GALNT12

Chr 9

polypeptide N-acetylgalactosaminyltransferase 12

Also known as: CRCS1, GalNAc-T12

The GALNT12 protein catalyzes the initial step of O-linked protein glycosylation by transferring N-acetylgalactosamine to serine or threonine residues, particularly important for mucin-type oligosaccharide biosynthesis in digestive organs. Mutations cause increased susceptibility to colorectal cancer with autosomal dominant inheritance. This gene is not highly constrained against loss-of-function variants, consistent with its role as a cancer susceptibility gene rather than causing severe developmental disorders.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 0.941 OMIM phenotype
Clinical SummaryGALNT12
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Gene-Disease Validity (ClinGen)
colorectal cancer, susceptibility to, 1 · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — GALNT12
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.77
OE 0.59 (0.390.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.891.08)
272 obs / 278.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.390.94)
00.351.4
Missense OE0.98 (0.891.08)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 13 / 22.0Missense obs/exp: 272 / 278.2Syn Z: 0.14
DN
0.6649th %ile
GOF
0.6930th %ile
LOF
0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GALNT12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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