CHST6

Summary

CHST6 (carbohydrate sulfotransferase 6, HGNC:6938) is a protein-coding gene on chromosome 16q23.1, encoding Carbohydrate sulfotransferase 6 (Q9GZX3). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues of keratan.

The protein encoded by this gene is an enzyme that catalyzes the transfer of a sulfate group to the GlcNAc residues of keratan. Keratan sulfate helps maintain corneal transparency. Defects in this gene are a cause of macular corneal dystrophy (MCD).

Source: NCBI Gene 4166 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macular corneal dystrophy (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 395 total — 29 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 15
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_021615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6938
Approved symbol	CHST6
Name	carbohydrate sulfotransferase 6
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183196
Ensembl biotype	protein_coding
OMIM	605294
Entrez	4166

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000332272, ENST00000390664, ENST00000649341, ENST00000649824, ENST00000970639

RefSeq mRNA: 1 — MANE Select: NM_021615 NM_021615

CCDS: CCDS10918

Canonical transcript exons

ENST00000332272 — 3 exons

Exon	Start	End
ENSE00001289993	75472052	75479844
ENSE00001296695	75481817	75481891
ENSE00003837799	75494940	75495441

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 93.77.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7747 / max 106.0555, expressed in 696 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158172	3.5630	690
158171	0.2118	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	93.77	gold quality
bronchus	UBERON:0002185	93.32	gold quality
nasal cavity epithelium	UBERON:0005384	90.62	silver quality
tibia	UBERON:0000979	84.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.75	gold quality
trachea	UBERON:0003126	82.60	gold quality
lateral globus pallidus	UBERON:0002476	81.46	gold quality
nasal cavity mucosa	UBERON:0001826	81.10	gold quality
inferior vagus X ganglion	UBERON:0005363	78.73	gold quality
subthalamic nucleus	UBERON:0001906	77.71	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.43	silver quality
substantia nigra	UBERON:0002038	77.13	gold quality
spinal cord	UBERON:0002240	77.07	gold quality
midbrain	UBERON:0001891	76.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.49	gold quality
epithelium of nasopharynx	UBERON:0001951	76.10	silver quality
corpus callosum	UBERON:0002336	75.84	gold quality
medulla oblongata	UBERON:0001896	75.24	gold quality
globus pallidus	UBERON:0001875	75.23	gold quality
superior vestibular nucleus	UBERON:0007227	74.38	gold quality
right adrenal gland cortex	UBERON:0035827	74.26	gold quality
right adrenal gland	UBERON:0001233	74.15	gold quality
ventral tegmental area	UBERON:0002691	73.87	silver quality
medial globus pallidus	UBERON:0002477	73.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.49	silver quality
substantia nigra pars compacta	UBERON:0001965	73.13	silver quality
left adrenal gland	UBERON:0001234	73.04	gold quality
left adrenal gland cortex	UBERON:0035825	72.31	gold quality
duodenum	UBERON:0002114	72.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

162 targeting CHST6, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• Novel mutations are thought to result in loss of corneal sulfotransferase function. (PMID:11818380)
• patients with MCD (macular corneal dystrophy) combined with those reported in previous studies indicated CHST6 mutational heterogeneity. (PMID:12824236)
• Two mutations (homozygoous R211W and compound heterozygous R211W/A217T) should be subclassified immunohistochemically into new phenotypes of macular corneal dystrophy. (PMID:12882769)
• Mutations identified in the CHST6 gene cosegregated with the disease phenotype in all but one family studied and thus caused macular corneal dystrophy. (PMID:12882775)
• novel frameshift and compound heterozygous mutations might be responsible for macular corneal dystrophy (PMID:12883341)
• Mutations in the coding region of the CHST6 gene are associated with type I MCD (macular corneal dystrophy) in a cohort of patients in southern India. (PMID:14609920)
• We identified 22 (5 nonsense, 5 frameshift, 2 insertion, and 10 missense) mutations in 36 patients from 31 families with MCD (macular corneal dystrophy) (PMID:14735064)
• mutations in the coding region of the CHST6 gene are associated with type I macular corneal dystrophy in a cohort of patients from the United States. (PMID:15013869)
• the stem region of GlcNAc6ST-1 influences substrate specificity, independent of its role in dimerization or Golgi retention. (PMID:15220337)
• These novel mutations are expected to result in loss of CHST6 function, which would account for the MCD (macular corneal dystrophy) phenotype. (PMID:15652851)
• These findings indicate that the predicted protein that is encoded by CHST6 is more severely affected in the individual with MCD type I than in the siblings with MCD type II. (PMID:15953452)
• Twenty-six different mutations of the CHST6 gene in macular corneal dystrophy in India were identified, of which 14 mutations are novel. (PMID:16207214)
• CHST6 mutations are cardinal to the pathogenesis of macular corneal dystrophy(MCD). MCD may result from other subtle changes in CHST6 or from genetic heterogeneity. (PMID:16568029)
• Homozygous p.A128V mutation in CHST6 gene and compound heterozygote for p.A128V and frameshift p.V6fs resulting from 10-base pair insertion in macular corneal dystrophy(MCD)I. Compound heterozygotes for p.A128V and p.V329L in MCD II. (PMID:17093400)
• In vivo laser confocal microscopy is capable of high-resolution visualization of characteristic corneal microstructural changes related to 3 types of genetically mapped corneal stromal dystrophies. (PMID:17846354)
• Novel homozygous missense mutation involving a highly conserved amino acid (c.518T > C; Leu173Pro). (PMID:17896316)
• study describes four CHST6 missense mutations present in seven of eight Czech macular corneal dystrophy (MCD) families of which the c.494G>A (p.C165Y) was novel; findings support a common founder effect for MCD in the Czech Republic (PMID:17962390)
• Our study shows the wide range of diagnostic findings and therapeutical options in patients suffering from macular corneal dystrophy depending on the genotype. (PMID:18500531)
• GlcNAc6ST-1 transcription is coordinated with the NF-kappaB/GATA-3 axis, which is known to figure heavily in Th2 cell differentiation (PMID:18849568)
• in macular corneal dystrophy (MCD) patients, there were no simple correlations between immunophenotypes and specific mutations in CHST6, suggesting that factors other than CHST6 mutations may be contributing to the immunophenotypes in MCD (PMID:19204788)
• study identified seven novel and three previously reported CHST6 mutations in our panel consisting of 20 Iranian macular corneal dystrophy patients from 12 families (PMID:19223992)
• The novel compound heterozygous mutations may contribute to the loss of CHST6 function, which induced the abnormal metabolism of keratan sulfate (KS) that deposited in the corneal stroma. (PMID:19365571)
• CHST6 mutations may be responsible for the pathogenesis of macular corneal dystrophy (MCD) in Chinese patients. (PMID:20539220)
• CHST6 gene sequencing revealed 2 heterozygous mutations in case 1, a p.Arg211Gln and a novel mutation of p.Arg177Gly and a novel homozygous mutation of p.Pro186Arg in case 2. (PMID:21242781)
• analysis of pathogenic mutations of TGFBI and CHST6 genes in Chinese patients with Avellino, lattice, and macular corneal dystrophies (PMID:21887843)
• Macular corneal dystrophy (MCD) may result from other changes in the regulatory elements of CHST6 or from genetic heterogeneity. (PMID:22261655)
• This novel gene mutation expands the mutation spectrum of the CHST6 gene and contributes to the study of molecular pathogenesis of corneal dystrophy. (PMID:24311932)
• This study improves the knowledge of the genetic features of Mexican patients with corneal stromal dystrophies by identifying mutations in the TGFBI, CHST6, and GSN genes. (PMID:24801599)
• Genetic mutation heterogeneity was revealed. No phenotype heterogeneity was revealed among patients with in vivo corneal morphology assessment or histological analysis. (PMID:24926691)
• Homozygous or compound heterozygous CHST6 mutations were identified in all cases, including two novel mutations, c.13C>T; p.(Arg5Cys) and c.289C>T; p.(Arg97Cys). (PMID:25081284)
• Three novel and six previously reported disease-causing CHST6 mutations were identified in Korean patients with macular corneal dystrophy. (PMID:26604660)
• E71Q mutation results in a non-conservative amino acid change in a highly conserved functional domain of the human CHST6 that is essential for enzyme activity as the cause of Macular corneal dystrophy. (PMID:27439461)
• This is the first molecular analysis of TGFBI and CHST6 in Turkish patients with different types of corneal dystrophies. (PMID:27829782)
• vast majority of variants likely to be protein-damaging (PMID:30716718)
• CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system. (PMID:32472422)
• Macular corneal dystrophy related to novel mutations of CHST6 in a Chinese family and clinical observation after penetrating keratoplasty. (PMID:34645431)
• Association of macular corneal dystrophy with excessive cell senescence and apoptosis induced by the novel mutant CHST6. (PMID:34826417)
• The Role of Functional Polymorphisms in the Extracellular Matrix Modulation-Related Genes on Dupuytren’s Contracture. (PMID:35627129)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG9550	FBGN0031826
drosophila_melanogaster	CG31637	FBGN0051637

Paralogs (6): CHST3 (ENSG00000122863), CHST5 (ENSG00000135702), CHST4 (ENSG00000140835), CHST7 (ENSG00000147119), CHST2 (ENSG00000175040), CHST1 (ENSG00000175264)

Protein

Protein identifiers

Carbohydrate sulfotransferase 6 — Q9GZX3 (reviewed: Q9GZX3)

Alternative names: Corneal N-acetylglucosamine-6-O-sulfotransferase, Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 4-beta, N-acetylglucosamine 6-O-sulfotransferase 5

All UniProt accessions (1): Q9GZX3

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 non-reducing N-acetylglucosamine (GlcNAc) residues of keratan. Cooperates with B4GALT4 galactosyltransferase and B3GNT7 N-acetylglucosaminyltransferase to construct and elongate the sulfated disaccharide unit [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Involved in biosynthesis of keratan sulfate in cornea, with an impact on proteoglycan fibril organization and corneal transparency. Involved in sulfation of endothelial mucins such as GLYCAM1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed in cornea. Mainly expressed in brain. Also expressed in spinal cord and trachea.

Disease relevance. Macular dystrophy, corneal (MCD) [MIM:217800] An ocular disease characterized by bilateral, progressive corneal opacification, and reduced corneal sensitivity. Onset occurs in the first decade, usually between ages 5 and 9. Painful attacks with photophobia, foreign body sensations, and recurrent erosions occur in most patients. The disease is due to deposition of an unsulfated keratan sulfate both within the intracellular space (within the keratocytes and endothelial cells) and in the extracellular corneal stroma. Macular corneal dystrophy is divided into the clinically indistinguishable types I, IA, and II based on analysis of the normally sulfated, or antigenic, keratan sulfate levels in serum and immunohistochemical evaluation of the cornea. Patients with types I and IA macular corneal dystrophy have undetectable serum levels of antigenic keratan sulfate, whereas those with type II macular corneal dystrophy have normal or low levels, depending on the population examined. The disease is caused by variants affecting the gene represented in this entry. CHST6 homozygous missense mutations have been observed in patients with macular corneal dystrophy type I, while type II patients show a large deletion and replacement in the upstream region of CHST6. The only missense mutation for type II is Cys-50, which is heterozygous with a replacement in the upstream region on the other allele of CHST6.

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

RefSeq proteins (1): NP_067628* (*=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

UniProt features (70 total): sequence variant 60, glycosylation site 4, topological domain 2, binding site 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZX3-F1	90.66	0.80

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): 49–55; 202–210

Glycosylation sites (4): 116, 229, 305, 328

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-3656225	Defective CHST6 causes MCDC1

MSigDB gene sets: 110 (showing top): RNGTGGGC_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOCC_TRANS_GOLGI_NETWORK, JIANG_TIP30_TARGETS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, HEN1_01, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_METABOLIC_PROCESS, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOCC_ORGANELLE_SUBCOMPARTMENT, GOBP_N_ACETYLGLUCOSAMINE_METABOLIC_PROCESS, GATA_C

GO Biological Process (4): carbohydrate metabolic process (GO:0005975), N-acetylglucosamine metabolic process (GO:0006044), sulfur compound metabolic process (GO:0006790), keratan sulfate proteoglycan biosynthetic process (GO:0018146)

GO Molecular Function (4): N-acetylglucosamine 6-O-sulfotransferase activity (GO:0001517), keratan sulfotransferase activity (GO:0045130), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
amino sugar metabolic process	1
metabolic process	1
proteoglycan biosynthetic process	1
keratan sulfate proteoglycan metabolic process	1
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
Golgi apparatus subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST6	SULT1C3	Q6IMI6	902
CHST6	SULT1C4	O75897	899
CHST6	SULT1B1	O43704	899
CHST6	LUM	P51884	852
CHST6	KERA	O60938	728
CHST6	B3GNT7	Q8NFL0	678
CHST6	UBIAD1	Q9Y5Z9	636
CHST6	B4GALT4	O60513	606
CHST6	SLC4A11	Q8NBS3	605
CHST6	CHST9	Q7L1S5	603
CHST6	KRT12	Q99456	595
CHST6	KRT3	P12035	583
CHST6	TGFBI	Q15582	570
CHST6	CHST11	Q9NPF2	565
CHST6	COL8A2	P25067	513

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CHST6	CANX	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
CHST5	SETD1A	psi-mi:“MI:0914”(association)	0.350
CHST6	HSPA5	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

BioGRID (30): CHST4 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), FAM3C (Affinity Capture-MS), BACE2 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), CANX (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), GPX8 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), CHST6 (Affinity Capture-MS)

ESM2 similar proteins: A6QNK1, O14792, O19058, O35310, O43916, O88199, Q10979, Q11127, Q29043, Q5E9W5, Q5RJQ0, Q5XPT3, Q6P7A1, Q6XQG8, Q6XQG9, Q6XQH0, Q712G6, Q7LGC8, Q7T3S3, Q800H9, Q80WV3, Q866C5, Q866C7, Q866D2, Q866D6, Q866D9, Q866E1, Q866E6, Q866E7, Q866E8, Q866F0, Q866F1, Q8HYJ3, Q8HYJ4, Q8HYJ7, Q8N3Y3, Q8NET6, Q92179, Q96RP7, Q99999

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

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	24
Uncertain significance	225
Likely benign	45
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2026508	NM_021615.5(CHST6):c.290_293dup (p.Val99fs)	Pathogenic
2114380	NM_021615.5(CHST6):c.601_621del (p.Val201_Val207del)	Pathogenic
2423621	NC_000016.9:g.(?75512539)(75576601_?)del	Pathogenic
2506044	NM_021615.5(CHST6):c.573dup (p.Ala192fs)	Pathogenic
2577141	NM_021615.5(CHST6):c.379C>T (p.Arg127Cys)	Pathogenic
2581187	NM_021615.5(CHST6):c.418C>T (p.Arg140Ter)	Pathogenic
2637472	NM_021615.5(CHST6):c.631C>T (p.Arg211Trp)	Pathogenic
2736373	NM_021615.5(CHST6):c.632G>A (p.Arg211Gln)	Pathogenic
2736374	NM_021615.5(CHST6):c.6_7delinsAA (p.Trp2_Leu3delinsTer)	Pathogenic
320606	NM_021615.5(CHST6):c.892C>T (p.Gln298Ter)	Pathogenic
3335959	NM_021615.5(CHST6):c.158C>T (p.Ser53Leu)	Pathogenic
3375062	NM_021615.5(CHST6):c.820G>A (p.Glu274Lys)	Pathogenic
3385288	NM_021615.5(CHST6):c.894dup (p.Leu299fs)	Pathogenic
3629653	NM_021615.5(CHST6):c.463_464del (p.Arg155fs)	Pathogenic
3722066	NM_021615.5(CHST6):c.680del (p.Gly227fs)	Pathogenic
3768560	NM_021615.5(CHST6):c.124C>T (p.His42Tyr)	Pathogenic
4075858	GRCh37/hg19 16q23.1(chr16:75494740-75549654)x1	Pathogenic
4525911	NM_021615.5(CHST6):c.613C>T (p.Arg205Trp)	Pathogenic
4710277	NM_021615.5(CHST6):c.614G>A (p.Arg205Gln)	Pathogenic
4710278	NM_021615.5(CHST6):c.231G>A (p.Trp77Ter)	Pathogenic
4710279	NM_021615.5(CHST6):c.51del (p.Gln18fs)	Pathogenic
4710280	NM_021615.5(CHST6):c.15_16insATGCTGTGCG (p.Val6fs)	Pathogenic
5071	NM_021615.5(CHST6):c.521A>G (p.Lys174Arg)	Pathogenic
5072	NM_021615.5(CHST6):c.609C>A (p.Asp203Glu)	Pathogenic
5073	CHST6, REPLACEMENT OF 5-PRIME REGION	Pathogenic
5074	CHST6, DELETION OF 5-PRIME REGION	Pathogenic
5075	NM_021615.5(CHST6):c.599T>G (p.Leu200Arg)	Pathogenic
5076	NM_021615.5(CHST6):c.304T>G (p.Cys102Gly)	Pathogenic
5077	NM_021615.5(CHST6):c.329A>G (p.Tyr110Cys)	Pathogenic
1325889	NM_021615.5(CHST6):c.211G>C (p.Glu71Gln)	Likely pathogenic

SpliceAI

964 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75494936:GTAC:G	donor_loss	1.0000
16:75494937:TAC:T	donor_loss	1.0000
16:75494938:A:AC	donor_gain	1.0000
16:75494938:AC:A	donor_gain	1.0000
16:75494938:ACC:A	donor_gain	1.0000
16:75494938:ACCC:A	donor_gain	1.0000
16:75494939:C:CC	donor_gain	1.0000
16:75494939:CC:C	donor_gain	1.0000
16:75494939:CCC:C	donor_gain	1.0000
16:75494939:CCCC:C	donor_gain	1.0000
16:75494939:CCCCA:C	donor_gain	1.0000
16:75481816:CCA:C	donor_gain	0.9900
16:75494935:CGTA:C	donor_gain	0.9800
16:75473467:TCTTC:T	acceptor_gain	0.9700
16:75473474:G:C	acceptor_gain	0.9700
16:75473474:G:GC	acceptor_gain	0.9700
16:75478615:AGCG:A	donor_gain	0.9700
16:75473468:C:G	acceptor_gain	0.9600
16:75479846:T:C	acceptor_gain	0.9600
16:75473471:C:CT	acceptor_gain	0.9500
16:75478602:T:A	donor_gain	0.9500
16:75481808:GGGAC:G	donor_loss	0.9500
16:75481809:GGAC:G	donor_loss	0.9500
16:75481810:GAC:G	donor_loss	0.9500
16:75481811:ACT:A	donor_loss	0.9500
16:75481812:CT:C	donor_loss	0.9500
16:75481814:CA:C	donor_loss	0.9500
16:75481815:A:AT	donor_loss	0.9500
16:75481816:C:A	donor_loss	0.9500
16:75482784:A:T	donor_gain	0.9500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000793 (16:75494705 C>T), RS1000145056 (16:75489220 G>A), RS1000200875 (16:75477607 T>C), RS1000221234 (16:75485069 A>G), RS1000252500 (16:75484869 A>G), RS1000269852 (16:75492244 G>C), RS1000321299 (16:75478519 G>A,C), RS1000332164 (16:75487605 T>C), RS1000418033 (16:75480048 C>A), RS1000431186 (16:75483223 C>T), RS1000592628 (16:75474949 C>T), RS1000862770 (16:75491453 T>A), RS1000872083 (16:75479886 C>T), RS1000872341 (16:75491081 C>G,T), RS1000982808 (16:75486462 C>A,G)

Disease associations

OMIM: gene MIM:605294 | disease phenotypes: MIM:217800, MIM:614970, MIM:615397

GenCC curated gene-disease

Disease	Classification	Inheritance
macular corneal dystrophy	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
macular corneal dystrophy	Definitive	AR

Mondo (3): macular corneal dystrophy (MONDO:0009020), Joubert syndrome 20 (MONDO:0013994), Meckel syndrome, type 11 (MONDO:0014164)

Orphanet (3): Macular corneal dystrophy (Orphanet:98969), Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000484	Hyperopic astigmatism
HP:0000495	Recurrent corneal erosions
HP:0000531	Corneal crystals
HP:0000613	Photophobia
HP:0001131	Corneal dystrophy
HP:0001141	Severely reduced visual acuity
HP:0001939	Abnormality of metabolism/homeostasis
HP:0003621	Juvenile onset
HP:0007754	Macular dystrophy
HP:0007759	Opacification of the corneal stroma
HP:0007856	Punctate opacification of the cornea
HP:0012155	Decreased corneal sensation
HP:0100689	Decreased corneal thickness
HP:0200026	Ocular pain

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002553_10	Pancreatic cancer	1.000000e-10
GCST004858_22	Dupuytren’s disease	5.000000e-10
GCST007612_2	Chronic obstructive pulmonary disease or coronary artery disease (pleiotropy)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537834	Macular dystrophy, corneal type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	4
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
bisphenol A	increases expression	2
Arsenic Trioxide	increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	affects methylation	1
poly-N-acetyllactosamine	increases sulfation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
pentanal	increases expression	1
2-hydroxychavicol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
apple polyphenol extract	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Amiodarone	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Dexamethasone	decreases expression	1
Diethylnitrosamine	increases expression	1
Estradiol	decreases expression, affects cotreatment, increases expression	1
Keratan Sulfate	increases chemical synthesis, increases sulfation	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B0PQ	GLNNFi001-A	Induced pluripotent stem cell	Male
CVCL_WU17	CSUASOi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04009668	PHASE2	COMPLETED	Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT00346853	PHASE1	COMPLETED	Phase 1 Pilot Study of 4-MP to Treat Stargardt Macular Dystrophy
NCT07267026	PHASE1	RECRUITING	A Study to Evaluate the Safety, Tolerability and PK of SK-09
NCT04571658	Not specified	RECRUITING	NEPTUNE Match Study
NCT04642729	Not specified	UNKNOWN	Fresh Corneal Lenticule Implantation in Macular Corneal Distrophy With Relex Smile Surgery
NCT05650619	Not specified	RECRUITING	Recurrence Post-transplant Observational Study in Focal Segmental Glomerulosclerosis and Minimal Change Disease