MAN1A1

protein-coding

mannosidase alpha class 1A member 1, the group of Mannosidases alpha class 1

Gene summary

This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

MANE transcript

NM_005907.4

Inheritance

—

ClinVar variants

U:89B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr6:119,177,205-119,349,761

External References & Databases

Ensembl (ENSG00000111885)

Transcript & Mutation Effects

hg38 • Region Span ~172.6 kb

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GenCC 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 MAN1A1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005907.4. 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			1 clinvar		1 clinvar	2
missense			86 clinvar	1 clinvar	1 clinvar	88
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	89	1	2	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005907.4	RefSeq	NP_005898.2	12	MANE Select
ENST00000368468.4	Ensembl	ENSP00000357453.3	12	MANE Select
ENST00000887750.1	Ensembl	ENSP00000557809.1	12	Standard
ENST00000887750.2	Ensembl	ENSP00000557809.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
N-Glycan biosynthesis - Homo sapiens (human)
Vesicle-mediated transport
er associated degradation (erad) pathway
Membrane Trafficking

Biological Process

protein glycosylation
N-glycan processing
Golgi apparatus mannose trimming

Molecular Function

mannosyl-oligosaccharide 1,2-alpha-mannosidase activity
calcium ion binding
mannosidase activity

Cellular Component

Golgi membrane
endoplasmic reticulum
endoplasmic reticulum-Golgi intermediate compartment
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368468
Coding exons: 12
Length: 172553
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125746
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	270	350	0.772	0.0000171	4244
Missense (PolyPhen)		81	154.55	0.52411		1882
Synonymous	0.780	126	138	0.915	0.00000712	1266
Loss of Function	3.86	8	31.3	0.256	0.00000161	376

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000069	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.515
RVIS EVS: -0.47
RVIS percentile EVS: 23.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.177

Gene Damage Prediction

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