SLC35A1

Chr 6AR

solute carrier family 35 member A1

Also known as: CDG2F, CMPST, CST, hCST

NCBI Gene: 10559ENSG00000164414UniProt: P78382

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]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIfMIM #603585
AR
140
ClinVar variants
21
Pathogenic / LP
0.68
pLI score
0
Active trials
Clinical Summary— SLC35A1
🧬
Gene-Disease Validity (ClinGen)
SLC35A1-congenital disorder of glycosylation · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 51 VUS of 140 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.46LOEUF
pLI 0.683
Z-score 3.12
OE 0.18 (0.08–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.27Z-score
OE missense 0.72 (0.62–0.84)
122 obs / 168.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.08–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.62–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 3 / 16.8Missense obs/exp: 122 / 168.4Syn Z: -0.18

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS51
Likely Benign48
Benign18
Conflicting2
19
Pathogenic
2
Likely Pathogenic
51
VUS
48
Likely Benign
18
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
16
0
19
Likely Pathogenic
0
2
0
0
2
VUS
2
36
13
0
51
Likely Benign
0
3
25
20
48
Benign
0
0
18
0
18
Conflicting
—2
Total3437220140

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC35A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC35A1-related congenital disorder of glycosylation

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type IIf

MIM #603585

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLC35A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Novel Missense Variant in Ultrarare SLC35A1-CDG Alters Cellular Glycosylation, Lipid, and Energy Metabolism Without Affecting CDG Serum Markers.
Falkenstein K et al.·Hum Mutat
2025Review
Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver.
Ma X et al.·Haematologica
2021
Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.
Marín-Quílez A et al.·Int J Mol Sci
2023Review
A functional splice variant of the human Golgi CMP-sialic acid transporter.
Salinas-Marín R et al.·Glycoconj J
2016Functional
Disease mutations in CMP-sialic acid transporter SLC35A1 result in abnormal α-dystroglycan O-mannosylation, independent from sialic acid.
Riemersma M et al.·Hum Mol Genet
2015
Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD.
Verstockt B et al.·BMJ Open Gastroenterol
2023
Knockout of the CMP-Sialic Acid Transporter SLC35A1 in Human Cell Lines Increases Transduction Efficiency of Adeno-Associated Virus 9: Implications for Gene Therapy Potency Assays.
Banning A et al.·Cells
2021
Single Particle Analysis of H3N2 Influenza Entry Differentiates the Impact of the Sialic Acids (Neu5Ac and Neu5Gc) on Virus Binding and Membrane Fusion.
Chien YA et al.·J Virol
2023
Identification of a Signature Comprising 5 Soluble Carrier Family Genes to Predict the Recurrence of Papillary Thyroid Carcinoma.
Han R et al.·Technol Cancer Res Treat
2021
Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1.
Ng BG et al.·Am J Med Genet A
2017Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools