190_13	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3e-16
GCST006195_56	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2e-15
GCST006231_32	Mean arterial pressure	2e-15
GCST006195_38	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3e-15
GCST006192_21	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5e-15
GCST006192_88	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2e-13
GCST006192_60	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1e-12
GCST90002404_119	Red cell distribution width	1e-11
GCST010796_2884	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_2885	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-9

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004327	electrocardiography
EFO:0009188	Red cell distribution width

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C535740	Congenital disorder of glycosylation type 1B *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2758 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 18,673 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,317
CHEMBL51085	EBSELEN	3	13,356

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

334 measured of 663 human assays (747 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
APOMORPHINE HYDROCHLORIDE	KI	296 nM
MLS000577188	IC50	623 nM
cid_25199559	EC50	663 nM
2-(4-fluorophenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	709 nM
(4E)-4-[[2-[2-(3,5-dimethylpyrazol-1-yl)-6-methyl-pyrimidin-4-yl]hydrazinyl]methylidene]-3-oxidanyl-cyclohexa-2,5-dien-1-one	EC50	831 nM
(Z)-(4-chlorodithiazol-5-ylidene)-(5-methyl-1,3,4-oxadiazol-2-yl)amine	IC50	1070 nM
N2,N2,N4,N4-tetramethyl-N6-[(phenylmethylidene)amino]pyrimidine-2,4,6-triamine	IC50	1100 nM
5-hydroxy-4-[[4-(2-hydroxyethyl)-1-piperazinyl]methyl]-2-methyl-3-benzo[g]benzofurancarboxylic acid ethyl ester	IC50	1130 nM
N-[2,3-bis(chloranyl)-1-methoxy-4-oxidanylidene-naphthalen-1-yl]-4-methyl-benzenesulfonamide	IC50	1270 nM
2-(2-fluorophenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	1450 nM
MLS000392355	IC50	1490 nM
MLS-0315804.0001	IC50	1590 nM
1,3,6-Trimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1610 nM
1,6-dimethyl-3-propyl-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1770 nM
2-(4-chlorophenyl)-5-fluoranyl-1,2-benzothiazol-3-one	IC50	1770 nM
cid_6040412	EC50	1810 nM
cid_868390	IC50	1940 nM
5-amino-N’-(4-chlorobenzylidene)-4-oxo-3-phenyl-3,4-dihydrothieno[3,4-d]pyridazine-1-carbohydrazide	IC50	1950 nM
2-[4-[chloranyl-bis(fluoranyl)methoxy]phenyl]-4,6-dinitro-1,2-benzothiazol-3-one	IC50	2140 nM
MLS000566872	IC50	2360 nM
2-(4-chlorophenyl)-1,2-benzothiazol-3-one	IC50	2450 nM
MLS000339614	IC50	2530 nM
4-bromanyl-2-(4-methoxyphenyl)-6-methyl-benzotriazol-5-amine	IC50	2530 nM
1-[[1-(4-methoxyphenyl)-3-pyrrolidinyl]methyl]-3-phenylurea	IC50	2580 nM
(3-chloro-4-ethoxy-5-methoxy-benzyl)-(4-pyrrolidinophenyl)amine	IC50	2690 nM
MLS000684518	IC50	2720 nM
2-[(6,7-dihydroxy-2-keto-chromen-4-yl)methylthio]-3-(3-methoxyphenyl)quinazolin-4-one	IC50	2720 nM
UK 14,304	KI	2820 nM
7-[[4-(2-hydroxyethyl)-1-piperazinyl]-thiophen-2-ylmethyl]-8-quinolinol	IC50	2820 nM
cid_757789	IC50	2900 nM
2-(3-chloranyl-2-methyl-phenyl)-6-nitro-4-[2,2,2-tris(fluoranyl)ethoxy]-1,2-benzothiazol-3-one	IC50	3030 nM
1-(3-methoxyphenyl)-3-[[1-(4-methoxyphenyl)-3-pyrrolidinyl]methyl]urea	IC50	3180 nM
(4-chlorodithiazol-5-ylidene)-(2-methoxy-4-nitro-phenyl)amine	IC50	3250 nM
2-(3-chlorophenyl)-1,2-benzothiazol-3-one	IC50	3430 nM
(4-chlorodithiazol-5-ylidene)-(2,4-dinitrophenyl)amine	IC50	3520 nM
SMR000369439	IC50	3520 nM
2,6,7-Trihydroxy-9-methyl-xanthen-3-one	IC50	3600 nM
CHEMBL3322971	IC50	3600 nM
(3-chloro-4,5-dimethoxy-benzyl)-(4-pyrrolidinophenyl)amine	EC50	3720 nM
MLS000571067	IC50	3730 nM
6,7-bis(oxidanyl)-4-[[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]chromen-2-one	IC50	3770 nM
5-Amino-4-cyano-3-methyl-thiophene-2-carboxylic acid [5-(2-nitro-phenyl)-furan-2-ylmethylene]-hydrazide	IC50	3780 nM
4-[(3-carbethoxy-5-hydroxy-2-methyl-benzo[g]benzofuran-4-yl)methyl]piperazine-1-carboxylic acid ethyl ester	IC50	3950 nM
SMR000152103	IC50	4090 nM
SMR000171789	EC50	4150 nM
2-(3-methoxyphenyl)-1,2-benzothiazol-3-one	IC50	4190 nM
3,4,5-trihydroxy-N’-((1E)-{4-methoxy-3-[(4-nitro-1H-pyrazol-1-yl)methyl]phenyl}methylene)benzohydrazide	IC50	4310 nM
4-[3-[(2Z)-2-(2-oxidanylidenenaphthalen-1-ylidene)hydrazinyl]thiophen-2-yl]butanoic acid	IC50	4400 nM
(4-chlorodithiazol-5-ylidene)-(4-methyl-2-nitro-phenyl)amine	IC50	4440 nM
(4-chlorodithiazol-5-ylidene)-(4-methyl-3-nitro-phenyl)amine	IC50	4460 nM

ChEMBL bioactivities

170 potent at pChembl≥5 of 395 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.72	IC50	190	nM	EBSELEN
6.57	IC50	270	nM	CHEMBL1410147
6.15	IC50	710	nM	CHEMBL1333250
6.15	IC50	707	nM	CHEMBL1333250
6.15	IC50	709	nM	CHEMBL1714665
6.08	IC50	828.8	nM	CHEMBL1993627
6.01	IC50	985	nM	CHEMBL1725120
6.00	IC50	1000	nM	CHEMBL1706034
6.00	IC50	1000	nM	CHEMBL1725120
6.00	IC50	1000	nM	CHEMBL1314602
5.99	IC50	1030	nM	CHEMBL1314602
5.97	IC50	1070	nM	CHEMBL1732102
5.96	IC50	1100	nM	CHEMBL1725120
5.91	IC50	1227	nM	CHEMBL1390840
5.90	IC50	1250	nM	CHEMBL1406130
5.89	IC50	1300	nM	CHEMBL1703200
5.89	IC50	1273	nM	CHEMBL1392651
5.89	IC50	1300	nM	CHEMBL1406130
5.85	IC50	1423	nM	CHEMBL1335945
5.84	IC50	1450	nM	CHEMBL1732623
5.83	IC50	1490	nM	CHEMBL1520143
5.82	IC50	1499	nM	CHEMBL1410147
5.80	IC50	1590	nM	CHEMBL1725977
5.78	IC50	1670	nM	CHEMBL1449845
5.75	IC50	1770	nM	CHEMBL1701846
5.75	IC50	1800	nM	CHEMBL1701846
5.73	IC50	1880	nM	CHEMBL1601716
5.72	IC50	1900	nM	CHEMBL98386
5.72	IC50	1900	nM	CHEMBL1714438
5.72	IC50	1900	nM	CHEMBL1601716
5.71	IC50	1940	nM	CHEMBL1352830
5.68	IC50	2101	nM	CHEMBL1392651
5.67	IC50	2140	nM	CHEMBL1717022
5.65	IC50	2250	nM	CHEMBL1411202
5.64	IC50	2300	nM	CHEMBL1411202
5.64	IC50	2300	nM	CHEMBL1717825
5.61	IC50	2450	nM	CHEMBL98386
5.58	IC50	2600	nM	CHEMBL1371792
5.58	IC50	2650	nM	CHEMBL1391552
5.57	IC50	2708	nM	CHEMBL3199050
5.57	IC50	2680	nM	CHEMBL1553163
5.55	IC50	2800	nM	CHEMBL1339149
5.55	IC50	2790	nM	CHEMBL1339149
5.54	IC50	2905	nM	CHEMBL1310318
5.54	IC50	2910	nM	CHEMBL1321637
5.54	IC50	2900	nM	CHEMBL1310318
5.52	IC50	3030	nM	CHEMBL1726776
5.51	IC50	3100	nM	CHEMBL1423690
5.51	IC50	3100	nM	CHEMBL1717825
5.51	IC50	3120	nM	CHEMBL1718013

PubChem BioAssay actives

49 with measured affinity, of 69 total; 39 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-[[3-(3-oxo-1,2-benzothiazol-2-yl)phenyl]sulfonylamino]benzoic acid	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	0.7100	uM
2-(2,5-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.0000	uM
6-fluoro-2-(4-methoxyphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	1.0000	uM
5-fluoro-2-(4-methoxyphenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.0000	uM
6-fluoro-2-phenyl-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	1.3000	uM
5-fluoro-2-phenyl-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.3000	uM
2-(4-chlorophenyl)-5-fluoro-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.8000	uM
2-(4-chlorophenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.9000	uM
2-(2,5-dimethylphenyl)-5-fluoro-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.9000	uM
2-[4-(dimethylamino)phenyl]-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	1.9000	uM
N-benzyl-3-(3-oxo-1,2-benzothiazol-2-yl)benzamide	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	2.3000	uM
2-(2-morpholin-4-yl-5-morpholin-4-ylsulfonylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	2.6000	uM
N,N-dimethyl-3-(3-oxo-1,2-benzothiazol-2-yl)benzenesulfonamide	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	2.8000	uM
6-fluoro-2-(2-methylphenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	2.9000	uM
2-(4-methyl-3-piperidin-1-ylsulfonylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	3.1000	uM
3-(3-oxo-1,2-benzothiazol-2-yl)benzoic acid	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	3.3000	uM
2-[3-(trifluoromethyl)phenyl]-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	3.4000	uM
2-(4-fluorophenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	3.4000	uM
6-fluoro-2-(4-fluorophenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	3.6000	uM
5-fluoro-2-(4-fluorophenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	3.6000	uM
2-(3-methoxyphenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	3.7000	uM
2-(4-methylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	3.9000	uM
2-[4-(2,4-dichlorophenoxy)butanoylamino]-1,3-dihydroindene-2-carboxamide	225397: Compound was evaluated for the inhibition constant against phosphomannose isomerase enzyme of Candida albicans (CaPMI)	ki	4.0000	uM
2-[4-(3,4-dichlorophenyl)sulfanylbutanoylamino]-N-hydroxy-1,3-dihydroindene-2-carboxamide	225397: Compound was evaluated for the inhibition constant against phosphomannose isomerase enzyme of Candida albicans (CaPMI)	ki	4.0000	uM
2-(3-iodophenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	4.3000	uM
5-fluoro-2-(2-fluorophenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	4.3000	uM
2-(3-chlorophenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	4.8000	uM
methyl 3-(3-oxo-1,2-benzothiazol-2-yl)benzoate	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	4.9000	uM
2-(4-tert-butylphenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	5.0000	uM
2-(3-methylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	6.0000	uM
2-phenyl-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	6.4000	uM
2-(2,5-dimethylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	6.6000	uM
ethyl 4-(3-oxo-1,2-benzothiazol-2-yl)benzoate	597374: Inhibition of human purified phosphomannose isomerase	ic50	7.2000	uM
2-(5-morpholin-4-ylsulfonyl-2-pyrrolidin-1-ylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	7.5000	uM
5-fluoro-2-(3-fluorophenyl)-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	8.3000	uM
2-[3-(dimethylamino)phenyl]-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	8.5000	uM
2-(4-chloro-3-morpholin-4-ylsulfonylphenyl)-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	8.6000	uM
2-naphthalen-2-yl-1,2-benzothiazol-3-one	597374: Inhibition of human purified phosphomannose isomerase	ic50	9.4000	uM
2-(2,3-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3-one	1187642: Inhibition of phosphomannose isomerase (unknown origin)	ic50	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, decreases reaction, increases abundance	3
sodium arsenite	decreases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613774	Binding	PUBCHEM_BIOASSAY: Confirmation of compounds inhibiting phosphomannose isomerase (PMI) via a fluorescence intensity assay using a high concentration of mannose 6-phosphate. (Class of assay: confirmatory) [Related pubchem assays (depositor de	PubChem BioAssay data set

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B9W3	Abcam HEK293T MPI KO	Transformed cell line	Female
CVCL_C9JJ	SDQLCHi059-A	Induced pluripotent stem cell	Female
CVCL_E1IV	HyCyte A-549 KO-hMPI	Cancer cell line	Male
CVCL_SY81	HAP1 MPI (-) 1	Cancer cell line	Male
CVCL_SY82	HAP1 MPI (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

2 trials:

NCT	Phase	Status	Title
NCT03404869	Phase 1/2	UNKNOWN	Study of ORL-1M (D-mannose) in Patients With CDG-Ib
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MPI across ~30M SureChEMBL compounds — explore on Sugi Predict.