GALNS

Chr 16AR

galactosamine (N-acetyl)-6-sulfatase

Also known as: GALNAC6S, GAS, GalN6S, MPS4A

NCBI Gene: 2588 ENSG00000141012 UniProt: P34059 OMIM: 612222

This gene encodes N-acetylgalactosamine-6-sulfatase, a lysosomal enzyme that degrades the glycosaminoglycans keratan sulfate and chondroitin 6-sulfate. Mutations cause mucopolysaccharidosis IVA (Morquio A syndrome), an autosomal recessive lysosomal storage disorder. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

This gene encodes N-acetylgalactosamine-6-sulfatase which is a lysosomal exohydrolase required for the degradation of the glycosaminoglycans, keratan sulfate, and chondroitin 6-sulfate. Sequence alterations including point, missense and nonsense mutations, as well as those that affect splicing, result in a deficiency of this enzyme. Deficiencies of this enzyme lead to Morquio A syndrome, a lysosomal storage disorder. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mucopolysaccharidosis IVAMIM #253000

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mucopolysaccharidosis type 4A · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.01

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — GALNS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.51

OE 0.69 (0.48–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.43Z-score

OE missense 1.07 (0.98–1.17)

324 obs / 302.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.48–1.01)

0≤0.351.4

Missense OE?1.07 (0.98–1.17)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 19 / 27.5Missense obs/exp: 324 / 302.7Syn Z: -2.90

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

961 rare PASS variants

Rare truncating (LoF)

1 in 420

166 rare PASS variants

Rare synonymous (reference)

1 in 98

429 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GALNS. 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 73	1 in 640
South Asian	~43k	1 in 47	1 in 810
Remaining (unassigned)	~30k	1 in 61	1 in 680
European (Finnish)	~27k	1 in 180	1 in 810
Admixed American	~22k	1 in 61	1 in 860
African / African American	~21k	1 in 43	1 in 610
East Asian	~20k	1 in 71	1 in 730
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 3,900
Middle Eastern	~2,884	1 in 49	≈ 1 in 650

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): 14 of 14 coding exons well covered in gnomAD exomes. Genomes: 13 of 14 (exon 1 below).? see exons ↓