GALNT2

protein-coding

polypeptide N-acetylgalactosaminyltransferase 2, the group of Polypeptide N-acetylgalactosaminyltransferases

Gene summary

This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

MANE transcript

NM_004481.5

Inheritance

ClinVar variants

P:10U:97B:55

Top phenotype

Congenital disorder of glycosylation, type IIt

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr1:230,057,990-230,282,122

External References & Databases

Ensembl (ENSG00000143641)

Transcript & Mutation Effects

hg38 • Region Span ~224.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital disorder of glycosylation, type iitSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030043

Submitter: ClinGen

GALNT2 was first reported in relation to autosomal receive congenital disorder of glycosylation, type IIt in 2012 ( Holleboom A, et al., 2012, PMID: 22152306). Congenital disorder of glycosylation, type IIt is a multisystemic metabolic disorder characterized by global developmental delay, poor overall growth, severely impaired intellectual development with absent language, and behavioral abnormalities. Most patients develop early-onset seizures. This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. (O'Leary NA et al., 2016, PMID: 26553804) Four variants (1 missense, 3 nonsense) that have been reported in approximately 4 probands in 1 publications (Zilmer M, et al., 2020, PMID: 32293671), are included in this curation. The mechanism of disease for Immunodeficiency 23 is gene mutations result in the production of an enzyme with reduced activity. This gene-disease relationship is also supported by experimental evidence including expression of enzymatic activity in mouse models (Greig KT, et al., 2007, PMID: 17548465). In summary, there is strong evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorder of Glycosylation Expert Panel on the meeting date 9/20/2023 (SOP Version 9).

congenital disorder of glycosylation, type iitSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030043

Submitter: Labcorp Genetics (formerly Invitae)

congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015286

Submitter: PanelApp Australia

congenital disorder of glycosylation, type iitSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030043

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Congenital disorder of glycosylation, type IItAR

Manifestation: Craniofacial; Endocrine; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 27508872; 32293671

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GALNT2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 131

Inborn genetic diseasesTotal: 69

Congenital disorder of glycosylation, type iitTotal: 17

GALNT2-related disorderTotal: 7

not specifiedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004481.5. 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	44 clinvar	8 clinvar	53
missense		4 clinvar	85 clinvar	3 clinvar		92
nonsense	3 clinvar	2 clinvar	2 clinvar			7
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	4	6	97	47	8	162

Highest pathogenic variant AF is 0.000004125027

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004481.5	RefSeq	NP_004472.1	16	MANE Select
ENST00000366672.5	Ensembl	ENSP00000355632.4	16	MANE Select
NM_001291866.2	RefSeq	NP_001278795.1	16	Standard
ENST00000868579.1	Ensembl	ENSP00000538638.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mucin type O-glycan biosynthesis - Homo sapiens (human)
Globo Sphingolipid Metabolism
Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification

Biological Process

immunoglobulin biosynthetic process
protein O-linked glycosylation
O-glycan processing
protein O-linked glycosylation via serine
protein O-linked glycosylation via threonine

Molecular Function

polypeptide N-acetylgalactosaminyltransferase activity
protein binding
manganese ion binding
carbohydrate binding

Cellular Component

Golgi membrane
extracellular region
endoplasmic reticulum membrane
Golgi apparatus
Golgi stack

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366672
Coding exons: 16
Length: 224335
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125746
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.00	243	348	0.698	0.0000216	3746
Missense (PolyPhen)		72	147.33	0.48871		1504
Synonymous	-0.243	139	135	1.03	0.00000879	1069
Loss of Function	3.99	11	37.3	0.295	0.00000218	385

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region. {ECO:0000269|PubMed:12438318, ECO:0000269|PubMed:16434399, ECO:0000269|PubMed:7592619, ECO:0000269|PubMed:9295285}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.566
RVIS EVS: -0.56
RVIS percentile EVS: 19.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.492

Gene Damage Prediction

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