GALNT3

Chr 2AR

polypeptide N-acetylgalactosaminyltransferase 3

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

NCBI Gene: 2591 ENSG00000115339 UniProt: Q14435 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

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

76 unique Pathogenic / Likely Pathogenic· 201 VUS of 546 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 OE?0.58 (0.40–0.86)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?0.94

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

This gene — mechanism propensity

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

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

546 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46

Likely Pathogenic30

VUS201

Likely Benign221

Benign27

Conflicting16

Pathogenic

Likely Pathogenic

201

VUS

221

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	34	5	7	0	46
Likely Pathogenic	17	10	3	0	30
VUS	1	176	22	2	201
Likely Benign	0	0	88	133	221
Benign	0	3	23	1	27
Conflicting	—				16
Total	52	194	143	136	541

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 63) ClinVar copy-number / structural variants overlap GALNT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →