CHST13

Chr 3

carbohydrate sulfotransferase 13

Also known as: C4ST3

NCBI Gene: 166012 ENSG00000180767 UniProt: Q8NET6 OMIM: 610124

The protein catalyzes the transfer of sulfate to the C4 hydroxyl of N-acetylgalactosamine residues in chondroitin, a major proteoglycan component of cartilage and extracellular matrices. Mutations cause Ehlers-Danlos syndrome musculocontractural type 1, a severe connective tissue disorder with congenital contractures, craniofacial abnormalities, and progressive multisystem involvement. This follows autosomal recessive inheritance and shows a high tolerance to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to the C4 hydroxyl of beta-1,4-linked N-acetylgalactosamine (GalNAc) flanked by glucuronic acid residue in chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— CHST13

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

62 VUS of 65 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score 0.12

OE 0.95 (0.51–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.25Z-score

OE missense 0.75 (0.65–0.86)

143 obs / 191.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.51–1.73)

0≤0.351.4

Missense OE?0.75 (0.65–0.86)

0≤0.61.4

Synonymous OE?0.70

0≤1.21.6

LoF obs/exp: 6 / 6.3Missense obs/exp: 143 / 191.9Syn Z: 2.21

This gene — mechanism propensity

0.6647th %ile

GOF

0.6247th %ile

LOF

0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	62	62
Likely Benign	0	0
Benign	0	0
Total	62	62

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap CHST13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →