CHST14

Chr 15

carbohydrate sulfotransferase 14

Also known as: ATCS, D4ST1, EDSMC1, HNK1ST

NCBI Gene: 113189 ENSG00000169105 UniProt: Q8NCH0

This gene encodes a sulfotransferase that catalyzes the transfer of sulfate to N-acetylgalactosamine residues in dermatan sulfate, playing a crucial role in dermatan sulfate biosynthesis and cerebellar neural network formation during postnatal brain development. Biallelic mutations cause Ehlers-Danlos syndrome, musculocontractural type 1, an autosomal recessive connective tissue disorder characterized by joint contractures, skin hyperextensibility, and skeletal abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.64), suggesting some tolerance to haploinsufficiency.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the HNK-1 family of sulfotransferases. The encoded protein transfers sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate. Mutations in this gene have been associated with adducted thumb-clubfoot syndrome.[provided by RefSeq, Mar 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEhlers-Danlos syndrome, musculocontractural type 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Ehlers-Danlos syndrome, musculocontractural type 1 · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CHST14

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.447

Z-score 2.31

OE 0.20 (0.08–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.68Z-score

OE missense 0.87 (0.77–0.98)

182 obs / 209.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.08–0.64)

0≤0.351.4

Missense OE?0.87 (0.77–0.98)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 9.8Missense obs/exp: 182 / 209.8Syn Z: 0.70

Background carrier burden — how many people carry a rare variant somewhere in CHST14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

495 rare PASS variants

Rare truncating (LoF)

1 in 3,400

56 rare PASS variants

Rare synonymous (reference)

1 in 190

250 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHST14. 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 210	1 in 5,100
South Asian	~43k	1 in 130	1 in 2,400
Remaining (unassigned)	~30k	1 in 140	1 in 4,100
European (Finnish)	~27k	1 in 270	1 in 3,500
Admixed American	~22k	1 in 200	≈ 1 in 11,000
African / African American	~21k	1 in 150	1 in 950
East Asian	~20k	1 in 160	≈ 1 in 5,900
Ashkenazi Jewish	~13k	1 in 610	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓