SLC35D3

Summary

SLC35D3 (solute carrier family 35 member D3, HGNC:15621) is a protein-coding gene on chromosome 6q23.3, encoding Solute carrier family 35 member D3 (Q5M8T2). Probable UDP-glucose transmembrane transporter involved in UDP-glucose transport from the cytosol to the lumen of synaptic vesicles.

Enables UDP-glucose transmembrane transporter activity. Involved in UDP-glucose transmembrane transport. Is active in synaptic vesicle membrane.

Source: NCBI Gene 340146 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001008783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15621
Approved symbol	SLC35D3
Name	solute carrier family 35 member D3
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182747
Ensembl biotype	protein_coding
OMIM	612519
Entrez	340146

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000331858

RefSeq mRNA: 1 — MANE Select: NM_001008783 NM_001008783

CCDS: CCDS34544

Canonical transcript exons

ENST00000331858 — 2 exons

Exon	Start	End
ENSE00001290762	136923885	136925660
ENSE00001329612	136922301	136922867

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 78.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3274 / max 38.0590, expressed in 112 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69982	0.1247	51
69983	0.1244	34
69981	0.0591	23
69980	0.0193	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	78.23	gold quality
pigmented layer of retina	UBERON:0001782	75.85	gold quality
caudate nucleus	UBERON:0001873	72.90	gold quality
putamen	UBERON:0001874	68.81	gold quality
nucleus accumbens	UBERON:0001882	68.47	gold quality
islet of Langerhans	UBERON:0000006	64.05	gold quality
monocyte	CL:0000576	63.83	gold quality
leukocyte	CL:0000738	62.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	60.59	silver quality
pancreatic ductal cell	CL:0002079	59.50	silver quality
hypothalamus	UBERON:0001898	55.48	gold quality
dorsal plus ventral thalamus	UBERON:0001897	55.24	gold quality
epithelial cell of pancreas	CL:0000083	54.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
substantia nigra	UBERON:0002038	52.92	gold quality
tibialis anterior	UBERON:0001385	52.69	silver quality
pancreas	UBERON:0001264	52.47	gold quality
substantia nigra pars compacta	UBERON:0001965	51.77	gold quality
midbrain	UBERON:0001891	51.59	gold quality
ileal mucosa	UBERON:0000331	50.56	silver quality
myocardium	UBERON:0002349	50.25	gold quality
deltoid	UBERON:0001476	49.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	48.86	gold quality
lower lobe of lung	UBERON:0008949	48.59	silver quality
body of pancreas	UBERON:0001150	47.14	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.74	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting SLC35D3, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-369-3P	99.85	70.52	2264

Literature-anchored findings (GeneRIF, showing 1)

• Our results suggest that the SLC35D3 gene, close to the D6S1009 locus, is a candidate gene for MetS, which is involved in metabolic control in the central nervous system by regulating dopamine signaling. (PMID:24550737)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	SLC35D3	ENSDARG00000107442
mus_musculus	Slc35d3	ENSMUSG00000050473
rattus_norvegicus	Slc35d3	ENSRNOG00000012311

Paralogs (9): SLC35C2 (ENSG00000080189), SLC35E4 (ENSG00000100036), SLC35D1 (ENSG00000116704), SLC35E1 (ENSG00000127526), SLC35D2 (ENSG00000130958), TMEM241 (ENSG00000134490), SLC35E3 (ENSG00000175782), SLC35C1 (ENSG00000181830), SLC35E2B (ENSG00000189339)

Protein

Protein identifiers

Solute carrier family 35 member D3 — Q5M8T2 (reviewed: Q5M8T2)

Alternative names: Fringe connection-like protein 1

All UniProt accessions (1): Q5M8T2

UniProt curated annotations — full annotation on UniProt →

Function. Probable UDP-glucose transmembrane transporter involved in UDP-glucose transport from the cytosol to the lumen of synaptic vesicles. It is involved in platelet dense granules maturation. Alternatively, could function as a molecular adapter enhancing the formation of the PI3KC3-C1/AIC/autophagy initiation complex to promote autophagy in dopaminergic neurons. Could also regulate the plasma membrane localization of the D(1A) dopamine receptor/DRD1 and dopamine signaling.

Subunit / interactions. Could interact with ATG14, BECN1 and PIK3C3 that form the PI3KC3-C1/AIC/autophagy initiation complex; enhancing the formation of the AIC and promoting autophagy.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Early endosome membrane. Endoplasmic reticulum membrane.

Activity regulation. Inhibited by proton uncouplers that directly abolish the proton electrochemical gradient.

Similarity. Belongs to the TPT transporter family. SLC35D subfamily.

RefSeq proteins (1): NP_001008783* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR050186	TPT_transporter	Family

Catalyzed reactions (Rhea), 1 shown:

• UDP-alpha-D-glucose(in) = UDP-alpha-D-glucose(out) (RHEA:76195)

UniProt features (13 total): transmembrane region 10, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5M8T2-F1	76.37	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, BENPORATH_ES_WITH_H3K27ME3, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, TATTATA_MIR374, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (7): positive regulation of autophagy (GO:0010508), UDP-glucose transmembrane transport (GO:0015786), protein exit from endoplasmic reticulum (GO:0032527), transmembrane transport (GO:0055085), platelet dense granule organization (GO:0060155), positive regulation of protein exit from endoplasmic reticulum (GO:0070863), energy homeostasis (GO:0097009)

GO Molecular Function (4): UDP-glucose transmembrane transporter activity (GO:0005460), antiporter activity (GO:0015297), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (10): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), synaptic vesicle membrane (GO:0030672), early endosome membrane (GO:0031901), endosome (GO:0005768), early endosome (GO:0005769), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
endomembrane system	3
intracellular membrane-bounded organelle	2
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
pyrimidine nucleotide-sugar transmembrane transport	1
intracellular protein transport	1
transport	1
cellular process	1
secretory granule organization	1
protein exit from endoplasmic reticulum	1
regulation of protein exit from endoplasmic reticulum	1
positive regulation of intracellular protein transport	1
multicellular organismal-level homeostasis	1
pyrimidine nucleotide-sugar transmembrane transporter activity	1
UDP-glucose transmembrane transport	1
secondary active transmembrane transporter activity	1
protein binding	1
molecular adaptor activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
synaptic vesicle	1
exocytic vesicle membrane	1
early endosome	1
endosome membrane	1
cytoplasmic vesicle	1
endosome	1
cellular anatomical structure	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35D3	SLC35A3	Q9Y2D2	956
SLC35D3	SLC35A1	P78382	920
SLC35D3	SLC35B4	Q969S0	883
SLC35D3	SLC35B3	Q9H1N7	850
SLC35D3	SLC35B2	Q8TB61	843
SLC35D3	SLC35B1	P78383	798
SLC35D3	SULT4A1	Q9BR01	743
SLC35D3	ADGRL1	O94910	727
SLC35D3	SLC35A2	P78381	677
SLC35D3	RAB27A	P51159	667
SLC35D3	SLC35C1	Q96A29	590
SLC35D3	SLC35A5	Q9BS91	586
SLC35D3	SLC35F1	Q5T1Q4	568
SLC35D3	SLC35E1	Q96K37	565
SLC35D3	SLC35H1	Q9NQQ7	558
SLC35D3	SLC35A4	Q96G79	558

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SLC35D3	GPCPD1	psi-mi:“MI:0915”(physical association)	0.670
SLC35D3	ATP6V0A1	psi-mi:“MI:0914”(association)	0.350
SLC35D3	ERLIN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): SLC35D3 (Biochemical Activity), GPCPD1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), GPCPD1 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), AP3M1 (Affinity Capture-MS), ARFGAP1 (Affinity Capture-MS), CORO1B (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), GPCPD1 (Affinity Capture-MS), KIAA0319L (Affinity Capture-MS), KIRREL (Affinity Capture-MS), SEC11A (Affinity Capture-MS), SPCS2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMG9, A4IFK2, A4IHW3, A6QM03, A7S1L6, A7TES5, O74750, Q02334, Q05B73, Q17CE7, Q1JQ66, Q29EY2, Q29Q28, Q3E6T0, Q5M8T2, Q5RA79, Q61420, Q6CR04, Q6FSF8, Q6GQ70, Q6PGC7, Q753T9, Q755H7, Q7Q5D4, Q7Z769, Q84L08, Q8AWB6, Q8AXS6, Q8BGF8, Q8BLX4, Q8VCX2, Q8WZJ9, Q90X48, Q91ZR7, Q93890, Q94EI9, Q968A5, Q96A29, Q96G79, Q9C8M1

Diamond homologs: A2AKQ0, A2VE55, Q15B89, Q5M8T2, Q5RDC9, Q8BGF8, Q94B65, Q9NTN3, Q18779, Q54YK1, Q95YI5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

201 predictions. Top by Δscore:

Variant	Effect	Δscore
6:136923850:C:CA	acceptor_gain	1.0000
6:136923854:C:CA	acceptor_gain	1.0000
6:136922865:CAG:C	donor_loss	0.9900
6:136922866:AGG:A	donor_loss	0.9900
6:136922867:GGT:G	donor_loss	0.9900
6:136922868:GTGA:G	donor_loss	0.9900
6:136922869:T:A	donor_loss	0.9900
6:136923855:G:A	acceptor_gain	0.9900
6:136923860:C:CA	acceptor_gain	0.9900
6:136923880:CGCA:C	acceptor_loss	0.9900
6:136923881:GCAG:G	acceptor_loss	0.9900
6:136923882:CAG:C	acceptor_loss	0.9900
6:136923883:A:AC	acceptor_loss	0.9900
6:136923883:A:AG	acceptor_gain	0.9900
6:136923884:G:A	acceptor_loss	0.9900
6:136923884:G:GT	acceptor_gain	0.9900
6:136923884:GGA:G	acceptor_gain	0.9900
6:136922865:C:T	donor_gain	0.9800
6:136923873:C:CA	acceptor_gain	0.9800
6:136923883:AG:A	acceptor_gain	0.9800
6:136923884:GG:G	acceptor_gain	0.9800
6:136923864:C:A	acceptor_gain	0.9700
6:136923877:C:CA	acceptor_gain	0.9700
6:136923861:G:A	acceptor_gain	0.9600
6:136925426:T:A	acceptor_gain	0.9600
6:136923882:CAGG:C	acceptor_gain	0.9500
6:136923883:AGGA:A	acceptor_gain	0.9500
6:136923884:GGAG:G	acceptor_gain	0.9500
6:136923884:GGAGC:G	acceptor_gain	0.9500
6:136922868:G:GG	donor_gain	0.9300

AlphaMissense

2657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:136922752:G:C	K108N	1.000
6:136922752:G:T	K108N	1.000
6:136922763:C:G	P112R	1.000
6:136922484:G:A	G19E	0.999
6:136922763:C:A	P112H	0.999
6:136922852:G:C	G142R	0.999
6:136922852:G:T	G142C	0.999
6:136922853:G:A	G142D	0.999
6:136923926:G:A	G161R	0.999
6:136923926:G:C	G161R	0.999
6:136924183:C:G	C246W	0.999
6:136924211:A:C	S256R	0.999
6:136924213:C:A	S256R	0.999
6:136924213:C:G	S256R	0.999
6:136924232:A:C	S263R	0.999
6:136924234:C:A	S263R	0.999
6:136924234:C:G	S263R	0.999
6:136924301:G:C	G286R	0.999
6:136924302:G:A	G286D	0.999
6:136924315:C:A	N290K	0.999
6:136924315:C:G	N290K	0.999
6:136924322:G:C	G293R	0.999
6:136924323:G:A	G293D	0.999
6:136922472:C:A	A15D	0.998
6:136922495:G:C	G23R	0.998
6:136922496:G:A	G23D	0.998
6:136922506:C:A	N26K	0.998
6:136922506:C:G	N26K	0.998
6:136922715:T:C	L96P	0.998
6:136922733:C:A	P102H	0.998

dbSNP variants (sampled 300 via entrez): RS1001131398 (6:136923669 C>T), RS1001477900 (6:136923532 C>T), RS1001872023 (6:136925001 C>A), RS1002860624 (6:136925080 G>C), RS1003134619 (6:136920567 A>G), RS1003894988 (6:136926158 C>G,T), RS1004364000 (6:136925529 G>A,C), RS1005109806 (6:136926041 C>T), RS1005349223 (6:136922025 GCAGCCGCCCCGGGGCGCC>G), RS1005643998 (6:136921356 G>A), RS1005807065 (6:136922288 C>G,T), RS1005923621 (6:136922329 C>A,T), RS1006007412 (6:136921022 C>A,T), RS1007610353 (6:136923791 G>C,T), RS1007943802 (6:136925053 A>G)

Disease associations

OMIM: gene MIM:612519 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004773_3	Type 2 diabetes	7.000000e-09
GCST007847_38	Type 2 diabetes	5.000000e-14
GCST008529_60	Tea consumption	2.000000e-06
GCST009379_59	Type 2 diabetes	6.000000e-09
GCST010118_141	Type 2 diabetes	9.000000e-14
GCST010397_42	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06
GCST011124_19	Caffeine consumption from tea	9.000000e-09
GCST011126_13	Caffeine consumption from coffee or tea	4.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010091	tea consumption measurement
EFO:0007874	gut microbiome measurement
EFO:0006781	coffee consumption measurement

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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	7
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	decreases reaction, increases expression	1
Niclosamide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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