MAN2C1

Summary

MAN2C1 (mannosidase alpha class 2C member 1, HGNC:6827) is a protein-coding gene on chromosome 15q24.2, encoding Alpha-mannosidase 2C1 (Q9NTJ4). Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues on cytoplasmic free oligosaccharides generated by N-glycoprotein degradation pathways.

Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. Implicated in congenital disorder of deglycosylation 2.

Source: NCBI Gene 4123 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of deglycosylation 2 (Strong, GenCC)
• Clinical variants (ClinVar): 255 total — 1 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 35
• MANE Select transcript: NM_006715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6827
Approved symbol	MAN2C1
Name	mannosidase alpha class 2C member 1
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140400
Ensembl biotype	protein_coding
OMIM	154580
Entrez	4123

Gene structure

Transcript identifiers

Ensembl transcripts: 96 — 59 protein_coding, 27 retained_intron, 6 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000267978, ENST00000421803, ENST00000561615, ENST00000561693, ENST00000562067, ENST00000562071, ENST00000562228, ENST00000562461, ENST00000563013, ENST00000563058, ENST00000563368, ENST00000563441, ENST00000563528, ENST00000563539, ENST00000563596, ENST00000563622, ENST00000563660, ENST00000563794, ENST00000564570, ENST00000564785, ENST00000564929, ENST00000565534, ENST00000565652, ENST00000565683, ENST00000565699, ENST00000565784, ENST00000565801, ENST00000565953, ENST00000566013, ENST00000566099, ENST00000566253, ENST00000566256, ENST00000566569, ENST00000566634, ENST00000567163, ENST00000567360, ENST00000568374, ENST00000568944, ENST00000569069, ENST00000569176, ENST00000569355, ENST00000569482, ENST00000570257, ENST00000631426, ENST00000854679, ENST00000854680, ENST00000854681, ENST00000854682, ENST00000854683, ENST00000854684, ENST00000854685, ENST00000854686, ENST00000854687, ENST00000854688, ENST00000854689, ENST00000854690, ENST00000854691, ENST00000854692, ENST00000854693, ENST00000854694, ENST00000854695, ENST00000854696, ENST00000854697, ENST00000854698, ENST00000854699, ENST00000854700, ENST00000854701, ENST00000854702, ENST00000854703, ENST00000854704, ENST00000854705, ENST00000854706, ENST00000854707, ENST00000854708, ENST00000912258, ENST00000964303, ENST00000964304, ENST00000964305, ENST00000964306, ENST00000964307, ENST00000964308, ENST00000964309, ENST00000964310, ENST00000964311, ENST00000964312, ENST00000964313, ENST00000964314, ENST00000964315, ENST00000964316, ENST00000964317, ENST00000964318, ENST00000964319, ENST00000964320, ENST00000964321, ENST00000964322, ENST00000964323

RefSeq mRNA: 4 — MANE Select: NM_006715 NM_001256494, NM_001256495, NM_001256496, NM_006715

CCDS: CCDS32298, CCDS58389, CCDS58390, CCDS58391

Canonical transcript exons

ENST00000267978 — 26 exons

Exon	Start	End
ENSE00001505559	75356110	75356219
ENSE00001505560	75356301	75356449
ENSE00002605937	75368483	75368607
ENSE00003464855	75359903	75359988
ENSE00003480695	75360090	75360211
ENSE00003509407	75359620	75359775
ENSE00003510040	75364488	75364665
ENSE00003513220	75359059	75359153
ENSE00003515483	75360565	75360688
ENSE00003531575	75361046	75361191
ENSE00003536529	75358201	75358344
ENSE00003538287	75368073	75368198
ENSE00003547369	75363999	75364188
ENSE00003586532	75361604	75361720
ENSE00003587455	75358704	75358808
ENSE00003596197	75358462	75358618
ENSE00003607848	75362642	75362748
ENSE00003608163	75356606	75356685
ENSE00003616740	75367511	75367634
ENSE00003624823	75359328	75359425
ENSE00003633853	75362343	75362453
ENSE00003641052	75356793	75356902
ENSE00003649797	75355792	75356032
ENSE00003671196	75361855	75361947
ENSE00003682458	75366522	75366592
ENSE00003694250	75361286	75361381

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8635 / max 335.2582, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150969	18.3870	1813
207591	0.3716	185
150968	0.1048	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.30	gold quality
adenohypophysis	UBERON:0002196	99.28	gold quality
right uterine tube	UBERON:0001302	99.24	gold quality
left lobe of thyroid gland	UBERON:0001120	99.22	gold quality
mucosa of stomach	UBERON:0001199	99.13	gold quality
left ovary	UBERON:0002119	99.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.12	gold quality
right ovary	UBERON:0002118	99.09	gold quality
metanephros cortex	UBERON:0010533	99.09	gold quality
right adrenal gland cortex	UBERON:0035827	99.04	gold quality
body of uterus	UBERON:0009853	99.02	gold quality
tibial nerve	UBERON:0001323	99.01	gold quality
endocervix	UBERON:0000458	99.00	gold quality
right adrenal gland	UBERON:0001233	98.97	gold quality
left adrenal gland cortex	UBERON:0035825	98.94	gold quality
left adrenal gland	UBERON:0001234	98.86	gold quality
left uterine tube	UBERON:0001303	98.83	gold quality
apex of heart	UBERON:0002098	98.78	gold quality
cerebellar hemisphere	UBERON:0002245	98.75	gold quality
upper lobe of left lung	UBERON:0008952	98.72	gold quality
ectocervix	UBERON:0012249	98.72	gold quality
right lung	UBERON:0002167	98.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.64	gold quality
body of stomach	UBERON:0001161	98.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.56	gold quality
right frontal lobe	UBERON:0002810	98.53	gold quality
left testis	UBERON:0004533	98.52	gold quality
minor salivary gland	UBERON:0001830	98.51	gold quality
lower esophagus	UBERON:0013473	98.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.94
E-GEOD-124858	no	86.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting MAN2C1, 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-3692-3P	99.98	70.27	2139
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4667-5P	97.61	66.67	1683

Literature-anchored findings (GeneRIF, showing 10)

• plays an important role in preventing oncosis-like death in BJAB cells (PMID:12643454)
• Results suggest that inhibition of alpha-mannosidase Man2c1 gene expression enhances adhesion of Jurkat T cells. (PMID:16721356)
• Inhibition of MAN2C1 gene expression suppresses growth of esophageal carcinoma cells through mitotic arrest and apoptosis. (PMID:19018777)
• Reduced antibody response to BSA was observed in transgenic mice, suggesting that specific antibody response to tumor antigens might be suppressed by hMan2c1 transgene. (PMID:19572206)
• regulation of Man2C1 expression is essential for maintaining efficient protein N-glycosylation (PMID:20978011)
• MAN2C1 methylation levels modify cumulative traumatic burden on risk of post traumatic stress disorder (PMID:21508515)
• MAN2C1 binds PTEN thereby inhibiting its phosphatidylinositol 3,4,5 triphosphate phosphatase activity (PMID:21556061)
• Man2C1 has dual functions: one in glycan catabolism and another in apoptotic signaling. (PMID:23486476)
• MAN2C1 may contribute to the verbal difficulties observed in microduplications and to the intellectual disability of microdeletion syndromes (PMID:27355585)
• Impaired catabolism of free oligosaccharides due to MAN2C1 variants causes a neurodevelopmental disorder. (PMID:35045343)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	man2c1	ENSDARG00000079835
mus_musculus	Man2c1	ENSMUSG00000032295
rattus_norvegicus	Man2c1	ENSRNOG00000030654

Paralogs (4): MAN2B2 (ENSG00000013288), MAN2B1 (ENSG00000104774), MAN2A1 (ENSG00000112893), MAN2A2 (ENSG00000196547)

Protein

Protein identifiers

Alpha-mannosidase 2C1 — Q9NTJ4 (reviewed: Q9NTJ4)

Alternative names: Alpha mannosidase 6A8B, Alpha-D-mannoside mannohydrolase, Mannosidase alpha class 2C member 1

All UniProt accessions (10): Q9NTJ4, A0A140VJN9, B4DH23, H3BMJ3, H3BQH9, H3BQJ2, H3BRI3, H3BRV3, H3BSE5, H3BUW3

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues on cytoplasmic free oligosaccharides generated by N-glycoprotein degradation pathways.

Subcellular location. Cytoplasm.

Disease relevance. Congenital disorder of deglycosylation 2 (CDDG2) [MIM:619775] An autosomal recessive disorder characterized by facial dysmorphism, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly inhibited by swainsonine. Also inhibited to a lesser extent by deoxymannojirimycin (DMM).

Similarity. Belongs to the glycosyl hydrolase 38 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NTJ4-1	1	yes
Q9NTJ4-2	2
Q9NTJ4-3	3
Q9NTJ4-4	4

RefSeq proteins (4): NP_001243423, NP_001243424, NP_001243425, NP_006706* (*=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
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
IPR041147	GH38_C	Domain
IPR054723	Ams1-like_N	Domain

Pfam: PF01074, PF07748, PF09261, PF17677, PF22907

Enzyme classification (BRENDA):

• EC 3.2.1.24 — alpha-mannosidase (BRENDA: 56 organisms, 210 substrates, 327 inhibitors, 108 Km, 36 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
P-NITROPHENYL-ALPHA-D-MANNOPYRANOSIDE	0.048–30	33
4-NITROPHENYL ALPHA-D-MANNOSIDE	0.11–2.9	22
4-METHYLUMBELLIFERYL-ALPHA-D-MANNOPYRANOSIDE	0.0073–5.2	9
4-METHYLUMBELLIFERYL ALPHA-D-MANNOPYRANOSIDE	0.0073–3.6	3
4-NITROPHENYL-ALPHA-D-MANNOPYRANOSIDE	0.0826–1.8	3
MAN9GLCNAC	0.037–0.46	3
2-O-ALPHA-D-MANNOPYRANOSYL-D-MANNOPYRANOSE	0.57–2	2
4-NITROPHENYL ALPHA-D-MANNOPYRANOSIDE	1.48–3.8	2
ALPHA-D-MAN-(1->2)-D-MAN	0.85–2.3	2
ALPHA-D-MAN-(1->4)-D-MAN	2–2.5	2
MAN-ALPHA(1-6)MAN	1.455	2
2,4-DINITROPHENYL ALPHA-D-MANNOSIDE	5	1
2,4-DINITROPHENYL-ALPHA-D-MANNOPYRANOSIDE	25	1
2-O-ALPHA-D-MANNOPYRANOSYL-D-MANNOSE	0.57	1
3-O-ALPHA-D-MANNOPYRANOSYL-ALPHA-D-MANNOPYRANOSE	27	1

UniProt features (21 total): sequence variant 8, sequence conflict 4, binding site 4, splice variant 3, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTJ4-F1	94.84	0.91

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): 372 (nucleophile)

Ligand- & substrate-binding residues (4): 260; 262; 372; 577

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: 269 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, MARTINEZ_RB1_TARGETS_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, BENPORATH_NOS_TARGETS, LIAN_NEUTROPHIL_GRANULE_CONSTITUENTS, PTF1BETA_Q6, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, MODULE_60, MODULE_38, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, BENPORATH_OCT4_TARGETS

GO Biological Process (3): mannose metabolic process (GO:0006013), oligosaccharide catabolic process (GO:0009313), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (6): alpha-mannosidase activity (GO:0004559), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

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
cellular anatomical structure	3
hexose metabolic process	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
primary metabolic process	1
mannosidase activity	1
binding	1
cation binding	1
molecular_function	1
catalytic activity	1
hydrolase activity	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAN2C1	MAN1B1	Q9UKM7	956
MAN2C1	EDEM1	Q92611	943
MAN2C1	MAN2B1	O00754	942
MAN2C1	MANBA	O00462	774
MAN2C1	EDEM2	Q9BV94	716
MAN2C1	CANX	P27824	665
MAN2C1	PTEN	P60484	661
MAN2C1	MAN1A1	P33908	651
MAN2C1	MGAM	O43451	647
MAN2C1	GUSB	P08236	646
MAN2C1	OS9	Q13438	644
MAN2C1	MOGS	Q13724	642
MAN2C1	DNAJC10	Q8IXB1	641
MAN2C1	ERLEC1	Q96DZ1	629
MAN2C1	UGGT1	Q9NYU2	612

IntAct

36 interactions, top by confidence:

A	B	Type	Score
DAP	MAN2C1	psi-mi:“MI:0915”(physical association)	0.400
MAN2C1	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
Sart1	PRPF4	psi-mi:“MI:0914”(association)	0.350
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
VWA5A	PIPSL	psi-mi:“MI:0914”(association)	0.350
PCMT1	YDJC	psi-mi:“MI:0914”(association)	0.350
CIMIP4	ATE1	psi-mi:“MI:0914”(association)	0.350
CDC20B	HMOX1	psi-mi:“MI:0914”(association)	0.350
SNCA	HCLS1	psi-mi:“MI:0914”(association)	0.350
CSAG1	NAP1L4	psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
E	SET	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KRT2	IFT56	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350
HOXA7	ANKRD28	psi-mi:“MI:0914”(association)	0.350
VWA5A	GTPBP6	psi-mi:“MI:0914”(association)	0.350
KAAG1	NME2P1	psi-mi:“MI:0914”(association)	0.350
HOXD11	LYPLA1	psi-mi:“MI:0914”(association)	0.350
SRA1	SEC24D	psi-mi:“MI:0914”(association)	0.350
EGFLAM	CLSTN1	psi-mi:“MI:0914”(association)	0.350
SRSF2	PARN	psi-mi:“MI:0914”(association)	0.350
MAN2C1	HSPA8	psi-mi:“MI:0914”(association)	0.350
CTTN	FECH	psi-mi:“MI:0914”(association)	0.350
ZC2HC1C	HSPA9	psi-mi:“MI:0914”(association)	0.350
CLLU1-AS1	USP11	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Two-hybrid), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Proximity Label-MS), MAN2C1 (Proximity Label-MS), MAN2C1 (Affinity Capture-MS), MAN2C1 (Affinity Capture-RNA)

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: P21139, P22855, Q54K67, Q91W89, Q9NTJ4, Q9UT61

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	8
Uncertain significance	196
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
4847124	NM_006715.4(MAN2C1):c.2568_2571del (p.Met856fs)	Pathogenic
1342928	NM_006715.4(MAN2C1):c.2612G>C (p.Cys871Ser)	Likely pathogenic
1342930	NM_006715.4(MAN2C1):c.607G>A (p.Gly203Arg)	Likely pathogenic
3366544	NM_006715.4(MAN2C1):c.2109_2141+4delinsAGT	Likely pathogenic
3375098	NM_006715.4(MAN2C1):c.600+1del	Likely pathogenic
3384737	NM_006715.4(MAN2C1):c.351+1G>A	Likely pathogenic
3779828	NM_006715.4(MAN2C1):c.1235G>A (p.Trp412Ter)	Likely pathogenic
4072347	NM_006715.4(MAN2C1):c.2569del (p.Asp857fs)	Likely pathogenic
4820271	NM_006715.4(MAN2C1):c.2221G>A (p.Val741Ile)	Likely pathogenic

SpliceAI

4431 predictions. Top by Δscore:

Variant	Effect	Δscore
15:75356108:A:AC	donor_gain	1.0000
15:75356109:C:CC	donor_gain	1.0000
15:75356119:T:TA	donor_gain	1.0000
15:75356604:AC:A	donor_gain	1.0000
15:75356605:CC:C	donor_gain	1.0000
15:75356791:A:AC	donor_gain	1.0000
15:75356792:C:CC	donor_gain	1.0000
15:75356898:CACAC:C	acceptor_gain	1.0000
15:75356900:CAC:C	acceptor_gain	1.0000
15:75356904:T:C	acceptor_loss	1.0000
15:75358345:CTGGG:C	acceptor_loss	1.0000
15:75358346:T:A	acceptor_loss	1.0000
15:75358807:CC:C	acceptor_gain	1.0000
15:75358808:CC:C	acceptor_gain	1.0000
15:75359156:T:TC	acceptor_gain	1.0000
15:75360219:C:CT	acceptor_gain	1.0000
15:75360219:C:T	acceptor_gain	1.0000
15:75360220:A:T	acceptor_gain	1.0000
15:75361040:CCTGA:C	donor_loss	1.0000
15:75361041:CTGAC:C	donor_loss	1.0000
15:75361042:TGA:T	donor_loss	1.0000
15:75361044:A:AG	donor_loss	1.0000
15:75361045:CC:C	donor_loss	1.0000
15:75361200:G:GC	acceptor_gain	1.0000
15:75361387:A:T	acceptor_gain	1.0000
15:75361389:C:CT	acceptor_gain	1.0000
15:75361598:GCTTA:G	donor_loss	1.0000
15:75361599:CTTAC:C	donor_loss	1.0000
15:75361600:TTAC:T	donor_loss	1.0000
15:75361602:A:AC	donor_gain	1.0000

AlphaMissense

6780 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:75359967:G:C	F576L	0.997
15:75359967:G:T	F576L	0.997
15:75359969:A:G	F576L	0.997
15:75359684:G:C	N628K	0.996
15:75359684:G:T	N628K	0.996
15:75356304:C:A	K961N	0.995
15:75356304:C:G	K961N	0.995
15:75360206:C:A	K530N	0.995
15:75360206:C:G	K530N	0.995
15:75361635:T:A	K396I	0.995
15:75361700:A:C	F374L	0.995
15:75361700:A:T	F374L	0.995
15:75361702:A:G	F374L	0.995
15:75362702:G:C	S279R	0.994
15:75362702:G:T	S279R	0.994
15:75362704:T:G	S279R	0.994
15:75360594:G:C	H519D	0.993
15:75358338:A:G	W804R	0.992
15:75358338:A:T	W804R	0.992
15:75358735:A:G	W739R	0.992
15:75358735:A:T	W739R	0.992
15:75359685:T:A	N628I	0.992
15:75359966:G:C	H577D	0.992
15:75361141:A:C	S455R	0.992
15:75361141:A:T	S455R	0.992
15:75361143:T:G	S455R	0.992
15:75361707:T:A	D372V	0.992
15:75362740:A:G	W267R	0.992
15:75362740:A:T	W267R	0.992
15:75364004:T:A	D262V	0.992

dbSNP variants (sampled 300 via entrez): RS1000139237 (15:75360370 C>G,T), RS1000515208 (15:75366056 C>T), RS1000833291 (15:75370126 T>C), RS1001015754 (15:75365066 T>C), RS1001277401 (15:75365744 C>A,G,T), RS1001450237 (15:75365437 G>A), RS1001833249 (15:75368943 G>A,C), RS1002117791 (15:75369191 C>A), RS1002148166 (15:75357911 G>A), RS1002285437 (15:75357676 G>A), RS1002423305 (15:75363745 G>A), RS1002442219 (15:75359890 T>C), RS1002571414 (15:75358913 A>G), RS1002747705 (15:75364907 C>A,T), RS1002755454 (15:75359685 T>C)

Disease associations

OMIM: gene MIM:154580 | disease phenotypes: MIM:619775, MIM:619755

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of deglycosylation 2	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital disorder of deglycosylation 2	Moderate	AR

Mondo (2): congenital disorder of deglycosylation 2 (MONDO:0030770), hypogonadotropic hypogonadism 27 without anosmia (MONDO:0030684)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000480	Retinal coloboma
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001776	Bilateral talipes equinovarus
HP:0001852	Sandal gap
HP:0002000	Short columella
HP:0002015	Dysphagia
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002282	Gray matter heterotopia
HP:0002444	Hypothalamic hamartoma
HP:0002553	Highly arched eyebrow
HP:0002816	Genu recurvatum
HP:0008551	Microtia
HP:0009487	Ulnar deviation of the hand
HP:0011265	Cleft earlobe

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4462560	MAN2C1, MIR631, NEIL1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
cobaltous chloride	decreases expression, increases activity	2
Arsenic	decreases expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation, affects cotreatment	1
titanium dioxide	decreases methylation	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
gossypol acetic acid	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
bisphenol S	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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