MAN2A1
protein-codingmannosidase alpha class 2A member 1, the group of Mannosidases alpha class 2
Gene summary
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. [provided by RefSeq, Dec 2013]
- MANA2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~179.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAN2A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002372.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 159 | 10 | 169 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 166 | 11 | 0 | 177 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002363.2 | 22 | MANE Select | |
| Ensembl | ENSP00000261483.4 | 22 | MANE Select | |
| Ensembl | ENSP00000550582.1 | 20 | Standard | |
| Ensembl | ENSP00000550582.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- N-Glycan biosynthesis - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Reactions specific to the complex N-glycan synthesis pathway
Biological Process
- in utero embryonic development
- liver development
- mannose metabolic process
- protein glycosylation
- N-glycan processing
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
Cellular Component
- Golgi membrane
- Golgi medial cisterna
- cis-Golgi network
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261483
- Coding exons
- 22
- Length
- 180260
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125747
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.427 | 560 | 589 | 0.950 | 0.0000296 | 7510 |
| Missense (PolyPhen) | 142 | 240.84 | 0.5896 | 3144 | ||
| Synonymous | -2.80 | 263 | 211 | 1.25 | 0.0000108 | 2115 |
| Loss of Function | 3.98 | 27 | 60.3 | 0.448 | 0.00000309 | 754 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00024 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000053 | 0.000046 | rare |
| European (Non-Finnish) | 0.000090 | 0.000088 | rare |
| South Asian | 0.00021 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. {ECO:0000250|UniProtKB:P28494}.;
Recessive Scores
- pRec
- 0.294
Intolerance Scores
- LoFtool
- 0.243
- RVIS EVS
- -1.57
- RVIS percentile EVS
- 3.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.352
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |