SLC35A1-congenital disorder of glycosylation

Summary

SLC35A1-congenital disorder of glycosylation (MONDO:0011342) is a disease caused by SLC35A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC35A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 58
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001875	Decreased total neutrophil count	Very frequent (80-99%)
HP:0001892	Abnormal bleeding	Very frequent (80-99%)
HP:0001902	Giant platelets	Very frequent (80-99%)
HP:0001933	Subcutaneous hemorrhage	Very frequent (80-99%)
HP:0002090	Pneumonia	Very frequent (80-99%)
HP:0002098	Respiratory distress	Very frequent (80-99%)
HP:0003010	Prolonged bleeding time	Very frequent (80-99%)
HP:0011883	Abnormal platelet granules	Very frequent (80-99%)
HP:0012143	Abnormal megakaryocyte morphology	Very frequent (80-99%)
HP:0012418	Hypoxemia	Very frequent (80-99%)
HP:0040223	Pulmonary hemorrhage	Very frequent (80-99%)
HP:0100658	Cellulitis	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	SLC35A1-congenital disorder of glycosylation
Mondo ID	MONDO:0011342
MeSH	C567040
OMIM	603585
Orphanet	238459
DOID	DOID:0070258
SNOMED CT	723624008
UMLS	C1970344
MedGen	370234
GARD	0012409
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IIf · CDG syndrome type IIf · CDG-IIf · CDG2F · CMP-sialic acid transporter deficiency · congenital disorder of glycosylation type 2f · congenital disorder of glycosylation type IIf · congenital disorder of glycosylation, type IIf · SLC35A1-CDG · SLC35A1-CDG (CDG-IIf) · SLC35A1-congenital disorder of glycosylation

Data availability: 58 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type II › SLC35A1-congenital disorder of glycosylation

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, MOGS-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type IIr, congenital disorder of glycosylation, type iit, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIw, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

58 retrieved; paginated sample, class counts are floors:

26 likely benign, 19 uncertain significance, 4 benign, 3 pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4844	NM_006416.4(SLC35A1):c.[147T>C;277delG;281delC]		Pathogenic	no assertion criteria provided
1703752	NM_006416.5(SLC35A1):c.439T>C (p.Ser147Pro)	SLC35A1	Pathogenic	no assertion criteria provided
488412	NM_006416.5(SLC35A1):c.303G>C (p.Gln101His)	SLC35A1	Pathogenic	no assertion criteria provided
488413	NM_006416.5(SLC35A1):c.467C>G (p.Thr156Arg)	SLC35A1	Pathogenic/Likely pathogenic	no assertion criteria provided
488414	NM_006416.5(SLC35A1):c.586G>A (p.Glu196Lys)	SLC35A1	Pathogenic/Likely pathogenic	no assertion criteria provided
358215	NM_006416.5(SLC35A1):c.133A>G (p.Thr45Ala)	SLC35A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95393	NM_006416.5(SLC35A1):c.7G>T (p.Ala3Ser)	SLC35A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1379806	NM_006416.5(SLC35A1):c.171G>T (p.Leu57Phe)	SLC35A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1385696	NM_006416.5(SLC35A1):c.883A>C (p.Ile295Leu)	SLC35A1	Uncertain significance	criteria provided, single submitter
1401885	NM_006416.5(SLC35A1):c.1007G>A (p.Gly336Asp)	SLC35A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1418148	NM_006416.5(SLC35A1):c.908C>G (p.Thr303Ser)	SLC35A1	Uncertain significance	criteria provided, single submitter
1508884	NM_006416.5(SLC35A1):c.763G>C (p.Val255Leu)	SLC35A1	Uncertain significance	criteria provided, single submitter
1676264	NM_006416.5(SLC35A1):c.379T>A (p.Cys127Ser)	SLC35A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1938456	NM_006416.5(SLC35A1):c.475C>T (p.Gln159Ter)	SLC35A1	Uncertain significance	criteria provided, single submitter
1976646	NM_006416.5(SLC35A1):c.523TTA[1] (p.Leu176del)	SLC35A1	Uncertain significance	criteria provided, single submitter
198841	NM_006416.5(SLC35A1):c.890T>G (p.Leu297Arg)	SLC35A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2037368	NM_006416.5(SLC35A1):c.855T>G (p.Ile285Met)	SLC35A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2064523	NM_006416.5(SLC35A1):c.7G>A (p.Ala3Thr)	SLC35A1	Uncertain significance	criteria provided, single submitter
2974340	NM_006416.5(SLC35A1):c.639G>A (p.Met213Ile)	SLC35A1	Uncertain significance	criteria provided, single submitter
3892476	NM_006416.5(SLC35A1):c.778A>G (p.Thr260Ala)	SLC35A1	Uncertain significance	criteria provided, single submitter
3892477	NM_006416.5(SLC35A1):c.89C>G (p.Ala30Gly)	SLC35A1	Uncertain significance	criteria provided, single submitter
4529499	NM_006416.5(SLC35A1):c.508-6T>C	SLC35A1	Uncertain significance	criteria provided, single submitter
468943	NM_006416.5(SLC35A1):c.757G>C (p.Ala253Pro)	SLC35A1	Uncertain significance	criteria provided, single submitter
566896	NM_006416.5(SLC35A1):c.569T>C (p.Phe190Ser)	SLC35A1	Uncertain significance	criteria provided, single submitter
665876	NM_006416.5(SLC35A1):c.699T>G (p.Ile233Met)	SLC35A1	Uncertain significance	criteria provided, single submitter
849369	NM_006416.5(SLC35A1):c.1000G>A (p.Val334Ile)	SLC35A1	Uncertain significance	criteria provided, single submitter
1096360	NM_006416.5(SLC35A1):c.48C>T (p.Cys16=)	SLC35A1	Likely benign	criteria provided, single submitter
1106981	NM_006416.5(SLC35A1):c.378G>A (p.Pro126=)	SLC35A1	Likely benign	criteria provided, multiple submitters, no conflicts
1115293	NM_006416.5(SLC35A1):c.752-9G>T	SLC35A1	Likely benign	criteria provided, single submitter
1166554	NM_006416.5(SLC35A1):c.887-9del	SLC35A1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC35A1	Strong	Autosomal recessive	SLC35A1-congenital disorder of glycosylation	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC35A1	Orphanet:238459	SLC35A1-CDG

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC35A1	HGNC:11021	ENSG00000164414	P78382	CMP-sialic acid transporter	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC35A1	CMP-sialic acid transporter	Transports CMP-sialic acid from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges CMP-sialic acid for CMP.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC35A1	Other/Unknown	no		Nuc_sug_transpt, EmrE-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC35A1	133	ubiquitous	marker	monocyte, rectum, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC35A1	1,477

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC35A1	P78382	88.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective transport by SLC35A1 causes congenital disorder of glycosylation 2F (CDG2F)	1	5710.0×	0.001	SLC35A1
Defective SLC35A1 in sialic acid metabolism causes congenital disorder of glycosylation 2F (CDG2F)	1	5710.0×	0.001	SLC35A1
Transport of nucleotide sugars	1	1142.0×	0.005	SLC35A1
Matriglycan biosynthesis on DAG1	1	815.7×	0.005	SLC35A1
Sialic acid metabolism	1	326.3×	0.008	SLC35A1
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.008	SLC35A1
Transport of vitamins, nucleosides, and related molecules	1	271.9×	0.008	SLC35A1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.009	SLC35A1
SLC transporter disorders	1	203.9×	0.009	SLC35A1
Disorders of transmembrane transporters	1	139.3×	0.011	SLC35A1
Asparagine N-linked glycosylation	1	60.1×	0.023	SLC35A1
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC35A1
Transport of small molecules	1	25.1×	0.049	SLC35A1
Post-translational protein modification	1	19.2×	0.060	SLC35A1
Disease	1	13.1×	0.081	SLC35A1
Metabolism of proteins	1	12.4×	0.081	SLC35A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
CMP-N-acetylneuraminate transmembrane transport	1	8426.0×	7e-04	SLC35A1
N-acetylneuraminate metabolic process	1	3370.4×	7e-04	SLC35A1
CMP-N-acetylneuraminate biosynthetic process	1	2808.7×	7e-04	SLC35A1
protein modification process	1	244.2×	0.005	SLC35A1
protein O-linked glycosylation	1	224.7×	0.005	SLC35A1
carbohydrate metabolic process	1	135.9×	0.007	SLC35A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC35A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC35A1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SLC35A1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC35A1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.