CHST4

Summary

CHST4 (carbohydrate sulfotransferase 4, HGNC:1972) is a protein-coding gene on chromosome 16q22.2, encoding Carbohydrate sulfotransferase 4 (Q8NCG5). Sulfotransferase involved in SELL/L-selectin ligand biosynthesis pathway.

This gene encodes an N-acetylglucosamine 6-O sulfotransferase. The encoded enzyme transfers sulfate from 3’phosphoadenosine 5’phospho-sulfate to the 6-hydroxyl group of N-acetylglucosamine on glycoproteins. This protein is localized to the Golgi and is involved in the modification of glycan structures on ligands of the lymphocyte homing receptor L-selectin. Alternate splicing in the 5’ UTR results in multiple transcript variants that encode the same protein.

Source: NCBI Gene 10164 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 79 total — 1 pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.34 (intermediate), LOEUF 1.84 (unconstrained)
• MANE Select transcript: NM_001166395
• Notable: 79 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1972
Approved symbol	CHST4
Name	carbohydrate sulfotransferase 4
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	HEC-GLCNAC-6-ST, LSST
Ensembl gene	ENSG00000140835
Ensembl biotype	protein_coding
Entrez	10164

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

MANE Select: ENST00000539698

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 4: 1

ENST00000539698, ENST00000338482, ENST00000572693, ENST00000866592, ENST00000927526, ENST00000927527, ENST00001137525

RefSeq mRNA: 2 — MANE Select: NM_001166395 NM_001166395, NM_005769

CCDS: CCDS10902

Canonical transcript exons

ENST00000539698 — 2 exons

Exon	Start	End
ENSE00002270267	71526426	71526495
ENSE00002635842	71536660	71538748

Expression profiles

Bgee: expression breadth broad, 94 present calls, max score 95.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2913 / max 55.5294, expressed in 76 samples.

Highest expression (Bgee): gall bladder, pancreatic ductal cell, male germ line stem cell (sensu Vertebrata) in testis, epithelial cell of pancreas, islet of Langerhans.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHST4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Minor Salivary Gland	eqtl	5.3e-05	-0.40	16:71432914:A:G
Stomach	eqtl	2.4e-04	-0.29	16:71519549:T:C
Adrenal Gland	eqtl	2.8e-04	+0.22	16:71605515:A:G
Pituitary	eqtl	1.8e-03	-0.36	16:71056412:A:AT
Lung	eqtl	3.0e-02	+0.59	16:70675728:C:T
Esophagus Mucosa	eqtl	3.7e-02	+0.14	16:71473080:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
154920	0.1550	57
154917	0.0611	29
154918	0.0495	26
154919	0.0258	8

Top tissues by expression

showing 100 of 253 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	95.78	gold quality
pancreatic ductal cell	CL:0002079	90.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.75	gold quality
epithelial cell of pancreas	CL:0000083	84.62	gold quality
islet of Langerhans	UBERON:0000006	75.90	gold quality
ileal mucosa	UBERON:0000331	74.49	gold quality
pancreas	UBERON:0001264	73.21	gold quality
body of pancreas	UBERON:0001150	72.19	gold quality
epithelium of bronchus	UBERON:0002031	71.22	gold quality
bronchus	UBERON:0002185	70.12	gold quality
secondary oocyte	CL:0000655	70.07	gold quality
sperm	CL:0000019	69.92	gold quality
cervix squamous epithelium	UBERON:0006922	69.65	gold quality
nasal cavity epithelium	UBERON:0005384	69.48	gold quality
male germ cell	CL:0000015	69.45	gold quality
bronchial epithelial cell	CL:0002328	69.15	gold quality
tibialis anterior	UBERON:0001385	68.74	silver quality
oviduct epithelium	UBERON:0004804	68.47	silver quality
germinal epithelium of ovary	UBERON:0001304	68.40	silver quality
right lobe of liver	UBERON:0001114	67.35	gold quality
liver	UBERON:0002107	65.72	gold quality
right uterine tube	UBERON:0001302	65.40	gold quality
right adrenal gland cortex	UBERON:0035827	64.89	gold quality
palpebral conjunctiva	UBERON:0001812	64.69	silver quality
right adrenal gland	UBERON:0001233	64.29	gold quality
fallopian tube	UBERON:0003889	63.73	gold quality
left adrenal gland	UBERON:0001234	63.66	gold quality
left adrenal gland cortex	UBERON:0035825	63.15	gold quality
epithelium of nasopharynx	UBERON:0001951	62.68	silver quality
adrenal cortex	UBERON:0001235	61.89	gold quality
oocyte	CL:0000023	61.82	gold quality
olfactory bulb	UBERON:0002264	61.76	gold quality
type B pancreatic cell	CL:0000169	61.58	gold quality
adrenal gland	UBERON:0002369	60.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	58.83	gold quality
nasal cavity mucosa	UBERON:0001826	58.14	gold quality
lymph node	UBERON:0000029	58.11	gold quality
parietal pleura	UBERON:0002400	56.86	gold quality
decidua	UBERON:0002450	56.55	gold quality
pleura	UBERON:0000977	56.53	gold quality
deltoid	UBERON:0001476	56.40	silver quality
diaphragm	UBERON:0001103	56.26	gold quality
cervix epithelium	UBERON:0004801	55.79	gold quality
visceral pleura	UBERON:0002401	54.33	gold quality
skin of hip	UBERON:0001554	52.90	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
quadriceps femoris	UBERON:0001377	51.53	gold quality
tonsil	UBERON:0002372	51.17	gold quality
thymus	UBERON:0002370	51.11	gold quality
minor salivary gland	UBERON:0001830	50.19	gold quality
vastus lateralis	UBERON:0001379	50.10	gold quality
pituitary gland	UBERON:0000007	49.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.55	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.23	gold quality
myocardium	UBERON:0002349	49.18	gold quality
saliva-secreting gland	UBERON:0001044	48.98	gold quality
upper leg skin	UBERON:0004262	48.90	gold quality
mouth mucosa	UBERON:0003729	48.89	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
smooth muscle tissue	UBERON:0001135	48.82	gold quality
muscle tissue	UBERON:0002385	48.76	gold quality
endometrium	UBERON:0001295	48.70	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
bone marrow cell	CL:0002092	47.72	gold quality
adenohypophysis	UBERON:0002196	47.69	gold quality
vermiform appendix	UBERON:0001154	47.52	gold quality
mucosa of transverse colon	UBERON:0004991	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
kidney epithelium	UBERON:0004819	47.02	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
renal glomerulus	UBERON:0000074	46.99	gold quality
metanephric glomerulus	UBERON:0004736	46.96	gold quality
cranial nerve II	UBERON:0000941	46.90	silver quality
nephron tubule	UBERON:0001231	46.88	gold quality
caecum	UBERON:0001153	46.80	gold quality
squamous epithelium	UBERON:0006914	46.32	gold quality
left uterine tube	UBERON:0001303	45.98	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
colonic epithelium	UBERON:0000397	45.38	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
peritoneum	UBERON:0002358	44.94	gold quality
omental fat pad	UBERON:0010414	44.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	44.68	gold quality
lung	UBERON:0002048	43.99	gold quality
metanephros	UBERON:0000081	43.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
adult mammalian kidney	UBERON:0000082	43.18	silver quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
substantia nigra pars compacta	UBERON:0001965	42.62	gold quality
dorsal plus ventral thalamus	UBERON:0001897	42.49	gold quality
trachea	UBERON:0003126	42.46	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	1215.44
E-MTAB-10553	yes	20.49
E-HCAD-9	yes	8.61
E-ANND-3	no	3.10

HPA expression

RNA tissue specificity: Tissue enriched

55 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Gallbladder	tissue	65.2	high
Pancreas	tissue	11.7	low
Cerebral cortex	tissue	7.0	not detected
Retrosplenial cortex	tissue	7.0
Retrosplenial and cingulate cortex	tissue	6.9
Insular cortex	tissue	6.7
Cerebellum	tissue	6.3	not detected
Prefrontal cortex	tissue	6.1
Hippocampal formation	tissue	6.1
Entorhinal cortex	tissue	6.1
Temporal cortex	tissue	6.0
Olfactory bulb	tissue	5.9
Occipital cortex	tissue	5.6
Motor cortex	tissue	5.5
Amygdala	tissue	5.5
Basal ganglia	tissue	5.3	not detected
Somatosensory cortex	tissue	5.2
Fallopian tube	tissue	5.0	low
Ventral forebrain	tissue	4.9
Corpus callosum	tissue	4.5
Septum	tissue	4.4
Putamen	tissue	4.1
Liver	tissue	4.1	low
Periaqueductal gray	tissue	4.1
Choroid plexus	tissue	4.0
Hypothalamus	tissue	3.8
Spinal cord	tissue	3.7
Medulla oblongata	tissue	3.4
Midbrain	tissue	3.0
Substantia nigra	tissue	2.9
Pons	tissue	2.7
Thalamus	tissue	2.6
Superior colliculi	tissue	2.5
Cervix	tissue	2.3	not detected
Tonsil	tissue	1.8	not detected
Lymph node	tissue	1.2	not detected
Adrenal gland	tissue	0.8	not detected
Pituitary gland	tissue	0.5
Salivary gland	tissue	0.3	not detected
Nucleus accumbens	tissue	0.3
Locus coeruleus	tissue	0.3
Hippocampus	tissue	0.3	not detected
Caudate putamen	tissue	0.3
Breast	tissue	0.2	not detected
Stomach 1	tissue	0.2	not detected
Esophagus	tissue	0.2	not detected
Frontal cortex	tissue	0.2
Thymus	tissue	0.2
Appendix	tissue	0.2	not detected
Retina	tissue	0.1
Smooth muscle	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Lung	tissue	0.1	not detected
Postcentral gyrus	tissue	0.1
Nasopharynx	tissue	-1.0	low

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Subiculum (5.1), White matter (4.5), Ventral hippocampus (4.3), Dorsal hippocampus (3.7), Ventral spinal cord (3.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, SP1, TBX21

miRNA regulators (miRDB)

Targeting CHST4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

30 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-4661-3P	96.81	66.02	342
HSA-MIR-6806-5P	96.37	68.74	587

Functional genomics

gnomAD constraint: pLI 0.343, LOEUF 1.84, missense Z 0.848 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000539698 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 6)

• Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma (PMID:12107080)
• involved in enzymatic synthesis in vitro of the disulfated disaccharide unit of corneal keratan sulfate (PMID:12218059)
• GlcNAc6ST2 could therefore be a good serological marker for detecting early-stage uterine cervical and corpus cancers. (PMID:19156517)
• A method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4. (PMID:24799377)
• Data suggest that GlcNAc6ST-2 (CHST4) is critical for biosynthesis of MECA-79 sulfated glycans in apical membranes of small-sized intrahepatic bile ducts and of cholangiolocellular carcinoma (CoCC) cells; MUC1 protein decorated with GlcNAc6ST-2-dependent MECA-79 sulfated glycans may serve as a useful CoCC marker. (PMID:27748735)
• mRNA transcript analyses on the genes involved in synthesizing GlcNAc-6-O-sulfated glycans in human colon cancer tissues indicated that GlcNAc6ST-2 (CHST4) is preferentially expressed in cancer cells … GlcNAc6ST-3 (CHST5) was only expressed in nonmalignant epithelial cells, whereas GlcNAc6ST-1 (CHST2) was expressed equally in both cancerous and nonmalignant epithelial cells. (PMID:30093410)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Chst4	ENSMUSG00000035930
rattus_norvegicus	Chst4	ENSRNOG00000016953
drosophila_melanogaster	CG9550	FBGN0031826
drosophila_melanogaster	CG31637	FBGN0051637

Paralogs (6): CHST3 (ENSG00000122863), CHST5 (ENSG00000135702), CHST7 (ENSG00000147119), CHST2 (ENSG00000175040), CHST1 (ENSG00000175264), CHST6 (ENSG00000183196)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1349479) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal leukocyte migration	2
abnormal lymph node morphology	1
abnormal lymph node primary follicle morphology	1
abnormal leukocyte adhesion	1
impaired leukocyte tethering or rolling	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q92179	75.6%	Diamond
Danio rerio	Q6DBY9	71.6%	Diamond
Tetronarce californica	O93403	59.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZNF19	protein-coding	7567
TAT-AS1	ncRNA	100132529
TAT	protein-coding	6898
ZNF23	protein-coding	7571

Protein

Protein identifiers

Carbohydrate sulfotransferase 4 — Q8NCG5 (reviewed: Q8NCG5)

Alternative names: Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 3, High endothelial cells N-acetylglucosamine 6-O-sulfotransferase, L-selectin ligand sulfotransferase, N-acetylglucosamine 6-O-sulfotransferase 2

All UniProt accessions (1): Q8NCG5

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase involved in SELL/L-selectin ligand biosynthesis pathway. Catalyzes the transfer of the sulfate group from 3’-phospho-5’-adenylyl sulfate (PAPS) onto the hydroxyl group at C-6 position of the non-reducing N-acetylglucosamine (GlcNAc) residue within O-linked mucin-type glycans. Contributes to generate sialyl 6-sulfo Lewis X determinant (also known as MECA-79 epitope) for SELL recognition, a prerequisite for continuous lymphocyte homing into peripheral lymph nodes and antigen immune surveillance. Transfers the sulfate group primarily on core 2 GlcNAcbeta1-6(Galbeta1-3)GalNAcalphaSer/Thr and extended core 1 GlcNAcbeta1-3Galbeta1-3GalNAcalphaSer/Thr based O-linked glycans on CD34 and GLYCAM1 peripheral node addressins (PNAds) expressed on the lumenal side of high endothelial venules (HEVs). The recognition of PNAds by SELL initiates a multistep process comprising tethering and rolling of blood lymphocytes on HEVs against the blood flow, followed by chemokine signaling, integrin-mediated lymphocyte adhesion onto endothelial cells and lymphocyte transendothelial migration. Modulates rolling velocity and differential T and B lymphocyte recruitment into peripheral lymph nodes, with a major role in B lymphocyte homing. Might be redundant in sulfation of MADCAM1 and lymphocyte trafficking to mesenteric lymph nodes. Can also sulfonate core 3 GlcNAcbeta1-3GalNAc-R based glycans as well as GlcNAcbeta1-3Galbeta1-Glc, GlcNAcbeta1-6ManOMe and GlcNAcbeta1-2Man oligosaccharides, which might be ectopically expressed during tumorigenesis.

Subunit / interactions. Monomer.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Specifically expressed in HEV. Weakly expressed in spleen. Not expressed in other tissues. Expressed in colonic mucinous adenocarcinoma.

Induction. Upon cytokine activation, it is expressed at low level.

Pathway. Protein modification; carbohydrate sulfation.

Miscellaneous. May serve as an anti-inflammatory target.

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

RefSeq proteins (2): NP_001159867, NP_005760 (=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

Catalyzed reactions (Rhea)

• 3-O-{N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + 3’-phosphoadenylyl sulfate = 3-O-{6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67856)
• a 3-O-{N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + 3’-phosphoadenylyl sulfate = a 3-O-{6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67860)
• a 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + 3’-phosphoadenylyl sulfate = 3-O-{beta-D-galactosyl-(1->3)-[6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67864)
• 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + 3’-phosphoadenylyl sulfate = 3-O-{beta-D-galactosyl-(1->3)-[6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67868)

UniProt features (11 total): glycosylation site 3, topological domain 2, binding site 2, chain 1, sequence conflict 1, transmembrane region 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCG5-F1	90.66	0.78

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
51–57	3’-phosphoadenylyl sulfate
205–213	3’-phosphoadenylyl sulfate

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	30, 308, 329

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-913709	O-linked glycosylation of mucins	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-5173105	O-linked glycosylation	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 113 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, AP1_01, chr16q22, GOBP_INFLAMMATORY_RESPONSE, GOBP_SULFATION, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_CELLULAR_EXTRAVASATION, GOBP_LEUKOCYTE_MIGRATION, AP1_Q4_01, GOCC_TRANS_GOLGI_NETWORK

GO Biological Process (10): carbohydrate metabolic process (GO:0005975), N-acetylglucosamine metabolic process (GO:0006044), protein sulfation (GO:0006477), sulfur compound metabolic process (GO:0006790), inflammatory response (GO:0006954), immune response (GO:0006955), cell adhesion (GO:0007155), cell-cell signaling (GO:0007267), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), positive regulation of leukocyte tethering or rolling (GO:1903238)

GO Molecular Function (3): N-acetylglucosamine 6-O-sulfotransferase activity (GO:0001517), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

GO Cellular Component (2): Golgi membrane (GO:0000139), trans-Golgi network (GO:0005802)

Reactome top-level categories

3 top-level categories:

Category	Pathways
O-linked glycosylation	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

21 GO namespaces:

Category	Terms
primary metabolic process	1
amino sugar metabolic process	1
protein modification process	1
sulfation	1
metabolic process	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
cell communication	1
signaling	1
protein O-linked glycosylation	1
leukocyte tethering or rolling	1
regulation of leukocyte tethering or rolling	1
positive regulation of leukocyte adhesion to vascular endothelial cell	1
sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
Golgi apparatus subcompartment	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
N-acetylglucosamine metabolic process	BP	direct assay
sulfur compound metabolic process	BP	direct assay
trans-Golgi network	CC	direct assay
N-acetylglucosamine 6-O-sulfotransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 400 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST4	NTAN1	Q96AB6	976
CHST4	FUT7	Q11130	656
CHST4	ST3GAL6	Q9Y274	612
CHST4	EMCN	Q9ULC0	538
CHST4	GCNT1	Q02742	537
CHST4	SELL	P14151	517
CHST4	B3GNT3	Q9Y2A9	514
CHST4	MADCAM1	Q13477	493
CHST4	CD300LG	Q6UXG3	489
CHST4	CHST13	Q8NET6	480
CHST4	GAL3ST3	Q96A11	453
CHST4	MIMS2	Q96KR6	440
CHST4	HECA	Q9UBI9	440
CHST4	CHST12	Q9NRB3	437
CHST4	C1GALT1	Q9NS00	433

IntAct

Human interaction partners of CHST4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
DCPS	physical association	0.370	1

BioGRID (9 interactions; top human partners by supporting records): CHST6 (Affinity Capture-MS; 2 records), DCPS (Two-hybrid), FAM91A1 (Cross-Linking-MS (XL-MS)), KIDINS220 (Cross-Linking-MS (XL-MS)), PARP15 (Proximity Label-MS), PRKAB2 (Affinity Capture-MS), SARNP (Cross-Linking-MS (XL-MS)), SPRTN (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CHST4: 79 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	67
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1706519	GRCh37/hg19 16q22.1-23.1(chr16:68971067-74823560)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CHST4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 123):

Position(s)	Effect	Δscore	Sites
16:71536658–71536659	acceptor_loss	0.9900	6
16:71526496–71526497	donor_loss	0.9800	3
16:71526496–71526497	donor_loss	0.9700	2
16:71536644	acceptor_loss	0.9700
16:71536648	acceptor_loss	0.9600
16:71536657	acceptor_gain	0.9600
16:71526479	donor_gain	0.9300
16:71536375	donor_gain	0.8900
16:71536754	acceptor_gain	0.8800
16:71536356	donor_gain	0.7600

AlphaMissense

644 missense substitutions predicted likely pathogenic (of 2,550 scored), across 176 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D206	8	0.969	0.988
F69	8	0.942	0.984
F62	8	0.911	0.975
D96	8	0.895	0.957
D224	8	0.766	0.880
H77	8	0.753	0.904
D193	8	0.693	0.912
C168	7	0.979	0.989
E73	7	0.974	0.990
C104	7	0.971	0.990
C133	7	0.966	0.984
W334	7	0.965	0.993
C250	7	0.963	0.982
F124	7	0.958	0.983
C138	7	0.944	0.969
C350	7	0.942	0.971
C152	7	0.933	0.968
K177	7	0.933	0.994
C156	7	0.931	0.972
F320	7	0.925	0.979

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Pancreatic Adenocarcinoma)

Disease associations

OMIM: gene `` | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2239 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	2
trichostatin A	increases expression	1
gallium arsenide	decreases 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	increases expression, affects cotreatment	1
erastin	increases reaction, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Doxycycline	increases expression, increases reaction	1
Estradiol	decreases expression, affects cotreatment	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	decreases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL681180	Binding	Inhibitory activity of compound was determined against human high endothelial cell (HEC) GlcNAc-6-ST sulfotransferase at 100 uM	Tyrosylprotein sulfotransferase inhibitors generated by combinatorial target-guided ligand assembly. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F4E2	HyCyte LS174T KO-hCHST4	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.