SLC35B2

Summary

SLC35B2 (solute carrier family 35 member B2, HGNC:16872) is a protein-coding gene on chromosome 6p21.1, encoding Adenosine 3’-phospho 5’-phosphosulfate transporter 1 (Q8TB61). Probably functions as a 3’-phosphoadenylyl sulfate:adenosine 3’,5’-bisphosphate antiporter at the Golgi membranes. It is a selective cancer dependency (DepMap: 21.4% of cell lines).

Sulfotransferases (e.g., SULT4A1; MIM 608359) use an activated form of sulfate, 3-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS), as a common sulfate donor for sulfation of glycoproteins, proteoglycans, and glycolipids in the endoplasmic reticulum and Golgi apparatus. SLC35B2 is located in the microsomal membrane and transports PAPS from the cytosol, where it is synthesized, into the Golgi lumen (Kamiyama et al., 2003 [PubMed 12716889]).

Source: NCBI Gene 347734 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, hypomyelinating, 26, with chondrodysplasia (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 101 total — 3 pathogenic
• Phenotypes (HPO): 32
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 21.4% of screened cell lines
• MANE Select transcript: NM_178148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16872
Approved symbol	SLC35B2
Name	solute carrier family 35 member B2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	UGTrel4
Ensembl gene	ENSG00000157593
Ensembl biotype	protein_coding
OMIM	610788
Entrez	347734

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000393810, ENST00000393812, ENST00000495706, ENST00000537814, ENST00000538577, ENST00000615337

RefSeq mRNA: 9 — MANE Select: NM_178148 NM_001286509, NM_001286510, NM_001286511, NM_001286512, NM_001286513, NM_001286517, NM_001286519, NM_001286520, NM_178148

CCDS: CCDS34462, CCDS69127, CCDS75462, CCDS75463

Canonical transcript exons

ENST00000393812 — 4 exons

Exon	Start	End
ENSE00001829166	44254101	44255644
ENSE00003516322	44256342	44256496
ENSE00003590173	44256685	44256878
ENSE00003847087	44257400	44257528

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.8672 / max 158.5219, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73752	38.5793	1802
73751	0.2879	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.32	gold quality
islet of Langerhans	UBERON:0000006	95.00	gold quality
right adrenal gland cortex	UBERON:0035827	92.90	gold quality
right adrenal gland	UBERON:0001233	92.88	gold quality
left adrenal gland cortex	UBERON:0035825	92.64	gold quality
left adrenal gland	UBERON:0001234	92.62	gold quality
pancreas	UBERON:0001264	92.50	gold quality
gall bladder	UBERON:0002110	92.42	gold quality
ventricular zone	UBERON:0003053	91.95	gold quality
apex of heart	UBERON:0002098	91.91	gold quality
body of pancreas	UBERON:0001150	91.74	gold quality
mucosa of transverse colon	UBERON:0004991	91.60	gold quality
metanephros cortex	UBERON:0010533	91.56	gold quality
ganglionic eminence	UBERON:0004023	91.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.43	gold quality
saliva-secreting gland	UBERON:0001044	91.42	gold quality
smooth muscle tissue	UBERON:0001135	91.41	gold quality
adrenal gland	UBERON:0002369	91.25	gold quality
minor salivary gland	UBERON:0001830	91.12	gold quality
placenta	UBERON:0001987	91.03	gold quality
body of stomach	UBERON:0001161	90.98	gold quality
rectum	UBERON:0001052	90.66	gold quality
adult mammalian kidney	UBERON:0000082	90.38	gold quality
granulocyte	CL:0000094	90.32	gold quality
cortex of kidney	UBERON:0001225	89.94	gold quality
fundus of stomach	UBERON:0001160	89.92	gold quality
transverse colon	UBERON:0001157	89.83	gold quality
stomach	UBERON:0000945	89.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting SLC35B2, 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-4283	100.00	66.42	2097
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3153	99.55	67.59	2337

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• PAPS1 has roles in PAPS transport and post-translational sulfation (PMID:12716889)
• 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)
• Results suggest that frequently downregulated miR-22 expression is associated with cell proliferation in medulloblastomas, and this may be at least in part via PAPST1, which is a novel target of miR-22 (PMID:24576181)
• High SLC35B2 expression is associated with invasive ductal breast carcinoma. (PMID:25124574)
• Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition. (PMID:33951064)
• Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy. (PMID:35325049)
• SLC35B2 Acts in a Dual Role in the Host Sulfation Required for EV71 Infection. (PMID:35420441)
• Differential genetic associations and expression of PAPST1/SLC35B2 in bipolar disorder and schizophrenia. (PMID:35501530)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc35b2	ENSDARG00000007886
mus_musculus	Slc35b2	ENSMUSG00000037089
rattus_norvegicus	Slc35b2	ENSRNOG00000019900
drosophila_melanogaster	sll	FBGN0038524
caenorhabditis_elegans		WBGENE00004206

Paralogs (3): SLC35B1 (ENSG00000121073), SLC35B3 (ENSG00000124786), SLC35B4 (ENSG00000205060)

Protein

Protein identifiers

Adenosine 3’-phospho 5’-phosphosulfate transporter 1 — Q8TB61 (reviewed: Q8TB61)

Alternative names: PAPS transporter 1, Putative MAPK-activating protein PM15, Putative NF-kappa-B-activating protein 48, Solute carrier family 35 member B2

All UniProt accessions (2): Q8TB61, A0A0A0MS46

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. Highly expressed in the placenta, pancreas, mammary gland and skeletal muscle. Weakly or not expressed in colon, heart and prostate. Expressed in the brain, predominantly in frontal lobe gray matter, subcortical frontal white matter and cerebellum.

Disease relevance. Leukodystrophy, hypomyelinating, 26, with chondrodysplasia (HLD26) [MIM:620269] A form of hypomyelinating leukodystrophy, a group of heterogeneous disorders characterized by persistent deficit of myelin observed on brain imaging. HLD26 is an autosomal recessive form characterized by severe psychomotor delay, limited or absent speech, abnormal development of brain white matter, corpus callosum hypoplasia, and cerebral atrophy. Other features include pre- and postnatal growth retardation, chondrodysplasia, and early-onset scoliosis. The disease may be caused by variants affecting the gene represented in this entry.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q8TB61-1	1	yes
Q8TB61-2	2
Q8TB61-3	3
Q8TB61-4	4
Q8TB61-5	5

RefSeq proteins (9): NP_001273438, NP_001273439, NP_001273440, NP_001273441, NP_001273442, NP_001273446, NP_001273448, NP_001273449, NP_835361* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013657	HUT1	Family
IPR037185	EmrE-like	Homologous_superfamily

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 (20 total): transmembrane region 9, splice variant 5, sequence variant 2, sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB61-F1	81.29	0.40

Functional residue map

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

Post-translational modifications (1): 427

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: 222 (showing top): GCM_GSPT1, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOCC_TRANS_GOLGI_NETWORK, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOTIDE_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_PURINE_NUCLEOTIDE_TRANSPORT

GO Biological Process (6): positive regulation of canonical NF-kappaB signal transduction (GO:0043123), 3’-phosphoadenosine 5’-phosphosulfate transport (GO:0046963), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), transmembrane transport (GO:0055085), 5’-adenylyl sulfate transmembrane transport (GO:1902558), 3’-phospho-5’-adenylyl sulfate transmembrane transport (GO:1902559)

GO Molecular Function (3): antiporter activity (GO:0015297), 3’-phosphoadenosine 5’-phosphosulfate transmembrane transporter activity (GO:0046964), protein binding (GO:0005515)

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
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
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
binding	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

1222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35B2	SULT4A1	Q9BR01	924
SLC35B2	SLC35D1	Q9NTN3	874
SLC35B2	SLC35D3	Q5M8T2	843
SLC35B2	SLC35D2	Q76EJ3	828
SLC35B2	B3GAT3	O94766	769
SLC35B2	TPST2	O60704	720
SLC35B2	EXTL3	O43909	704
SLC35B2	B4GALT7	Q9UBV7	686
SLC35B2	EXT2	Q93063	670
SLC35B2	XYLT2	Q9H1B5	584
SLC35B2	K7EP71	K7EP71	567
SLC35B2	NDST1	P52848	565
SLC35B2	HS2ST1	Q7LGA3	559
SLC35B2	EXT1	Q16394	554
SLC35B2	UXS1	Q8NBZ7	543
SLC35B2	B3GALT6	Q96L58	543

IntAct

93 interactions, top by confidence:

A	B	Type	Score
SLC35B2	GOLM1	psi-mi:“MI:0915”(physical association)	0.670
GOLM1	SLC35B2	psi-mi:“MI:0915”(physical association)	0.670
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
SLC35B2	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	RNF170	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
CD69	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	CLDN15	psi-mi:“MI:0915”(physical association)	0.560
ASGR2	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	TMEM248	psi-mi:“MI:0915”(physical association)	0.560
SHISAL1	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
SLC35B2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
TEX29	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (289): SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: O64503, P78383, P97858, Q4P9R2, Q54I86, Q55DM5, Q5R9A1, Q66HX0, Q6BMV3, Q6C4X5, Q6GQ70, Q6NM25, Q6NMB6, Q6V7K3, Q8AWB6, Q8AXS6, Q8MII5, Q8MXJ9, Q8TB61, Q8WZJ9, Q91ZN5, Q9M9S6, Q9VDD7, Q9VEI3, P0CP32, P0CP33, Q4WJM7, Q5B5W2, Q5R831, Q922Q5, Q9H1N7, Q6CR04, Q12520, Q5ADN8, Q6FSF8, Q755H7, Q17CE7, Q7Q5D4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	85
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2443960	NM_178148.4(SLC35B2):c.1224_1225del (p.Arg408fs)	Pathogenic
4532809	NM_178148.4(SLC35B2):c.885dup (p.Lys296Ter)	Pathogenic
984534	NM_178148.4(SLC35B2):c.1218_1220del (p.Leu407del)	Pathogenic

SpliceAI

718 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44255640:GACAC:G	acceptor_gain	1.0000
6:44255641:ACAC:A	acceptor_gain	1.0000
6:44255642:CAC:C	acceptor_gain	1.0000
6:44255642:CACC:C	acceptor_gain	1.0000
6:44255643:AC:A	acceptor_gain	1.0000
6:44255644:CC:C	acceptor_gain	1.0000
6:44255645:C:CC	acceptor_gain	1.0000
6:44255645:CT:C	acceptor_loss	1.0000
6:44255657:G:C	acceptor_gain	1.0000
6:44255657:G:GC	acceptor_gain	1.0000
6:44256338:CCA:C	donor_loss	1.0000
6:44256340:A:C	donor_loss	1.0000
6:44256656:G:C	donor_gain	1.0000
6:44256663:T:TA	donor_gain	1.0000
6:44256664:C:A	donor_gain	1.0000
6:44256669:C:CA	donor_gain	1.0000
6:44256681:ACACC:A	donor_loss	1.0000
6:44256683:A:AC	donor_gain	1.0000
6:44256684:C:CC	donor_gain	1.0000
6:44256684:CCGGT:C	donor_gain	1.0000
6:44256703:T:TA	donor_gain	1.0000
6:44255648:T:C	acceptor_gain	0.9900
6:44255648:T:TC	acceptor_gain	0.9900
6:44256337:CCCA:C	donor_gain	0.9900
6:44256493:CTAC:C	acceptor_gain	0.9900
6:44256495:AC:A	acceptor_gain	0.9900
6:44256496:CC:C	acceptor_gain	0.9900
6:44256660:A:AC	donor_gain	0.9900
6:44256661:C:CC	donor_gain	0.9900
6:44256717:TG:T	donor_gain	0.9900

AlphaMissense

2759 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44255160:T:A	D282V	1.000
6:44255379:A:C	F209C	1.000
6:44255435:G:C	S190R	1.000
6:44255435:G:T	S190R	1.000
6:44255437:T:G	S190R	1.000
6:44255084:A:C	N307K	0.999
6:44255084:A:T	N307K	0.999
6:44255138:C:A	Q289H	0.999
6:44255138:C:G	Q289H	0.999
6:44255156:G:C	S283R	0.999
6:44255156:G:T	S283R	0.999
6:44255158:T:G	S283R	0.999
6:44255159:G:C	D282E	0.999
6:44255159:G:T	D282E	0.999
6:44255160:T:C	D282G	0.999
6:44255160:T:G	D282A	0.999
6:44255161:C:G	D282H	0.999
6:44255246:A:C	F253L	0.999
6:44255246:A:T	F253L	0.999
6:44255248:A:G	F253L	0.999
6:44255252:G:C	S251R	0.999
6:44255252:G:T	S251R	0.999
6:44255254:T:G	S251R	0.999
6:44255259:C:T	G249E	0.999
6:44255260:C:G	G249R	0.999
6:44255260:C:T	G249R	0.999
6:44255340:G:C	P222R	0.999
6:44255340:G:T	P222H	0.999
6:44255348:C:A	K219N	0.999
6:44255348:C:G	K219N	0.999

dbSNP variants (sampled 300 via entrez): RS1000894460 (6:44259307 G>A), RS1001629813 (6:44254364 G>A,C), RS1002161394 (6:44254403 G>A,C), RS1002388382 (6:44259719 A>G), RS1002861252 (6:44258598 C>T), RS1003334363 (6:44256437 A>G), RS1004403108 (6:44257197 C>G,T), RS1004838666 (6:44256955 T>C,G), RS1004870283 (6:44256122 C>G), RS1006477190 (6:44258378 C>T), RS1006892334 (6:44254004 C>T), RS1006910039 (6:44258652 T>C), RS1006944494 (6:44253807 A>G), RS1007468448 (6:44257494 C>A,T), RS1007505776 (6:44258986 G>A)

Disease associations

OMIM: gene MIM:610788 | disease phenotypes: MIM:248390, MIM:616494, MIM:620269

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, hypomyelinating, 26, with chondrodysplasia	Moderate	Autosomal recessive

Mondo (3): Treacher Collins syndrome 3 (MONDO:0009558), hypomyelinating leukodystrophy 11 (MONDO:0014666), leukodystrophy, hypomyelinating, 26, with chondrodysplasia (MONDO:0859518)

Orphanet (3): Treacher-Collins syndrome (Orphanet:861), Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Orphanet:88637), Primary bone dysplasia with multiple joint dislocations (Orphanet:93441)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000162	Glossoptosis
HP:0000175	Cleft palate
HP:0000201	Pierre-Robin sequence
HP:0000278	Retrognathia
HP:0000666	Horizontal nystagmus
HP:0001181	Adducted thumb
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001344	Absent speech
HP:0001382	Joint hypermobility
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0002415	Leukodystrophy
HP:0002451	Limb dystonia
HP:0002650	Scoliosis
HP:0002673	Coxa valga
HP:0003026	Short long bone
HP:0003042	Elbow dislocation
HP:0003593	Infantile onset
HP:0004233	Advanced ossification of carpal bones
HP:0004322	Short stature
HP:0004626	Lumbar scoliosis
HP:0004976	Knee dislocation
HP:0008434	Hypoplastic cervical vertebrae
HP:0008936	Axial hypotonia
HP:0010585	Small epiphyses
HP:0011968	Feeding difficulties
HP:0012368	Flat face

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535707	Mandibulofacial dysostosis, Treacher Collins type, autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066411 (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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	Kd	21.77	nM	CHEMBL3752910
7.66	ED50	21.77	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149419: Binding affinity to human SLC35B2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0218	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Uranium Compounds	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652461	Binding	Binding affinity to human SLC35B2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2G0	Abcam HeLa SLC35B2 KO	Cancer cell line	Female
CVCL_D4M1	HCT116-SLC35B2-KO-c4	Cancer cell line	Male
CVCL_D4M2	HCT116-SLC35B2-KO-c5	Cancer cell line	Male
CVCL_DX58	HAP1 SLC35B2 (-) XYLT2 (-)	Cancer cell line	Male
CVCL_TN10	HAP1 SLC35B2 (-) 1	Cancer cell line	Male
CVCL_XT19	HAP1 SLC35B2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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