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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.73

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CHST13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

620 rare PASS variants

Rare truncating (LoF)

1 in 1,600

76 rare PASS variants

Rare synonymous (reference)

1 in 120

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHST13. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 2,100
South Asian	~43k	1 in 100	1 in 650
Remaining (unassigned)	~30k	1 in 150	1 in 1,300
European (Finnish)	~27k	1 in 420	≈ 1 in 8,100
Admixed American	~22k	1 in 130	1 in 3,000
African / African American	~21k	1 in 86	1 in 1,300
East Asian	~20k	1 in 79	1 in 500
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 67	≈ 1 in 1,500

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓