SLC35B3

Summary

SLC35B3 (solute carrier family 35 member B3, HGNC:21601) is a protein-coding gene on chromosome 6p24.3, encoding Adenosine 3’-phospho 5’-phosphosulfate transporter 2 (Q9H1N7). Probably functions as a 3’-phosphoadenylyl sulfate:adenosine 3’,5’-bisphosphate antiporter at the Golgi membranes.

This gene is a member of the solute carrier family. The encoded protein is involved in the transport of 3-prime phosphoadenosine 5-prime phosphosulfate (PAPS) from the nucleus or the cytosol to the Golgi lumen. This gene has been reported to be expressed preferentially in the human colon tissues. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51000 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001370479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21601
Approved symbol	SLC35B3
Name	solute carrier family 35 member B3
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-19, dJ453H5.1, PAPST2
Ensembl gene	ENSG00000124786
Ensembl biotype	protein_coding
OMIM	610845
Entrez	51000

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 39 protein_coding, 2 nonsense_mediated_decay

ENST00000379660, ENST00000644923, ENST00000648867, ENST00000648987, ENST00000649788, ENST00000710437, ENST00000894865, ENST00000894866, ENST00000894867, ENST00000894868, ENST00000894869, ENST00000894870, ENST00000894871, ENST00000894872, ENST00000894873, ENST00000894874, ENST00000894875, ENST00000894876, ENST00000894877, ENST00000894878, ENST00000894879, ENST00000894880, ENST00000894881, ENST00000894882, ENST00000894883, ENST00000894884, ENST00000894885, ENST00000894886, ENST00000894887, ENST00000894888, ENST00000928245, ENST00000928246, ENST00000968342, ENST00000968343, ENST00000968344, ENST00000968345, ENST00000968346, ENST00000968347, ENST00000968348, ENST00000968349, ENST00000968350

RefSeq mRNA: 7 — MANE Select: NM_001370479 NM_001142540, NM_001142541, NM_001370476, NM_001370477, NM_001370478, NM_001370479, NM_015948

CCDS: CCDS4508, CCDS93854

Canonical transcript exons

ENST00000710437 — 10 exons

Exon	Start	End
ENSE00000847978	8414908	8414977
ENSE00000847979	8416884	8416995
ENSE00000847980	8417402	8417494
ENSE00000847981	8419580	8419677
ENSE00000847982	8420721	8420828
ENSE00000847983	8422470	8422624
ENSE00000847984	8427937	8428058
ENSE00000847985	8429864	8430157
ENSE00003818265	8435343	8435545
ENSE00003824978	8411435	8413699

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8724 / max 202.2756, expressed in 1807 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71645	9.6257	1778
71644	5.8605	1736
203849	0.3604	181
71646	0.0258	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.14	gold quality
epithelial cell of pancreas	CL:0000083	97.70	gold quality
tibia	UBERON:0000979	97.13	gold quality
bronchial epithelial cell	CL:0002328	96.31	gold quality
ileal mucosa	UBERON:0000331	96.28	gold quality
bronchus	UBERON:0002185	95.95	gold quality
corpus epididymis	UBERON:0004359	95.67	gold quality
colonic mucosa	UBERON:0000317	95.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.28	gold quality
germinal epithelium of ovary	UBERON:0001304	95.27	gold quality
palpebral conjunctiva	UBERON:0001812	95.27	gold quality
epithelium of nasopharynx	UBERON:0001951	95.05	gold quality
amniotic fluid	UBERON:0000173	94.52	gold quality
seminal vesicle	UBERON:0000998	94.45	gold quality
parietal pleura	UBERON:0002400	94.08	gold quality
visceral pleura	UBERON:0002401	93.91	gold quality
jejunal mucosa	UBERON:0000399	93.62	gold quality
esophagus squamous epithelium	UBERON:0006920	93.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.85	gold quality
rectum	UBERON:0001052	92.69	gold quality
nasal cavity epithelium	UBERON:0005384	92.61	gold quality
endometrium	UBERON:0001295	92.05	gold quality
caput epididymis	UBERON:0004358	91.69	gold quality
cauda epididymis	UBERON:0004360	91.48	gold quality
endothelial cell	CL:0000115	91.31	gold quality
duodenum	UBERON:0002114	91.31	gold quality
upper arm skin	UBERON:0004263	91.29	gold quality
parotid gland	UBERON:0001831	91.24	gold quality
oviduct epithelium	UBERON:0004804	91.08	gold quality
mucosa of transverse colon	UBERON:0004991	90.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting SLC35B3, 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-9-5P	100.00	72.28	2361
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-4662A-5P	98.48	67.18	1007

Literature-anchored findings (GeneRIF, showing 3)

• PAPST2 is a PAPS transporter gene involved in the synthesis of sulfated glycoconjugates in the colon (PMID:16492677)
• PAPS transporters play a role in the proliferation of colorectal carcinoma cells themselves and take part in a desmoplastic reaction to support cancer growth by controlling their sulfation status. (PMID:20978009)
• The specifically up-regulated non-coding gene HULC in HepG2 cell line has some effects on the expression of its neighboring gene SLC35B3. (PMID:21211351)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc35b3	ENSDARG00000045437
mus_musculus	Slc35b3	ENSMUSG00000021432
rattus_norvegicus	Slc35b3	ENSRNOG00000016174
drosophila_melanogaster	Papst2	FBGN0036695
caenorhabditis_elegans		WBGENE00018827

Paralogs (3): SLC35B1 (ENSG00000121073), SLC35B2 (ENSG00000157593), SLC35B4 (ENSG00000205060)

Protein

Protein identifiers

Adenosine 3’-phospho 5’-phosphosulfate transporter 2 — Q9H1N7 (reviewed: Q9H1N7)

Alternative names: 3’-phosphoadenosine 5’-phosphosulfate transporter, PAPS transporter 2, Solute carrier family 35 member B3

All UniProt accessions (3): A0A024QZW4, A0A3B3IRN3, Q9H1N7

UniProt curated annotations — full annotation on UniProt →

Function. Probably functions as a 3’-phosphoadenylyl sulfate:adenosine 3’,5’-bisphosphate antiporter at the Golgi membranes. Mediates the transport from the cytosol into the lumen of the Golgi of 3’-phosphoadenylyl sulfate/adenosine 3’-phospho 5’-phosphosulfate (PAPS), a universal sulfuryl donor for sulfation events that take place in that compartment.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Preferentially and highly expressed in colon.

Similarity. Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H1N7-1	1	yes
Q9H1N7-2	2
Q9H1N7-3	3

RefSeq proteins (7): NP_001136012, NP_001136013, NP_001357405, NP_001357406, NP_001357407, NP_001357408, NP_057032 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013657	HUT1	Family

Pfam: PF08449

Catalyzed reactions (Rhea), 1 shown:

• 3’-phosphoadenylyl sulfate(in) + adenosine 3’,5’-bisphosphate(out) = 3’-phosphoadenylyl sulfate(out) + adenosine 3’,5’-bisphosphate(in) (RHEA:76063)

UniProt features (18 total): transmembrane region 10, splice variant 4, glycosylation site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1N7-F1	77.40	0.36

Functional residue map

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

Glycosylation sites (3): 12, 71, 254

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-174362	Transport and metabolism of PAPS
R-HSA-727802	Transport of nucleotide sugars
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-211859	Biological oxidations
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-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 124 (showing top): chr6p24, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOTIDE_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, GARY_CD5_TARGETS_DN, GOBP_PURINE_NUCLEOTIDE_TRANSPORT, MAF_Q6, CHANDRAN_METASTASIS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_TRANSPORT

GO Biological Process (4): 3’-phosphoadenosine 5’-phosphosulfate transport (GO:0046963), transmembrane transport (GO:0055085), 5’-adenylyl sulfate transmembrane transport (GO:1902558), 3’-phospho-5’-adenylyl sulfate transmembrane transport (GO:1902559)

GO Molecular Function (2): antiporter activity (GO:0015297), 3’-phosphoadenosine 5’-phosphosulfate transmembrane transporter activity (GO:0046964)

GO Cellular Component (5): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism	2
Glycosaminoglycan metabolism	1
Transport of vitamins, nucleosides, and related molecules	1
Biological oxidations	1
Phase II - Conjugation of compounds	1
Metabolism of carbohydrates and carbohydrate derivatives	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide transport	2
adenine nucleotide transport	2
sulfur compound transport	2
purine-containing compound transmembrane transport	2
nucleotide transmembrane transport	2
transport	1
cellular process	1
3’-phosphoadenosine 5’-phosphosulfate transport	1
secondary active transmembrane transporter activity	1
adenine nucleotide transmembrane transporter activity	1
purine ribonucleotide transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
3’-phospho-5’-adenylyl sulfate transmembrane transport	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35B3	SLC35D3	Q5M8T2	850
SLC35B3	SLC35D1	Q9NTN3	841
SLC35B3	SLC35D2	Q76EJ3	813
SLC35B3	SLC35C1	Q96A29	687
SLC35B3	SLC35H1	Q9NQQ7	664
SLC35B3	SLC35A5	Q9BS91	582
SLC35B3	SLC35A1	P78382	564
SLC35B3	B3GAT3	O94766	561
SLC35B3	SLC35A4	Q96G79	528
SLC35B3	SLC35E1	Q96K37	513
SLC35B3	SLC35B2	Q8TB61	509
SLC35B3	GLCE	O94923	504
SLC35B3	TMEM144	Q7Z5S9	504
SLC35B3	SLC35F1	Q5T1Q4	493
SLC35B3	SLC39A2	Q9NP94	458

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SLC35B3	RBM42	psi-mi:“MI:0915”(physical association)	0.400
SLC35B3	MTX2	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (36): SLC35B3 (Affinity Capture-RNA), SLC35B3 (Proximity Label-MS), SLC35B3 (Biochemical Activity), SLC35B3 (Negative Genetic), RBM42 (Affinity Capture-MS), SLC35B3 (Affinity Capture-RNA), SLC35B3 (Proximity Label-MS), AMFR (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), APLP2 (Affinity Capture-MS), APP (Affinity Capture-MS), CAND1 (Affinity Capture-MS), CHCHD3 (Affinity Capture-MS), CLU (Affinity Capture-MS), DNAJB2 (Affinity Capture-MS)

ESM2 similar proteins: A2AWR3, A6QL92, A6QPI1, B9FMX4, D3ZWZ9, F4IKF6, O35458, O35633, P58355, Q12791, Q28CE7, Q4LE88, Q4V3B8, Q569T7, Q5M8T2, Q5R4D7, Q5R6J3, Q5R831, Q5R9A7, Q5RD30, Q5ZLF4, Q62976, Q6DCG9, Q6DG36, Q6DIV6, Q6P499, Q6PF45, Q6UWJ1, Q7Z3F1, Q8BGF8, Q8BGN5, Q8BH01, Q8BUV8, Q8CA03, Q8R314, Q8R4H9, Q8RWF4, Q8RWH8, Q8TAD4, Q8WV83

Diamond homologs: O64503, P0CP32, P0CP33, P78383, P97858, Q4P9R2, Q4WJM7, Q54I86, Q5B5W2, Q5R831, Q5R9A1, Q66HX0, Q6C4X5, Q6GQ70, Q6NM25, Q6NMB6, Q6V7K3, Q8AWB6, Q8AXS6, Q8MII5, Q8TB61, Q8WZJ9, Q91ZN5, Q922Q5, Q9H1N7, Q9M9S6, Q9VDD7, Q9VEI3, Q17CE7, Q20787, Q29EY2, Q29Q28, Q61LC0, Q7Q5D4, Q9LDX3, Q9VVD9, Q55DM5

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	41
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2171 predictions. Top by Δscore:

Variant	Effect	Δscore
6:8414906:A:AC	donor_gain	1.0000
6:8414907:C:CC	donor_gain	1.0000
6:8414976:CA:C	acceptor_gain	1.0000
6:8414977:AC:A	acceptor_loss	1.0000
6:8414978:C:CC	acceptor_gain	1.0000
6:8414978:CTGTA:C	acceptor_loss	1.0000
6:8414979:T:G	acceptor_loss	1.0000
6:8416878:TCCTA:T	donor_loss	1.0000
6:8416879:CCTAC:C	donor_loss	1.0000
6:8416880:CTACC:C	donor_loss	1.0000
6:8416881:TAC:T	donor_loss	1.0000
6:8416883:C:CT	donor_loss	1.0000
6:8416883:CCTG:C	donor_gain	1.0000
6:8416992:GATT:G	acceptor_gain	1.0000
6:8416993:ATT:A	acceptor_gain	1.0000
6:8416994:TT:T	acceptor_gain	1.0000
6:8416996:C:A	acceptor_loss	1.0000
6:8416996:C:CC	acceptor_gain	1.0000
6:8416997:T:C	acceptor_loss	1.0000
6:8419574:ATTT:A	donor_loss	1.0000
6:8419575:TTTA:T	donor_loss	1.0000
6:8419576:TTAC:T	donor_loss	1.0000
6:8419577:TA:T	donor_loss	1.0000
6:8419578:ACC:A	donor_loss	1.0000
6:8419579:C:CG	donor_loss	1.0000
6:8419614:G:C	donor_gain	1.0000
6:8419688:G:C	acceptor_gain	1.0000
6:8419688:G:GC	acceptor_gain	1.0000
6:8419691:T:TC	acceptor_gain	1.0000
6:8420717:TTA:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000026439 (6:8424242 T>A), RS1000094122 (6:8416545 G>A), RS1000179985 (6:8436440 A>G), RS1000280391 (6:8436095 C>G,T), RS1000373944 (6:8430328 T>G), RS1000377446 (6:8423947 T>G), RS1000488287 (6:8430313 A>G,T), RS1000591454 (6:8411517 C>T), RS1000876808 (6:8432122 A>G,T), RS1001010171 (6:8417289 T>C), RS1001177227 (6:8435820 G>T), RS1001629803 (6:8436065 C>G), RS1001715948 (6:8435717 C>T), RS1001885140 (6:8423571 G>C), RS1001994126 (6:8423499 GA>G)

Disease associations

OMIM: gene MIM:610845 | 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
GCST002726_55	Glucose homeostasis traits	7.000000e-06
GCST003983_16	Male-pattern baldness	3.000000e-13
GCST003992_7	Photic sneeze reflex	2.000000e-10
GCST005024_70	Pursuit maintenance gain	2.000000e-07
GCST008504_10	Fasting glucose change (long-term)	5.000000e-06
GCST008504_4	Fasting glucose change (long-term)	1.000000e-06
GCST008892_10	Working memory	2.000000e-06
GCST009172_2	Response to (pegylated) interferon in HBeAg-negative hepatitis B	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006833	glucose effectiveness measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0008433	pursuit maintenance gain measurement
EFO:0004335	short-term memory
EFO:0007859	response to interferon

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
Phenylmercuric Acetate	increases expression, affects cotreatment	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
N-butyrylglucosamine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	increases expression, affects cotreatment	1
Tunicamycin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Oxyquinoline	decreases expression	1
Zidovudine	increases expression	1
Aflatoxin M1	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4D5	HCT116-SLC35B3-KO-c11	Cancer cell line	Male
CVCL_D4D6	HCT116-SLC35B3-KO-c9	Cancer cell line	Male
CVCL_TN11	HAP1 SLC35B3 (-) 1	Cancer cell line	Male
CVCL_XT20	HAP1 SLC35B3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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