CHST3

Summary

CHST3 (carbohydrate sulfotransferase 3, HGNC:1971) is a protein-coding gene on chromosome 10q22.1, encoding Carbohydrate sulfotransferase 3 (Q7LGC8). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin.

This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis.

Source: NCBI Gene 9469 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepiphyseal dysplasia with congenital joint dislocations (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 470 total — 32 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 148
• MANE Select transcript: NM_004273

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1971
Approved symbol	CHST3
Name	carbohydrate sulfotransferase 3
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	C6ST, C6ST1
Ensembl gene	ENSG00000122863
Ensembl biotype	protein_coding
OMIM	603799
Entrez	9469

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000373115, ENST00000879006, ENST00000943244

RefSeq mRNA: 1 — MANE Select: NM_004273 NM_004273

CCDS: CCDS7312

Canonical transcript exons

ENST00000373115 — 3 exons

Exon	Start	End
ENSE00001459536	72007172	72013558
ENSE00001459537	72005736	72005982
ENSE00001459538	71964395	71964694

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 96.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5410 / max 81.0053, expressed in 1356 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105468	3.4949	999
105467	3.1586	1218
105470	0.7456	419
105469	0.5935	365
105475	0.2926	146
105471	0.2557	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	96.05	gold quality
cartilage tissue	UBERON:0002418	91.53	gold quality
ventricular zone	UBERON:0003053	88.52	gold quality
right coronary artery	UBERON:0001625	87.90	gold quality
popliteal artery	UBERON:0002250	87.47	gold quality
tibial artery	UBERON:0007610	87.44	gold quality
descending thoracic aorta	UBERON:0002345	87.42	gold quality
decidua	UBERON:0002450	87.29	gold quality
aorta	UBERON:0000947	87.19	gold quality
thoracic aorta	UBERON:0001515	87.11	gold quality
ascending aorta	UBERON:0001496	87.06	gold quality
left coronary artery	UBERON:0001626	86.49	gold quality
right ovary	UBERON:0002118	85.85	gold quality
coronary artery	UBERON:0001621	85.54	gold quality
left ovary	UBERON:0002119	85.35	gold quality
stromal cell of endometrium	CL:0002255	85.22	gold quality
cranial nerve II	UBERON:0000941	84.90	gold quality
tibial nerve	UBERON:0001323	84.57	gold quality
left uterine tube	UBERON:0001303	83.81	gold quality
inferior olivary complex	UBERON:0002127	83.61	gold quality
gastrocnemius	UBERON:0001388	83.28	gold quality
right atrium auricular region	UBERON:0006631	83.23	gold quality
smooth muscle tissue	UBERON:0001135	82.89	gold quality
right adrenal gland	UBERON:0001233	82.88	gold quality
left adrenal gland	UBERON:0001234	82.84	gold quality
cardiac atrium	UBERON:0002081	82.84	gold quality
heart left ventricle	UBERON:0002084	82.81	gold quality
ovary	UBERON:0000992	82.80	gold quality
sural nerve	UBERON:0015488	82.75	gold quality
left adrenal gland cortex	UBERON:0035825	82.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB3L1, KDM5B

miRNA regulators (miRDB)

223 targeting CHST3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930

Literature-anchored findings (GeneRIF, showing 17)

• report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations (PMID:18513679)
• Sulfation of the galactose residues in the glycosaminoglycan-protein linkage region by recombinant human chondroitin 6-O-sulfotransferase-1. (PMID:18697746)
• homozygous missense mutation (T141M) in exon 3 in all three family members with spondyloepiphyseal dysplasia with cardiac involvement (PMID:19320654)
• Vertebral changes, normal carpal age, lack of facial flattening, and recessive inheritance are characteristic and distinguishes CHST3 deficiency from other disorders with congenital dislocations. (PMID:20830804)
• The results of this study indicated that the critical period for cortical plasticity is regulated by the 4S/6S ratio of CSPGs, which determines the maturation of parvalbumin-expressing interneurons. (PMID:22246436)
• expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of subjects carrying the A allele of rs4148941 (PMID:24216480)
• Sequencing of CHST3 detected a previously unreported homozygous duplication c.407_426dup (p.Thr143Cysfs*80). The mutation is predicted to lead to frameshift and introduction of a premature stopcodon. (PMID:24300290)
• A novel CHST3 allele associated with spondyloepiphyseal dysplasia and hearing loss has been described in a consanguineous Pakistani pedigree. (PMID:26572954)
• We describe three consanguineous Indian families with a distinct form of spondyloepiphyseal dysplasia (SED Omani type). It is an autosomal recessive disorder due to mutation in CHST3 gene. (PMID:27753269)
• We show that the CHST3 and CHST13 alleles are significantly more frequent in pulmonary arterial hypertension patients with elevated aminotransferases during therapy with bosentan than those in patients without liver injury. This is the first pharmacogenomics study linking proteoglycan sulfating genes to drug-induced liver dysfunction. (PMID:30118797)
• Abnormal expression of chondroitin sulfate sulfotransferases in the articular cartilage of pediatric patients with Kashin-Beck disease. (PMID:31845005)
• Lysophosphatidic acid receptor 5 transactivation of TGFBR1 stimulates the mRNA expression of proteoglycan synthesizing genes XYLT1 and CHST3. (PMID:32920014)
• Chondroitin 6-sulfate represses keratinocyte proliferation in mouse skin, which is associated with psoriasis. (PMID:33495490)
• Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds. (PMID:36042462)
• CHST3-related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum. (PMID:37183573)
• Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway. (PMID:37621132)
• Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations. (PMID:37876363)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chst3a	ENSDARG00000061070
mus_musculus	Chst3	ENSMUSG00000057337
rattus_norvegicus	Chst3	ENSRNOG00000000572
drosophila_melanogaster	CG9550	FBGN0031826
drosophila_melanogaster	CG31637	FBGN0051637

Paralogs (6): CHST5 (ENSG00000135702), CHST4 (ENSG00000140835), CHST7 (ENSG00000147119), CHST2 (ENSG00000175040), CHST1 (ENSG00000175264), CHST6 (ENSG00000183196)

Protein

Protein identifiers

Carbohydrate sulfotransferase 3 — Q7LGC8 (reviewed: Q7LGC8)

Alternative names: Chondroitin 6-O-sulfotransferase 1, Chondroitin 6-sulfotransferase, Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 0

All UniProt accessions (1): Q7LGC8

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 the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Catalyzes with a lower efficiency the sulfation of Gal residues of keratan sulfate, another glycosaminoglycan. Can also catalyze the sulfation of the Gal residues in sialyl N-acetyllactosamine (sialyl LacNAc) oligosaccharides. May play a role in the maintenance of naive T-lymphocytes in the spleen.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed in adult tissues. Expressed in heart, placenta, skeletal muscle and pancreas. Also expressed in various immune tissues such as spleen, lymph node, thymus and appendix.

Post-translational modifications. N-glycosylated.

Disease relevance. Spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD) [MIM:143095] A bone dysplasia clinically characterized by dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The disorder is usually evident at birth, with short stature and multiple joint dislocations or subluxations that dominate the neonatal clinical and radiographic picture. During childhood, the dislocations improve, both spontaneously and with surgical treatment, and features of spondyloepiphyseal dysplasia become apparent, leading to arthritis of the hips and spine with intervertebral disk degeneration, rigid kyphoscoliosis, and trunk shortening by late childhood. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_004264* (*=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 2.8.2.17 — chondroitin 6-sulfotransferase (BRENDA: 7 organisms, 62 substrates, 14 inhibitors, 31 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3’-PHOSPHOADENYLYL SULFATE	0.0003–0.0042	6
CHONDROITIN	0.0008–0.15	6
3’-PHOSPHOADENYLYLSULFATE	0.0001–0.0333	5
CHONDROITIN 4-SULFATE	0.0005–0.038	2
KERATAN SULFATE	0.0029–0.005	2
DECASACCHARIDE	0.9	1
DESULFATED CHONDROITIN SULFATE	1.8	1
DODECASACCHARIDE	0.48	1
GLCUABETA(1->3)GALNAC(4S)BETA(1->4)GLCUABETA(1->	0.05	1
HEXASACCHARIDE	5	1
N-ACETYLGALACTOSAMINE 4-SULFATE	0.36	1
NATIVE CHONDROITIN	0.06	1
OCTASACCHARIDE	2.5	1
UDP-N-ACETYLGALACTOSAMINE 4-SULFATE	0.027	1

Catalyzed reactions (Rhea), 1 shown:

• chondroitin beta-D-glucuronate + n 3’-phosphoadenylyl sulfate = chondroitin 6’-sulfate + n adenosine 3’,5’-bisphosphate + n H(+) (RHEA:11108)

UniProt features (22 total): sequence variant 7, glycosylation site 6, topological domain 2, sequence conflict 2, binding site 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LGC8-F1	80.58	0.57

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): 141–147; 301–309

Glycosylation sites (6): 256, 420, 464, 63, 74, 96

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-2022870	CS-GAG biosynthesis
R-HSA-3595172	Defective CHST3 causes SEDCJD

MSigDB gene sets: 489 (showing top): MODULE_52, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, MODULE_118, BROWNE_HCMV_INFECTION_48HR_DN, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, CAGCAGG_MIR370, ONKEN_UVEAL_MELANOMA_UP, MODULE_379, AMIT_EGF_RESPONSE_120_HELA, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), N-acetylglucosamine metabolic process (GO:0006044), sulfur compound metabolic process (GO:0006790), keratan sulfate proteoglycan biosynthetic process (GO:0018146), T cell homeostasis (GO:0043029), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650)

GO Molecular Function (6): N-acetylglucosamine 6-O-sulfotransferase activity (GO:0001517), chondroitin 6-sulfotransferase activity (GO:0008459), keratan sulfotransferase activity (GO:0045130), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740), proteoglycan sulfotransferase activity (GO:0050698)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1
Chondroitin sulfate/dermatan sulfate metabolism	1
Diseases associated with glycosaminoglycan metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteoglycan biosynthetic process	2
sulfotransferase activity	2
primary metabolic process	1
amino sugar metabolic process	1
metabolic process	1
keratan sulfate proteoglycan metabolic process	1
lymphocyte homeostasis	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
chondroitin sulfotransferase activity	1
proteoglycan sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST3	SULT1C4	O75897	762
CHST3	SULT1C3	Q6IMI6	750
CHST3	LUM	P51884	749
CHST3	SULT1B1	O43704	748
CHST3	CHST12	Q9NRB3	744
CHST3	CHST11	Q9NPF2	739
CHST3	CHST13	Q8NET6	738
CHST3	CHST15	Q7LFX5	731
CHST3	KERA	O60938	691
CHST3	CHST14	Q8NCH0	668
CHST3	CHSY1	Q86X52	635
CHST3	CSGALNACT2	Q8N6G5	610
CHST3	CSGALNACT1	Q8TDX6	608
CHST3	CHPF	Q8IZ52	595
CHST3	NTAN1	Q96AB6	590
CHST3	HS2ST1	Q7LGA3	590

IntAct

28 interactions, top by confidence:

A	B	Type	Score
OFD1	DYNLL1	psi-mi:“MI:0914”(association)	0.890
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
AVP	ATE1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
AVP	B4GALT5	psi-mi:“MI:0914”(association)	0.350
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
MSMB	ADAM11	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
ADIPOQ	AGRN	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DKK3	CCN2	psi-mi:“MI:0914”(association)	0.350
FCN1	CUL3	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
PATE1	AGRN	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHST3	OFD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), OFD1 (Affinity Capture-MS), CHST3 (Affinity Capture-RNA), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), CHST3 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	20
Uncertain significance	216
Likely benign	145
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1039079	NM_004273.5(CHST3):c.334G>T (p.Glu112Ter)	Pathogenic
1406206	NM_004273.5(CHST3):c.362dup (p.Glu122fs)	Pathogenic
1445618	NM_004273.5(CHST3):c.271C>T (p.Gln91Ter)	Pathogenic
1452559	NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs)	Pathogenic
1454776	NM_004273.5(CHST3):c.763del (p.Leu255fs)	Pathogenic
1458337	NM_004273.5(CHST3):c.238del (p.Ser79_Leu80insTer)	Pathogenic
1474566	NM_004273.5(CHST3):c.1177del (p.Pro392_Leu393insTer)	Pathogenic
1685635	NM_004273.5(CHST3):c.141-1G>C	Pathogenic
1996399	NM_004273.5(CHST3):c.58_77dup (p.Leu26_Phe27insTer)	Pathogenic
2083760	NM_004273.5(CHST3):c.83T>A (p.Leu28Ter)	Pathogenic
2087753	NM_004273.5(CHST3):c.855del (p.Leu286fs)	Pathogenic
225684	NM_004273.5(CHST3):c.1063G>A (p.Gly355Arg)	Pathogenic
2428494	NM_004273.5(CHST3):c.976dup (p.Asp326fs)	Pathogenic
3676659	NM_004273.5(CHST3):c.685_686del (p.Cys229fs)	Pathogenic
3720938	NM_004273.5(CHST3):c.718A>T (p.Lys240Ter)	Pathogenic
4709735	NM_004273.5(CHST3):c.802G>T (p.Glu268Ter)	Pathogenic
4716158	NM_004273.5(CHST3):c.696dup (p.Val233fs)	Pathogenic
4742464	NM_004273.5(CHST3):c.723dup (p.Phe242fs)	Pathogenic
478822	NM_004273.5(CHST3):c.904G>C (p.Asp302His)	Pathogenic
478823	NM_004273.5(CHST3):c.491C>T (p.Pro164Leu)	Pathogenic
522996	NM_004273.5(CHST3):c.1312C>T (p.Gln438Ter)	Pathogenic
6041	NM_004273.5(CHST3):c.776T>C (p.Leu259Pro)	Pathogenic
6042	NM_004273.5(CHST3):c.1114G>A (p.Glu372Lys)	Pathogenic
6043	NM_004273.5(CHST3):c.664C>T (p.Arg222Trp)	Pathogenic
6044	NM_004273.5(CHST3):c.920T>C (p.Leu307Pro)	Pathogenic
6045	NM_004273.5(CHST3):c.1086del (p.Arg363fs)	Pathogenic
6046	NM_004273.5(CHST3):c.603C>A (p.Tyr201Ter)	Pathogenic
6047	NM_004273.5(CHST3):c.857T>C (p.Leu286Pro)	Pathogenic
6050	NM_004273.5(CHST3):c.481C>T (p.Leu161Phe)	Pathogenic
6051	NM_004273.5(CHST3):c.988C>T (p.Gln330Ter)	Pathogenic

SpliceAI

584 predictions. Top by Δscore:

Variant	Effect	Δscore
10:72007167:CACA:C	acceptor_loss	1.0000
10:72007168:ACAG:A	acceptor_gain	1.0000
10:72007169:CA:C	acceptor_loss	1.0000
10:72007170:A:AG	acceptor_gain	1.0000
10:72007170:AG:A	acceptor_gain	1.0000
10:72007171:G:GT	acceptor_gain	1.0000
10:72007171:GG:G	acceptor_gain	1.0000
10:72005732:GCAG:G	acceptor_loss	0.9900
10:72005735:G:T	acceptor_loss	0.9900
10:72005900:A:G	donor_gain	0.9900
10:72005939:A:AG	donor_gain	0.9900
10:72005963:G:GT	donor_gain	0.9900
10:72005964:A:T	donor_gain	0.9900
10:72007168:A:AG	acceptor_gain	0.9900
10:72007168:ACAGG:A	acceptor_gain	0.9900
10:72007169:C:G	acceptor_gain	0.9900
10:72007170:AGG:A	acceptor_gain	0.9900
10:72007171:GGG:G	acceptor_gain	0.9900
10:72007171:GGGT:G	acceptor_gain	0.9900
10:72007171:GGGTC:G	acceptor_gain	0.9900
10:71964692:GGG:G	donor_gain	0.9800
10:71964693:GG:G	donor_gain	0.9800
10:71964693:GGG:G	donor_gain	0.9800
10:71964694:GG:G	donor_gain	0.9800
10:72005734:A:AG	acceptor_gain	0.9800
10:72005735:G:GG	acceptor_gain	0.9800
10:72005793:C:G	donor_gain	0.9800
10:72005904:G:GT	donor_gain	0.9800
10:72005938:GAT:G	donor_gain	0.9800
10:72005982:GGTG:G	donor_loss	0.9800

AlphaMissense

3117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:72007519:A:T	E163V	1.000
10:72007850:G:C	K273N	1.000
10:72007850:G:T	K273N	1.000
10:72008315:G:C	W428C	1.000
10:72008315:G:T	W428C	1.000
10:72007515:T:C	F162L	0.999
10:72007517:C:A	F162L	0.999
10:72007517:C:G	F162L	0.999
10:72007518:G:A	E163K	0.999
10:72007520:G:C	E163D	0.999
10:72007520:G:T	E163D	0.999
10:72007522:C:A	P164Q	0.999
10:72007522:C:G	P164R	0.999
10:72007623:T:A	C198S	0.999
10:72007624:G:A	C198Y	0.999
10:72007624:G:C	C198S	0.999
10:72007624:G:T	C198F	0.999
10:72007689:T:C	F220L	0.999
10:72007691:C:A	F220L	0.999
10:72007691:C:G	F220L	0.999
10:72007704:A:C	S225R	0.999
10:72007706:C:A	S225R	0.999
10:72007706:C:G	S225R	0.999
10:72007716:T:A	C229S	0.999
10:72007717:G:A	C229Y	0.999
10:72007717:G:C	C229S	0.999
10:72007731:T:A	C234S	0.999
10:72007732:G:A	C234Y	0.999
10:72007732:G:C	C234S	0.999
10:72007733:T:G	C234W	0.999

dbSNP variants (sampled 300 via entrez): RS1000002466 (10:71976340 T>C), RS1000033704 (10:71996875 G>A,T), RS1000070713 (10:72010070 C>T), RS1000223030 (10:71964845 G>A,C,T), RS1000230520 (10:71990947 C>G,T), RS1000253979 (10:71964655 G>A), RS1000319336 (10:72008729 G>A,T), RS1000427342 (10:71975260 A>G), RS1000515241 (10:71970547 C>T), RS1000519214 (10:71974976 G>A,C), RS1000522642 (10:72011366 G>A), RS1000583402 (10:71965882 C>T), RS1000589181 (10:71980558 A>G), RS1000636517 (10:72006215 C>T), RS1000687908 (10:71986710 T>C)

Disease associations

OMIM: gene MIM:603799 | disease phenotypes: MIM:143095, MIM:245600, MIM:150250

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepiphyseal dysplasia with congenital joint dislocations	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spondyloepiphyseal dysplasia with congenital joint dislocations	Definitive	AR

Mondo (3): spondyloepiphyseal dysplasia with congenital joint dislocations (MONDO:0007738), Larsen-like syndrome, B3GAT3 type (MONDO:0009511), Larsen syndrome (MONDO:0007875)

Orphanet (3): CHST3-related skeletal dysplasia (Orphanet:263463), Larsen-like syndrome, B3GAT3 type (Orphanet:284139), Larsen syndrome (Orphanet:503)

HPO phenotypes

148 total (30 of 148 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000274	Small face
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000574	Thick eyebrow
HP:0000592	Blue sclerae
HP:0000646	Amblyopia
HP:0000684	Delayed eruption of teeth
HP:0000687	Widely spaced teeth
HP:0000691	Microdontia
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000776	Congenital diaphragmatic hernia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002225_1	Disc degeneration (lumbar)	4.000000e-08
GCST002225_2	Disc degeneration (lumbar)	1.000000e-06
GCST004862_135	Itch intensity from mosquito bite adjusted by bite size	8.000000e-06
GCST007102_18	Seasonality and depression	6.000000e-06
GCST012255_1	Response to antioxidants and zinc in age-related macular degeneration (disease progression)	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0006876	seasonality measurement
EFO:0008336	disease progression measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C537283	Gollop Coates syndrome (supp.)
C580241	Larsen Syndrome (supp.)
C537874	Larsen syndrome, recessive type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12418	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs1871450	Efficacy,Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms
rs4148943	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs4148945	Efficacy,Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms
rs4148947	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs4148950	Efficacy,Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms
rs730720	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12418	CHST3	3	2.00	1	docetaxel;thalidomide
rs730720	CHST3	3	2.00	1	docetaxel;thalidomide
rs1871450	CHST3	3	3.50	1	docetaxel;thalidomide
rs4148943	CHST3	3	2.00	1	docetaxel;thalidomide
rs4148945	CHST3	3	3.00	1	docetaxel;thalidomide
rs4148947	CHST3	3	2.00	1	docetaxel;thalidomide
rs4148950	CHST3	3	3.50	1	docetaxel;thalidomide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
2-palmitoylglycerol	increases expression	1
clothianidin	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
apple polyphenol extract	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Biological Factors	decreases expression	1
Calcitriol	increases expression	1
Chromium	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05052554	PHASE1	WITHDRAWN	Study With QR-504a to Evaluate Safety, Tolerability & Corneal Endothelium Molecular Biomarker(s) in Subjects With FECD3