SLC35A3

Summary

SLC35A3 (solute carrier family 35 member A3, HGNC:11023) is a protein-coding gene on chromosome 1p21.2, encoding UDP-N-acetylglucosamine transporter (Q9Y2D2). Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP.

This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23443 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism spectrum disorder - epilepsy - arthrogryposis syndrome (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 367 total — 27 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_012243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11023
Approved symbol	SLC35A3
Name	solute carrier family 35 member A3
Location	1p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117620
Ensembl biotype	protein_coding
OMIM	605632
Entrez	23443

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 27 protein_coding, 8 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000370153, ENST00000370155, ENST00000422078, ENST00000427993, ENST00000465289, ENST00000532693, ENST00000533028, ENST00000638336, ENST00000638338, ENST00000638371, ENST00000638876, ENST00000638929, ENST00000638988, ENST00000639088, ENST00000639148, ENST00000639221, ENST00000639807, ENST00000639994, ENST00000640178, ENST00000640360, ENST00000640600, ENST00000640715, ENST00000640726, ENST00000640732, ENST00000852947, ENST00000852948, ENST00000852949, ENST00000852950, ENST00000852951, ENST00000852952, ENST00000852953, ENST00000923275, ENST00000923276, ENST00000952984, ENST00000952985, ENST00000952986, ENST00000952987

RefSeq mRNA: 3 — MANE Select: NM_012243 NM_001271684, NM_001271685, NM_012243

CCDS: CCDS60204, CCDS60205, CCDS762

Canonical transcript exons

ENST00000533028 — 8 exons

Exon	Start	End
ENSE00001451960	99969996	99970162
ENSE00002606472	100022386	100035634
ENSE00003488106	100007034	100007156
ENSE00003491408	99999261	99999415
ENSE00003604622	100017682	100017815
ENSE00003622900	100015302	100015420
ENSE00003675499	100011365	100011533
ENSE00003795035	99993537	99993741

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8824 / max 270.4276, expressed in 1825 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4201	26.5688	1824
4202	0.6556	409
4203	0.2189	86
4204	0.1584	55
4199	0.1412	25
4205	0.0701	30
4200	0.0352	17
4198	0.0206	9
4197	0.0136	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	98.06	gold quality
jejunal mucosa	UBERON:0000399	98.03	gold quality
colonic mucosa	UBERON:0000317	97.97	gold quality
rectum	UBERON:0001052	97.51	gold quality
bronchial epithelial cell	CL:0002328	97.32	gold quality
ileal mucosa	UBERON:0000331	96.60	gold quality
duodenum	UBERON:0002114	96.25	gold quality
epithelium of bronchus	UBERON:0002031	95.90	gold quality
bronchus	UBERON:0002185	95.67	gold quality
nasal cavity epithelium	UBERON:0005384	93.84	gold quality
nasal cavity mucosa	UBERON:0001826	93.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.97	gold quality
mucosa of transverse colon	UBERON:0004991	92.84	gold quality
epithelium of nasopharynx	UBERON:0001951	92.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.69	gold quality
oral cavity	UBERON:0000167	92.50	gold quality
palpebral conjunctiva	UBERON:0001812	92.31	gold quality
endometrium epithelium	UBERON:0004811	92.08	gold quality
transverse colon	UBERON:0001157	91.52	gold quality
seminal vesicle	UBERON:0000998	90.78	gold quality
jejunum	UBERON:0002115	90.76	gold quality
gall bladder	UBERON:0002110	90.74	gold quality
esophagus squamous epithelium	UBERON:0006920	90.25	gold quality
secondary oocyte	CL:0000655	89.81	gold quality
intestine	UBERON:0000160	89.80	gold quality
small intestine	UBERON:0002108	89.72	gold quality
large intestine	UBERON:0000059	89.68	gold quality
minor salivary gland	UBERON:0001830	89.42	gold quality
colonic epithelium	UBERON:0000397	89.41	gold quality
endometrium	UBERON:0001295	89.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	201.30
E-ANND-3	yes	5.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

206 targeting SLC35A3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759

Literature-anchored findings (GeneRIF, showing 11)

• A mutation in the SLC35A3 gene is associated with vertebral malformations in cattle. A missense mutation likely effects signal transduction which relies on glycosylation. (PMID:16344554)
• SLC35A3 is an unlikely candidate for the pathogenesis of vertebral malformations because no mutation was found in this cohort study. (PMID:16691598)
• 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)
• Identified deleterious mutations in SLC35A3 in eight patients from a large kindred, who suffered from autism spectrum disorder, arthrogryposis and epilepsy. (PMID:24031089)
• UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats). (PMID:25944901)
• Recessive mutations in SLC35A3 caused early onset epileptic encephalopathy with skeletal defects in two siblings in an Italian non-consanguineous family. (PMID:28328131)
• SLC35A3 missense homozygous mutation is associated with skeletal dysplasia. (PMID:28777481)
• Serum bikunin isoforms in congenital disorders of glycosylation and linkeropathies. (PMID:32700771)
• Biosynthesis of GlcNAc-rich N- and O-glycans in the Golgi apparatus does not require the nucleotide sugar transporter SLC35A3. (PMID:32938718)
• Identification of HIF-dependent alternative splicing in gastrointestinal cancers and characterization of a long, coding isoform of SLC35A3. (PMID:33418078)
• Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis. (PMID:38172565)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc35a3a	ENSDARG00000013222
danio_rerio	slc35a3b	ENSDARG00000020981
mus_musculus	Slc35a3	ENSMUSG00000027957
rattus_norvegicus	Mfsd14a	ENSRNOG00000015502

Paralogs (4): SLC35A2 (ENSG00000102100), SLC35A5 (ENSG00000138459), SLC35A1 (ENSG00000164414), SLC35A4 (ENSG00000176087)

Protein

Protein identifiers

UDP-N-acetylglucosamine transporter — Q9Y2D2 (reviewed: Q9Y2D2)

Alternative names: Golgi UDP-GlcNAc transporter, Solute carrier family 35 member A3

All UniProt accessions (15): A0A1C7CYW3, A0A1W2PNF0, A0A1W2PNY6, A0A1W2PP85, A0A1W2PPH4, A0A1W2PPW2, A0A1W2PQ60, A0A1W2PQH2, A0A1W2PQL8, Q9Y2D2, A0A1W2PR66, A0A1W2PRN3, A0A1W2PRT7, A0A1W2PSD1, E9PPQ9

UniProt curated annotations — full annotation on UniProt →

Function. Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP. May supply UDP-GlcNAc as substrate for Golgi-resident glycosyltransferases that generate highly branched, multiantennary complex N-glycans and keratan sulfate. However, the exact role of SLC35A3 still needs to be elucidated, it could be a member of a catalytically more efficient multiprotein complex rather than function independently as a single transporter.

Subunit / interactions. Interacts with SLC35A2; the interaction is reduced in the presence of SLC35A4. Found in a complex with SLC35A2 and SLC35A4. Interacts with MGAT4B.

Subcellular location. Golgi apparatus membrane.

Post-translational modifications. O-Glcnacylation regulates the stability of SLC35A3 and the specific complex formation with MGAT4B.

Disease relevance. Arthrogryposis, impaired intellectual development, and seizures (AMRS) [MIM:615553] A disease characterized by arthrogryposis, intellectual disability, autism spectrum disorder, and epilepsy. Additional features include limb malformations, distal joint involvement, microcephaly, retromicrognathia, and general muscle hypotonia. The disease is caused by variants affecting the gene represented in this entry. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar is significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y2D2-1	1	yes
Q9Y2D2-2	2
Q9Y2D2-3	3

RefSeq proteins (3): NP_001258613, NP_001258614, NP_036375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007271	Nuc_sug_transpt	Family
IPR037185	EmrE-like	Homologous_superfamily

Pfam: PF04142

Catalyzed reactions (Rhea), 1 shown:

• UMP(out) + UDP-N-acetyl-alpha-D-glucosamine(in) = UMP(in) + UDP-N-acetyl-alpha-D-glucosamine(out) (RHEA:72695)

UniProt features (13 total): transmembrane region 8, splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2D2-F1	89.31	0.71

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5619083	Defective SLC35A3 causes arthrogryposis, mental retardation, and seizures (AMRS)
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: 270 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, TAATAAT_MIR126, FARMER_BREAST_CANCER_CLUSTER_7, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, MARTINEZ_RB1_TARGETS_UP, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (5): UDP-N-acetylglucosamine metabolic process (GO:0006047), transmembrane transport (GO:0055085), UDP-N-acetylglucosamine transmembrane transport (GO:1990569), UDP-galactose transmembrane transport (GO:0072334), pyrimidine nucleotide-sugar transmembrane transport (GO:0090481)

GO Molecular Function (5): UDP-galactose transmembrane transporter activity (GO:0005459), UDP-N-acetylglucosamine transmembrane transporter activity (GO:0005462), antiporter activity (GO:0015297), protein binding (GO:0005515), pyrimidine nucleotide-sugar transmembrane transporter activity (GO:0015165)

GO Cellular Component (3): Golgi membrane (GO:0000139), 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	3
pyrimidine nucleotide-sugar transmembrane transporter activity	2
amino sugar metabolic process	1
nucleotide-sugar metabolic process	1
transport	1
cellular process	1
nucleotide-sugar transmembrane transport	1
UDP-galactose transmembrane transport	1
UDP-N-acetylglucosamine 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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35A3	SLC35D2	Q76EJ3	958
SLC35A3	SLC35D3	Q5M8T2	956
SLC35A3	SLC35D1	Q9NTN3	934
SLC35A3	SLC35B4	Q969S0	920
SLC35A3	CHID1	Q9BWS9	488
SLC35A3	MGAT4B	Q9UQ53	451
SLC35A3	SLC35E1	Q96K37	443
SLC35A3	SLC35A2	P78381	438
SLC35A3	SLC35A4	Q96G79	428
SLC35A3	RAB14	P35287	413
SLC35A3	SLC35C1	Q96A29	391
SLC35A3	DPM3	Q9P2X0	382
SLC35A3	EEIG2	Q5T8I3	379
SLC35A3	MGAT5	Q09328	376
SLC35A3	UBOX5	O94941	369

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SLC35A2	SLC35A3	psi-mi:“MI:0915”(physical association)	0.470
SLC35A3	SLC35A2	psi-mi:“MI:0915”(physical association)	0.470
SLC35A3	SLC35A2	psi-mi:“MI:2364”(proximity)	0.470
SLC35A2	SLC35A3	psi-mi:“MI:2364”(proximity)	0.470
MEP1B	SLC35A3	psi-mi:“MI:0915”(physical association)	0.370
SLC35A3	CRADD	psi-mi:“MI:0915”(physical association)	0.370
SLC35A3	TP63	psi-mi:“MI:0915”(physical association)	0.370
SLC35A3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SLC35A4	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC35A3	SLC35A3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (137): SLC35A3 (Affinity Capture-RNA), SLC35A3 (Affinity Capture-RNA), SLC35A3 (Proximity Label-MS), SLC35A3 (Proximity Label-MS), SLC35A3 (Proximity Label-MS), SLC35A3 (Proximity Label-MS), SLC35A3 (Proximity Label-MS), SLC35A3 (Affinity Capture-MS), ABCB8 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), ACAD9 (Affinity Capture-MS), ACADSB (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ALOX5 (Affinity Capture-MS), AMFR (Affinity Capture-MS)

ESM2 similar proteins: A2SWM2, A2WSD3, A2WSD8, A2YZ24, A6QQU6, A8MRY9, B3LFA3, F4JKQ7, O77592, Q0D7E4, Q0J349, Q3SWX0, Q5A5P7, Q5KQN0, Q5M7K3, Q5R7Q3, Q5RD30, Q6AXR5, Q6K1C4, Q6P499, Q6YBV0, Q6YC49, Q7Z5S9, Q7ZU13, Q8AVC3, Q8BGN5, Q8CH36, Q8GWX2, Q8GYS1, Q8H184, Q8H4H5, Q8L783, Q8L7A0, Q8L9J7, Q8LR09, Q8N8Q9, Q8R1T4, Q8VEH0, Q8W0K2, Q93890

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, B8B350, F4JN00, O08520, P87041, B8A7Q8, Q5N855, Q93890, Q09875, Q5R4D7, Q8LES0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	18
Uncertain significance	93
Likely benign	173
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069535	NM_012243.3(SLC35A3):c.234_235insTTTTTTTTNNNNNNNNNNTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCATGATGAAATTCTT (p.Asn79fs)	Pathogenic
1069573	NC_000001.10:g.(?100436083)(100480986_?)del	Pathogenic
1071714	NC_000001.10:g.(?100472580)(100477099_?)del	Pathogenic
1420251	NM_012243.3(SLC35A3):c.842C>A (p.Ser281Ter)	Pathogenic
1454316	NM_012243.3(SLC35A3):c.595G>T (p.Glu199Ter)	Pathogenic
1456328	NC_000001.10:g.(?100316589)(100488042_?)del	Pathogenic
1459700	NC_000001.10:g.(?100459083)(100459307_?)del	Pathogenic
1686985	NM_012243.3(SLC35A3):c.-18-1G>T	Pathogenic
1996483	NM_012243.3(SLC35A3):c.45del (p.Gln16fs)	Pathogenic
2010868	NM_012243.3(SLC35A3):c.699del (p.Asn234fs)	Pathogenic
2045066	NM_012243.3(SLC35A3):c.615G>A (p.Trp205Ter)	Pathogenic
2078274	NM_012243.3(SLC35A3):c.735G>A (p.Trp245Ter)	Pathogenic
2103148	NM_012243.3(SLC35A3):c.783del (p.Ile262fs)	Pathogenic
2107218	NM_012243.3(SLC35A3):c.340C>T (p.Gln114Ter)	Pathogenic
2415865	NM_012243.3(SLC35A3):c.754_755del (p.Ala252fs)	Pathogenic
2425784	NC_000001.10:g.(?100436083)(100477099_?)del	Pathogenic
2736290	NM_012243.3(SLC35A3):c.588_589del (p.Leu197fs)	Pathogenic
2767724	NM_012243.3(SLC35A3):c.205del (p.Ala68_Leu69insTer)	Pathogenic
2843303	NM_012243.3(SLC35A3):c.609_610del (p.Trp205fs)	Pathogenic
2850548	NM_012243.3(SLC35A3):c.605_606insGGAGGCAGAGGTTGCAGTGAGCCGAGATTGCACCACTGCACTCCACCCAGACAACAGAGCAAGACTCCGTCTCANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAGAAACAAAACA (p.Ser203fs)	Pathogenic
2983315	NM_012243.3(SLC35A3):c.423G>A (p.Trp141Ter)	Pathogenic
2996209	NM_012243.3(SLC35A3):c.287_288del (p.Leu96fs)	Pathogenic
4735216	NM_012243.3(SLC35A3):c.770del (p.Val257fs)	Pathogenic
583744	NC_000001.11:g.(?100007014)(100011553_?)del	Pathogenic
642862	NM_012243.3(SLC35A3):c.762_763dup (p.Gly255fs)	Pathogenic
863664	NM_012243.3(SLC35A3):c.751C>T (p.Gln251Ter)	Pathogenic
89029	NM_012243.3(SLC35A3):c.514C>T (p.Gln172Ter)	Pathogenic
1686984	NM_012243.3(SLC35A3):c.899_900delinsA (p.Leu300fs)	Likely pathogenic
2795343	NM_012243.3(SLC35A3):c.635-2A>T	Likely pathogenic
2807529	NM_012243.3(SLC35A3):c.188-1G>T	Likely pathogenic

SpliceAI

1659 predictions. Top by Δscore:

Variant	Effect	Δscore
1:100011363:A:AG	acceptor_gain	1.0000
1:100011364:G:GG	acceptor_gain	1.0000
1:100011364:GT:G	acceptor_gain	1.0000
1:100015416:TTCAG:T	donor_loss	1.0000
1:100015417:TCAGG:T	donor_loss	1.0000
1:100015418:CAG:C	donor_loss	1.0000
1:100015419:AG:A	donor_loss	1.0000
1:100015420:GG:G	donor_loss	1.0000
1:100015422:T:A	donor_loss	1.0000
1:99993737:CAGCA:C	donor_gain	1.0000
1:99993738:AGCA:A	donor_gain	1.0000
1:99993739:GCA:G	donor_gain	1.0000
1:99993739:GCAG:G	donor_gain	1.0000
1:99993740:CA:C	donor_gain	1.0000
1:99993742:G:GG	donor_gain	1.0000
1:99999411:ATCAG:A	donor_loss	1.0000
1:99999412:TCAG:T	donor_loss	1.0000
1:99999413:CAG:C	donor_loss	1.0000
1:99999414:AG:A	donor_loss	1.0000
1:99999415:GG:G	donor_loss	1.0000
1:99999417:T:A	donor_loss	1.0000
1:100007170:A:G	donor_gain	0.9900
1:100011363:AGT:A	acceptor_gain	0.9900
1:100011363:AGTG:A	acceptor_gain	0.9900
1:100011364:GTG:G	acceptor_gain	0.9900
1:100011364:GTGG:G	acceptor_gain	0.9900
1:99970159:GGAG:G	donor_gain	0.9900
1:99970160:GAG:G	donor_gain	0.9900
1:99970160:GAGG:G	donor_gain	0.9900
1:99970160:GAGGT:G	donor_loss	0.9900

AlphaMissense

2072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:100017738:A:C	K270N	1.000
1:100017738:A:T	K270N	1.000
1:100007051:A:C	K120N	0.999
1:100007051:A:T	K120N	0.999
1:100007065:C:A	A125E	0.999
1:100007112:T:A	W141R	0.999
1:100007112:T:C	W141R	0.999
1:100007131:T:G	L147W	0.999
1:100007139:G:A	G150R	0.999
1:100007139:G:C	G150R	0.999
1:100007140:G:A	G150E	0.999
1:100011422:G:A	G175R	0.999
1:100011422:G:C	G175R	0.999
1:100011423:G:A	G175E	0.999
1:100011447:G:A	C183Y	0.999
1:100011448:T:G	C183W	0.999
1:100011455:A:C	S186R	0.999
1:100011457:T:A	S186R	0.999
1:100011457:T:G	S186R	0.999
1:100011458:G:C	G187R	0.999
1:100011459:G:A	G187D	0.999
1:100011465:C:A	A189D	0.999
1:100011467:G:A	G190R	0.999
1:100011467:G:C	G190R	0.999
1:100011467:G:T	G190W	0.999
1:100011468:G:A	G190E	0.999
1:100011480:A:T	E194V	0.999
1:100011481:G:C	E194D	0.999
1:100011481:G:T	E194D	0.999
1:100011523:T:A	N208K	0.999

dbSNP variants (sampled 300 via entrez): RS1000023518 (1:99975064 T>C), RS1000028546 (1:100014466 C>T), RS1000167410 (1:100028383 A>G), RS1000181834 (1:99974374 A>T), RS1000215784 (1:100011434 G>A,T), RS1000244924 (1:99968413 C>A), RS1000278587 (1:100000897 A>G), RS1000291887 (1:99988901 G>A), RS1000329760 (1:100035242 T>A), RS1000330310 (1:100008040 C>T), RS1000416704 (1:100020902 T>C), RS1000471770 (1:100028208 G>A), RS1000496998 (1:100002281 T>C,G), RS1000504509 (1:100026850 T>C), RS1000547774 (1:99968628 A>C)

Disease associations

OMIM: gene MIM:605632 | disease phenotypes: MIM:615553, MIM:617468

GenCC curated gene-disease

Disease	Classification	Inheritance
autism spectrum disorder - epilepsy - arthrogryposis syndrome	Strong	Autosomal recessive

Mondo (2): autism spectrum disorder - epilepsy - arthrogryposis syndrome (MONDO:0014248), arthrogryposis multiplex congenita (MONDO:0015168)

Orphanet (2): Autism spectrum disorder-epilepsy-arthrogryposis syndrome (Orphanet:370943), Arthrogryposis multiplex congenita (Orphanet:1037)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000308	Microretrognathia
HP:0000729	Autistic behavior
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001385	Hip dysplasia
HP:0001765	Hammertoe
HP:0002121	Generalized non-motor (absence) seizure
HP:0002342	Moderate intellectual disability
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0002827	Hip dislocation
HP:0003577	Congenital onset
HP:0004976	Knee dislocation
HP:0008807	Acetabular dysplasia
HP:0010864	Severe intellectual disability
HP:0011153	Focal motor seizure
HP:0011461	Fetal onset
HP:0100490	Camptodactyly of finger

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007734_1	Incident chronic kidney disease	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
Benzo(a)pyrene	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
2-butenal	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cocaine	increases expression	1
Coumestrol	decreases expression	1
Gallic Acid	increases expression	1
Manganese	increases abundance, increases expression	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4LV	HCT116-SLC35A3-KO-c5	Cancer cell line	Male
CVCL_D4LW	HCT116-SLC35A3-KO-c7	Cancer cell line	Male
CVCL_TN05	HAP1 SLC35A3 (-) 1	Cancer cell line	Male
CVCL_TN06	HAP1 SLC35A3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3