GALNT2

Chr 1AR

polypeptide N-acetylgalactosaminyltransferase 2

Also known as: CDG2T, GalNAc-T2

NCBI Gene: 2590 ENSG00000143641 UniProt: Q10471 OMIM: 602274

The protein catalyzes the initial step in O-linked oligosaccharide biosynthesis by transferring N-acetyl-D-galactosamine to serine or threonine residues on target proteins, with particular involvement in immunoglobulin A1 hinge region glycosylation and HDL-C metabolism regulation. Mutations cause congenital disorder of glycosylation type IIt with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.488).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.491 OMIM phenotype

Clinical Summary— GALNT2

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Gene-Disease Validity (ClinGen)

congenital disorder of glycosylation, type iit · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.008

Z-score 3.99

OE 0.29 (0.18–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.00Z-score

OE missense 0.70 (0.63–0.78)

243 obs / 348.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.29 (0.18–0.49)

0≤0.351.4

Missense OE?0.70 (0.63–0.78)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 11 / 37.3Missense obs/exp: 243 / 348.1Syn Z: -0.24

This gene — mechanism propensity

0.6453th %ile

GOF

0.6149th %ile

LOF

0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.