GALNT8

Chr 12

polypeptide N-acetylgalactosaminyltransferase 8

Also known as: GALNAC-T8

The GALNT8 protein catalyzes the initial step of O-linked glycosylation by transferring N-acetyl-D-galactosamine to serine and threonine residues on target proteins in the Golgi apparatus. Mutations in GALNT8 cause autosomal recessive intellectual developmental disorder with cardiac arrhythmia, affecting neurological development and cardiac conduction. The gene shows tolerance to loss-of-function variants (low constraint), which is consistent with the recessive inheritance pattern observed in affected families.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.39
Clinical SummaryGALNT8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 97 VUS of 172 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.39LOEUF
pLI 0.000
Z-score -0.09
OE 1.02 (0.761.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.02Z-score
OE missense 1.00 (0.921.09)
369 obs / 367.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.02 (0.761.39)
00.351.4
Missense OE1.00 (0.921.09)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 29 / 28.5Missense obs/exp: 369 / 367.8Syn Z: 0.40
DN
0.6745th %ile
GOF
0.5954th %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.

ClinVar Variant Classifications

172 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic5
VUS97
Likely Benign5
Benign5
Conflicting1
52
Pathogenic
5
Likely Pathogenic
97
VUS
5
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
5
0
5
VUS
0
90
7
0
97
Likely Benign
0
5
0
0
5
Benign
0
3
1
1
5
Conflicting
1
Total098651165

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

View in ClinVar →

Protein Context — Lollipop Plot

GALNT8 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗