GALNT8

Chr 12

polypeptide N-acetylgalactosaminyltransferase 8

Also known as: GALNAC-T8

NCBI Gene: 26290 ENSG00000130035 UniProt: Q9NY28 OMIM: 606250

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.39

Clinical Summary— GALNT8

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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 VUS of 107 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score -0.09

OE 1.02 (0.76–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.92–1.09)

369 obs / 367.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.02 (0.76–1.39)

0≤0.351.4

Missense OE?1.00 (0.92–1.09)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 29 / 28.5Missense obs/exp: 369 / 367.8Syn Z: 0.40

This gene — mechanism propensity

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

107 submitted variants in ClinVar

ClinVar

Classification Summary

VUS90

Likely Benign5

Benign5

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	90	0	0	90
Likely Benign	0	5	0	0	5
Benign	0	3	1	1	5
Conflicting	—				1
Total	0	98	1	1	101

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap GALNT8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →