FUCA1

Chr 1

alpha-L-fucosidase 1

Also known as: FUCA

NCBI Gene: 2517ENSG00000179163UniProt: P04066

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]

Primary Disease Associations & Inheritance

UniProtFucosidosis
509
ClinVar variants
98
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FUCA1
🧬
Gene-Disease Validity (ClinGen)
fucosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 167 VUS of 509 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.78
OE 0.62 (0.42–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.85Z-score
OE missense 0.85 (0.76–0.95)
218 obs / 256.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.42–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 16 / 25.7Missense obs/exp: 218 / 256.1Syn Z: 0.21

ClinVar Variant Classifications

509 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic35
VUS167
Likely Benign204
Benign22
Conflicting18
63
Pathogenic
35
Likely Pathogenic
167
VUS
204
Likely Benign
22
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
3
38
0
63
Likely Pathogenic
18
5
12
0
35
VUS
1
137
28
1
167
Likely Benign
0
14
73
117
204
Benign
0
5
16
1
22
Conflicting
—18
Total41164167119509

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

View in ClinVar →

Protein Context — Lollipop Plot

FUCA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FUCA1-related fucosidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — FUCA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Novel Homozygous Mutation in the FUCA1 Gene Highlighting Fucosidosis as a Cause of Dystonia: Case Report and Literature Review.
Wali G et al.·Neuropediatrics
2019Review
Fucosidosis-Clinical Manifestation, Long-Term Outcomes, and Genetic Profile-Review and Case Series.
Stepien KM et al.·Genes (Basel)
2020Review
Fucosidosis with Pathogenic Variant in FUCA1 Gene.
Gowda VK et al.·Indian J Pediatr
2020
Novel FUCA1 variants in two families, including the first report of a contiguous gene deletion syndrome involving FUCA1 and HMGCL.
Kılıç M et al.·Turk J Pediatr
2025Case report
Novel mutations in the FUCA1 gene that cause fucosidosis.
Panmontha W et al.·Genet Mol Res
2016Case report
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions.
Valero-Rubio D et al.·Exp Dermatol
2018
Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme.
Chkioua L et al.·BMC Med Genomics
2021Cohort
FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status.
Tsuchida N et al.·Int J Oncol
2017
Clinical relevance of glycosylation in triple negative breast cancer: a review.
Chakraborty M et al.·Glycoconj J
2024Review
Spectrum of mutations in fucosidosis.
Willems PJ et al.·Eur J Hum Genet
1999Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools