MAN2C1

mannosidase alpha class 2C member 1, the group of Mannosidases alpha class 2

Basic information

Region (hg38): 15:75355207-75368612

Previous symbols: [ "MANA1", "MANA" ]

Links

ENSG00000140400 ∙ NCBI:4123 ∙ OMIM:154580 ∙ HGNC:6827 ∙ Uniprot:Q9NTJ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of deglycosylation 2 (Moderate), mode of inheritance: AR
• congenital disorder of deglycosylation 2 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of deglycosylation 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	35045343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAN2C1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAN2C1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense		1	85	2		88
nonsense			1			1
start loss						0
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding					1	1
Total	0	2	89	4	1

Variants in MAN2C1

This is a list of pathogenic ClinVar variants found in the MAN2C1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-75355914-G-A		not specified	Uncertain significance (Oct 20, 2023)
15-75355916-G-A		not specified	Uncertain significance (Aug 28, 2024)
15-75355976-C-T		not specified	Uncertain significance (Apr 18, 2023)
15-75355977-G-A		not specified	Uncertain significance (Jan 23, 2023)
15-75355995-A-T		not specified	Uncertain significance (Sep 07, 2022)
15-75356003-G-C		not specified	Uncertain significance (Oct 09, 2024)
15-75356033-C-A		Congenital disorder of deglycosylation 2	Uncertain significance (May 22, 2022)
15-75356198-G-A		not specified	Uncertain significance (Dec 28, 2022)
15-75356200-C-T		not specified	Uncertain significance (Aug 12, 2024)
15-75356321-C-T		not specified	Uncertain significance (Apr 13, 2022)
15-75356339-C-T		not specified	Uncertain significance (Jan 16, 2024)
15-75356378-G-A		not specified	Uncertain significance (Jan 31, 2024)
15-75356435-C-T		not specified	Uncertain significance (Feb 27, 2024)
15-75356608-TTG-T		Congenital disorder of deglycosylation 2	Likely pathogenic (Jun 24, 2022)
15-75356613-C-T			Likely benign (Mar 01, 2023)
15-75356621-G-C		not specified	Uncertain significance (Aug 05, 2024)
15-75356626-T-C		not specified	Uncertain significance (Aug 26, 2024)
15-75356641-C-T		Congenital disorder of deglycosylation 2	Uncertain significance (Sep 02, 2022)
15-75356642-G-A		not specified	Uncertain significance (Jun 06, 2023)
15-75356665-G-A		not specified	Uncertain significance (Oct 04, 2024)
15-75356680-C-T		not specified	Uncertain significance (Jun 01, 2023)
15-75356794-G-A		not specified	Uncertain significance (Mar 01, 2024)
15-75356838-C-G		Congenital disorder of deglycosylation 2	Pathogenic (Mar 09, 2022)
15-75356848-G-A		not specified	Uncertain significance (Oct 28, 2024)
15-75356853-G-A		not specified	Uncertain significance (May 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAN2C1	protein_coding	protein_coding	ENST00000565683	26	12839

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.77e-29	0.00263	124999	1	748	125748	0.00298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.155	627	638	0.983	0.0000386	6789
Missense in Polyphen		174	201.14	0.86505		2415
Synonymous	0.177	262	266	0.986	0.0000164	2135
Loss of Function	1.06	49	57.7	0.850	0.00000288	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00309	0.00306
Ashkenazi Jewish	0.00103	0.000993
East Asian	0.0108	0.0108
Finnish	0.000790	0.000786
European (Non-Finnish)	0.00346	0.00338
Middle Eastern	0.0108	0.0108
South Asian	0.00131	0.00131
Other	0.00269	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues from glycoproteins. Involved in the degradation of free oligosaccharides in the cytoplasm. {ECO:0000269|PubMed:16848760}.
• Pathway: Other glycan degradation - Homo sapiens (human);er associated degradation (erad) pathway;Lysosomal oligosaccharide catabolism;Metabolism of carbohydrates;Metabolism (Consensus)

Recessive Scores

• pRec: 0.267

Intolerance Scores

• loftool: 0.746
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.21

Haploinsufficiency Scores

• pHI: 0.254
• hipred: N
• hipred_score: 0.204
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.886

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Man2c1
• Phenotype: renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; hematopoietic system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: mannose metabolic process;oligosaccharide catabolic process
• Cellular component: nucleoplasm;cytosol
• Molecular function: alpha-mannosidase activity;carbohydrate binding;metal ion binding