PMM2

Summary

PMM2 (phosphomannomutase 2, HGNC:9115) is a protein-coding gene on chromosome 16p13.2, encoding Phosphomannomutase 2 (O15305). Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. It is a selective cancer dependency (DepMap: 28.6% of cell lines).

The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I.

Source: NCBI Gene 5373 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PMM2-congenital disorder of glycosylation (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 891 total — 76 pathogenic, 106 likely-pathogenic
• Phenotypes (HPO): 137
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 28.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9115
Approved symbol	PMM2
Name	phosphomannomutase 2
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CDGS, CDG1a, PMI, PMI1
Ensembl gene	ENSG00000140650
Ensembl biotype	protein_coding
OMIM	601785
Entrez	5373

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 13 nonsense_mediated_decay, 12 protein_coding, 8 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000268261, ENST00000562025, ENST00000562318, ENST00000562448, ENST00000564030, ENST00000564069, ENST00000564919, ENST00000565221, ENST00000565837, ENST00000565896, ENST00000565934, ENST00000566196, ENST00000566540, ENST00000566604, ENST00000566983, ENST00000567697, ENST00000568602, ENST00000569958, ENST00000570076, ENST00000570134, ENST00000613908, ENST00000682008, ENST00000682393, ENST00000683094, ENST00000683274, ENST00000683435, ENST00000683761, ENST00000684347, ENST00000859785, ENST00000859786, ENST00000859787, ENST00000859788, ENST00000932321, ENST00000932322, ENST00000932323, ENST00000966170

RefSeq mRNA: 1 — MANE Select: NM_000303 NM_000303

CCDS: CCDS10536

Canonical transcript exons

ENST00000268261 — 8 exons

Exon	Start	End
ENSE00001010802	8797839	8797948
ENSE00001320601	8847724	8849325
ENSE00003475576	8806316	8806407
ENSE00003480867	8812991	8813106
ENSE00003509032	8811638	8811713
ENSE00003514942	8804767	8804843
ENSE00003587294	8811079	8811178
ENSE00003685108	8801799	8801910

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 93.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.4996 / max 664.7939, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152667	35.1368	1819
152666	1.2600	925
207744	0.1028	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	93.10	gold quality
calcaneal tendon	UBERON:0003701	92.48	gold quality
rectum	UBERON:0001052	92.37	gold quality
bone marrow cell	CL:0002092	92.11	gold quality
pancreas	UBERON:0001264	91.94	gold quality
mucosa of transverse colon	UBERON:0004991	91.87	gold quality
sural nerve	UBERON:0015488	91.67	gold quality
tonsil	UBERON:0002372	90.94	gold quality
duodenum	UBERON:0002114	90.66	gold quality
placenta	UBERON:0001987	90.56	gold quality
right lobe of liver	UBERON:0001114	90.39	gold quality
endometrium	UBERON:0001295	90.35	gold quality
islet of Langerhans	UBERON:0000006	90.04	gold quality
liver	UBERON:0002107	89.89	gold quality
esophagus mucosa	UBERON:0002469	89.67	gold quality
transverse colon	UBERON:0001157	89.26	gold quality
granulocyte	CL:0000094	89.23	gold quality
monocyte	CL:0000576	89.03	gold quality
leukocyte	CL:0000738	88.87	gold quality
saliva-secreting gland	UBERON:0001044	88.79	gold quality
minor salivary gland	UBERON:0001830	88.71	gold quality
adrenal tissue	UBERON:0018303	88.41	gold quality
vermiform appendix	UBERON:0001154	88.07	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.02	gold quality
body of stomach	UBERON:0001161	87.95	gold quality
stromal cell of endometrium	CL:0002255	87.79	gold quality
colonic epithelium	UBERON:0000397	87.76	gold quality
stomach	UBERON:0000945	87.69	gold quality
adipose tissue	UBERON:0001013	87.67	gold quality
lower esophagus mucosa	UBERON:0035834	87.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.00
E-CURD-112	yes	4.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting PMM2, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 28.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• The presence of this deletion-insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. (PMID:11891694)
• Congenital disorder of glycosylation type Ia: benign clinical course in a new genetic variant. a new, previously undescribed, combination of mutations of the PMM gene locus on chromosome 16p13 (647,691). (PMID:11935250)
• A Japanese patient with congenital disorder of glycosylation type Ia had a novel nonsense mutation (R194X) in the PMM2 gene. (PMID:13129599)
• enzymatic activity of PMM2 is upregulated by insulin treatment and that Sgk1 completely inhibits PMM2 activity both in the absence and in the presence of insulin stimulation. (PMID:15342340)
• 11 novel mutations in the PMM2 gene are described as associated with Congenital disorder of Glycosylation type Ia. (PMID:15844218)
• Based on SNP and STR genotypic analysis, we ascertained an association between the R141H substitution and a particular haplotype, suggesting a common origin for all the mutated chromosomes. (PMID:17166182)
• We describe the characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. (PMID:17307006)
• three siblings of congenital disorder of glycosylation type 1a are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. (PMID:17451957)
• Two CDG-Ia patients,who presented with ataxia and cerebellar hypoplasia and with a normal or only slightly abnormal transferrin but the activity of the corresponding enzyme phosphomannomutase was clearly deficient in leucocytes and fibroblasts. (PMID:17694350)
• Val231Met and Arg148Met heterozygosity can present as primary skeletal dysplasia with congenital glycosylation type Ia disorder. (PMID:18203160)
• This work reports the study of two new nucleotide changes (c.256-1G>C and c.640-9T>G) identified in the PMM2 gene in congenital disorders of glycosylation type 1a patients, and of a previously described deep intronic nucleotide change in intron 7. (PMID:19235233)
• When non-immune hydrops fetalis remains unexplained despite exhaustive obstetrical screening, analysis of PMM activity in the parents’ leucocytes is possible and might be performed easily during pregnancy (PMID:20638314)
• Identification of exclusively catalytic protein change, catalytic protein changes affecting protein stability, two protein changes disrupting the dimer interface and several misfolding changes . (PMID:21541725)
• Hypertrophic cardiomyopathy with cardiac rupture and tamponade caused by congenital disorder of glycosylation type Ia with PMM2 mutations in two siblings. (PMID:22374380)
• We conclude that electroretinogram signs of on-pathway dysfunction can be detected in the early stages of PMM2-Congenital disorder of glycosylation. (PMID:23430200)
• Two young sisters are compound heterozygous for mutations p.Leu32Arg and p.Arg141His, while two paternal great-aunts are compound heterozygosity for p.Leu32Arg and p.Thr237Met, with congenital disorder of glycosylation. (PMID:23988505)
• Data indicate genome-wide significant association at multiple single nucleotide polymorphism (SNPs) near ATP binding cassette transporter 1 (ABCA1) at 9q31.1 and suggestive evidence of association in phosphomannomutase 2 (PMM2) at 16p13.2. (PMID:25173107)
• conformational response to ligand binding in phosphomannomutase2 (PMID:25324542)
• A mild neurological phenotype of PMM2-CDG marked by preserved ambulatory ability and autonomy and associated with L32R mutation is particularly frequent in Italy. (PMID:25355454)
• work describes the functional analysis of 9 PMM2 mutant proteins frequently found in congenital disorder of glycosylation type Ia(PMM2-CDG)patients; results suggest that some loss-of-function mutations detected in PMM2-CDG patients could be destabilizing (PMID:26014514)
• the activity of phosphomannomutase2 R141H/F119L heterodimers in vitro, which reproduces the protein found in patients, has the same activity of wild type/R141H, which reproduces the protein found in healthy carriers. (PMID:26488408)
• This functional mouse model of PMM2-CDG, in vitro assays and identification of the novel gp130 biomarker all shed light on the human disease, and moreover, provide the essential tools to test potential therapeutics for this untreatable disease. (PMID:27053713)
• We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy (PMID:28373276)
• Four patients were diagnosed with PMM2-CDG at the age of 8 years or later as their neurological symptoms were quite mild and they had been able to participate in regular school programs. We report patients with p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys genotypes which may cause milder variants of PMM2-CDG (PMID:28425223)
• PMM2-CDG clinical phenotype is heterogeneous in terms of clinical course, with no clear division between neurological and visceral presentations. (PMID:28954837)
• clinical variables to detect risk factors for Stroke-like episodes in a series of 43 phosphomannomutase deficiency patients. (PMID:29470411)
• The biochemical analysis of mutants does not allow a precise genotypephenotype correlation for PMM2-Type I disorders of glycosylation. PMM2 is very tolerant to missense and loss of function mutations, suggesting that a partial deficiency of activity might be beneficial under certain circumstances. (PMID:30061496)
• Pathogenic variant in PMM2 gene is associated with premature ovarian insufficiency. (PMID:30406445)
• patient’s condition may be attributed to the compound heterozygous variants c.458_462delTAAGA and c.395T>C of the PMM2 gene (PMID:30950015)
• Both observational and experimental findings suggest that hypolipidaemia in PMM2-CDG may be partially mediated by loss of PCSK9 N-glycosylation and/or its regulators. (PMID:31391289)
• Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency. (PMID:31902100)
• Genotypes and estimated prevalence of phosphomannomutase 2 deficiency in Turkey differ significantly from those in Europe. (PMID:31981409)
• Proteostasis regulators as potential rescuers of PMM2 activity. (PMID:32222543)
• In Vitro Fertilisation (IVF) Associated with Preimplantation Genetic Testing for Monogenic Diseases (PGT-M) in a Romanian Carrier Couple for Congenital Disorder of Glycosylation Type Ia (CDG-Ia): A Case Report. (PMID:32630370)
• Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia. (PMID:32841164)
• Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes. (PMID:33580824)
• Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG). (PMID:33619652)
• Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD). (PMID:33811480)
• Genotype-Phenotype Correlations in PMM2-CDG. (PMID:34828263)
• A functional platform for the selection of pathogenic variants of PMM2 amenable to rescue via the use of pharmacological chaperones. (PMID:35789514)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pmm2	ENSDARG00000037654
mus_musculus	Pmm2	ENSMUSG00000022711
rattus_norvegicus	Pmm2	ENSRNOG00000002615
drosophila_melanogaster	Pmm2	FBGN0036300
caenorhabditis_elegans		WBGENE00009925

Paralogs (1): PMM1 (ENSG00000100417)

Protein

Protein identifiers

Phosphomannomutase 2 — O15305 (reviewed: O15305)

All UniProt accessions (11): A0A0S2Z4J6, A0A804HKA7, O15305, H3BM92, H3BNY9, H3BPH4, H3BR08, H3BRM0, H3BT06, H3BV34, H3BV55

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Disease relevance. Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065] 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. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism. The disease is caused by variants affecting the gene represented in this entry.

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

Similarity. Belongs to the eukaryotic PMM family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15305-1	1	yes
O15305-2	2

RefSeq proteins (1): NP_000294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005002	PMM	Family
IPR006379	HAD-SF_hydro_IIB	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR043169	PMM_cap	Homologous_superfamily

Pfam: PF03332

Enzyme classification (BRENDA):

• EC 5.4.2.8 — phosphomannomutase (BRENDA: 45 organisms, 84 substrates, 44 inhibitors, 90 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.006–0.4516	31
ALPHA-D-MANNOSE 1-PHOSPHATE	0.0056–1.37	22
GLUCOSE 1-PHOSPHATE	0.0013–0.022	14
MANNOSE 1-PHOSPHATE	0.003–0.2	5
D-GLUCOSE-1-PHOSPHATE	0.0135–3	4
D-MANNOSE 1-PHOSPHATE	0.018–0.15	4
D-MANNOSE-1-PHOSPHATE	0.016–3.2	3
D-GLUCOSE 1-PHOSPHATE	0.0075–0.0654	2
2-DEOXYRIBOSE-1-PHOSPHATE	3.5	1
D-MANNOSE 6-PHOSPHATE	0.0482	1
MANNOSE 6-PHOSPHATE	0.074	1

Catalyzed reactions (Rhea), 1 shown:

• alpha-D-mannose 1-phosphate = D-mannose 6-phosphate (RHEA:11140)

UniProt features (117 total): sequence variant 71, binding site 12, strand 11, helix 11, turn 4, modified residue 2, splice variant 2, active site 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7O58	X-RAY DIFFRACTION	1.97
7O5Z	X-RAY DIFFRACTION	2.07
2AMY	X-RAY DIFFRACTION	2.09
2Q4R	X-RAY DIFFRACTION	2.09
7O4G	X-RAY DIFFRACTION	2.66
7O0C	X-RAY DIFFRACTION	2.8
7O1B	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15305-F1	96.66	0.96

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 (2): 12 (nucleophile); 14 (proton donor/acceptor)

Ligand- & substrate-binding residues (12): 179; 181; 209; 221; 223; 226; 12; 14; 21; 123; 134; 141

Post-translational modifications (2): 2, 149

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-4043911	Defective PMM2 causes PMM2-CDG
R-HSA-446205	Synthesis of GDP-mannose

MSigDB gene sets: 459 (showing top): GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_16, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, ONKEN_UVEAL_MELANOMA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, DANG_BOUND_BY_MYC

GO Biological Process (7): mannose metabolic process (GO:0006013), protein N-linked glycosylation (GO:0006487), glycoprotein biosynthetic process (GO:0009101), GDP-mannose biosynthetic process (GO:0009298), obsolete GDP-mannose biosynthetic process from mannose (GO:0061728), obsolete GDP-D-mannose biosynthetic process from fructose-6-phosphate (GO:0061729), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (4): phosphomannomutase activity (GO:0004615), metal ion binding (GO:0046872), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytosol (GO:0005829), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), neuronal cell body (GO:0043025), ciliary tip (GO:0097542), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with glycosylation precursor biosynthesis	1
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
hexose metabolic process	1
glycoprotein biosynthetic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
phosphomannomutase activity	1
nucleotide-sugar biosynthetic process	1
GDP-mannose metabolic process	1
intramolecular phosphotransferase activity	1
cation binding	1
binding	1
catalytic activity	1
nuclear lumen	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
somatodendritic compartment	1
cell body	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMM2	MPI	P34949	955
PMM2	ALG2	Q9H553	912
PMM2	ALG6	Q9Y672	908
PMM2	DPAGT1	Q9H3H5	891
PMM2	DOLK	Q9UPQ8	886
PMM2	ALG11	Q2TAA5	871
PMM2	SRD5A3	Q9H8P0	861
PMM2	ALG8	Q9BVK2	858
PMM2	RFT1	Q96AA3	777
PMM2	ALG1	Q9BT22	772
PMM2	MOGS	Q13724	759
PMM2	SLC35A1	P78382	741
PMM2	DPM3	Q9P2X0	720
PMM2	ALG3	Q92685	706
PMM2	ALG9	Q9H6U8	700

IntAct

50 interactions, top by confidence:

A	B	Type	Score
PMM2	ACY3	psi-mi:“MI:0915”(physical association)	0.810
ACY3	PMM2	psi-mi:“MI:0915”(physical association)	0.810
PMM2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
PMM2	SGK2	psi-mi:“MI:0915”(physical association)	0.560
PMM1	PMM2	psi-mi:“MI:0914”(association)	0.530
PMM2	E2	psi-mi:“MI:0915”(physical association)	0.370
L3MBTL4	GAPDHS	psi-mi:“MI:0914”(association)	0.350
SETD4	PMM2	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
ABCA9	PMM2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270

BioGRID (62): ACY3 (Two-hybrid), PMM2 (Affinity Capture-MS), PMM2 (Co-fractionation), PMM2 (Co-fractionation), PMM2 (Affinity Capture-MS), PMM2 (Affinity Capture-MS), PMM2 (Affinity Capture-RNA), ACY3 (Two-hybrid), PMM2 (Affinity Capture-MS), PMM2 (Positive Genetic), PMM2 (Affinity Capture-MS), PMM2 (Two-hybrid), PMM2 (Two-hybrid), PMM2 (Two-hybrid), PMM2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, B4G0F3, B8BKI7, B9N1F9, C6JS30, E0CSI1, M2VWL5, O14023, O15305, O24653, O35077, O35621, O57656, O80840, P00949, P38652, Q02908, Q08DP0, Q1W374, Q1W377, Q1ZXC6, Q23651, Q259G4, Q29NT9, Q2R483, Q3SZJ9, Q3ULJ0, Q4R5E4, Q5TNH5, Q5XIZ6, Q5ZID6, Q5ZJ08, Q5ZKF6, Q60HD6, Q60LW7, Q7SYN4, Q7XPW5, Q8GWU0

Diamond homologs: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, M2VWL5, O15305, O35621, O43976, O80840, P07283, P31353, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q3SZJ9, Q54X03, Q60HD6, Q7XPW5, Q86B09, Q8SVM5, Q92871, Q9UTJ2, Q9VTZ6, Q9XUE6, Q9Z2M7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	76
Likely pathogenic	106
Uncertain significance	244
Likely benign	271
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069079	NM_000303.3(PMM2):c.243_244del (p.Leu82fs)	Pathogenic
1072807	NM_000303.3(PMM2):c.73dup (p.Thr25fs)	Pathogenic
1072868	NM_000303.3(PMM2):c.458_462del (p.Ile153fs)	Pathogenic
1073046	NM_000303.3(PMM2):c.457dup (p.Ile153fs)	Pathogenic
1073938	NM_000303.3(PMM2):c.66+1G>A	Pathogenic
1074658	NC_000016.9:g.(?8895646)(8895777_?)del	Pathogenic
1342149	NM_000303.3(PMM2):c.696del (p.Ala233fs)	Pathogenic
1358766	NM_000303.3(PMM2):c.451G>T (p.Glu151Ter)	Pathogenic
1367452	NM_000303.3(PMM2):c.59del (p.Pro20fs)	Pathogenic
1440145	NM_000303.3(PMM2):c.523+1del	Pathogenic
188744	NM_000303.3(PMM2):c.24del (p.Cys9fs)	Pathogenic
2034426	NM_000303.3(PMM2):c.255+2T>G	Pathogenic
2041195	NM_000303.3(PMM2):c.17_28del (p.Pro6_Cys9del)	Pathogenic
2046218	NM_000303.3(PMM2):c.562del (p.Asp188fs)	Pathogenic
2054945	NM_000303.3(PMM2):c.67-2A>G	Pathogenic
2070897	NM_000303.3(PMM2):c.467_468delinsT (p.Lys156fs)	Pathogenic
2098914	NM_000303.3(PMM2):c.34G>C (p.Asp12His)	Pathogenic
2099388	NM_000303.3(PMM2):c.197_198del (p.Tyr66fs)	Pathogenic
21143	NM_000303.3(PMM2):c.415G>A (p.Glu139Lys)	Pathogenic
21145	NM_000303.3(PMM2):c.710C>T (p.Thr237Met)	Pathogenic
2125541	NM_000303.3(PMM2):c.460A>T (p.Arg154Ter)	Pathogenic
2137776	NM_000303.3(PMM2):c.303C>G (p.Asn101Lys)	Pathogenic
2137782	NM_000303.3(PMM2):c.715A>T (p.Arg239Trp)	Pathogenic
2422838	NC_000016.9:g.(?8905475)(8905590_?)del	Pathogenic
2422839	NC_000016.9:g.(?8906828)(8906983_?)del	Pathogenic
2422840	NC_000016.9:g.(?8900163)(8941692_?)del	Pathogenic
2677886	NM_000303.3(PMM2):c.64C>T (p.Gln22Ter)	Pathogenic
2697642	NM_000303.3(PMM2):c.208G>T (p.Glu70Ter)	Pathogenic
2706935	NM_000303.3(PMM2):c.639+2T>C	Pathogenic
2764297	NM_000303.3(PMM2):c.124G>T (p.Gly42Ter)	Pathogenic

SpliceAI

2234 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8797944:GGCAG:G	donor_gain	1.0000
16:8797945:GCAG:G	donor_gain	1.0000
16:8797945:GCAGG:G	donor_gain	1.0000
16:8797947:AGGT:A	donor_loss	1.0000
16:8797948:GGT:G	donor_loss	1.0000
16:8797949:G:GA	donor_loss	1.0000
16:8797949:G:GG	donor_gain	1.0000
16:8797950:T:A	donor_loss	1.0000
16:8801797:A:AG	acceptor_gain	1.0000
16:8801798:G:GG	acceptor_gain	1.0000
16:8801798:GA:G	acceptor_gain	1.0000
16:8801798:GAA:G	acceptor_gain	1.0000
16:8801798:GAAA:G	acceptor_gain	1.0000
16:8801798:GAAAA:G	acceptor_gain	1.0000
16:8801910:GGTA:G	donor_loss	1.0000
16:8801911:G:GC	donor_loss	1.0000
16:8801912:T:G	donor_loss	1.0000
16:8804765:A:AG	acceptor_gain	1.0000
16:8804766:G:GG	acceptor_gain	1.0000
16:8811179:G:GG	donor_gain	1.0000
16:8812975:C:A	acceptor_gain	1.0000
16:8812982:A:AG	acceptor_gain	1.0000
16:8812982:ACCC:A	acceptor_gain	1.0000
16:8812983:C:G	acceptor_gain	1.0000
16:8812985:C:CA	acceptor_gain	1.0000
16:8812988:CAG:C	acceptor_loss	1.0000
16:8812989:A:C	acceptor_loss	1.0000
16:8812990:G:A	acceptor_loss	1.0000
16:8813102:TGCCA:T	donor_gain	1.0000
16:8813103:GCCA:G	donor_gain	1.0000

AlphaMissense

1636 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:8813002:A:C	S179R	0.999
16:8813004:C:A	S179R	0.999
16:8813004:C:G	S179R	0.999
16:8813034:G:C	K189N	0.999
16:8813034:G:T	K189N	0.999
16:8797923:A:T	D14V	0.998
16:8811115:C:A	N128K	0.998
16:8811115:C:G	N128K	0.998
16:8811129:G:A	G133E	0.998
16:8811153:G:C	R141P	0.998
16:8813032:A:C	K189Q	0.998
16:8813033:A:T	K189M	0.998
16:8847732:T:A	N216K	0.998
16:8847732:T:G	N216K	0.998
16:8847733:G:C	D217H	0.998
16:8847734:A:C	D217A	0.998
16:8847734:A:T	D217V	0.998
16:8847735:C:A	D217E	0.998
16:8847735:C:G	D217E	0.998
16:8797917:A:T	D12V	0.997
16:8797918:C:A	D12E	0.997
16:8797918:C:G	D12E	0.997
16:8797922:G:C	D14H	0.997
16:8797924:T:A	D14E	0.997
16:8797924:T:G	D14E	0.997
16:8811099:G:C	R123P	0.997
16:8811152:C:A	R141S	0.997
16:8811161:T:C	F144L	0.997
16:8811163:C:A	F144L	0.997
16:8811163:C:G	F144L	0.997

dbSNP variants (sampled 300 via entrez): RS1000006005 (16:8845530 A>G), RS1000071621 (16:8823985 G>A), RS1000111351 (16:8797159 G>C), RS1000266355 (16:8847227 C>G,T), RS1000378091 (16:8833484 A>G), RS1000461509 (16:8816431 G>A), RS1000486 (16:8819783 C>G), RS1000561221 (16:8819053 C>A,G), RS1000578780 (16:8798240 A>G), RS1000638658 (16:8801603 T>G), RS1000673713 (16:8829892 G>A), RS1000686078 (16:8849636 C>G), RS1000688476 (16:8834152 G>A), RS1000718467 (16:8824193 A>T), RS1000738039 (16:8849492 T>C)

Disease associations

OMIM: gene MIM:601785 | disease phenotypes: MIM:212065, MIM:213000, MIM:613163

GenCC curated gene-disease

Disease	Classification	Inheritance
PMM2-congenital disorder of glycosylation	Definitive	Autosomal recessive
congenital disorder of glycosylation type I	Definitive	Autosomal recessive
hyperinsulinemic hypoglycemia with polycystic kidney disease	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
hyperinsulinemic hypoglycemia with polycystic kidney disease	Moderate	AR
PMM2-congenital disorder of glycosylation	Definitive	AR

Mondo (14): PMM2-congenital disorder of glycosylation (MONDO:0008907), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), intellectual disability (MONDO:0001071), GABA aminotransaminase deficiency (MONDO:0013166), cerebellar ataxia (MONDO:0000437), diabetes mellitus (MONDO:0005015), congenital disorder of glycosylation type I (MONDO:0005500), cerebral palsy (MONDO:0006497), congenital disorder of glycosylation (MONDO:0015286), muscular dystrophy (MONDO:0020121), focal segmental glomerulosclerosis (MONDO:0100313), primary ovarian failure (MONDO:0005387), pituitary stalk interruption syndrome (MONDO:0019828), hyperinsulinemic hypoglycemia with polycystic kidney disease (MONDO:1030000)

Orphanet (10): PMM2-CDG (Orphanet:79318), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), Gamma-aminobutyric acid transaminase deficiency (Orphanet:2066), Rare ataxia (Orphanet:102002), Congenital disorder of glycosylation (Orphanet:137), Muscular dystrophy (Orphanet:98473), Pituitary stalk interruption syndrome (Orphanet:95496), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

137 total (30 of 137 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000091	Abnormal renal tubule morphology
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000107	Renal cyst
HP:0000114	Proximal tubulopathy
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000377	Abnormal pinna morphology
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002581_2	Glaucoma (high intraocular pressure)	2.000000e-07

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D002547	Cerebral Palsy	C10.228.140.140.254
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C562568	Cerebellar Hypoplasia (supp.)
C535739	Congenital disorder of glycosylation type 1A (supp.)
C535407	Gamma aminobutyric acid transaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741162 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,237 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL51085	EBSELEN	3	13,237

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

Binding affinities (BindingDB)

93 measured of 167 human assays (175 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(4-fluorophenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	709 nM
(Z)-(4-chlorodithiazol-5-ylidene)-(5-methyl-1,3,4-oxadiazol-2-yl)amine	IC50	1070 nM
2-(2-fluorophenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	1450 nM
MLS-0315804.0001	IC50	1590 nM
5-(3-chlorophenyl)-1,2-dihydro-1,2,4-triazole-3-thione	IC50	1940 nM
(Z)-(4-chlorodithiazol-5-ylidene)-(1,3,4-thiadiazol-2-yl)amine	IC50	2300 nM
3-[3-(3-bromophenyl)-4-[(4,6-diketo-2-thioxo-hexahydropyrimidin-5-ylidene)methyl]pyrazol-1-yl]propionic acid	IC50	2390 nM
2-(4-chlorophenyl)-1,2-benzothiazol-3-one	IC50	2450 nM
2-(3-chloranyl-2-methyl-phenyl)-6-nitro-4-[2,2,2-tris(fluoranyl)ethoxy]-1,2-benzothiazol-3-one	IC50	3030 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
5-(2,3-dihydro-1,4-benzodioxin-3-yl)-1,2-dihydro-1,2,4-triazole-3-thione	IC50	3890 nM
4-[(4-chloranyl-1,2,3-dithiazol-5-ylidene)amino]benzenecarbonitrile	IC50	4140 nM
2-(3-methoxyphenyl)-1,2-benzothiazol-3-one	IC50	4190 nM
(4-chlorodithiazol-5-ylidene)-(2,5-dimethoxyphenyl)amine	IC50	4350 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
2-(3-methylphenyl)-1,2-benzothiazol-3-one	IC50	5290 nM
5-(3-bromophenyl)-1,2-dihydro-1,2,4-triazole-3-thione	IC50	6150 nM
2-(3-iodanylphenyl)-1,2-benzothiazol-3-one	IC50	6530 nM
(3-bromo-2-nitro-phenyl)-(4-chlorodithiazol-5-ylidene)amine	IC50	7370 nM
2-(4-bromophenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	8140 nM
2-[(4-chloranyl-1,2,3-dithiazol-5-ylidene)amino]aniline	IC50	9430 nM
2-[(4-chloranyl-1,2,3-dithiazol-5-ylidene)amino]-N-(4-chlorophenyl)aniline	IC50	9770 nM
2-(2-naphthalenyl)-1,2-benzothiazol-3-one	IC50	10700 nM
2-[3-(dimethylamino)phenyl]-1,2-benzothiazol-3-one	IC50	11200 nM
(4-chlorodithiazol-5-ylidene)-(4-fluorophenyl)amine	IC50	11600 nM
(2-bromophenyl)-(4-chlorodithiazol-5-ylidene)amine	IC50	11900 nM
(4-chlorodithiazol-5-ylidene)-(2-methoxyethyl)amine	IC50	11900 nM
2-(3-chloranyl-4-fluoranyl-phenyl)-4,6-dinitro-1,2-benzothiazol-3-one	IC50	12000 nM
4-[(4-chloranyl-1,2,3-dithiazol-5-ylidene)amino]-N,N-dimethyl-aniline	IC50	12400 nM
3-(3-keto-1,2-benzothiazol-2-yl)-N,N-dimethyl-benzenesulfonamide	IC50	13000 nM
(Z)-(4-chlorodithiazol-5-ylidene)-(5-ethyl-1,3,4-thiadiazol-2-yl)amine	IC50	13100 nM
(4-chlorodithiazol-5-ylidene)-(3-pyridyl)amine	IC50	13200 nM
2-(1,3-thiazol-2-yl)-1,2-benzothiazol-3-one	IC50	13500 nM
(4-chlorodithiazol-5-ylidene)-(2-naphthyl)amine	IC50	14100 nM
2-(2,4-dichlorophenyl)-6-fluoranyl-1,2-benzothiazol-3-one	IC50	14400 nM
(4-chloro-2,5-dimethoxy-phenyl)-(4-chlorodithiazol-5-ylidene)amine	IC50	15200 nM
2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one	IC50	15200 nM
(4-chlorodithiazol-5-ylidene)-p-anisyl-amine	IC50	15500 nM
(4-chlorodithiazol-5-ylidene)-cyclobutyl-amine	IC50	15600 nM
4-[(4-methylbenzylidene)amino]-3-(4-pyridyl)-1H-1,2,4-triazole-5-thione	IC50	16100 nM
(4-chlorodithiazol-5-ylidene)-(3,4-dichlorophenyl)amine	IC50	16900 nM
(4-chlorodithiazol-5-ylidene)-(3,4,5-trimethoxyphenyl)amine	IC50	20400 nM
(Z)-(4-chlorodithiazol-5-ylidene)-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amine	IC50	20800 nM
2-[4-(dimethylamino)phenyl]-1,2-benzothiazol-3-one	IC50	21400 nM
(4-chlorodithiazol-5-ylidene)-(2-methoxy-5-methyl-phenyl)amine	IC50	22500 nM
5-(4-methoxybenzyl)-1,3,4-thiadiazole-2-thiol	IC50	22500 nM
(4-chlorodithiazol-5-ylidene)-(3,5-dimethoxyphenyl)amine	IC50	22600 nM

ChEMBL bioactivities

20 potent at pChembl≥5 of 69 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.17	IC50	672	nM	EBSELEN
5.90	IC50	1260	nM	CHEMBL1725457
5.68	IC50	2080	nM	CHEMBL1724427
5.61	IC50	2460	nM	CHEMBL1714665
5.47	IC50	3370	nM	CHEMBL1733472
5.38	IC50	4220	nM	CHEMBL1732623
5.34	IC50	4570	nM	CHEMBL1725120
5.32	IC50	4800	nM	CHEMBL1704102
5.29	IC50	5150	nM	CHEMBL1333250
5.28	IC50	5200	nM	CHEMBL1333250
5.14	IC50	7300	nM	CHEMBL1725120
5.06	IC50	8740	nM	CHEMBL1711440
5.04	IC50	9110	nM	CHEMBL1314602
5.04	IC50	9060	nM	CHEMBL1726776
5.04	IC50	9100	nM	CHEMBL1314602
5.03	IC50	9440	nM	CHEMBL1725977
5.01	IC50	9870	nM	CHEMBL1371792
5.00	IC50	9900	nM	CHEMBL1371792
5.00	IC50	9950	nM	CHEMBL1725120

PubChem BioAssay actives

5 with measured affinity, of 51 total; 4 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	1187643: Inhibition of PMM2 (unknown origin)	ic50	5.2000	uM
2-(2,5-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3-one	1187643: Inhibition of PMM2 (unknown origin)	ic50	7.3000	uM
5-fluoro-2-(4-methoxyphenyl)-1,2-benzothiazol-3-one	597375: Inhibition of human purified PMM2	ic50	9.1000	uM
2-(2-morpholin-4-yl-5-morpholin-4-ylsulfonylphenyl)-1,2-benzothiazol-3-one	1187643: Inhibition of PMM2 (unknown origin)	ic50	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Smoke	decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	increases expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Rotenone	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738097	Binding	PUBCHEM_BIOASSAY: Counter screen SAR assay for PMM2 inhibitors via a fluorescence intensity assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1545, AID1574]	PubChem BioAssay data set

Cellosaurus cell lines

21 cell lines: 13 transformed cell line, 6 finite cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A9Y1	B-LCL-CDG2	Transformed cell line	Female
CVCL_C0VC	B-LCL-CDG3	Transformed cell line	Female
CVCL_C0VF	B-LCL-CDG1	Transformed cell line	Female
CVCL_C0VI	B-LCL-CDG10	Transformed cell line	Male
CVCL_C0VJ	B-LCL-CDG11	Transformed cell line	Male
CVCL_C0VK	B-LCL-CDG12	Transformed cell line	Female
CVCL_C0VL	B-LCL-CDG13	Transformed cell line	Female
CVCL_C0VM	B-LCL-CDG14	Transformed cell line	Female
CVCL_C0VN	B-LCL-CDG15	Transformed cell line	Male
CVCL_C0VP	B-LCL-CDG16	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04925960	PHASE3	TERMINATED	Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT05549219	PHASE2	COMPLETED	24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Participants With PMM2-CDG
NCT06657859	PHASE2	ENROLLING_BY_INVITATION	Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04679389	PHASE2/PHASE3	TERMINATED	Acetazolamide Efficacy in Ataxia in PMM2-CDG
NCT06892288	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
NCT03173300	Not specified	ACTIVE_NOT_RECRUITING	Natural History Study Protocol in PMM2-CDG (CDG-Ia)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study