MAN2B2

Summary

MAN2B2 (mannosidase alpha class 2B member 2, HGNC:29623) is a protein-coding gene on chromosome 4p16.1, encoding Epididymis-specific alpha-mannosidase (Q9Y2E5). Specifically cleaves terminal alpha 1,6-linked mannose residues on Man3GlcNAc and Man2GlcNAc core oligosaccharides generated by N-glycan degradation pathways, having little activity, if any, on larger mannose oligosaccharides.

Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process and oligosaccharide catabolic process. Located in extracellular exosome.

Source: NCBI Gene 23324 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 359 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 64
• Druggable target: yes
• MANE Select transcript: NM_015274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29623
Approved symbol	MAN2B2
Name	mannosidase alpha class 2B member 2
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0935, EpMAN
Ensembl gene	ENSG00000013288
Ensembl biotype	protein_coding
OMIM	618899
Entrez	23324

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000285599, ENST00000504248, ENST00000504960, ENST00000505907, ENST00000510427, ENST00000868569, ENST00000868570, ENST00000868571, ENST00000868572, ENST00000868573, ENST00000868574, ENST00000868575, ENST00000937741

RefSeq mRNA: 2 — MANE Select: NM_015274 NM_001292038, NM_015274

CCDS: CCDS33951, CCDS77898

Canonical transcript exons

ENST00000285599 — 19 exons

Exon	Start	End
ENSE00001019910	6576578	6576724
ENSE00001019915	6578393	6578498
ENSE00001080305	6589045	6589160
ENSE00001080306	6609798	6610050
ENSE00001080309	6617380	6617492
ENSE00001080311	6600623	6600756
ENSE00001080313	6610880	6610990
ENSE00001080314	6605055	6605329
ENSE00001080317	6594534	6594732
ENSE00001080318	6614218	6614355
ENSE00001080319	6611086	6611278
ENSE00001080324	6597113	6597303
ENSE00001192663	6598198	6598354
ENSE00001192676	6593173	6593350
ENSE00001282115	6621188	6623362
ENSE00001282225	6619927	6620044
ENSE00001282232	6586996	6587168
ENSE00002081768	6575189	6575348
ENSE00003517734	6609107	6609298

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 94.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.0325 / max 160.0783, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46775	29.0325	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	94.31	gold quality
stromal cell of endometrium	CL:0002255	94.07	gold quality
descending thoracic aorta	UBERON:0002345	94.01	gold quality
right coronary artery	UBERON:0001625	93.69	gold quality
thoracic aorta	UBERON:0001515	93.32	gold quality
ascending aorta	UBERON:0001496	93.21	gold quality
decidua	UBERON:0002450	92.20	gold quality
aorta	UBERON:0000947	92.14	gold quality
parotid gland	UBERON:0001831	91.78	gold quality
synovial joint	UBERON:0002217	91.59	gold quality
popliteal artery	UBERON:0002250	91.25	gold quality
tibial artery	UBERON:0007610	91.24	gold quality
coronary artery	UBERON:0001621	91.08	gold quality
left coronary artery	UBERON:0001626	90.86	gold quality
granulocyte	CL:0000094	89.95	gold quality
urethra	UBERON:0000057	89.88	gold quality
cardia of stomach	UBERON:0001162	89.79	gold quality
superficial temporal artery	UBERON:0001614	89.56	gold quality
endometrium epithelium	UBERON:0004811	89.53	gold quality
layer of synovial tissue	UBERON:0007616	89.18	gold quality
corpus epididymis	UBERON:0004359	88.62	gold quality
lower lobe of lung	UBERON:0008949	88.46	gold quality
right ovary	UBERON:0002118	88.44	gold quality
left ovary	UBERON:0002119	88.36	gold quality
blood	UBERON:0000178	88.22	gold quality
saphenous vein	UBERON:0007318	87.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.66	gold quality
cardiac atrium	UBERON:0002081	87.16	gold quality
right atrium auricular region	UBERON:0006631	87.14	gold quality
cauda epididymis	UBERON:0004360	86.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting MAN2B2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-633	98.35	69.45	1167

Literature-anchored findings (GeneRIF, showing 1)

• Expressed MAN2B1 and MAN2B2 in Drosophila S2 cells and functionally characterized them. MAN2B1 and MAN2B2 were significantly inhibited by the class II alpha-mannosidase inhibitors, swainsonine and mannostatin A. (PMID:19722277)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	man2b2	ENSDARG00000079463
mus_musculus	Man2b2	ENSMUSG00000029119
rattus_norvegicus	Mrfap1	ENSRNOG00000056162

Paralogs (4): MAN2B1 (ENSG00000104774), MAN2A1 (ENSG00000112893), MAN2C1 (ENSG00000140400), MAN2A2 (ENSG00000196547)

Protein

Protein identifiers

Epididymis-specific alpha-mannosidase — Q9Y2E5 (reviewed: Q9Y2E5)

Alternative names: Alpha-1,6-mannosidase, Core-specific lysosomal alpha-1,6-Mannosidase, Mannosidase alpha class 2B member 2

All UniProt accessions (3): Q9Y2E5, E9PCD7, H0YA68

UniProt curated annotations — full annotation on UniProt →

Function. Specifically cleaves terminal alpha 1,6-linked mannose residues on Man3GlcNAc and Man2GlcNAc core oligosaccharides generated by N-glycan degradation pathways, having little activity, if any, on larger mannose oligosaccharides. Does not cleave terminal alpha 1,6-linked mannose on Man3GlcNAc2, and is also unable to hydrolyze terminal alpha 1,3-mannose linkages.

Subcellular location. Secreted.

Tissue specificity. Widely expressed.

Disease relevance. Congenital disorder of glycosylation 1EE with or without immunodeficiency (CDG1EE) [MIM:621140] 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. CDG1EE is an autosomal recessive form characterized by severe developmental delay, dysmorphic facial features, and coagulopathy. Some patients have immune deficiency. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly stimulated by Co(2+) and less efficiently by Zn(2+), Mg(2+) and Mn(2+). Inhibited by swainsonine, swainsonine derivatives, and mannostatin A.

Cofactor. Binds 1 zinc ion per subunit. Binds 1 zinc ion per subunit. Can bind cobalt probably on a site different from the zinc binding site.

Similarity. Belongs to the glycosyl hydrolase 38 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2E5-1	1	yes
Q9Y2E5-2	2

RefSeq proteins (2): NP_001278967, NP_056089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000602	Glyco_hydro_38_N	Domain
IPR011013	Gal_mutarotase_sf_dom	Homologous_superfamily
IPR011330	Glyco_hydro/deAcase_b/a-brl	Homologous_superfamily
IPR011682	Glyco_hydro_38_C	Domain
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR015341	Glyco_hydro_38_cen	Domain
IPR027291	Glyco_hydro_38_N_sf	Homologous_superfamily
IPR028995	Glyco_hydro_57/38_cen_sf	Homologous_superfamily
IPR037094	Glyco_hydro_38_cen_sf	Homologous_superfamily
IPR050843	Glycosyl_Hydrlase_38	Family

Pfam: PF01074, PF07748, PF09261

Catalyzed reactions (Rhea), 2 shown:

• alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-D-GlcNAc + H2O = alpha-D-Man-(1->3)-beta-D-Man-(1->4)-D-GlcNAc + D-mannose (RHEA:84971)
• alpha-D-Man-(1->6)-beta-D-Man-(1->4)-D-GlcNAc + H2O = 4-O-beta-D-mannopyranosyl-N-acetyl-D-glucosamine + D-mannose (RHEA:84987)

UniProt features (33 total): glycosylation site 12, sequence variant 10, binding site 4, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2E5-F1	91.55	0.84

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): 151 (nucleophile)

Ligand- & substrate-binding residues (4): 36; 38; 151; 420

Glycosylation sites (12): 294, 336, 516, 608, 670, 675, 748, 808, 812, 890, 226, 249

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8853383	Lysosomal oligosaccharide catabolism
R-HSA-1430728	Metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 259 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, chr4p16, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (4): mannose metabolic process (GO:0006013), glycoprotein catabolic process (GO:0006516), oligosaccharide catabolic process (GO:0009313), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (9): alpha-mannosidase activity (GO:0004559), mannan endo-1,6-alpha-mannosidase activity (GO:0008496), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), mannosyl-oligosaccharide 1,6-alpha-mannosidase activity (GO:0052767), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (4): lysosome (GO:0005764), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of carbohydrates and carbohydrate derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
hexose metabolic process	1
glycoprotein metabolic process	1
protein catabolic process	1
carbohydrate derivative catabolic process	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
primary metabolic process	1
mannosidase activity	1
alpha-mannosidase activity	1
cation binding	1
mannosyl-oligosaccharide mannosidase activity	1
molecular_function	1
catalytic activity	1
hydrolase activity	1
lytic vacuole	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAN2B2	ZPBP2	Q6X784	459
MAN2B2	ENOSF1	Q7L5Y1	456
MAN2B2	DDX25	Q9UHL0	449
MAN2B2	LRP11	Q86VZ4	447
MAN2B2	ACOT13	Q9NPJ3	433
MAN2B2	MYADM	Q96S97	433
MAN2B2	MAN1B1	Q9UKM7	417
MAN2B2	ENPP2	Q13822	415
MAN2B2	MAN1A1	P33908	413
MAN2B2	GSTM4	Q03013	409
MAN2B2	PHYH	O14832	404
MAN2B2	ENO1	P06733	404
MAN2B2	MOGS	Q13724	403
MAN2B2	AGL	P35573	400
MAN2B2	GLB1	P16278	393

IntAct

101 interactions, top by confidence:

A	B	Type	Score
PRR14	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
ORF4b	KPNA3	psi-mi:“MI:0914”(association)	0.620
APPBP2	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-2	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
LIME1	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
GPX8	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
CISD2	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
MAN2B2	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
FUCA2	HSPA5	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SIAE	COCH	psi-mi:“MI:0914”(association)	0.350
NAAA	NRP2	psi-mi:“MI:0914”(association)	0.350
FUCA2	UQCRH	psi-mi:“MI:0914”(association)	0.350
CSAG1	NAP1L4	psi-mi:“MI:0914”(association)	0.350
SPANXN4	UBA6	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
TCF7	RBFOX3	psi-mi:“MI:0914”(association)	0.350
CCDC74A	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), MAN2B2 (Affinity Capture-RNA), APPBP2 (Two-hybrid), FKBP7 (Two-hybrid), CISD2 (Two-hybrid), CREB3L1 (Two-hybrid), GPX8 (Two-hybrid)

ESM2 similar proteins: A3KGW5, C0HJB3, O00754, O09159, O14773, O18835, O35632, O46432, O54782, O89023, O97524, P04066, P10253, P27046, P28494, P54802, P70699, P79403, Q04519, Q0V8B6, Q12891, Q14697, Q16706, Q28949, Q29451, Q4FAT7, Q4R4N7, Q5E985, Q5IS74, Q5R5N6, Q5R7A9, Q5RDJ3, Q5RFL1, Q5U309, Q60HE9, Q60HF8, Q60HH1, Q69ZQ1, Q6P7A9, Q6RHW4

Diamond homologs: O54782, Q28949, Q5RDJ3, Q9Y2E5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of carbohydrates and carbohydrate derivatives	6	11.8×	2e-03
Neutrophil degranulation	14	5.3×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	11.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	251
Likely benign	38
Benign	31

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3774402	MAN2B2, 3-BP DEL, 440CTC	Pathogenic
3774403	NM_015274.3(MAN2B2):c.2368G>A (p.Glu790Lys)	Pathogenic
3774404	NM_015274.3(MAN2B2):c.384G>T (p.Gln128His)	Pathogenic
3774405	NM_015274.3(MAN2B2):c.926T>A (p.Ile309Asn)	Pathogenic
1801373	NM_015274.3(MAN2B2):c.1843C>T (p.Gln615Ter)	Likely pathogenic
4529497	NM_015274.3(MAN2B2):c.852G>A (p.Trp284Ter)	Likely pathogenic

SpliceAI

3799 predictions. Top by Δscore:

Variant	Effect	Δscore
4:6575347:AGGT:A	donor_loss	1.0000
4:6575349:G:C	donor_loss	1.0000
4:6575349:G:GG	donor_gain	1.0000
4:6576722:CAGG:C	donor_loss	1.0000
4:6576723:AG:A	donor_loss	1.0000
4:6576724:GGTAA:G	donor_loss	1.0000
4:6576725:G:T	donor_loss	1.0000
4:6576726:T:G	donor_loss	1.0000
4:6578376:T:TA	acceptor_gain	1.0000
4:6578380:T:TA	acceptor_gain	1.0000
4:6578385:A:AG	acceptor_gain	1.0000
4:6578385:AT:A	acceptor_gain	1.0000
4:6578386:T:G	acceptor_gain	1.0000
4:6578386:T:TA	acceptor_gain	1.0000
4:6578390:A:AG	acceptor_gain	1.0000
4:6578390:AAG:A	acceptor_gain	1.0000
4:6578391:A:AC	acceptor_loss	1.0000
4:6578391:A:G	acceptor_gain	1.0000
4:6578392:G:GC	acceptor_loss	1.0000
4:6578392:G:GG	acceptor_gain	1.0000
4:6578392:GGTCC:G	acceptor_gain	1.0000
4:6587160:G:GT	donor_gain	1.0000
4:6587166:CGGGT:C	donor_loss	1.0000
4:6587167:GG:G	donor_gain	1.0000
4:6587168:GG:G	donor_gain	1.0000
4:6587168:GGT:G	donor_loss	1.0000
4:6587170:T:A	donor_loss	1.0000
4:6589035:C:CA	acceptor_gain	1.0000
4:6589040:TGCA:T	acceptor_loss	1.0000
4:6589041:GCA:G	acceptor_loss	1.0000

AlphaMissense

6545 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:6575322:G:C	D38H	0.998
4:6575323:A:T	D38V	0.998
4:6575331:T:A	W41R	0.998
4:6575331:T:C	W41R	0.998
4:6575333:G:C	W41C	0.998
4:6575333:G:T	W41C	0.998
4:6587061:T:C	F153L	0.998
4:6587063:T:A	F153L	0.998
4:6587063:T:G	F153L	0.998
4:6575313:A:C	S35R	0.997
4:6575315:C:A	S35R	0.997
4:6575315:C:G	S35R	0.997
4:6575323:A:C	D38A	0.997
4:6594541:A:T	D289V	0.997
4:6575324:C:A	D38E	0.996
4:6575324:C:G	D38E	0.996
4:6598222:G:T	G425W	0.996
4:6611099:G:C	R795P	0.996
4:6576674:T:C	F79L	0.995
4:6576676:T:A	F79L	0.995
4:6576676:T:G	F79L	0.995
4:6578454:A:T	D116V	0.995
4:6587062:T:G	F153C	0.995
4:6594541:A:C	D289A	0.995
4:6575323:A:G	D38G	0.994
4:6587046:T:A	W148R	0.994
4:6587046:T:C	W148R	0.994
4:6587056:A:G	D151G	0.994
4:6587056:A:T	D151V	0.994
4:6597146:C:T	S364F	0.994

dbSNP variants (sampled 300 via entrez): RS10000264 (4:6605444 G>A,T), RS1000079264 (4:6621623 C>A,T), RS1000138745 (4:6612848 T>C), RS1000247550 (4:6593054 A>T), RS1000377278 (4:6604168 G>A), RS1000435674 (4:6598292 A>G), RS1000501118 (4:6603745 C>T), RS1000573310 (4:6603955 G>C,T), RS1000734358 (4:6609032 G>A,C), RS1000744826 (4:6614036 G>A), RS1000764307 (4:6599556 C>T), RS1000818558 (4:6599404 T>A,C), RS1000952114 (4:6618992 C>A), RS1000960826 (4:6588587 T>C), RS1000991597 (4:6583552 G>A)

Disease associations

OMIM: gene MIM:618899 | disease phenotypes: MIM:621140

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation	Moderate	Autosomal recessive
MAN2B2 deficiency	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
MAN2B2 deficiency	Limited	AR

Mondo (3): congenital disorder of glycosylation (MONDO:0015286), congenital disorder of glycosylation type 1EE with or without immunodeficiency (MONDO:0976261), MAN2B2 deficiency (MONDO:0800141)

Orphanet (2): Congenital disorder of glycosylation (Orphanet:137), MAN2B2-CDG (Orphanet:695110)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000047	Hypospadias
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000486	Strabismus
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001392	Abnormality of the liver
HP:0001727	Thromboembolic stroke
HP:0001873	Thrombocytopenia
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0001944	Dehydration
HP:0001954	Recurrent fever
HP:0002028	Chronic diarrhea
HP:0002171	Gliosis
HP:0002240	Hepatomegaly
HP:0002329	Drowsiness
HP:0002421	Poor head control
HP:0002572	Episodic vomiting
HP:0002633	Vasculitis
HP:0002721	Immunodeficiency
HP:0003160	Abnormal isoelectric focusing of serum transferrin
HP:0003212	Increased circulating IgE concentration

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2261	Blood protein levels	6.000000e-44
GCST009391_1609	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010377	phosphatidylcholine 34:3 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2682 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
sulindac sulfide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases mutagenesis	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression, decreases expression	1
Doxorubicin	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL830540	Binding	Percent inhibition of alpha-mannosidase of rat epididymis 1000 uM	Biological properties of D- and L-1-deoxyazasugars. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism