CSGALNACT1

Chr 8AR

chondroitin sulfate N-acetylgalactosaminyltransferase 1

Also known as: CSGalNAcT-1, ChGn, ChGn-1, SDJLABA, beta4GalNAcT

NCBI Gene: 55790 ENSG00000147408 OMIM: 616615

This enzyme transfers N-acetylgalactosamine to glucuronic acid residues during chondroitin sulfate biosynthesis, which is essential for cartilage formation and endochondral ossification. Autosomal recessive mutations cause skeletal dysplasia with joint laxity and advanced bone age, primarily affecting the musculoskeletal system. The gene shows low constraint against loss-of-function variants (LOEUF 1.338), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that transfers N-acetylglucosamine (GalNAc) to the core tetrasaccharide linker and to elongating chondroitin sulfate chains in proteoglycans. Knockout of the orthologous mouse gene indicates that the protein is necessary for normal cartilage development and aggrecan metabolism. Mutations in this gene are associated with multiple sclerosis progression, and with mild skeletal dysplasia and joint laxity. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.341 OMIM phenotype

Clinical Summary— CSGALNACT1

🧬

Gene-Disease Validity (ClinGen)

skeletal dysplasia, mild, with joint laxity and advanced bone age · ARModerate

Moderate evidence — consider for supplementary testing

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

21 unique Pathogenic / Likely Pathogenic· 189 VUS of 388 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?

1.34LOEUF

pLI 0.000

Z-score 0.31

OE 0.93 (0.66–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.63Z-score

OE missense 1.43 (1.32–1.55)

425 obs / 297.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.66–1.34)

0≤0.351.4

Missense OE?1.43 (1.32–1.55)

0≤0.61.4

Synonymous OE?1.49

0≤1.21.6

LoF obs/exp: 21 / 22.6Missense obs/exp: 425 / 297.4Syn Z: -4.14

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic6

VUS189

Likely Benign130

Benign30

Conflicting5

Pathogenic

Likely Pathogenic

189

VUS

130

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	4	0	15
Likely Pathogenic	2	3	1	0	6
VUS	2	180	6	1	189
Likely Benign	1	10	39	80	130
Benign	0	5	18	7	30
Conflicting	—				5
Total	16	198	68	88	375

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

View in ClinVar →

80 pathogenic / likely-pathogenic (of 113) ClinVar copy-number / structural variants overlap CSGALNACT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →