GALNT3

Chr 2AR

polypeptide N-acetylgalactosaminyltransferase 3

Also known as: GalNAc-T3, HFTC, HFTC1, HHS

NCBI Gene: 2591ENSG00000115339UniProt: Q14435OMIM: 601756

UDP-GalNAc transferase 3 catalyzes the initial step in O-linked oligosaccharide biosynthesis by transferring N-acetyl-D-galactosamine to serine or threonine residues on protein substrates, including glycosylation of FGF23. Biallelic mutations cause hyperphosphatemic familial tumoral calcinosis type 1, inherited in an autosomal recessive pattern. This gene is not highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.861 OMIM phenotype
Clinical Summary— GALNT3
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Gene-Disease Validity (ClinGen)
tumoral calcinosis, hyperphosphatemic, familial, 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
90 unique Pathogenic / Likely Pathogenic· 150 VUS of 407 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — GALNT3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.16
OE 0.58 (0.40–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.39Z-score
OE missense 0.94 (0.86–1.03)
317 obs / 336.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.40–0.86)
0≤0.351.4
Missense OE0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 18 / 30.9Missense obs/exp: 317 / 336.9Syn Z: 0.49
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGALNT3-related calcinosis, tumoral with hyperphosphataemiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.7029th %ile
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

407 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic21
VUS150
Likely Benign120
Benign26
Conflicting16
69
Pathogenic
21
Likely Pathogenic
150
VUS
120
Likely Benign
26
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
5
40
0
69
Likely Pathogenic
12
5
4
0
21
VUS
0
115
35
0
150
Likely Benign
0
0
48
72
120
Benign
0
3
22
1
26
Conflicting
—16
Total3612814973402

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GALNT3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Research progress in the role and mechanism of GALNT3 in human diseases (Review).
Su L et al.·Biomed Rep
2026Open AccessReview
Clinical and Functional Characterization of Novel GALNT3 Mutations in a Chinese Child with Hyperphosphatemic Familial Tumoral Calcinosis.
Gao Y et al.·Int J Mol Sci
2026Open AccessFunctional
GALNT3 Inhibits the Progression of Cerebral Ischemia-Reperfusion Injury by Stabilizing TREM2 via O-GalNAc Glycosylation.
Fei X et al.·CNS Neurosci Ther
2026Open Access
GALNT3-mediated AKT1 glycosylation activates the AKT1/CREB signaling pathway to inhibit high glucose-induced spermatogenic cell apoptosis and mitochondrial dysfunction.
Zhao Y et al.·Biochem Biophys Res Commun
2026
A Large Deletion With a Large Impact: Homozygous 5,600 bp Deletion of the GALNT3 Gene Causing Hyperphosphatemic Tumoral Calcinosis.
Portmann JM et al.·Kidney Med
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients