FUCA1

Chr 1AR

alpha-L-fucosidase 1

Also known as: FUCA

NCBI Gene: 2517 ENSG00000179163 UniProt: P04066 OMIM: 612280

Alpha-L-fucosidase hydrolyzes alpha-1,6-linked fucose from glycoproteins in lysosomes. Mutations cause fucosidosis, an autosomal recessive lysosomal storage disease that typically presents in early childhood with progressive neurodegeneration, coarse facial features, and developmental regression.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a lysosomal enzyme involved in the degradation of fucose-containing glycoproteins and glycolipids. Mutations in this gene are associated with fucosidosis (FUCA1D), which is an autosomal recessive lysosomal storage disease. A pseudogene of this locus is present on chr 2.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

FucosidosisMIM #230000

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · fucosidosis · 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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FUCA1

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?

0.94LOEUF

pLI 0.000

Z-score 1.78

OE 0.62 (0.42–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.85 (0.76–0.95)

218 obs / 256.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.42–0.94)

0≤0.351.4

Missense OE?0.85 (0.76–0.95)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 16 / 25.7Missense obs/exp: 218 / 256.1Syn Z: 0.21

Background carrier burden — how many people carry a rare variant somewhere in FUCA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

600 rare PASS variants

Rare truncating (LoF)

1 in 1,600

109 rare PASS variants

Rare synonymous (reference)

1 in 150

244 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FUCA1. 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 140	1 in 1,700
South Asian	~43k	1 in 84	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 820
European (Finnish)	~27k	1 in 250	≈ 1 in 26,000
Admixed American	~22k	1 in 96	1 in 1,300
African / African American	~21k	1 in 95	1 in 900
East Asian	~20k	1 in 110	1 in 1,000
Ashkenazi Jewish	~13k	1 in 340	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,200

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 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓