GALNT3

Chr 2AR

polypeptide N-acetylgalactosaminyltransferase 3

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

NCBI Gene: 2591ENSG00000115339UniProt: Q14435

This gene encodes UDP-GalNAc transferase 3, a member of the GalNAc-transferases family. This family transfers an N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. Individual GalNAc-transferases have distinct activities and initiation of O-glycosylation is regulated by a repertoire of GalNAc-transferases. The protein encoded by this gene is highly homologous to other family members, however the enzymes have different substrate specificities. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Tumoral calcinosis, hyperphosphatemic, familial, 1MIM #211900
AR
608
ClinVar variants
99
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GALNT3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 194 VUS of 608 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.000
Z-score 2.16
OE 0.58 (0.40–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.39Z-score
OE missense 0.94 (0.86–1.03)
317 obs / 336.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.40–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 18 / 30.9Missense obs/exp: 317 / 336.9Syn Z: 0.49

ClinVar Variant Classifications

608 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic27
VUS194
Likely Benign160
Benign26
Conflicting15
72
Pathogenic
27
Likely Pathogenic
194
VUS
160
Likely Benign
26
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
4
52
0
72
Likely Pathogenic
13
7
7
0
27
VUS
1
153
38
2
194
Likely Benign
0
1
65
94
160
Benign
0
3
22
1
26
Conflicting
—15
Total3016818497494

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.

Gene2Phenotype Curations

GALNT3-related calcinosis, tumoral with hyperphosphataemia

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Tumoral calcinosis, hyperphosphatemic, familial, 1

MIM #211900

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Whole exome sequencing analysis of 167 men with primary infertility.
Zhou H et al.·BMC Med Genomics
2024
Hyperphosphatemic Familial Tumoral Calcinosis.
Kaszycki M et al.·South Med J
2024Case report
Long-term clinical outcome and phenotypic variability in hyperphosphatemic familial tumoral calcinosis and hyperphosphatemic hyperostosis syndrome caused by a novel GALNT3 mutation; case report and review of the literature.
Rafaelsen S et al.·BMC Genet
2014Review
Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and αKlotho).
Farrow EG et al.·Best Pract Res Clin Rheumatol
2011Review
Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management.
Boyce AM et al.·Front Endocrinol (Lausanne)
2020Review
Rare and Common Variants in GALNT3 May Affect Bone Mass Independently of Phosphate Metabolism.
Hassan N et al.·J Bone Miner Res
2023Case report
GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells.
Raghu D et al.·Cell Rep
2019
Variant in GALNT3 Gene Linked with Reduced Coronary Artery Disease Risk in Chinese Population.
Guo L et al.·DNA Cell Biol
2017
GALNT3 is a novel target driving lymphomagenesis via O-glycosylation of FGFR2.
Sun R et al.·Cell Commun Signal
2025
Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.
Shu G et al.·Oncogene
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
2026🔓 Open Access
Identification of O-GalNAc-modified proteins interacting with GALNT3 using proximity labeling method.
Xu B et al.·Carbohydr Res
2025
Single-cell and spatial transcriptome analysis revealed cellular heterogeneity of glycosyltransferases in cervical cancer, and identified GALNT3-negative epithelial cells as a protective factor: a retrospective cohort study based on public database.
Xiao J et al.·Int J Surg
2025Cohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools