FUCA1

alpha-L-fucosidase 1, the group of Alpha-L-fucosidases

Basic information

Region (hg38): 1:23845077-23868290

Links

ENSG00000179163

∙ NCBI:2517 ∙ OMIM:612280 ∙ HGNC:4006 ∙ Uniprot:P04066 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

fucosidosis (Definitive), mode of inheritance: AR
fucosidosis (Strong), mode of inheritance: AR
fucosidosis (Definitive), mode of inheritance: AR
fucosidosis (Strong), mode of inheritance: AR
fucosidosis (Supportive), mode of inheritance: AR
fucosidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fucosidosis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Dermatologic; Musculoskeletal; Neurologic	4172303; 4241464; 4247654; 5026163; 1214294; 4128078; 7460371; 6538300; 2903667; 3409541; 2642067; 2012122; 8719750; 9039984; 9762612; 10094192; 12408193; 17427030; 18504684

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FUCA1 gene.

Fucosidosis (393 variants)
Inborn_genetic_diseases (60 variants)
not_provided (44 variants)
FUCA1-related_disorder (13 variants)
not_specified (11 variants)
Intellectual_disability (3 variants)
Abnormality_of_the_nervous_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FUCA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000147.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	121 clinvar	1 clinvar	123
missense	3 clinvar	8 clinvar	133 clinvar	15 clinvar	2 clinvar	161
nonsense	25 clinvar	11 clinvar	1 clinvar			37
start loss			1			1
frameshift	17 clinvar	9 clinvar				26
splice donor/acceptor (+/-2bp)	3 clinvar	10 clinvar				13
Total	48	38	136	136	3

Highest pathogenic variant AF is 0.000022304694

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FUCA1	protein_coding	protein_coding	ENST00000374479	8	23218

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.70e-8	0.911	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.845	218	256	0.851	0.0000129	3003
Missense in Polyphen		83	97.872	0.84804		1199
Synonymous	0.206	98	101	0.974	0.00000514	896
Loss of Function	1.78	16	25.7	0.621	0.00000120	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N- acetylglucosamine of the carbohydrate moieties of glycoproteins.;
Disease: DISEASE: Fucosidosis (FUCA1D) [MIM:230000]: An autosomal recessive lysosomal storage disease characterized by accumulation of fucose- containing glycolipids and glycoproteins in various tissues. Clinical signs include facial dysmorphism, dysostosis multiplex, moderate hepatomegaly, severe intellectual deficit, deafness, and according to age, angiokeratomas. {ECO:0000269|PubMed:7874128, ECO:0000269|PubMed:8504303, ECO:0000269|PubMed:9762612}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Neutrophil degranulation;Post-translational protein modification;Reactions specific to the complex N-glycan synthesis pathway;N-glycan antennae elongation in the medial/trans-Golgi;Metabolism of proteins;Innate Immune System;Immune System;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

pRec: 0.293

Intolerance Scores

loftool: 0.869
rvis_EVS: 0.66
rvis_percentile_EVS: 84.55

Haploinsufficiency Scores

pHI: 0.0887
hipred: Y
hipred_score: 0.564
ghis: 0.382

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.861

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Fuca1
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; homeostasis/metabolism phenotype; cellular phenotype;

Gene ontology

Biological process: fucose metabolic process;glycosaminoglycan catabolic process;glycoside catabolic process;glycolipid catabolic process;neutrophil degranulation
Cellular component: extracellular region;cytoplasm;lysosome;azurophil granule lumen;lysosomal lumen;extracellular exosome
Molecular function: alpha-L-fucosidase activity