CHST8

Summary

CHST8 (carbohydrate sulfotransferase 8, HGNC:15993) is a protein-coding gene on chromosome 19q13.11, encoding Carbohydrate sulfotransferase 8 (Q9H2A9). Catalyzes the transfer of sulfate 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 predominantly expressed in the pituitary gland, and is localized to the golgi membrane. This protein catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. It is responsible for sulfation of GalNAc on luteinizing hormone (LH), which is required for production of the sex hormones. Mice lacking this enzyme, exhibit increased levels of circulating LH, and precocious sexual maturation of both male and female mice. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 64377 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peeling skin syndrome type A (Supportive, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_001127895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15993
Approved symbol	CHST8
Name	carbohydrate sulfotransferase 8
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	GALNAC4ST-1
Ensembl gene	ENSG00000124302
Ensembl biotype	protein_coding
OMIM	610190
Entrez	64377

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262622, ENST00000434302, ENST00000438847, ENST00000591231, ENST00000604556, ENST00000650847, ENST00000914938, ENST00000914939, ENST00000914940, ENST00000914941, ENST00000914942, ENST00000914943, ENST00000959496

RefSeq mRNA: 3 — MANE Select: NM_001127895 NM_001127895, NM_001127896, NM_022467

CCDS: CCDS12433

Canonical transcript exons

ENST00000650847 — 5 exons

Exon	Start	End
ENSE00001611342	33667767	33667843
ENSE00003703767	33689176	33689391
ENSE00003842830	33771957	33773506
ENSE00003844089	33621953	33622296
ENSE00003889633	33771413	33771450

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 92.95.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7277 / max 231.4864, expressed in 505 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175094	3.6952	505
175095	0.0325	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.95	gold quality
pituitary gland	UBERON:0000007	90.75	gold quality
adenohypophysis	UBERON:0002196	90.30	gold quality
pancreatic ductal cell	CL:0002079	87.88	silver quality
right hemisphere of cerebellum	UBERON:0014890	82.51	gold quality
cerebellar hemisphere	UBERON:0002245	81.96	gold quality
cerebellar cortex	UBERON:0002129	81.89	gold quality
type B pancreatic cell	CL:0000169	81.40	silver quality
cerebellum	UBERON:0002037	80.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.59	gold quality
anterior cingulate cortex	UBERON:0009835	78.70	gold quality
cingulate cortex	UBERON:0003027	78.68	gold quality
spinal cord	UBERON:0002240	78.52	gold quality
inferior olivary complex	UBERON:0002127	77.50	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	77.34	silver quality
Ammon’s horn	UBERON:0001954	77.25	gold quality
hypothalamus	UBERON:0001898	76.66	gold quality
cortical plate	UBERON:0005343	76.37	gold quality
right frontal lobe	UBERON:0002810	75.29	gold quality
prefrontal cortex	UBERON:0000451	75.22	gold quality
neocortex	UBERON:0001950	74.63	gold quality
cerebral cortex	UBERON:0000956	74.24	gold quality
frontal cortex	UBERON:0001870	74.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.60	gold quality
monocyte	CL:0000576	73.37	gold quality
superior frontal gyrus	UBERON:0002661	73.21	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.95	gold quality
mononuclear cell	CL:0000842	72.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.81	gold quality
brain	UBERON:0000955	72.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	44.22
E-GEOD-75367	no	446.77
E-ANND-3	no	2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting CHST8, 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-218-5P	99.93	72.22	2103
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-549A-5P	96.35	68.08	587

Literature-anchored findings (GeneRIF, showing 3)

• analysis of enzymatic properties and expression of GalNAc-4-sulfotransferase-1 and GalNAc-4-sulfotransferase-2 (PMID:16079414)
• A missense mutation in the CHST8 gene, encoding GalNAc4-ST1, is the underlying cause of type A non-inflammatory peeling skin syndrome in this family. (PMID:22289416)
• These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a “passenger” distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a “driver” disease-causing mutation that accounts for peeling skin syndrome (PMID:28204496)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	CHST8	ENSDARG00000074560
mus_musculus	Chst8	ENSMUSG00000060402
rattus_norvegicus	Chst8	ENSRNOG00000070506

Paralogs (6): CHST10 (ENSG00000115526), CHST12 (ENSG00000136213), CHST9 (ENSG00000154080), CHST14 (ENSG00000169105), CHST11 (ENSG00000171310), CHST13 (ENSG00000180767)

Protein

Protein identifiers

Carbohydrate sulfotransferase 8 — Q9H2A9 (reviewed: Q9H2A9)

Alternative names: GalNAc-4-O-sulfotransferase 1, N-acetylgalactosamine-4-O-sulfotransferase 1

All UniProt accessions (2): Q9H2A9, K7ENM3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Transfers sulfate to the 4-position of GalNAc in the context of GalNAcbeta1->4GlcNAcbeta1->R attached to both N-linked and core 2 branched O-linked oligosaccharides. Required for biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Not active toward chondroitin and dermatan.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Predominantly expressed in pituitary gland. In brain, it is expressed in pituitary gland, cerebellum, medulla oblongata, pons, thalamus and spinal cord. Expressed in the epidermis. Expressed at lower level in lung, spleen, adrenal gland, placenta, prostate, testis, mammary gland and trachea.

Induction. Down-regulated (17-fold) in prion-infected cells.

Pathway. Protein modification; carbohydrate sulfation.

Similarity. Belongs to the sulfotransferase 2 family.

RefSeq proteins (3): NP_001121367, NP_001121368, NP_071912 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005331	Sulfotransferase	Family
IPR018011	Carb_sulfotrans_8-10	Family

Pfam: PF03567

UniProt features (15 total): glycosylation site 4, topological domain 2, sequence variant 2, binding site 2, chain 1, sequence conflict 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-Q9H2A9-F1	79.90	0.62

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): 198–204; 258–266

Glycosylation sites (4): 367, 415, 128, 294

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway

MSigDB gene sets: 107 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_HORMONE_LEVELS, CHX10_01, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, SRF_Q5_01, IRF7_01, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, HFH4_01, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, PPAR_DR1_Q2, AACTTT_UNKNOWN, IK2_01, IK3_01

GO Biological Process (5): sulfur compound metabolic process (GO:0006790), central nervous system development (GO:0007417), carbohydrate biosynthetic process (GO:0016051), proteoglycan biosynthetic process (GO:0030166), hormone biosynthetic process (GO:0042446)

GO Molecular Function (4): dermatan 4-sulfotransferase activity (GO:0001537), sulfotransferase activity (GO:0008146), 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
N-glycan antennae elongation in the medial/trans-Golgi	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biosynthetic process	2
metabolic process	1
nervous system development	1
system development	1
carbohydrate metabolic process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
hormone metabolic process	1
dermatan sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	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

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST8	CA6	P23280	875
CHST8	CSTA	P01040	529
CHST8	TGM5	O43548	519
CHST8	CHST6	Q9GZX3	472
CHST8	MALRD1	Q5VYJ5	452
CHST8	KCTD15	Q96SI1	449
CHST8	SH2B1	Q9NRF2	447
CHST8	CLIP3	Q96DZ5	443
CHST8	BCDIN3D	Q7Z5W3	442
CHST8	PALD1	Q9ULE6	441
CHST8	TCERG1L	Q5VWI1	437
CHST8	CDSN	Q15517	434
CHST8	SLC35G1	Q2M3R5	432
CHST8	ZBTB7C	A1YPR0	427
CHST8	LRRC25	Q8N386	423

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CHST8	CANX	psi-mi:“MI:0914”(association)	0.640
CHST8	CHAT	psi-mi:“MI:0915”(physical association)	0.560
CHST8	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
CHST8	GSN	psi-mi:“MI:0915”(physical association)	0.560
CHST8	CLSTN1	psi-mi:“MI:0914”(association)	0.350
CHST8	CALU	psi-mi:“MI:0914”(association)	0.350
CHST8	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): TMED1 (Affinity Capture-MS), CANX (Affinity Capture-MS), FREM2 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), TMEM160 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), RBM27 (Affinity Capture-MS), TOR3A (Affinity Capture-MS), RBM23 (Affinity Capture-MS), CLSTN1 (Affinity Capture-MS), YBEY (Affinity Capture-MS), ARL10 (Affinity Capture-MS), SEPN1 (Affinity Capture-MS), TMED9 (Affinity Capture-MS)

ESM2 similar proteins: A2AIR5, A2RRU4, A4Q9F4, A6QM06, C0HL12, D4A6L0, E1BBQ2, H2Q5A1, K7GET2, O14514, O46547, O75077, O97741, P37088, P37089, P55270, P55926, P56726, P97260, Q12770, Q13563, Q16515, Q3UHD1, Q5E9P6, Q5MNU5, Q60HE8, Q61180, Q62962, Q6GQT6, Q6NXK8, Q708S5, Q7TNS7, Q7TSQ1, Q80UW0, Q8BQ86, Q8NHH1, Q8TCU5, Q92075, Q924S4, Q925H0

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2554 predictions. Top by Δscore:

Variant	Effect	Δscore
19:33689170:CCGTA:C	acceptor_loss	1.0000
19:33689171:CGTA:C	acceptor_loss	1.0000
19:33689172:GTA:G	acceptor_loss	1.0000
19:33689173:TAGA:T	acceptor_loss	1.0000
19:33689174:A:AG	acceptor_gain	1.0000
19:33689174:AGAT:A	acceptor_loss	1.0000
19:33689175:G:GA	acceptor_gain	1.0000
19:33689175:G:GC	acceptor_loss	1.0000
19:33689175:GAT:G	acceptor_gain	1.0000
19:33689175:GATCT:G	acceptor_gain	1.0000
19:33689389:CAGG:C	donor_loss	1.0000
19:33689392:GT:G	donor_loss	1.0000
19:33771451:G:GG	donor_gain	1.0000
19:33771953:CCAG:C	acceptor_loss	1.0000
19:33771954:CA:C	acceptor_loss	1.0000
19:33771955:A:AG	acceptor_gain	1.0000
19:33771956:G:A	acceptor_loss	1.0000
19:33771956:G:GG	acceptor_gain	1.0000
19:33622292:GCCAG:G	donor_gain	0.9900
19:33622296:GGTA:G	donor_loss	0.9900
19:33622297:G:C	donor_loss	0.9900
19:33622297:G:GG	donor_gain	0.9900
19:33622298:T:A	donor_loss	0.9900
19:33623459:G:T	donor_gain	0.9900
19:33680870:G:GG	donor_gain	0.9900
19:33689175:GA:G	acceptor_gain	0.9900
19:33689175:GATC:G	acceptor_gain	0.9900
19:33689392:G:GG	donor_gain	0.9900
19:33714804:T:A	acceptor_gain	0.9900
19:33771407:TTTCA:T	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016736 (19:33633763 GTT>G), RS1000027547 (19:33764315 C>A,T), RS1000040989 (19:33672595 C>T), RS1000054090 (19:33769004 G>A), RS1000099522 (19:33655445 G>A), RS1000112596 (19:33647379 G>A), RS1000113610 (19:33627130 G>A), RS1000122225 (19:33770065 G>A), RS1000137510 (19:33660170 G>A), RS1000144486 (19:33666376 C>A,T), RS1000190382 (19:33677357 G>A), RS1000191015 (19:33721369 C>A,G,T), RS1000210287 (19:33739059 G>A), RS1000216564 (19:33701484 T>C), RS1000222870 (19:33677615 A>G)

Disease associations

OMIM: gene MIM:610190 | disease phenotypes: MIM:616265

GenCC curated gene-disease

Disease	Classification	Inheritance
peeling skin syndrome type A	Supportive	Autosomal recessive

Mondo (1): peeling skin syndrome type A (MONDO:0014555)

Orphanet (2): Generalized peeling skin syndrome (Orphanet:263543), Peeling skin syndrome type A (Orphanet:263548)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000296_10	Body mass index	7.000000e-12
GCST000299_9	Weight	5.000000e-09
GCST000883_1	Response to antipsychotic treatment in schizophrenia (working memory)	6.000000e-07
GCST001850_24	Major depressive disorder	5.000000e-06
GCST002740_31	Inflammatory skin disease	4.000000e-07
GCST007473_10	Rapid automatized naming of pictures	2.000000e-06
GCST008154_62	Trunk fat mass	5.000000e-06
GCST008157_72	Body fat mass	6.000000e-06
GCST009266_16	Dental caries (decayed and filled deciduous tooth surfaces)	1.000000e-06
GCST009269_19	Dental caries (decayed and filled deciduous teeth)	8.000000e-07
GCST009897_7	Reading disability	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0004335	short-term memory
EFO:0005301	reading and spelling ability

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects expression, increases reaction, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
methylmercuric chloride	increases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Gallic Acid	decreases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Rotenone	increases expression	1
Tretinoin	increases expression	1
Urethane	affects expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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