ST6GALNAC4
protein-codingST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 4, the group of Sialyltransferases
Gene summary
The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein prefers glycoproteins rather than glycolipids as substrates and shows restricted substrate specificity, utilizing only the trisaccharide sequence Neu5Ac-alpha-2,3-Gal-beta-1,3-GalNAc. In addition, it is involved in the synthesis of ganglioside GD1A from GM1B. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Transcript variants encoding different isoforms have been found for this gene. Readthrough transcripts exist for this gene and the downstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]
- SIAT7D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ST6GALNAC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_175039.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 53 | 2 | 55 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 57 | 2 | 2 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_778204.1 | 5 | MANE Select | |
| Ensembl | ENSP00000336733.5 | 5 | MANE Select | |
| RefSeq | NP_778205.1 | 3 | Standard | |
| Ensembl | ENSP00000355130.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human)
- Globo Sphingolipid Metabolism
- Post-translational protein modification
- Metabolism of proteins
- Glycosphingolipid biosynthesis - ganglioseries
Biological Process
- glycolipid metabolic process
- O-glycan processing
- sialylation
Molecular Function
- alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase activity
- sialyltransferase activity
- (alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3)-N-acetyl-galactosaminide 6-alpha-sialyltransferase activity
Cellular Component
- Golgi membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000335791
- Coding exons
- 5
- Length
- 9153
- Individuals with no LoFs
- 125651
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 86
- Defined
- 125739
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.764 | 174 | 205 | 0.850 | 0.0000142 | 1941 |
| Missense (PolyPhen) | 74 | 92.428 | 0.80062 | 846 | ||
| Synonymous | 0.408 | 86 | 90.9 | 0.946 | 0.00000683 | 607 |
| Loss of Function | 0.540 | 11 | 13.1 | 0.839 | 7.29e-7 | 138 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.0024 | 0.0023 | notable |
| European (Non-Finnish) | 0.00016 | 0.00013 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the biosynthesis of ganglioside GD1A from GM1B. Transfers CMP-NeuAc with an alpha-2,6-linkage to GalNAc residue on NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc of glycoproteins and glycolipids. Prefers glycoproteins to glycolipids (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.556
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.156
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |