CHST9

Summary

CHST9 (carbohydrate sulfotransferase 9, HGNC:19898) is a protein-coding gene on chromosome 18q11.2, encoding Carbohydrate sulfotransferase 9 (Q7L1S5). Catalyzes the transfer of sulfate from 3’-phosphoadenylyl sulfate (PAPS) to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans.

The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Sulfate groups on carbohydrates confer highly specific functions to glycoproteins, glycolipids, and proteoglycans, and are critical for cell-cell interaction, signal transduction, and embryonic development. Alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 83539 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• MANE Select transcript: NM_031422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19898
Approved symbol	CHST9
Name	carbohydrate sulfotransferase 9
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	GALNAC4ST-2, GALNAC-4-ST2
Ensembl gene	ENSG00000154080
Ensembl biotype	protein_coding
OMIM	610191
Entrez	83539

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000580774, ENST00000581714, ENST00000618847, ENST00000932774, ENST00000951345

RefSeq mRNA: 3 — MANE Select: NM_031422 NM_001256316, NM_001398493, NM_031422

CCDS: CCDS42422, CCDS58618

Canonical transcript exons

ENST00000618847 — 6 exons

Exon	Start	End
ENSE00001747587	27048465	27048503
ENSE00001799249	27185136	27185308
ENSE00001806362	26944329	26944366
ENSE00002245432	27142689	27142905
ENSE00003730900	26906481	26917350
ENSE00003740352	27024116	27024157

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.34.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4858 / max 113.8425, expressed in 342 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171487	0.6791	261
171488	0.4681	234
171486	0.2838	80
171485	0.0413	26
171489	0.0136	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.34	gold quality
bronchus	UBERON:0002185	98.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.32	gold quality
nasal cavity epithelium	UBERON:0005384	94.38	gold quality
nasal cavity mucosa	UBERON:0001826	92.93	gold quality
epithelium of nasopharynx	UBERON:0001951	90.70	gold quality
islet of Langerhans	UBERON:0000006	89.99	gold quality
trachea	UBERON:0003126	88.53	gold quality
epithelial cell of pancreas	CL:0000083	85.65	gold quality
parotid gland	UBERON:0001831	85.22	gold quality
right uterine tube	UBERON:0001302	81.10	gold quality
pancreas	UBERON:0001264	79.11	gold quality
saliva-secreting gland	UBERON:0001044	78.38	gold quality
minor salivary gland	UBERON:0001830	77.79	gold quality
ventricular zone	UBERON:0003053	77.31	gold quality
oviduct epithelium	UBERON:0004804	76.58	gold quality
body of pancreas	UBERON:0001150	74.56	gold quality
mouth mucosa	UBERON:0003729	73.33	gold quality
gall bladder	UBERON:0002110	70.48	gold quality
ganglionic eminence	UBERON:0004023	67.92	gold quality
right lung	UBERON:0002167	67.67	gold quality
fallopian tube	UBERON:0003889	66.80	gold quality
spleen	UBERON:0002106	65.68	gold quality
heart left ventricle	UBERON:0002084	65.51	gold quality
right testis	UBERON:0004534	65.47	gold quality
cardiac ventricle	UBERON:0002082	65.23	gold quality
urethra	UBERON:0000057	65.11	silver quality
left ventricle myocardium	UBERON:0006566	65.06	gold quality
testis	UBERON:0000473	64.56	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	522.18
E-CURD-114	yes	54.16
E-GEOD-130148	yes	12.56
E-ANND-3	yes	11.58
E-MTAB-9388	yes	10.15
E-HCAD-1	yes	8.04
E-GEOD-124858	no	0.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting CHST9, 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-548C-3P	99.99	74.01	7587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 3)

• the copy number variations of CHST9 have been shown to associate with hematologic malignancies (PMID:21156230)
• CHST9 rs1436904 polymorphism significantly contributes to prognosis of early-stage TNBC, suggesting its clinical potential in the screening of high-risk TNBC patients for recurrence and the possibility of patient-tailored therapeutic decisions. (PMID:28924212)
• A Frameshift Variant in the CHST9 Gene Identified by Family-Based Whole Genome Sequencing Is Associated with Schizophrenia in Chinese Population. (PMID:31481703)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Chst9	ENSMUSG00000047161
rattus_norvegicus	Chst9	ENSRNOG00000015867

Paralogs (6): CHST10 (ENSG00000115526), CHST8 (ENSG00000124302), CHST12 (ENSG00000136213), CHST14 (ENSG00000169105), CHST11 (ENSG00000171310), CHST13 (ENSG00000180767)

Protein

Protein identifiers

Carbohydrate sulfotransferase 9 — Q7L1S5 (reviewed: Q7L1S5)

Alternative names: GalNAc-4-O-sulfotransferase 2, N-acetylgalactosamine-4-O-sulfotransferase 2

All UniProt accessions (1): Q7L1S5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of sulfate from 3’-phosphoadenylyl sulfate (PAPS) to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Transfers sulfate to the C-4 hydroxyl of terminal beta-1,4-linked GalNAc in the sequence GalNAc-beta-1,4GlcNAcbeta-R found on N-linked oligosaccharides and to the nonterminal beta-1,4-linked GalNAc in chondroitin and dermatan. Required for biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Active against chondroitin but not against terminal beta-1,4-linked GalNAc.

Subcellular location. Golgi apparatus membrane Secreted.

Tissue specificity. Highly expressed in trachea. Also expressed in fetal lung, adult pancreas, testis and salivary gland. Expressed at low level in pituitary gland, apex of the heart, adult lung, prostate and mammary gland. Weakly or not expressed in heart, liver and spinal cord.

Pathway. Protein modification; carbohydrate sulfation.

Similarity. Belongs to the sulfotransferase 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L1S5-1	1	yes
Q7L1S5-2	2

RefSeq proteins (3): NP_001243245, NP_001385422, NP_113610* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005331	Sulfotransferase	Family
IPR018011	Carb_sulfotrans_8-10	Family

Pfam: PF03567

UniProt features (20 total): glycosylation site 4, sequence conflict 4, topological domain 2, splice variant 2, sequence variant 2, binding site 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L1S5-F1	78.39	0.61

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): 220–226; 280–288

Glycosylation sites (4): 324, 437, 159, 243

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2022870	CS-GAG biosynthesis

MSigDB gene sets: 153 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, AAGCAAT_MIR137, MODULE_255, MODULE_317, GOBP_REGULATION_OF_HORMONE_LEVELS, TAL1ALPHAE47_01, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, CEBPB_01, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GRE_C

GO Biological Process (6): sulfur compound metabolic process (GO:0006790), carbohydrate biosynthetic process (GO:0016051), proteoglycan biosynthetic process (GO:0030166), glycosaminoglycan metabolic process (GO:0030203), hormone biosynthetic process (GO:0042446), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650)

GO Molecular Function (4): dermatan 4-sulfotransferase activity (GO:0001537), sulfotransferase activity (GO:0008146), chondroitin 4-sulfotransferase activity (GO:0047756), transferase activity (GO:0016740)

GO Cellular Component (4): Golgi membrane (GO:0000139), extracellular region (GO:0005576), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chondroitin sulfate/dermatan sulfate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biosynthetic process	2
cellular anatomical structure	2
metabolic process	1
carbohydrate metabolic process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
aminoglycan metabolic process	1
hormone metabolic process	1
proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
dermatan sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	1
chondroitin sulfotransferase activity	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST9	CA6	P23280	858
CHST9	CHST6	Q9GZX3	603
CHST9	CHST1	O43916	539
CHST9	TTC32	Q5I0X7	527
CHST9	RGS13	O14921	487
CHST9	RGS18	Q9NS28	485
CHST9	CHST3	Q7LGC8	455
CHST9	NOG	Q13253	429
CHST9	Q3MI93	Q3MI93	397
CHST9	CHST2	Q9Y4C5	390
CHST9	PROSER2	Q86WR7	389
CHST9	B4GALNT3	Q6L9W6	378
CHST9	TPST2	O60704	377
CHST9	TPBGL	P0DKB5	373
CHST9	ANTXRL	A6NF34	370

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CHST8	CANX	psi-mi:“MI:0914”(association)	0.640
CHST9	LRP5	psi-mi:“MI:0914”(association)	0.530
CHST9	STX6	psi-mi:“MI:0914”(association)	0.350
CHST9	ISLR	psi-mi:“MI:0914”(association)	0.350
S1PR1	ISLR	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CANX (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), STX5 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), CANX (Affinity Capture-MS), CHST9 (Affinity Capture-MS), CHST9 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), CANX (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), HLA-DRA (Affinity Capture-MS), LRRC15 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2LVE3, A0MGZ5, A0MGZ7, A1A4K5, A2BGL3, D4PHA7, O08889, O43916, O88199, O93336, O95461, P25722, P69478, P79948, Q24342, Q2TBF2, Q5R621, Q5RJQ0, Q5XHM7, Q64610, Q66PG1, Q66PG2, Q66PG3, Q6DBY9, Q6KFX9, Q6XQH0, Q76EC5, Q76KB1, Q7L1S5, Q7LFX5, Q7LGA3, Q7LGC8, Q7T3S3, Q800H9, Q8BQ86, Q8CHI9, Q8JHF2, Q8R3H7, Q91XQ5, Q92179

Diamond homologs: O43529, O54702, P69478, Q5RBZ6, Q5XHM7, Q5ZIE4, Q6AXM1, Q6GNS1, Q6PGK7, Q76EC5, Q7L1S5, Q7T3S3, Q805E5, Q8BQ86, Q8NET6, Q99LL3, Q9H2A9, Q9JME2, Q9NPF2, Q9NRB3, Q80V53, Q8NCH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340066	GRCh37/hg19 18p11.32-q12.1(chr18:136226-25252276)x3	Pathogenic

SpliceAI

2279 predictions. Top by Δscore:

Variant	Effect	Δscore
18:27024108:TTAC:T	donor_loss	1.0000
18:27024109:TACT:T	donor_loss	1.0000
18:27024110:ACT:A	donor_loss	1.0000
18:27024111:CTCA:C	donor_gain	1.0000
18:27024112:TCAC:T	donor_loss	1.0000
18:27024113:CACTG:C	donor_loss	1.0000
18:27024114:A:AC	donor_gain	1.0000
18:27024114:A:T	donor_loss	1.0000
18:27024115:C:CA	donor_gain	1.0000
18:27024115:C:T	donor_loss	1.0000
18:27024115:CTG:C	donor_gain	1.0000
18:27024115:CTGA:C	donor_gain	1.0000
18:27024115:CTGAT:C	donor_gain	1.0000
18:27024153:CCATC:C	acceptor_gain	1.0000
18:27024154:CATCC:C	acceptor_gain	1.0000
18:27024157:CCTGA:C	acceptor_loss	1.0000
18:27024158:C:CA	acceptor_loss	1.0000
18:27048462:TAC:T	donor_loss	1.0000
18:27048463:A:AG	donor_loss	1.0000
18:27048464:C:CG	donor_loss	1.0000
18:27142684:GTTAC:G	donor_loss	1.0000
18:27142685:TTA:T	donor_loss	1.0000
18:27142686:TAC:T	donor_loss	1.0000
18:27142906:CTAG:C	acceptor_loss	1.0000
18:27185131:GTTAC:G	donor_loss	1.0000
18:27185132:TTACC:T	donor_loss	1.0000
18:27185133:TACC:T	donor_loss	1.0000
18:27185134:A:AT	donor_loss	1.0000
18:27185135:C:CA	donor_loss	1.0000
18:26917349:TT:T	acceptor_gain	0.9900

AlphaMissense

2950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:26916541:C:A	W350C	0.999
18:26916541:C:G	W350C	0.999
18:26916543:A:G	W350R	0.999
18:26916543:A:T	W350R	0.999
18:26916520:G:C	C357W	0.998
18:26916521:C:T	C357Y	0.998
18:26916546:G:C	H349D	0.998
18:26916712:T:A	K293N	0.998
18:26916712:T:G	K293N	0.998
18:26916713:T:A	K293I	0.998
18:26916752:C:G	R280P	0.998
18:26916912:A:G	W227R	0.998
18:26916912:A:T	W227R	0.998
18:26916940:A:C	C217W	0.998
18:26916941:C:T	C217Y	0.998
18:26916714:T:C	K293E	0.997
18:26916714:T:G	K293Q	0.997
18:26916721:A:C	F290L	0.997
18:26916721:A:T	F290L	0.997
18:26916723:A:G	F290L	0.997
18:26916928:C:A	K221N	0.997
18:26916928:C:G	K221N	0.997
18:26916522:A:G	C357R	0.996
18:26916544:G:C	H349Q	0.996
18:26916544:G:T	H349Q	0.996
18:26916552:C:G	D347H	0.996
18:26916592:A:C	F333L	0.996
18:26916592:A:T	F333L	0.996
18:26916593:A:G	F333S	0.996
18:26916594:A:G	F333L	0.996

dbSNP variants (sampled 300 via entrez): RS1000000772 (18:26935339 G>C), RS1000003074 (18:26956962 A>G), RS1000016813 (18:26940531 G>T), RS1000020581 (18:27185625 C>G,T), RS1000023176 (18:27052733 T>C), RS1000036271 (18:27185029 C>T), RS1000038659 (18:27003950 A>G), RS1000041010 (18:27047834 A>G,T), RS1000051666 (18:27186091 C>G), RS1000075101 (18:27065024 G>A), RS1000075412 (18:26984476 A>G,T), RS1000076180 (18:27054773 C>T), RS1000081618 (18:26906646 A>C), RS1000095925 (18:27011381 G>A), RS1000099829 (18:27046232 A>G)

Disease associations

OMIM: gene MIM:610191 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001786_24	Dental caries	5.000000e-06
GCST001937_14	Breast cancer	3.000000e-08
GCST002104_2	Bronchopulmonary dysplasia	3.000000e-06
GCST002363_11	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	2.000000e-07
GCST004988_194	Breast cancer	1.000000e-14
GCST006585_959	Blood protein levels	2.000000e-27
GCST009391_1586	Metabolite levels	9.000000e-06
GCST009391_1725	Metabolite levels	3.000000e-06
GCST009391_47	Metabolite levels	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010342	cholesteryl ester 16:1 measurement
EFO:0010114	citrate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	5
Cyclosporine	decreases expression, decreases methylation	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
methylmercuric chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	decreases expression	1
perfluorotetradecanoic acid	decreases expression	1
dicrotophos	decreases expression	1
decabromobiphenyl ether	affects expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorobutyric acid	decreases expression	1
dinophysistoxin 1	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases 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	increases expression, affects cotreatment	1
Azathioprine	decreases expression	1
Biological Factors	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1

Clinical trials (associated diseases)

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