SLC35C1
protein-codingsolute carrier family 35 member C1, the group of Solute carrier family 35
Gene summary
This gene encodes a GDP-fucose transporter that is found in the Golgi apparatus. Mutations in this gene result in congenital disorder of glycosylation type IIc. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: ClinGen
SLC35C1 was first reported in relation to autosomal recessive leukocyte adhesion deficiency type II in 2001 (Lühn et al., PMID 11326279; Lübke et al. PMID 11326280). At least nine variants (missense, frameshift, nonsense, in-frame deletions) that have been reported in 8 probands in 7 publications (PMIDs 11326279, 11326280, 24403049, 16455955, 35338746, 30630937, 12406889) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached. Patients have a range of symptoms, including developmental delay, growth delay, dysmorphic features, recurrent infections, hypotonia, and impaired neutrophil motility. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. This gene-disease relationship is supported by in vitro and in vivo assays showing a defect in fucosylation (PMIDs 11326279, 24403049, 16455955) as well as a mouse model (PMID 17276979). In summary, there is definitive evidence to support the relationship between SLC35C1 and autosomal recessive leukocyte adhesion deficiency type II. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date November 3, 2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009953
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Biochemical; Neurologic
Intervention: Allergy/Immunology/Infectious; Biochemical; Hematologic
Rationale: Treatment with fucose has been described as effective in some individuals; Surveillance for and prompt treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery
Comments: Hepatic-metabolized agents should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC35C1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018389.5. 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 | 114 | 115 | |||
| missense | 2 | 3 | 136 | 8 | 1 | 150 |
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 3 | 2 | 5 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 4 | 139 | 122 | 1 | 273 |
Highest pathogenic variant AF is 0.0006752642
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060859.4 | 2 | MANE Select | |
| Ensembl | ENSP00000313318.3 | 2 | MANE Select | |
| RefSeq | NP_001138737.1 | 2 | Standard | |
| RefSeq | NP_001138738.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Purine metabolism
- Transport of vitamins, nucleosides, and related molecules
- SLC-mediated transmembrane transport
Biological Process
- carbohydrate transport
- lipid glycosylation
- protein O-linked fucosylation
- GDP-fucose import into Golgi lumen
- negative regulation of Notch signaling pathway
Molecular Function
- GDP-fucose transmembrane transporter activity
- antiporter activity
- transmembrane transporter activity
Cellular Component
- Golgi membrane
- Golgi apparatus
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314134
- Coding exons
- 2
- Length
- 8944
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125700
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.16 | 172 | 221 | 0.780 | 0.0000149 | 2320 |
| Missense (PolyPhen) | 29 | 60.833 | 0.47672 | 663 | ||
| Synonymous | -1.10 | 126 | 111 | 1.13 | 0.00000880 | 802 |
| Loss of Function | 1.63 | 4 | 9.39 | 0.426 | 4.08e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in GDP-fucose import from the cytoplasm into the Golgi lumen.;
- Disease
- DISEASE: Congenital disorder of glycosylation 2C (CDG2C) [MIM:266265]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in 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. The clinical features of CDG2C include mental retardation, short stature, facial stigmata, and recurrent bacterial peripheral infections with persistently elevated peripheral leukocytes. Biochemically, CDG2C is characterized by a lack of fucosylated glycoconjugates, including selectin ligands. {ECO:0000269|PubMed:11326279, ECO:0000269|PubMed:11326280}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.309
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.138
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |