MAN2A2

mannosidase alpha class 2A member 2, the group of Mannosidases alpha class 2

Basic information

Region (hg38): 15:90902218-90922584

Links

ENSG00000196547 ∙ NCBI:4122 ∙ OMIM:600988 ∙ HGNC:6825 ∙ Uniprot:P49641 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• disorder of glycosylation (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAN2A2 gene.

• not_specified (174 variants)
• not_provided (6 variants)
• Neurodevelopmental_delay (2 variants)
• Aganglionic_megacolon (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAN2A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006122.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense		1	164	11		176
nonsense		1				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	164	12	3

Highest pathogenic variant AF is 0.0000013681145

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAN2A2	protein_coding	protein_coding	ENST00000360468	22	20367

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-10	1.00	125361	0	387	125748	0.00154

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	650	730	0.891	0.0000471	7476
Missense in Polyphen		221	294.27	0.751		3174
Synonymous	-1.45	336	304	1.11	0.0000199	2367
Loss of Function	3.96	27	60.1	0.449	0.00000343	583

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00361	0.00338
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000324	0.000323
European (Non-Finnish)	0.00204	0.00204
Middle Eastern	0.000381	0.000381
South Asian	0.000458	0.000457
Other	0.00293	0.00294

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Vesicle-mediated transport;er associated degradation (erad) pathway;Membrane Trafficking;Post-translational protein modification;Reactions specific to the complex N-glycan synthesis pathway;N-glycan antennae elongation in the medial/trans-Golgi;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Intra-Golgi traffic;N-Glycan biosynthesis;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.285
• rvis_EVS: -1.45
• rvis_percentile_EVS: 3.93

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.554
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Man2a2
• Phenotype: renal/urinary system phenotype; respiratory system phenotype; liver/biliary system phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype

Gene ontology

• Biological process: mannose metabolic process;protein glycosylation;N-glycan processing;protein deglycosylation
• Cellular component: Golgi membrane;integral component of membrane
• Molecular function: alpha-mannosidase activity;mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity;hydrolase activity, hydrolyzing N-glycosyl compounds;carbohydrate binding;metal ion binding