CHST1

Summary

CHST1 (carbohydrate sulfotransferase 1, HGNC:1969) is a protein-coding gene on chromosome 11p11.2, encoding Carbohydrate sulfotransferase 1 (O43916). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of internal galactose (Gal) residues of keratan.

This locus encodes a member of the keratin sulfotransferase family of proteins. The encoded enzyme catalyzes the sulfation of the proteoglycan keratin.

Source: NCBI Gene 8534 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_003654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1969
Approved symbol	CHST1
Name	carbohydrate sulfotransferase 1
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	C6ST, KSGal6ST
Ensembl gene	ENSG00000175264
Ensembl biotype	protein_coding
OMIM	603797
Entrez	8534

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 26 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000308064, ENST00000531322, ENST00000533673, ENST00000891796, ENST00000891797, ENST00000891798, ENST00000891799, ENST00000891800, ENST00000891801, ENST00000891802, ENST00000891803, ENST00000891804, ENST00000891805, ENST00000891806, ENST00000891807, ENST00000891808, ENST00000891809, ENST00000891810, ENST00000891811, ENST00000891812, ENST00000891813, ENST00000924349, ENST00000924350, ENST00000960329, ENST00000960330, ENST00000960331, ENST00000960332, ENST00000960333

RefSeq mRNA: 1 — MANE Select: NM_003654 NM_003654

CCDS: CCDS7913

Canonical transcript exons

ENST00000308064 — 4 exons

Exon	Start	End
ENSE00001182468	45651993	45652090
ENSE00001182471	45652521	45652606
ENSE00001182482	45647689	45650965
ENSE00001252542	45665178	45665622

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.03.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3584 / max 194.6610, expressed in 717 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119476	5.1761	712
119475	0.1513	74
119474	0.0310	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	97.03	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.76	gold quality
middle frontal gyrus	UBERON:0002702	94.29	gold quality
parietal lobe	UBERON:0001872	93.19	gold quality
amygdala	UBERON:0001876	93.11	gold quality
anterior cingulate cortex	UBERON:0009835	92.95	gold quality
right frontal lobe	UBERON:0002810	92.94	gold quality
cingulate cortex	UBERON:0003027	92.93	gold quality
postcentral gyrus	UBERON:0002581	92.67	gold quality
orbitofrontal cortex	UBERON:0004167	92.66	gold quality
frontal cortex	UBERON:0001870	92.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.09	gold quality
temporal lobe	UBERON:0001871	92.03	gold quality
caudate nucleus	UBERON:0001873	91.82	gold quality
putamen	UBERON:0001874	91.81	gold quality
prefrontal cortex	UBERON:0000451	91.72	gold quality
neocortex	UBERON:0001950	91.72	gold quality
nucleus accumbens	UBERON:0001882	91.71	gold quality
superior frontal gyrus	UBERON:0002661	91.60	gold quality
cerebral cortex	UBERON:0000956	91.42	gold quality
Ammon’s horn	UBERON:0001954	91.38	gold quality
telencephalon	UBERON:0001893	91.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.45	gold quality
entorhinal cortex	UBERON:0002728	90.28	gold quality
forebrain	UBERON:0001890	90.11	gold quality
hypothalamus	UBERON:0001898	89.94	gold quality
ventral tegmental area	UBERON:0002691	89.53	gold quality
superior vestibular nucleus	UBERON:0007227	87.80	gold quality
medial globus pallidus	UBERON:0002477	87.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting CHST1, 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-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-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 6)

• C4ST-1 and C6ST-1 differ from each other in the recognition of uronic acid residues adjacent to the targeted GalNAc residue (PMID:15324304)
• The first to identify upregulated CHST1 protein gene expression correlating with the motility of Schwann cells that guide growing axons through both developmental and injured environments. (PMID:16495484)
• sulfated keratan sulfate is produced by beta3GNT7, beta4GalT4, CGn6ST, and KSG6ST (PMID:17690104)
• A new point mutation in C6ST-1 is associated with spondyloepiphyseal dysplasia, Omani type. (PMID:18698629)
• Epitope expressing changes with suppression or over-expression of the Gal6ST (Gal 6-O-sulfotransferase) gene, suggesting that Gal6ST is involved in the biosynthesis of the unique epitopes of KL-6/mAb. (PMID:21880669)
• found endogenous expression of the long form of the enzyme in human tissue, predominantly in the trans-Golgi network of endothelial cells that form human high endothelial venules. (PMID:22260995)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chst1	ENSDARG00000088593
mus_musculus	Chst1	ENSMUSG00000027221
rattus_norvegicus	Chst1	ENSRNOG00000007989
drosophila_melanogaster	CG9550	FBGN0031826
drosophila_melanogaster	CG31637	FBGN0051637

Paralogs (6): CHST3 (ENSG00000122863), CHST5 (ENSG00000135702), CHST4 (ENSG00000140835), CHST7 (ENSG00000147119), CHST2 (ENSG00000175040), CHST6 (ENSG00000183196)

Protein

Protein identifiers

Carbohydrate sulfotransferase 1 — O43916 (reviewed: O43916)

Alternative names: Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 1, Keratan sulfate Gal-6 sulfotransferase

All UniProt accessions (1): O43916

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of internal galactose (Gal) residues of keratan. Cooperates with B4GALT4 and B3GNT7 glycosyltransferases and CHST6 sulfotransferase to construct and elongate disulfated disaccharide unit [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Has a preference for sulfating keratan sulfate, but it also transfers sulfate to the unsulfated polymer. Involved in biosynthesis of phosphacan, a major keratan sulfate proteoglycan in the developing brain. Involved in biosynthesis of 6-sulfoGalbeta-containing O-linked glycans in high endothelial venules of lymph nodes. May act in a synergistic manner with CHST4 to generate sialyl 6’,6-disulfo Lewis X motif, a recognition determinant for immune cell receptors implicated in leukocyte trafficking. Catalyzes sulfation of N-acetyllactosamine (LacNAc) oligosaccharides with highest efficiency for sialylated LacNAc structures.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed at low level. Expressed in brain and skeletal muscle. Expressed by high endothelial cells (HEVs) and leukocytes.

Pathway. Glycan metabolism.

Similarity. Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.

RefSeq proteins (1): NP_003645* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR016469	Carbohydrate_sulfotransferase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR051135	Gal/GlcNAc/GalNAc_ST	Family

Pfam: PF00685

Enzyme classification (BRENDA):

• EC 2.8.2.21 — keratan sulfotransferase (BRENDA: 5 organisms, 27 substrates, 11 inhibitors, 3 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
KERATAN SULFATE	0.025–0.38	2
3’-PHOSPHOADENYLYLSULFATE	0.0006	1

UniProt features (11 total): glycosylation site 4, topological domain 2, binding site 2, chain 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43916-F1	87.90	0.71

Functional residue map

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

Ligand- & substrate-binding residues (2): 69–75; 234–242

Glycosylation sites (4): 334, 56, 145, 189

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis

MSigDB gene sets: 205 (showing top): MODULE_52, HORIUCHI_WTAP_TARGETS_DN, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, RORA1_01, LI_WILMS_TUMOR, MODULE_45, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, ROVERSI_GLIOMA_COPY_NUMBER_UP, MODULE_317, MODULE_16, MORF_RAD51L3, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MODULE_66, AP1_Q4_01

GO Biological Process (8): polysaccharide metabolic process (GO:0005976), galactose metabolic process (GO:0006012), N-acetylglucosamine metabolic process (GO:0006044), sulfur compound metabolic process (GO:0006790), inflammatory response (GO:0006954), keratan sulfate proteoglycan biosynthetic process (GO:0018146), keratan sulfate proteoglycan metabolic process (GO:0042339), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (5): N-acetylglucosamine 6-O-sulfotransferase activity (GO:0001517), sulfotransferase activity (GO:0008146), keratan sulfotransferase activity (GO:0045130), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate metabolic process	1
macromolecule metabolic process	1
hexose metabolic process	1
amino sugar metabolic process	1
metabolic process	1
defense response	1
proteoglycan biosynthetic process	1
keratan sulfate proteoglycan metabolic process	1
proteoglycan metabolic process	1
primary metabolic process	1
sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	1
proteoglycan sulfotransferase activity	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST1	LUM	P51884	756
CHST1	SULT1C3	Q6IMI6	756
CHST1	SULT1C4	O75897	729
CHST1	KERA	O60938	727
CHST1	SULT1B1	O43704	722
CHST1	NTAN1	Q96AB6	636
CHST1	CHST9	Q7L1S5	539
CHST1	B3GNT7	Q8NFL0	499
CHST1	GCNT1	Q02742	492
CHST1	B4GALT4	O60513	435
CHST1	SIAE	Q9HAT2	410
CHST1	CHST12	Q9NRB3	410
CHST1	SIGLEC8	Q9NYZ4	403
CHST1	GAL3ST3	Q96A11	400
CHST1	ELOA	Q14241	399

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CHST1	STOM	psi-mi:“MI:0915”(physical association)	0.560
CHST1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
CHST1	SNU13	psi-mi:“MI:0915”(physical association)	0.370
SFN	CHST1	psi-mi:“MI:0915”(physical association)	0.370
CHST1	GPX8	psi-mi:“MI:0915”(physical association)	0.000
CHST1	STOM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): CHST1 (Two-hybrid), CHST1 (Two-hybrid), CHST1 (Two-hybrid), CHST1 (Two-hybrid), HSP90AB1 (Cross-Linking-MS (XL-MS)), NHP2L1 (Two-hybrid)

ESM2 similar proteins: A0A8C2LVE3, A2BGL3, F4HXW9, O08889, O17645, O43909, O43916, O93336, O93403, O95461, P25722, P69478, P79948, Q0IIY2, Q2TBF2, Q5NDE4, Q5NDE5, Q5NDE6, Q5NDE7, Q5NDE8, Q5NVB3, Q5R621, Q5RJQ0, Q5XHM7, Q66PG1, Q66PG2, Q66PG3, Q6DBY9, Q6NVP8, Q6P9A2, Q6PA90, Q76EC5, Q76KB1, Q7LFX5, Q7LGA3, Q7LGC8, Q7T3S3, Q800H9, Q8BUB6, Q8CHI9

Diamond homologs: O43916, O88199, O93403, Q0VBN2, Q5RJQ0, Q6DBY9, Q6XQG8, Q7LGC8, Q80WV3, Q8IZU8, Q8NCG5, Q92179, Q9EP78, Q9EQC0, Q9GZS9, Q9GZX3, Q9NS84, Q9QUP4, Q9QZL2, Q9R1I1, Q9Y4C5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

862 predictions. Top by Δscore:

Variant	Effect	Δscore
11:45650966:C:CC	acceptor_gain	1.0000
11:45651988:CTTA:C	donor_loss	1.0000
11:45651989:TTA:T	donor_loss	1.0000
11:45651990:TA:T	donor_loss	1.0000
11:45651991:A:AC	donor_gain	1.0000
11:45651992:C:A	donor_loss	1.0000
11:45651992:C:CC	donor_gain	1.0000
11:45652086:GCAGA:G	acceptor_gain	1.0000
11:45652087:CAGA:C	acceptor_gain	1.0000
11:45652087:CAGAC:C	acceptor_gain	1.0000
11:45652088:AGA:A	acceptor_gain	1.0000
11:45652089:GA:G	acceptor_gain	1.0000
11:45652090:AC:A	acceptor_loss	1.0000
11:45652091:C:CC	acceptor_gain	1.0000
11:45650961:GAGGT:G	acceptor_gain	0.9900
11:45650963:GGT:G	acceptor_gain	0.9900
11:45650964:GT:G	acceptor_gain	0.9900
11:45650964:GTC:G	acceptor_loss	0.9900
11:45650965:TCTG:T	acceptor_loss	0.9900
11:45650966:C:A	acceptor_loss	0.9900
11:45650967:T:G	acceptor_loss	0.9900
11:45652088:AGACT:A	acceptor_gain	0.9900
11:45652089:GACTG:G	acceptor_gain	0.9900
11:45652090:ACTGC:A	acceptor_gain	0.9900
11:45652091:CTGCA:C	acceptor_gain	0.9900
11:45650962:AGGT:A	acceptor_gain	0.9800
11:45651986:CACTT:C	donor_loss	0.9800
11:45651987:ACTTA:A	donor_loss	0.9800
11:45652094:C:CT	acceptor_gain	0.9800
11:45651740:CTGGC:C	acceptor_gain	0.9700

AlphaMissense

2650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:45649844:C:A	W360C	1.000
11:45649844:C:G	W360C	1.000
11:45649846:A:G	W360R	1.000
11:45649846:A:T	W360R	1.000
11:45649931:C:A	W331C	1.000
11:45649931:C:G	W331C	1.000
11:45649933:A:G	W331R	1.000
11:45649933:A:T	W331R	1.000
11:45650306:C:A	K206N	1.000
11:45650306:C:G	K206N	1.000
11:45650468:G:C	F152L	1.000
11:45650468:G:T	F152L	1.000
11:45650470:A:G	F152L	1.000
11:45650649:G:T	P92H	1.000
11:45650652:T:A	E91V	1.000
11:45650654:A:C	F90L	1.000
11:45650654:A:T	F90L	1.000
11:45650656:A:G	F90L	1.000
11:45649796:G:C	C376W	0.999
11:45649797:C:G	C376S	0.999
11:45649797:C:T	C376Y	0.999
11:45649798:A:G	C376R	0.999
11:45649798:A:T	C376S	0.999
11:45649872:C:G	R351P	0.999
11:45649932:C:G	W331S	0.999
11:45650007:G:T	A306D	0.999
11:45650010:A:G	L305P	0.999
11:45650016:T:A	E303V	0.999
11:45650023:G:T	R301S	0.999
11:45650046:A:G	L293P	0.999

dbSNP variants (sampled 300 via entrez): RS1000103267 (11:45667408 A>C), RS1000256847 (11:45661489 C>T), RS1000484296 (11:45667074 C>T), RS1000594521 (11:45662708 G>A), RS1000627076 (11:45662942 C>A), RS1000696577 (11:45661833 A>AGGGCC), RS1000808888 (11:45649559 T>C,G), RS1000809366 (11:45657545 G>A,C), RS1000888858 (11:45665622 C>A,T), RS1000918353 (11:45665931 G>A), RS1000969290 (11:45657195 C>G), RS1001063246 (11:45660002 A>G), RS1001226186 (11:45667058 T>C), RS1001298228 (11:45660360 C>T), RS1001348098 (11:45661546 C>A)

Disease associations

OMIM: gene MIM:603797 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003671_3	Diastolic blood pressure	4.000000e-07
GCST004487_9	Peak insulin response	4.000000e-09
GCST004575_6	Acute insulin response	4.000000e-09
GCST006585_2780	Blood protein levels	3.000000e-08
GCST008437_4	Alzheimer’s disease in hypertension-negative individuals	4.000000e-07
GCST010002_237	Refractive error	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0008000	peak insulin response measurement
EFO:0006831	acute insulin response measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9787901	Toxicity	3	imatinib	Gastrointestinal Stromal Tumors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
potassium perchlorate	decreases expression	1
methylparaben	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
tri-o-cresyl phosphate	decreases expression	1
butylparaben	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentanal	increases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Arsenicals	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dust	increases expression	1
Estradiol	increases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Silicon Dioxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1MX	HyCyte TE-1 KO-hCHST1	Cancer cell line	Male

Clinical trials (associated diseases)

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