FUCA1

Chr 1AR

alpha-L-fucosidase 1

Also known as: FUCA

NCBI Gene: 2517 ENSG00000179163 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…

LOFmechanismARLOEUF 0.941 OMIM phenotype

Clinical Summary— FUCA1

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Gene-Disease Validity (ClinGen)

fucosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

96 unique Pathogenic / Likely Pathogenic· 160 VUS of 510 total submissions

Explore recent and relevant literature in Research Assistant →

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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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveFUCA1-related fucosidosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6358th %ile

GOF

0.6346th %ile

LOF

0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

510 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59

Likely Pathogenic37

VUS160

Likely Benign204

Benign22

Conflicting18

Pathogenic

Likely Pathogenic

160

VUS

204

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	48	3	8	0	59
Likely Pathogenic	30	5	2	0	37
VUS	2	140	17	1	160
Likely Benign	0	14	73	117	204
Benign	0	5	16	1	22
Conflicting	—				18
Total	80	167	116	119	500

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap FUCA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →