MAN2A1

Summary

MAN2A1 (mannosidase alpha class 2A member 1, HGNC:6824) is a protein-coding gene on chromosome 5q21.3, encoding Alpha-mannosidase 2 (Q16706). Catalyzes the first committed step in the biosynthesis of complex N-glycans.

This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus.

Source: NCBI Gene 4124 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 199 total
• Druggable target: yes
• MANE Select transcript: NM_002372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6824
Approved symbol	MAN2A1
Name	mannosidase alpha class 2A member 1
Location	5q21.3
Locus type	gene with protein product
Status	Approved
Aliases	GOLIM7, MANII
Ensembl gene	ENSG00000112893
Ensembl biotype	protein_coding
OMIM	154582
Entrez	4124

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000261483, ENST00000502261, ENST00000503970, ENST00000505313, ENST00000508043, ENST00000513921, ENST00000880523, ENST00000880524, ENST00000880525, ENST00000880526, ENST00000880527, ENST00000929782, ENST00000929783, ENST00000968351, ENST00000968352, ENST00000968353

RefSeq mRNA: 1 — MANE Select: NM_002372 NM_002372

CCDS: CCDS34209

Canonical transcript exons

ENST00000261483 — 22 exons

Exon	Start	End
ENSE00000759872	109767535	109767708
ENSE00000759873	109770355	109770541
ENSE00000759874	109774788	109774965
ENSE00000759875	109781396	109781598
ENSE00000759876	109784744	109784926
ENSE00000759877	109788934	109789048
ENSE00000759878	109789460	109789527
ENSE00000759881	109820220	109820342
ENSE00000759882	109823723	109823837
ENSE00000759883	109842328	109842461
ENSE00000759884	109845865	109846006
ENSE00000759885	109847657	109847790
ENSE00000759886	109855140	109855334
ENSE00000972069	109713520	109713774
ENSE00000972070	109716120	109716264
ENSE00000972071	109729342	109729513
ENSE00000972072	109755329	109755456
ENSE00001272120	109866846	109869625
ENSE00002058569	109689927	109690552
ENSE00003606337	109819669	109819887
ENSE00003625073	109817273	109817438
ENSE00003664577	109865036	109865146

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0747 / max 467.2555, expressed in 1819 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57926	15.6921	1788
57921	12.6611	1785
57928	0.8858	441
57925	0.8443	495
57927	0.6803	365
57922	0.4636	232
57923	0.3973	163
57929	0.2816	115
57924	0.1685	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.66	gold quality
adrenal tissue	UBERON:0018303	98.03	gold quality
calcaneal tendon	UBERON:0003701	97.60	gold quality
jejunal mucosa	UBERON:0000399	97.22	gold quality
inferior vagus X ganglion	UBERON:0005363	97.01	gold quality
stromal cell of endometrium	CL:0002255	96.91	gold quality
pigmented layer of retina	UBERON:0001782	96.82	gold quality
retina	UBERON:0000966	96.80	gold quality
endothelial cell	CL:0000115	96.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.80	gold quality
colonic mucosa	UBERON:0000317	95.58	gold quality
duodenum	UBERON:0002114	95.58	gold quality
spinal cord	UBERON:0002240	95.26	gold quality
tibia	UBERON:0000979	95.00	gold quality
subthalamic nucleus	UBERON:0001906	94.96	gold quality
inferior olivary complex	UBERON:0002127	94.96	gold quality
middle frontal gyrus	UBERON:0002702	94.94	gold quality
visceral pleura	UBERON:0002401	94.39	gold quality
medulla oblongata	UBERON:0001896	94.23	gold quality
ileal mucosa	UBERON:0000331	94.17	gold quality
eye	UBERON:0000970	94.03	gold quality
skin of hip	UBERON:0001554	93.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.73	gold quality
palpebral conjunctiva	UBERON:0001812	93.28	gold quality
upper leg skin	UBERON:0004262	93.28	gold quality
globus pallidus	UBERON:0001875	93.23	gold quality
medial globus pallidus	UBERON:0002477	93.21	gold quality
islet of Langerhans	UBERON:0000006	93.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.04	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	3381.52
E-HCAD-25	yes	2343.93
E-GEOD-98556	yes	316.04
E-ANND-3	yes	14.66
E-GEOD-180759	no	3517.55
E-MTAB-4850	no	597.29
E-MTAB-11011	no	275.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

224 targeting MAN2A1, 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-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 7)

• This article discribes experiments in which the MAN2A1 homologue in mouse was deleted, resulting in a systemic autoimmune disease in the mice which is similar to human systemic lupus erythematosus. (PMID:11158608)
• The disruption of Golgi alpha-mannosidase II activity by swainsonine in human embryonic kidney cells is capable of inducing a novel class of hybrid-type glycosylation containing a partially processed mannose moiety. (PMID:17466984)
• KCNQ and AP3S1, but not MAN2A1 or ALDH7A1 have a role in risk of type 2 diabetes in the Chinese Northern Han population (PMID:20512086)
• he QSAR models with the fragmented QM-DFT descriptors may find a useful application in structure-based drug design where pure empirical and force field methods reached their limits and where quantum mechanics effects are critical for ligand-receptor interactions. The optimized models will apply in lead optimization processes for GMII drug developments. (PMID:27035259)
• Many human tumor types and cancer cell lines express the MAN2A1-FER fusion, which increases proliferation and invasiveness of cancer cell lines and has liver oncogenic activity in mice. (PMID:28245430)
• Golgi Alpha-Mannosidase II as a Novel Biomarker Predicts Prognosis in Clear Cell Renal Cell Carcinoma. (PMID:32403105)
• Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors. (PMID:32723834)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	man2a1	ENSDARG00000102200
mus_musculus	Man2a1	ENSMUSG00000024085
rattus_norvegicus	Man2a1	ENSRNOG00000015439
drosophila_melanogaster	alpha-Man-IIa	FBGN0011740
caenorhabditis_elegans		WBGENE00010284
caenorhabditis_elegans	aman-3	WBGENE00018594

Paralogs (4): MAN2B2 (ENSG00000013288), MAN2B1 (ENSG00000104774), MAN2C1 (ENSG00000140400), MAN2A2 (ENSG00000196547)

Protein

Protein identifiers

Alpha-mannosidase 2 — Q16706 (reviewed: Q16706)

Alternative names: Golgi alpha-mannosidase II, Mannosidase alpha class 2A member 1, Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase

All UniProt accessions (1): Q16706

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Golgi apparatus membrane.

Post-translational modifications. Glycosylated.

Cofactor. Binds 1 zinc ion per subunit.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyl hydrolase 38 family.

RefSeq proteins (1): NP_002363* (*=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
IPR048534	Man2a1-like_dom	Domain
IPR050843	Glycosyl_Hydrlase_38	Family

Pfam: PF01074, PF07748, PF09261, PF21260

Catalyzed reactions (Rhea), 1 shown:

• N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 H2O = 2 alpha-D-mannopyranose + an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] (RHEA:56052)

UniProt features (17 total): binding site 4, glycosylation site 3, topological domain 2, modified residue 2, sequence conflict 2, chain 1, sequence variant 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16706-F1	90.36	0.78

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): 289 (nucleophile)

Ligand- & substrate-binding residues (4): 175; 177; 289; 569

Post-translational modifications (2): 82, 80

Glycosylation sites (3): 78, 93, 1125

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic
R-HSA-9694548	Maturation of spike protein
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway
R-HSA-1643685	Disease
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (13): in utero embryonic development (GO:0001701), liver development (GO:0001889), mannose metabolic process (GO:0006013), N-glycan processing (GO:0006491), mitochondrion organization (GO:0007005), vacuole organization (GO:0007033), respiratory gaseous exchange by respiratory system (GO:0007585), viral protein processing (GO:0019082), lung alveolus development (GO:0048286), positive regulation of neurogenesis (GO:0050769), retina morphogenesis in camera-type eye (GO:0060042), carbohydrate metabolic process (GO:0005975), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (9): alpha-mannosidase activity (GO:0004559), mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity (GO:0004572), hydrolase activity, hydrolyzing N-glycosyl compounds (GO:0016799), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), catalytic activity (GO:0003824), mannosidase activity (GO:0015923), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (7): Golgi membrane (GO:0000139), Golgi medial cisterna (GO:0005797), cis-Golgi network (GO:0005801), membrane (GO:0016020), extracellular exosome (GO:0070062), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Translation of Structural Proteins	1
N-glycan antennae elongation in the medial/trans-Golgi	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1
Membrane Trafficking	1
Asparagine N-linked glycosylation	1
Viral Infection Pathways	1
SARS-CoV Infections	1
Late SARS-CoV-2 Infection Events	1
Transport to the Golgi and subsequent modification	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	2
Golgi apparatus	2
intracellular membrane-bounded organelle	2
chordate embryonic development	1
gland development	1
hepaticobiliary system development	1
hexose metabolic process	1
protein N-linked glycosylation	1
glycoprotein biosynthetic process	1
multicellular organismal process	1
viral process	1
viral gene expression	1
lung development	1
anatomical structure development	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
anatomical structure morphogenesis	1
camera-type eye morphogenesis	1
retina development in camera-type eye	1
primary metabolic process	1
mannosidase activity	1
mannosyl-oligosaccharide mannosidase activity	1
hydrolase activity, acting on glycosyl bonds	1
binding	1
cation binding	1
molecular_function	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
catalytic activity	1
hydrolase activity	1
bounding membrane of organelle	1
Golgi cisterna	1
cellular anatomical structure	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAN2A1	MAN1A1	P33908	941
MAN2A1	MAN1B1	Q9UKM7	930
MAN2A1	MAN1A2	O60476	862
MAN2A1	B4GALT1	P15291	849
MAN2A1	SLC35C1	Q96A29	826
MAN2A1	EDEM3	Q9BZQ6	817
MAN2A1	EDEM2	Q9BV94	811
MAN2A1	MGAT2	Q10469	790
MAN2A1	SLC35D1	Q9NTN3	770
MAN2A1	SLC35D2	Q76EJ3	767
MAN2A1	MGAT1	P26572	731
MAN2A1	MGAT5	Q09328	667
MAN2A1	FUT8	Q9BYC5	657
MAN2A1	MAN1C1	Q9NR34	647
MAN2A1	EDEM1	Q92611	622

IntAct

77 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
IL13RA2	CHEK1	psi-mi:“MI:0914”(association)	0.640
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	TPST1	psi-mi:“MI:0914”(association)	0.530
PIGT	ZNF609	psi-mi:“MI:0914”(association)	0.530
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
FUT8	ITGAV	psi-mi:“MI:0914”(association)	0.350
	TOR1B	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), CAPN1 (Co-fractionation), MAN2A1 (Co-fractionation), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-MS), MAN2A1 (Affinity Capture-RNA), MAN2A1 (Affinity Capture-MS)

ESM2 similar proteins: A1CNK4, B8NWY6, C0HJB3, C3YWU0, D4B0X3, F4J6T7, O09159, O18497, O43451, O54782, P14410, P16406, P17164, P27046, P28494, P34098, P48980, P49713, P94078, Q00662, Q10RB4, Q16706, Q24451, Q28949, Q29451, Q2KIM0, Q2TW69, Q60HE9, Q66H12, Q6AYS4, Q6P7A9, Q6ZJJ0, Q8BVW0, Q8K2I4, Q8LPJ3, Q8TET4, Q8W0A1, Q92442, Q92457, Q99LJ1

Diamond homologs: O18497, P27046, P28494, P49641, Q16706, Q24451, Q8BRK9, Q9LFR0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
Neutrophil degranulation	14	5.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	41.8×	7e-05
intracellular zinc ion homeostasis	5	28.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	155
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5432 predictions. Top by Δscore:

Variant	Effect	Δscore
5:109716261:CCAGG:C	donor_loss	1.0000
5:109716263:AGG:A	donor_loss	1.0000
5:109716264:GGT:G	donor_loss	1.0000
5:109716265:GTA:G	donor_loss	1.0000
5:109755327:A:AG	acceptor_gain	1.0000
5:109755328:G:GG	acceptor_gain	1.0000
5:109755328:GT:G	acceptor_gain	1.0000
5:109755328:GTT:G	acceptor_gain	1.0000
5:109755328:GTTT:G	acceptor_gain	1.0000
5:109755328:GTTTA:G	acceptor_gain	1.0000
5:109755452:TATAG:T	donor_gain	1.0000
5:109755457:G:GG	donor_gain	1.0000
5:109755458:T:G	donor_loss	1.0000
5:109767636:A:T	donor_gain	1.0000
5:109767652:T:G	donor_gain	1.0000
5:109774774:T:TA	acceptor_gain	1.0000
5:109774783:T:A	acceptor_gain	1.0000
5:109774783:TGTAG:T	acceptor_loss	1.0000
5:109774784:GTAGG:G	acceptor_loss	1.0000
5:109774785:TAGGG:T	acceptor_gain	1.0000
5:109774786:A:AG	acceptor_gain	1.0000
5:109774786:AG:A	acceptor_gain	1.0000
5:109774786:AGG:A	acceptor_gain	1.0000
5:109774787:G:A	acceptor_gain	1.0000
5:109774787:G:GA	acceptor_gain	1.0000
5:109774787:GGG:G	acceptor_gain	1.0000
5:109774787:GGGC:G	acceptor_gain	1.0000
5:109774787:GGGCT:G	acceptor_gain	1.0000
5:109774961:T:G	donor_gain	1.0000
5:109774964:AGG:A	donor_loss	1.0000

AlphaMissense

7564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:109847681:G:C	R956P	1.000
5:109729344:T:A	W180R	0.999
5:109729344:T:C	W180R	0.999
5:109781531:T:A	W504R	0.999
5:109781531:T:C	W504R	0.999
5:109847698:G:C	D962H	0.999
5:109847699:A:T	D962V	0.999
5:109847705:G:C	R964P	0.999
5:109690449:G:A	G11D	0.998
5:109690451:A:C	S12R	0.998
5:109690453:T:A	S12R	0.998
5:109690453:T:G	S12R	0.998
5:109690463:T:C	C16R	0.998
5:109713569:T:C	L62P	0.998
5:109716173:G:C	W148C	0.998
5:109716173:G:T	W148C	0.998
5:109716250:C:T	S174F	0.998
5:109716252:C:G	H175D	0.998
5:109716259:A:G	D177G	0.998
5:109716259:A:T	D177V	0.998
5:109729346:G:C	W180C	0.998
5:109729346:G:T	W180C	0.998
5:109729450:A:T	E215V	0.998
5:109767555:T:A	W286R	0.998
5:109767555:T:C	W286R	0.998
5:109767637:G:T	R313I	0.998
5:109767656:A:C	K319N	0.998
5:109767656:A:T	K319N	0.998
5:109770423:T:C	C360R	0.998
5:109770427:G:A	G361E	0.998

dbSNP variants (sampled 300 via entrez): RS1000001277 (5:109788057 A>G,T), RS1000016306 (5:109834605 A>G), RS1000030571 (5:109751108 A>G), RS1000035062 (5:109715438 T>C), RS1000087913 (5:109833477 G>A,T), RS1000093877 (5:109849501 A>T), RS1000129815 (5:109811854 T>C), RS1000130733 (5:109708039 A>C,G), RS1000167044 (5:109849715 T>C,G), RS1000178894 (5:109756221 A>C,G), RS1000189127 (5:109833013 C>G,T), RS1000206885 (5:109751147 C>G), RS1000209121 (5:109755680 A>G,T), RS1000216334 (5:109714742 G>C), RS1000219434 (5:109772270 G>A)

Disease associations

OMIM: gene MIM:154582 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001915_9	Alzheimer’s disease (cognitive decline)	9.000000e-13
GCST002539_59	Schizophrenia	3.000000e-08
GCST003064_1	Exploratory eye movement dysfunction in schizophrenia (cognitive search score)	7.000000e-08
GCST003065_11	Exploratory eye movement dysfunction in schizophrenia (responsive search score)	3.000000e-06
GCST003068_12	Exploratory eye movement dysfunction in schizophrenia (number of eye fixations)	5.000000e-07
GCST004521_161	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004946_49	Schizophrenia	8.000000e-09
GCST005316_638	Intelligence (MTAG)	2.000000e-09
GCST006803_47	Schizophrenia	6.000000e-07
GCST007201_412	Schizophrenia	2.000000e-06
GCST007201_442	Schizophrenia	2.000000e-08
GCST007326_22	Number of sexual partners	3.000000e-08
GCST010396_319	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-06
GCST011743_40	HDL cholesterol levels in HIV infection	2.000000e-06
GCST012048_3	Triglyceride levels	6.000000e-08
GCST012048_4	Triglyceride levels	3.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007700	exploratory eye movement measurement
EFO:0004337	intelligence
EFO:0007874	gut microbiome measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4056 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 17 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.36	Ki	4350	nM	CHEMBL2206824
5.19	Ki	6470	nM	CHEMBL2206821
5.11	Ki	7770	nM	CHEMBL188227
5.04	Ki	9140	nM	CHEMBL2206819

PubChem BioAssay actives

4 with measured affinity, of 30 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-bromo-N-[(2R)-2-[[(2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl]methylamino]-2-phenylethyl]benzamide	717597: Inhibition of human golgi alpha mannosidase 2	ki	4.3500	uM
(2R,3R,4S)-2-[[[(1R)-2-[(4-fluorophenoxy)methoxy]-1-phenylethyl]amino]methyl]pyrrolidine-3,4-diol	717597: Inhibition of human golgi alpha mannosidase 2	ki	6.4700	uM
(2R,3R,4S)-2-[[[(1R,2S)-2-hydroxy-1,2-diphenylethyl]amino]methyl]pyrrolidine-3,4-diol	717597: Inhibition of human golgi alpha mannosidase 2	ki	7.7700	uM
(2R,3R,4S)-2-[[[(1R)-2-[(3-fluorophenyl)methoxy]-1-phenylethyl]amino]methyl]pyrrolidine-3,4-diol	717597: Inhibition of human golgi alpha mannosidase 2	ki	9.1400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	6
trichostatin A	decreases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
arsenite	affects binding, decreases reaction	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
corosolic acid	increases expression	1
K 7174	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2215203	Binding	Inhibition of human golgi alpha mannosidase 2	Virtual screening and QSAR study of some pyrrolidine derivatives as α-mannosidase inhibitors for binding feature analysis. — Bioorg Med Chem

Clinical trials (associated diseases)

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