SLC35A2

Summary

SLC35A2 (solute carrier family 35 member A2, HGNC:11022) is a protein-coding gene on chromosome Xp11.23, encoding UDP-galactose translocator (P78381). Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 7355 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 377 total — 34 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 109
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11022
Approved symbol	SLC35A2
Name	solute carrier family 35 member A2
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	UGAT, UGT, UGT1, UGT2, UGTL, UDP-Gal-Tr
Ensembl gene	ENSG00000102100
Ensembl biotype	protein_coding
OMIM	314375
Entrez	7355

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 2 nonsense_mediated_decay

ENST00000247138, ENST00000376512, ENST00000376515, ENST00000376521, ENST00000376529, ENST00000413561, ENST00000445167, ENST00000446885, ENST00000452555, ENST00000616181, ENST00000634461, ENST00000634665, ENST00000635015, ENST00000635238, ENST00000635285, ENST00000635460, ENST00000635589, ENST00000635628, ENST00000876225

RefSeq mRNA: 8 — MANE Select: NM_005660 NM_001032289, NM_001042498, NM_001282647, NM_001282648, NM_001282649, NM_001282650, NM_001282651, NM_005660

CCDS: CCDS14311, CCDS35247, CCDS43937, CCDS65253, CCDS65254, CCDS75973, CCDS75974, CCDS75975

Canonical transcript exons

ENST00000247138 — 5 exons

Exon	Start	End
ENSE00000867194	48906392	48906543
ENSE00001150986	48904746	48905482
ENSE00001184799	48903183	48903465
ENSE00001563804	48911546	48911646
ENSE00003638072	48909814	48909996

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 94.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3031 / max 83.3627, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199192	18.3031	1807

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.18	gold quality
bronchial epithelial cell	CL:0002328	93.70	gold quality
epithelium of bronchus	UBERON:0002031	93.38	gold quality
bronchus	UBERON:0002185	93.21	gold quality
palpebral conjunctiva	UBERON:0001812	92.57	gold quality
oocyte	CL:0000023	92.45	gold quality
esophagus squamous epithelium	UBERON:0006920	92.12	gold quality
stromal cell of endometrium	CL:0002255	92.07	gold quality
mucosa of transverse colon	UBERON:0004991	91.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.02	gold quality
epithelium of esophagus	UBERON:0001976	91.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.00	gold quality
rectum	UBERON:0001052	89.96	gold quality
squamous epithelium	UBERON:0006914	89.91	gold quality
epithelium of nasopharynx	UBERON:0001951	89.76	gold quality
right uterine tube	UBERON:0001302	89.72	gold quality
colonic mucosa	UBERON:0000317	89.54	gold quality
tibia	UBERON:0000979	89.40	gold quality
islet of Langerhans	UBERON:0000006	89.38	gold quality
nasal cavity epithelium	UBERON:0005384	89.06	gold quality
nasal cavity mucosa	UBERON:0001826	88.88	gold quality
oviduct epithelium	UBERON:0004804	88.84	gold quality
body of pancreas	UBERON:0001150	88.45	gold quality
fallopian tube	UBERON:0003889	88.22	gold quality
pancreas	UBERON:0001264	88.01	gold quality
esophagus mucosa	UBERON:0002469	87.93	gold quality
cervix squamous epithelium	UBERON:0006922	87.83	silver quality
left adrenal gland	UBERON:0001234	87.72	gold quality
right lobe of liver	UBERON:0001114	87.64	gold quality
gingival epithelium	UBERON:0001949	87.64	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CEBPB, HNF1A

miRNA regulators (miRDB)

20 targeting SLC35A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-5195-5P	90.84	65.09	287

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 19)

• localization of the UDP-Gal transporter may depend on the presence of the partner splice variant (PMID:21918738)
• Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. (PMID:23561849)
• The data further supports the hypothesis that UGT and NGT cooperate in the UDP-Gal delivery for glycosyltransferases located in the Golgi apparatus. (PMID:23583405)
• De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy. (PMID:24115232)
• The short N-terminal region composed of 35 N-terminal amino-acid residues of UGT was crucial for galactosylation of N-glycans. (PMID:25451267)
• UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats). (PMID:25944901)
• nonsynonymous variants in SCL35A2 were detected in the brains of 2 males with intractable epilepsy (PMID:29679388)
• SLC35A2 missense mutation is associated with congenital disorder of glycosylation. (PMID:29907092)
• Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, the data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2. (PMID:30746764)
• Data characterize 26 new variants in the single largest study involving SLC35A2-congenital disorders of glycosylation. These variants had normal transferrin glycosylation. The biochemical assay assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts of the patients that seems to be directly correlated to the ratio of wild-type to mutant alleles. (PMID:30817854)
• [Clinical characteristics of SLC35A2 gene variants related congenital disorders of glycosylation type]. (PMID:32605344)
• Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). (PMID:33407896)
• SLC35A2-CDG: novel variants with two ends of the spectrum. (PMID:34161696)
• A three-pocket model for substrate coordination and selectivity by the nucleotide sugar transporters SLC35A1 and SLC35A2. (PMID:34384782)
• Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene. (PMID:36307217)
• Nucleotide sugar transporter SLC35A2 is involved in promoting hepatocellular carcinoma metastasis by regulating cellular glycosylation. (PMID:36454514)
• SLC35A2 deficiency reduces protein levels of core 1 beta-1,3-galactosyltransferase 1 (C1GalT1) and its chaperone Cosmc and affects their subcellular localization. (PMID:36933771)
• SLC35A2 somatic variants in drug resistant epilepsy: FCD and MOGHE. (PMID:37739137)
• SLC35A2 expression drives breast cancer progression via ERK pathway activation. (PMID:38143314)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc35a2	ENSDARG00000058990
mus_musculus	Slc35a2	ENSMUSG00000031156
rattus_norvegicus	Slc35a2	ENSRNOG00000024801
drosophila_melanogaster	Ugalt	FBGN0024994

Paralogs (4): SLC35A3 (ENSG00000117620), SLC35A5 (ENSG00000138459), SLC35A1 (ENSG00000164414), SLC35A4 (ENSG00000176087)

Protein

Protein identifiers

UDP-galactose translocator — P78381 (reviewed: P78381)

Alternative names: Solute carrier family 35 member A2, UDP-galactose transporter

All UniProt accessions (13): P78381, A0A0U1RR48, A0A0U1RR61, A0A0U1RRB4, A0A0U1RRG4, A0A0U1RRN1, A0A0X1KG77, A6NFI1, A6NGW4, A6NKM8, B4DE15, B4DSH7, C9JCV5

UniProt curated annotations — full annotation on UniProt →

Function. Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP. It is also able to exchange UDP-galactose for AMP and CMP, and to transport UDP-N-acetylgalactosamine (UDP-GalNAc) and other nucleotide sugars. As a provider of UDP-galactose to galactosyltransferases present in the Golgi apparatus, it is necessary for globotriaosylceramide/globoside (Gb3Cer) synthesis from lactosylceramide.

Subunit / interactions. Interacts with SLC35A3; the interaction is reduced in the presence of SLC35A4. Found in a complex with SLC35A3 and SLC35A4. Interacts with B4GALT4.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane Golgi apparatus membrane.

Disease relevance. Congenital disorder of glycosylation 2M (CDG2M) [MIM:300896] An X-linked dominant, severe neurologic disorder characterized by developmental delay, hypotonia, ocular anomalies, and brain malformations. Othere more variable clinical features included seizures, hypsarrhythmia, poor feeding, microcephaly, recurrent infections, dysmorphic features, shortened limbs, and coagulation defects. Congenital disorders of glycosylation are caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins and a wide variety of clinical features. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P78381-1	1, UGT2	yes
P78381-2	2, UGT1
P78381-3	3
P78381-4	4
P78381-5	5

RefSeq proteins (8): NP_001027460, NP_001035963, NP_001269576, NP_001269577, NP_001269578, NP_001269579, NP_001269580, NP_005651* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007271	Nuc_sug_transpt	Family
IPR037185	EmrE-like	Homologous_superfamily

Pfam: PF04142

Catalyzed reactions (Rhea), 11 shown:

• UMP(out) + UDP-N-acetyl-alpha-D-glucosamine(in) = UMP(in) + UDP-N-acetyl-alpha-D-glucosamine(out) (RHEA:72695)
• UMP(out) + UDP-alpha-D-galactose(in) = UMP(in) + UDP-alpha-D-galactose(out) (RHEA:72703)
• UMP(out) + UDP-alpha-D-glucose(in) = UMP(in) + UDP-alpha-D-glucose(out) (RHEA:72731)
• UDP-N-acetyl-alpha-D-galactosamine(in) + UMP(out) = UDP-N-acetyl-alpha-D-galactosamine(out) + UMP(in) (RHEA:72735)
• UDP-alpha-D-galactose(in) + AMP(out) = UDP-alpha-D-galactose(out) + AMP(in) (RHEA:74599)
• UDP-alpha-D-galactose(in) + CMP(out) = UDP-alpha-D-galactose(out) + CMP(in) (RHEA:74603)
• UDP-N-acetyl-alpha-D-galactosamine(out) + UDP-alpha-D-galactose(in) = UDP-N-acetyl-alpha-D-galactosamine(in) + UDP-alpha-D-galactose(out) (RHEA:74607)
• UDP-N-acetyl-alpha-D-glucosamine(out) + UDP-alpha-D-galactose(in) = UDP-N-acetyl-alpha-D-glucosamine(in) + UDP-alpha-D-galactose(out) (RHEA:74611)
• UDP-alpha-D-galactose(in) + UDP-alpha-D-glucose(out) = UDP-alpha-D-galactose(out) + UDP-alpha-D-glucose(in) (RHEA:74615)
• UMP(out) + CMP(in) = UMP(in) + CMP(out) (RHEA:74619)
• UMP(out) + AMP(in) = UMP(in) + AMP(out) (RHEA:74623)

UniProt features (75 total): sequence variant 30, mutagenesis site 26, transmembrane region 10, splice variant 4, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78381-F1	80.59	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (26):

Position	Phenotype
65	no effect on localization to golgi apparatus.
75	partially rescues defective gb3cer expression in slc35a2-deficient cells suggesting reduced udp-galactose transport. no
78	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport.
125	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport; when
126	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport; when
129	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport; when
141	no effect on localization to golgi apparatus.
142	no effect on localization to golgi apparatus.
145	no effect on localization to golgi apparatus.
146	no effect on localization to golgi apparatus.
148	partially rescues defective gb3cer expression in slc35a2-deficient cells suggesting reduced udp-galactose transport. no
152	no effect on localization to golgi apparatus.
152	partially rescues defective gb3cer expression in slc35a2-deficient cells suggesting reduced udp-galactose transport. no
202	partially rescues defective gb3cer expression in slc35a2-deficient cells suggesting reduced udp-galactose transport.
213	no effect on localization to golgi apparatus.
214	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport.
235	no effect on localization to golgi apparatus.
239	no effect on localization to golgi apparatus.
277	no effect on localization to golgi apparatus.
278	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport; when
285	no effect on localization to golgi apparatus.
294	no effect on localization to golgi apparatus.
297	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport.
297	does not rescue defective gb3cer expression in slc35a2-deficient cells suggesting loss of udp-galactose transport. no ef
301	no effect on localization to golgi apparatus.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5619072	Defective SLC35A2 causes congenital disorder of glycosylation 2M (CDG2M)
R-HSA-727802	Transport of nucleotide sugars
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 391 (showing top): OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, MARTINEZ_RB1_TARGETS_UP, FREAC3_01, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_GALACTOSE_METABOLIC_PROCESS, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANIC_ANION_TRANSPORT, GATA1_04, LYF1_01, IK2_01, DBP_Q6, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (3): galactose metabolic process (GO:0006012), UDP-galactose transmembrane transport (GO:0072334), pyrimidine nucleotide-sugar transmembrane transport (GO:0090481)

GO Molecular Function (4): UDP-galactose transmembrane transporter activity (GO:0005459), antiporter activity (GO:0015297), protein binding (GO:0005515), pyrimidine nucleotide-sugar transmembrane transporter activity (GO:0015165)

GO Cellular Component (6): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SLC transporter disorders	1
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine nucleotide-sugar transmembrane transport	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
hexose metabolic process	1
nucleotide-sugar transmembrane transport	1
pyrimidine nucleotide-sugar transmembrane transporter activity	1
UDP-galactose transmembrane transport	1
secondary active transmembrane transporter activity	1
binding	1
nucleotide-sugar transmembrane transporter activity	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35A2	UGT1A6	P19224	991
SLC35A2	UGT1A4	P22310	991
SLC35A2	UGT1A10	Q9HAW8	990
SLC35A2	UGT1A7	Q9HAW7	990
SLC35A2	UGT1A8	Q9HAW9	990
SLC35A2	UGT1A1	P22309	984
SLC35A2	UGT1A9	P36509	980
SLC35A2	UGT3A1	Q6NUS8	973
SLC35A2	UGT3A2	Q3SY77	973
SLC35A2	UGT2B10	P36537	972
SLC35A2	UGT2B4	P06133	972
SLC35A2	UGT2B15	P23765	972
SLC35A2	UGT1A3	P35503	970
SLC35A2	UGT2B7	P16662	967
SLC35A2	UGT1A5	P35504	960

IntAct

17 interactions, top by confidence:

A	B	Type	Score
	SLC35A2	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1	SLC35A2	psi-mi:“MI:0915”(physical association)	0.550
PLCG2	SLC35A2	psi-mi:“MI:0915”(physical association)	0.500
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
MDFI	SLC35A2	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC35A2	PRSS2	psi-mi:“MI:0914”(association)	0.350
PLCG2	NME2P1	psi-mi:“MI:0914”(association)	0.350
SLC35A2	GPAA1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (59): KRTAP10-3 (Two-hybrid), SLC35A2 (Two-hybrid), SLC35A2 (Two-hybrid), SLC35A2 (Affinity Capture-Western), SLC35A2 (Synthetic Lethality), PRSS2 (Affinity Capture-MS), SLC35A2 (Proximity Label-MS), SLC35A2 (Proximity Label-MS), SLC35A2 (Proximity Label-MS), SLC35A2 (Proximity Label-MS), SLC35A2 (Affinity Capture-RNA), SLC35A2 (Proximity Label-MS), COL8A1 (Two-hybrid), SLC35A2 (Affinity Capture-MS), SLC35A2 (Proximity Label-MS)

ESM2 similar proteins: A4IFK2, A4IHW3, A7S1L6, A9UUB8, O08520, O16658, O77592, P78381, P78382, P78383, P87041, P97858, Q02334, Q18779, Q1JQ66, Q29Q28, Q3E6T0, Q55DM5, Q58DA6, Q61420, Q66HX0, Q6AXR5, Q6GQ70, Q6PGC7, Q6V7K3, Q6YC49, Q753T9, Q7Z769, Q8AWB6, Q8AXS6, Q8MII5, Q8MXJ9, Q8R1T4, Q8WMS0, Q93890, Q94EI9, Q95YI5, Q968A5, Q9C8M1, Q9LFN3

Diamond homologs: A0JMG9, A4IHW3, B8B7Q4, O16658, O77592, P78381, P78382, Q01IU9, Q02334, Q05B73, Q58DA6, Q5RA79, Q61420, Q654D9, Q6AXR5, Q6K8S7, Q6YC49, Q6ZL17, Q7X7C4, Q8GY97, Q8LGE9, Q8MIA3, Q8R1T4, Q8WMS0, Q91ZR7, Q96G79, Q9C5H6, Q9D321, Q9R0M8, Q9Y2D2, B8A7Q8, B8B350, Q5N855, F4JN00, Q93890, O08520, P87041, Q09875, Q5R4D7, Q8LES0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC35A2	“up-regulates quantity”	UDP-D-galactose	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

377 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	19
Uncertain significance	113
Likely benign	119
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030061	NM_005660.3(SLC35A2):c.340A>T (p.Lys114Ter)	Pathogenic
1042432	NM_005660.3(SLC35A2):c.991_993del (p.Val331del)	Pathogenic
1064526	NM_005660.3(SLC35A2):c.426+1G>A	Pathogenic
1064527	NM_005660.3(SLC35A2):c.781del (p.Arg261fs)	Pathogenic
1064529	NM_005660.3(SLC35A2):c.601del (p.Ala201fs)	Pathogenic
1072202	NM_005660.3(SLC35A2):c.656_660del (p.Val218_Tyr219insTer)	Pathogenic
1072227	NC_000023.10:g.(?48762413)(48763384_?)del	Pathogenic
1072618	NM_005660.3(SLC35A2):c.327T>G (p.Tyr109Ter)	Pathogenic
135674	NM_005660.3(SLC35A2):c.433_434del (p.Tyr145fs)	Pathogenic
135675	NM_005660.3(SLC35A2):c.972del (p.Phe324fs)	Pathogenic
135676	NM_005660.3(SLC35A2):c.638C>T (p.Ser213Phe)	Pathogenic
1449566	NM_005660.3(SLC35A2):c.385C>T (p.Gln129Ter)	Pathogenic
1457955	NM_005660.3(SLC35A2):c.136C>T (p.Gln46Ter)	Pathogenic
1686209	NM_005660.3(SLC35A2):c.1A>T (p.Met1Leu)	Pathogenic
2575887	NM_005660.3(SLC35A2):c.832C>T (p.Gln278Ter)	Pathogenic
2772188	NM_005660.3(SLC35A2):c.68dup (p.Leu23fs)	Pathogenic
2850025	NM_005660.3(SLC35A2):c.92-12C>A	Pathogenic
2907575	NM_005660.3(SLC35A2):c.923C>T (p.Ser308Phe)	Pathogenic
373073	NM_005660.3(SLC35A2):c.634TCC[1] (p.Ser213del)	Pathogenic
374354	NM_005660.3(SLC35A2):c.617_620del (p.Val206fs)	Pathogenic
412239	NM_005660.3(SLC35A2):c.426+287_775del	Pathogenic
4526870	NM_005660.3(SLC35A2):c.424C>T (p.Gln142Ter)	Pathogenic
50363	SLC35A2:c.15_91+48delinsA	Pathogenic
50364	NM_005660.3(SLC35A2):c.991G>A (p.Val331Ile)	Pathogenic
50365	NM_005660.3(SLC35A2):c.3G>A (p.Met1Ile)	Pathogenic
520858	NM_005660.3(SLC35A2):c.795del (p.Phe265fs)	Pathogenic
541105	NM_005660.3(SLC35A2):c.348del (p.Val117fs)	Pathogenic
586961	NM_005660.3(SLC35A2):c.233A>G (p.Lys78Arg)	Pathogenic
635117	NM_005660.3(SLC35A2):c.634_635del (p.Ser212fs)	Pathogenic
817834	NM_005660.3(SLC35A2):c.7del (p.Ala3fs)	Pathogenic

SpliceAI

900 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48906387:CTCA:C	donor_loss	1.0000
X:48906391:C:A	donor_loss	1.0000
X:48906430:A:AC	donor_gain	1.0000
X:48906431:C:CC	donor_gain	1.0000
X:48906539:GTTAC:G	acceptor_gain	1.0000
X:48906540:TTAC:T	acceptor_gain	1.0000
X:48906541:TAC:T	acceptor_gain	1.0000
X:48906542:ACCT:A	acceptor_loss	1.0000
X:48906544:CT:C	acceptor_loss	1.0000
X:48906548:G:C	acceptor_gain	1.0000
X:48909801:C:A	donor_gain	1.0000
X:48909809:CGTAC:C	donor_loss	1.0000
X:48909810:GTA:G	donor_loss	1.0000
X:48909811:TAC:T	donor_loss	1.0000
X:48909812:A:AC	donor_gain	1.0000
X:48909812:AC:A	donor_gain	1.0000
X:48909812:ACC:A	donor_gain	1.0000
X:48909813:C:CC	donor_gain	1.0000
X:48909813:C:CG	donor_loss	1.0000
X:48909813:CC:C	donor_gain	1.0000
X:48909813:CCC:C	donor_gain	1.0000
X:48909813:CCCCT:C	donor_gain	1.0000
X:48909864:T:TA	donor_gain	1.0000
X:48909992:GTGAG:G	acceptor_gain	1.0000
X:48909993:TGAG:T	acceptor_gain	1.0000
X:48909994:GAG:G	acceptor_gain	1.0000
X:48909995:AG:A	acceptor_gain	1.0000
X:48909996:GCT:G	acceptor_loss	1.0000
X:48909997:C:CC	acceptor_gain	1.0000
X:48909997:C:CG	acceptor_loss	1.0000

AlphaMissense

2491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48905018:C:A	K297N	1.000
X:48905018:C:G	K297N	1.000
X:48905247:T:A	E221V	1.000
X:48906435:A:G	L128P	1.000
X:48906440:A:C	N126K	1.000
X:48906440:A:T	N126K	1.000
X:48906443:C:A	Q125H	1.000
X:48906443:C:G	Q125H	1.000
X:48906465:G:T	P118H	1.000
X:48905010:G:T	A300D	0.999
X:48905012:A:C	F299L	0.999
X:48905012:A:T	F299L	0.999
X:48905014:A:G	F299L	0.999
X:48905027:A:C	N294K	0.999
X:48905027:A:T	N294K	0.999
X:48905031:T:A	D293V	0.999
X:48905035:C:G	A292P	0.999
X:48905052:G:T	A286D	0.999
X:48905067:C:T	G281D	0.999
X:48905173:C:G	G246R	0.999
X:48905196:A:G	L238P	0.999
X:48905204:G:C	N235K	0.999
X:48905204:G:T	N235K	0.999
X:48905238:A:G	L224P	0.999
X:48905238:A:T	L224H	0.999
X:48905246:C:A	E221D	0.999
X:48905246:C:G	E221D	0.999
X:48905248:C:T	E221K	0.999
X:48905259:C:T	G217D	0.999
X:48905260:C:G	G217R	0.999

dbSNP variants (sampled 300 via entrez): RS1000841619 (X:48908209 G>A), RS1000934331 (X:48908621 G>A), RS1001841502 (X:48910150 C>A), RS1001934856 (X:48910610 T>A), RS1002939452 (X:48912364 C>G), RS1003964262 (X:48913837 C>A), RS1004316838 (X:48913469 C>T), RS1004968573 (X:48907588 A>G), RS1005983472 (X:48909682 A>G), RS1006985677 (X:48911722 G>A), RS1007934553 (X:48912712 T>C), RS1008591300 (X:48903364 T>G), RS1008938189 (X:48906912 G>A), RS1009163257 (X:48906041 G>A), RS1009546735 (X:48909269 A>C)

Disease associations

OMIM: gene MIM:314375 | disease phenotypes: MIM:300896, MIM:209850, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
SLC35A2-congenital disorder of glycosylation	Definitive	X-linked
X-linked complex neurodevelopmental disorder	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (6): SLC35A2-congenital disorder of glycosylation (MONDO:0010478), X-linked complex neurodevelopmental disorder (MONDO:0100148), congenital disorder of glycosylation (MONDO:0015286), autism (MONDO:0005260), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 1 (MONDO:0010632)

Orphanet (3): SLC35A2-CDG (Orphanet:356961), Congenital disorder of glycosylation (Orphanet:137), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

109 total (30 of 109 shown, HPO-id order):

HPO	Term
HP:0000074	Ureteropelvic junction obstruction
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000474	Thickened nuchal skin fold
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000574	Thick eyebrow
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000707	Abnormality of the nervous system
HP:0000822	Hypertension
HP:0000826	Precocious puberty
HP:0000924	Abnormality of the skeletal system
HP:0000938	Osteopenia
HP:0000951	Abnormality of the skin
HP:0001010	Hypopigmentation of the skin
HP:0001155	Abnormality of the hand
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002745_2	Total bilirubin levels in HIV-1 infection	5.000000e-16
GCST002745_3	Total bilirubin levels in HIV-1 infection	7.000000e-31
GCST002745_5	Total bilirubin levels in HIV-1 infection	1.000000e-22
GCST002745_6	Total bilirubin levels in HIV-1 infection	7.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3430867 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC35 family of nucleotide sugar transporters

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
CGP 52608	affects binding, increases reaction	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	decreases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Zinc	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6099976	ADMET	Substrate activity at UGT in pooled human liver microsomes preincubated with compound followed by UDPGA addition measured upto 45 mins by LC-MS/MS analysis	Phenotype-Led Identification of IL-10 Upregulators in Human CD4+ T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2FY	Abcam HeLa SLC35A2 KO	Cancer cell line	Female
CVCL_D4LT	HCT116-SLC35A2-KO-c2	Cancer cell line	Male
CVCL_D4LU	HCT116-SLC35A2-KO-c4	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms