MGAT4A

protein-coding

alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A, the group of Mannosyl-glycoprotein N-acetylglucosaminyltransferases

Gene summary

This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme B, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012214.3

Inheritance

—

ClinVar variants

U:60B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr2:98,619,106-98,731,132

External References & Databases

Ensembl (ENSG00000071073)

Transcript & Mutation Effects

hg38 • Region Span ~112.0 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 MGAT4A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012214.3. 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
missense			60 clinvar		1 clinvar	61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	60	0	2	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012214.3	RefSeq	NP_036346.1	15	MANE Select
ENST00000393487.6	Ensembl	ENSP00000377127.1	15	MANE Select
NM_001160154.2	RefSeq	NP_001153626.1	13	Standard
ENST00000264968.7	Ensembl	ENSP00000264968.2	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

N-Glycan biosynthesis - Homo sapiens (human)
Post-translational protein phosphorylation
Post-translational protein modification
N-Glycan antennae elongation
N-glycan antennae elongation in the medial/trans-Golgi

Biological Process

protein N-linked glycosylation
N-glycan processing
post-translational protein modification
cellular protein metabolic process

Molecular Function

alpha-1,3-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase activity
metal ion binding

Cellular Component

Golgi membrane
endoplasmic reticulum lumen
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264968
Coding exons: 15
Length: 112021
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125745
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.50	203	273	0.744	0.0000136	3513
Missense (PolyPhen)		19	59.34	0.32019		758
Synonymous	0.0906	94	95.1	0.988	0.00000485	974
Loss of Function	3.12	13	32.1	0.405	0.00000170	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Glycosyltransferase that participates in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N- linked glycans. Catalyzes the formation of the GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans. Essential for the production of tri- and tetra-antennary N-linked sugar chains. Involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation, thereby controlling cell-surface expression of SLC2A2 in pancreatic beta cells.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.710
RVIS EVS: 0.04
RVIS percentile EVS: 57.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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