SLC35A1
protein-codingsolute carrier family 35 member A1, the group of Solute carrier family 35
Gene summary
The protein encoded by this gene is found in the membrane of the Golgi apparatus, where it transports nucleotide sugars into the Golgi. One such nucleotide sugar is CMP-sialic acid, which is imported into the Golgi by the encoded protein and subsequently glycosylated. Defects in this gene are a cause of congenital disorder of glycosylation type 2F (CDG2F). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011342
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011342
Submitter: ClinGen
*SLC35A1* was first reported in relation to autosomal recessive SLC35A1-congenital disorder of glycosylation (originally called Congenital disorder of glycosylation, type IIf) in 2005 (Martinez-Duncker I et al., PMID:15576474). *SLC35A1* functions by transporting CMP-sialic acid from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges CMP-sialic acid for CMP. Moving nucleotide sugars across the membrane is essential for glycosylation reactions that take place within the Golgi apparatus. Patient with disrupted *SLC35A1* show characteristics of macrothrombocytopenia, thrombocytopenia, global developmental delay, seizures, and cognitive impairment. Seven variants that have been reported in five probands in five publications (PMIDs: 28856833, 30115659, 23873973, 15576474, 40613041) are included in this curation. Probands presented with considerable decrease in the amount of N- and O-glycans terminating in sialic acid as evidence by primary fibroblasts and serum levels. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by a mouse model (PMID: 32303557) in a knockout mouse line. Lectin-based flow cytometry showed the mouse had thrombocytopenia, seen in humans as well. Functional alteration studies (PMID: 25552652) using flow cytometry showed Ac5SiaNPoc was completely absent in the knockout cell lines (Fig. 2D). In knockout cells complemented with a wild-type *SLC35A1* construct, Ac5SiaNPoc incorporation was completely restored, whereas complementation with mutant *SLC35A1* restored Ac5SiaNPoc incorporation for only ∼20%. While the other study confirmed the loss of terminal sialic acids showing show that *SLC35A1* is essential for synthesis of the functional O-mannose glycan on α-DG, by a mechanism that is independent from sialylation. In summary, there is moderate evidence supporting the relationship between *SLC35A1* autosomal recessive SLC35A1-congenital disorder of glycosylation. This classification was approved by the ClinGen CDG GCEP on the meeting date November 17, 2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0011342
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0011342
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Hematologic; Neurologic
Intervention: Allergy/Immunology/Infectious; Hematologic
Rationale: The condition can include infectious risks (as well as other hematologic anomalies), and antiinnfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery
Comments: Hepatic-metabolized medications should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC35A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006416.5. 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 | 26 | 27 | |||
| missense | 2 | 2 | 40 | 5 | 49 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 2 | 46 | 31 | 0 | 81 |
Highest pathogenic variant AF is 0.0000013681613
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006407.1 | 8 | MANE Select | |
| Ensembl | ENSP00000358565.4 | 8 | MANE Select | |
| RefSeq | NP_001161870.1 | 7 | Standard | |
| Ensembl | ENSP00000358569.3 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Transport of vitamins, nucleosides, and related molecules
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- carbohydrate metabolic process
- cellular protein modification process
- carbohydrate transport
- sialic acid transport
- CMP-N-acetylneuraminate transmembrane transport
Molecular Function
- CMP-N-acetylneuraminate transmembrane transporter activity
- sialic acid transmembrane transporter activity
Cellular Component
- Golgi membrane
- Golgi apparatus
- integral component of plasma membrane
- integral component of Golgi membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369552
- Coding exons
- 8
- Length
- 41714
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 122 | 168 | 0.724 | 0.00000804 | 2115 |
| Missense (PolyPhen) | 16 | 39.669 | 0.40334 | 509 | ||
| Synonymous | -0.180 | 70 | 68.1 | 1.03 | 0.00000360 | 688 |
| Loss of Function | 3.12 | 3 | 16.8 | 0.178 | 7.04e-7 | 245 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000070 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transports CMP-sialic acid from the cytosol into Golgi vesicles where glycosyltransferases function.;
- Disease
- DISEASE: Congenital disorder of glycosylation 2F (CDG2F) [MIM:603585]: CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:15576474}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.362
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |