FUCA1

Summary

FUCA1 (alpha-L-fucosidase 1, HGNC:4006) is a protein-coding gene on chromosome 1p36.11, encoding Tissue alpha-L-fucosidase (P04066). 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.

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.

Source: NCBI Gene 2517 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fucosidosis (Definitive, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 504 total — 58 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 83
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4006
Approved symbol	FUCA1
Name	alpha-L-fucosidase 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179163
Ensembl biotype	protein_coding
OMIM	612280
Entrez	2517

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000374479, ENST00000881205, ENST00000965619

RefSeq mRNA: 1 — MANE Select: NM_000147 NM_000147

CCDS: CCDS244

Canonical transcript exons

ENST00000374479 — 8 exons

Exon	Start	End
ENSE00001270536	23846074	23846173
ENSE00001270544	23848649	23848839
ENSE00001270556	23854360	23854560
ENSE00001270569	23859798	23859903
ENSE00001270579	23863134	23863271
ENSE00001270588	23865491	23865625
ENSE00001463623	23867898	23868290
ENSE00001881597	23845077	23845855

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.0806 / max 4371.5907, expressed in 1713 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11015	34.0400	1712
11014	0.0407	16

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	98.89	gold quality
colonic mucosa	UBERON:0000317	98.88	gold quality
ileal mucosa	UBERON:0000331	98.77	gold quality
jejunal mucosa	UBERON:0000399	98.40	gold quality
rectum	UBERON:0001052	98.39	gold quality
corpus epididymis	UBERON:0004359	98.00	gold quality
duodenum	UBERON:0002114	97.36	gold quality
nasal cavity epithelium	UBERON:0005384	97.31	gold quality
palpebral conjunctiva	UBERON:0001812	97.18	gold quality
renal medulla	UBERON:0000362	97.15	gold quality
pancreatic ductal cell	CL:0002079	97.12	gold quality
lymph node	UBERON:0000029	97.10	gold quality
seminal vesicle	UBERON:0000998	96.88	gold quality
placenta	UBERON:0001987	96.64	gold quality
type B pancreatic cell	CL:0000169	96.29	gold quality
epithelium of nasopharynx	UBERON:0001951	96.18	gold quality
caput epididymis	UBERON:0004358	95.95	gold quality
mucosa of transverse colon	UBERON:0004991	95.88	gold quality
parotid gland	UBERON:0001831	95.81	gold quality
cauda epididymis	UBERON:0004360	95.48	gold quality
nasal cavity mucosa	UBERON:0001826	95.44	gold quality
gall bladder	UBERON:0002110	95.44	gold quality
trachea	UBERON:0003126	95.44	gold quality
pylorus	UBERON:0001166	95.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.26	gold quality
decidua	UBERON:0002450	94.92	gold quality
synovial joint	UBERON:0002217	94.81	gold quality
islet of Langerhans	UBERON:0000006	94.79	gold quality
bronchus	UBERON:0002185	94.73	gold quality
epithelium of bronchus	UBERON:0002031	94.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	312.00
E-ANND-3	yes	12.24
E-MTAB-7249	yes	11.52
E-MTAB-6678	yes	11.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting FUCA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-1-5P	98.70	68.66	1017

Literature-anchored findings (GeneRIF, showing 31)

• The purified alpha-L-fucosidase from primary hepatocarcinoma (PHC) is different in its properties from alpha-L-fucosidase in human other organs. The polyclonal antibody prepared in this experiment can be applied to the diagnosis of PHC. (PMID:16773698)
• The fucosidase has a role in the intimate species signature interactions between sperm and oocyte. (PMID:17133604)
• following HIV infection, there is an increased rate of catabolism of glycoconjugates in saliva resulting from changes in the proportions of the activity of isoenzymes A and B of N-acetyl-beta-hexosaminidase, beta-galactosidase and alpha-fucosidase (PMID:18217416)
• Data show that the correlation between the fluorescence activity of the enzyme AFU by the developed procedures and the standard method was positive and highly significant in patients and controls. (PMID:19782187)
• In the serum of patients with Lyme disease, GAL activity significantly increased (p = 0.029), and the activity of FUC had a tendency to increase (p = 0.153), compared to the control group. (PMID:22763966)
• We observed significant lower values of GAL, alpha-fucosidase and tendency to decrease of MAN and GLU concentration in nasal polyps (PMID:23911047)
• Diminished FUCA1 mRNA levels in tumors, indicate that expression of tissue alpha-L-fucosidase could be regulated at transcriptional level in colorectal cancer. (PMID:23965968)
• IL-13, IL-4 and IL-5 have no effect on the expression of FUCA1 and FUCA2, but its expression is upregulated by IFN-gamma, a Th1 cytokine. (PMID:24469468)
• Preoperative serum AFU is a prognostic predictor of hepatocellular carcinoma. (PMID:24569461)
• Serum alpha-L-fucosidase levels were significantly elevated in hepatocellular carcinoma. (PMID:25129443)
• FUCA1 downregulation confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface (PMID:26204487)
• results show that protein defucosylation mediated by FUCA1 is involved in tumor suppression (PMID:26998741)
• RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. (PMID:27315169)
• whole exome sequencing and array-based comparative genomic hybridization analysis revealed that the patient was compound heterozygous for a single base-pair deletion inherited from his father, and a 3281-base-pair deletion covering exon 3 inherited from his mother. Neither mutation has been reported before so the FUCA1 mutational spectrum is herein expanded. (PMID:27706744)
• the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer. (PMID:28404918)
• the possibility that the higher fucose levels on cell surface glycans of aggressive anaplastic thyroid cancer samples (ATCs), compared to those of less aggressive papillary thyroid cancer samples(PTC), may be at least in part responsible for the more aggressive and metastatic phenotype of ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely related in these two types of cancers. (PMID:28440416)
• alterations in plasma levels of FUCA-1 were significantly associated with chronic inflammatory and autoimmune disorders, both in children and adults (PMID:28808940)
• Taken together, our results have shown that FUCA1 down-regulation leads to expression disturbances regarding genes mainly related to keratinocyte differentiation/epidermal development and immune responses. (PMID:29518279)
• Homozygous frameshift mutation in the FUCA1 gene causes both severe and mild fucosidosis. (PMID:29588375)
• the beta-d-galactosidase, beta-d-glucuronidase and alpha-l-fucosidase activities in serums from hemolyzed blood, were determined. (PMID:29885630)
• FUCA1 is a useful marker to distinguish mucoepidermoid carcinoma from oral squamous cell carcinoma (PMID:30729618)
• serum alpha-l-fucosidase activities are not only useful for liver cancer diagnosis but also valuable indicators for different types of human diseases. (PMID:30905462)
• Alterations in plasma levels of alpha-L-FUCA-1 were significantly associated with Sjogren’s syndrome. (PMID:31419081)
• Fucosidosis with Pathogenic Variant in FUCA1 Gene. (PMID:32125660)
• Clinical relevance of serum alpha-l-fucosidase activity in the SARS-CoV-2 infection. (PMID:33826953)
• Comparative studies on the substrate specificity and defucosylation activity of three alpha-l-fucosidases using synthetic fucosylated glycopeptides and glycoproteins as substrates. (PMID:34126284)
• Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme. (PMID:34425818)
• Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis. (PMID:35907402)
• The long-awaited structure of human fucosidase FucA1 opens novel avenues for the treatment of fucosidosis. (PMID:36206736)
• Extended analysis of exome sequencing data reveals a novel homozygous deletion of exons 3 and 4 in FUCA1 gene causing fucosidosis in an Indian family. (PMID:36876340)
• Potential predictive value of immune-related genes FUCA1 and NCKAP1L for osteosarcoma metastasis. (PMID:38844271)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fuca1.2	ENSDARG00000035879
danio_rerio	fuca1.1	ENSDARG00000035890
mus_musculus	Fuca1	ENSMUSG00000028673
rattus_norvegicus	Fuca1	ENSRNOG00000009325
drosophila_melanogaster	Fuca	FBGN0285958
caenorhabditis_elegans		WBGENE00012225

Paralogs (1): FUCA2 (ENSG00000001036)

Protein

Protein identifiers

Tissue alpha-L-fucosidase — P04066 (reviewed: P04066)

Alternative names: Alpha-L-fucosidase I, Alpha-L-fucoside fucohydrolase 1

All UniProt accessions (1): P04066

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homotetramer.

Subcellular location. Lysosome.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. There are two common alleles of FUCA1; FUCA11; also known as Fu1; has Arg-281 and FUCA12; also known as Fu2; has Gln-281.

Similarity. Belongs to the glycosyl hydrolase 29 family.

RefSeq proteins (1): NP_000138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000933	Glyco_hydro_29	Family
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR016286	FUC_metazoa-typ	Family
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR018526	Glyco_hydro_29_CS	Conserved_site
IPR031919	Fucosidase_C	Domain
IPR057739	Glyco_hydro_29_N	Domain

Pfam: PF01120, PF16757

Enzyme classification (BRENDA):

• EC 3.2.1.51 — alpha-L-fucosidase (BRENDA: 111 organisms, 264 substrates, 196 inhibitors, 214 Km, 120 kcat entries)

Substrate kinetics (BRENDA)

40 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL-ALPHA-L-FUCOPYRANOSIDE	0.02–17	72
4-NITROPHENYL ALPHA-L-FUCOPYRANOSIDE	0.0681–3.3	23
4-NITROPHENYL ALPHA-L-FUCOSIDE	0.02–0.385	22
4-METHYLUMBELLIFERYL-ALPHA-L-FUCOPYRANOSIDE	0.022–0.4	15
P-NITROPHENYL ALPHA-L-FUCOPYRANOSIDE	0.11–1.06	14
P-NITROPHENYL ALPHA-L-FUCOSIDE	0.028–2.1	9
2’-FUCOSYLLACTOSE	0.63–58	7
4-METHYLUMBELLIFERYL ALPHA-L-FUCOPYRANOSIDE	0.0484–0.85	6
ALPHA-L-FUCOSYL FLUORIDE	0.075–2.5	4
2-NITROPHENYL ALPHA-L-FUCOPYRANOSIDE	0.27–5.2	3
4-NITROPHENYL-ALPHA-L-FUCOSIDE	0.0287–5.8	3
2’-FUCOSYLLACTITOL	0.67–1.18	2
3’-FUCOSYLLACTOSE	1.25–1.9	2
4-METHYLUMBELLIFERYL-BETA-FUCOSIDE	0.0032–0.0182	2
2-CHLORO-4-NITROPHENYL ALPHA-L-FUCOPYRANOSIDE	0.063	1

Catalyzed reactions (Rhea), 3 shown:

• an alpha-L-fucoside + H2O = L-fucose + an alcohol (RHEA:12288)
• a neolactoside IV(2)-alpha-Fuc-nLc4Cer(d18:1(4E)) + H2O = a neolactoside nLc4Cer(d18:1(4E)) + L-fucose (RHEA:48224)
• a neolactoside IV(2)-alpha-Fuc-nLc4Cer(d18:0) + H2O = a neolactoside nLc4Cer(d18:0) + L-fucose (RHEA:49308)

UniProt features (63 total): strand 18, helix 17, sequence variant 9, sequence conflict 8, turn 4, glycosylation site 3, signal peptide 1, chain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7PLS	ELECTRON MICROSCOPY	2.49
7PM4	ELECTRON MICROSCOPY	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04066-F1	93.60	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 296 (may be important for catalysis)

Post-translational modifications (1): 170

Glycosylation sites (3): 241, 268, 382

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway

MSigDB gene sets: 452 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, MODULE_255, GOCC_SECRETORY_GRANULE, MODULE_151, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MODULE_317, HSIAO_HOUSEKEEPING_GENES, KEGG_LYSOSOME, CHANDRAN_METASTASIS_DN, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, BEIER_GLIOMA_STEM_CELL_DN

GO Biological Process (5): fucose metabolic process (GO:0006004), glycoside catabolic process (GO:0016139), glycolipid catabolic process (GO:0019377), carbohydrate metabolic process (GO:0005975), lipid metabolic process (GO:0006629)

GO Molecular Function (4): alpha-L-fucosidase activity (GO:0004560), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (7): extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), membrane (GO:0016020), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
N-glycan antennae elongation in the medial/trans-Golgi	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
primary metabolic process	2
vacuolar lumen	2
hexose metabolic process	1
glycoside metabolic process	1
glycosyl compound catabolic process	1
glycolipid metabolic process	1
lipid catabolic process	1
carbohydrate derivative catabolic process	1
fucosidase activity	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular anatomical structure	1
lytic vacuole	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUCA1	PGM1	P36871	829
FUCA1	PGD	P52209	766
FUCA1	AK2	P54819	727
FUCA1	PGM2	Q96G03	724
FUCA1	ALPL	P05186	703
FUCA1	CMPK1	P30085	689
FUCA1	RHCE	P18577	675
FUCA1	GLB1	P16278	661
FUCA1	H3BT10	H3BT10	661
FUCA1	ENO1	P06733	625
FUCA1	DHCR24	Q15392	600
FUCA1	PGC	P20142	594
FUCA1	FGR	P09769	593
FUCA1	MANBA	O00462	590
FUCA1	GLA	P06280	584

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FUCA1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
FUCA1	CIB1	psi-mi:“MI:0915”(physical association)	0.560
FUCA1	MED10	psi-mi:“MI:0915”(physical association)	0.560
FUCA1		psi-mi:“MI:0915”(physical association)	0.370
ORF10	NUP42	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
FUCA1	TIPRL	psi-mi:“MI:0914”(association)	0.350
USP21	ANKRD28	psi-mi:“MI:0914”(association)	0.350
MARK2	SMAP	psi-mi:“MI:0914”(association)	0.350
	FUCA1	psi-mi:“MI:0914”(association)	0.350
PRKD3	NDUFA4	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
MRPL38	FUCA1	psi-mi:“MI:0915”(physical association)	0.000
FUCA1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
FUCA1	CIB1	psi-mi:“MI:0915”(physical association)	0.000
FUCA1	MED10	psi-mi:“MI:0915”(physical association)	0.000
FUCA1	VAV2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): MARK2 (Affinity Capture-MS), PRKD1 (Affinity Capture-MS), CHCHD5 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), TIPRL (Affinity Capture-MS), FUCA2 (Affinity Capture-MS), SUMF1 (Affinity Capture-MS), FUCA1 (Affinity Capture-MS), FUCA1 (Affinity Capture-MS), FUCA1 (Two-hybrid), CIB1 (Two-hybrid), UBQLN2 (Two-hybrid), FUCA1 (Reconstituted Complex), TIPRL (Affinity Capture-MS), CHCHD5 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A6QNR0, O18835, O35632, O77695, O88202, O97524, P04066, P06760, P06865, P07686, P08236, P10253, P12265, P16444, P17164, P22412, P29416, P31429, P31430, P43477, P48300, P54802, P70699, P79403, Q0V8R6, Q12891, Q14697, Q3SZM7, Q3U4H6, Q4FAT7, Q4QR99, Q4R4N7, Q5R5N6, Q5R7A9, Q5RC84, Q5RFI5, Q60HF8, Q641X3, Q6AYS4

Diamond homologs: C3YWU0, P04066, P10901, P17164, P48300, P49713, Q2KIM0, Q5RFI5, Q60HF8, Q6AYS4, Q7XUR3, Q8GW72, Q99KR8, Q99LJ1, Q9BTY2, Q9VTJ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

504 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	27
Uncertain significance	158
Likely benign	195
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100721	NM_000147.5(FUCA1):c.790C>T (p.Arg264Ter)	Pathogenic
1076611	NC_000001.10:g.(?24140670)(24194786_?)del	Pathogenic
1328977	NM_000147.5(FUCA1):c.1285_1286insT (p.Asp429fs)	Pathogenic
1457587	NM_000147.5(FUCA1):c.671del (p.Pro224fs)	Pathogenic
1727210	NM_000147.5(FUCA1):c.577dup (p.Tyr193fs)	Pathogenic
198046	NM_000147.5(FUCA1):c.1125G>A (p.Trp375Ter)	Pathogenic
2185928	NM_000147.5(FUCA1):c.1206G>A (p.Trp402Ter)	Pathogenic
2202728	NM_000147.5(FUCA1):c.459G>A (p.Trp153Ter)	Pathogenic
2202729	NM_000147.5(FUCA1):c.194G>A (p.Gly65Asp)	Pathogenic
2222033	NM_000147.5(FUCA1):c.1164T>G (p.Tyr388Ter)	Pathogenic
2422463	NC_000001.10:g.(?24172205)(24194776_?)del	Pathogenic
2422464	NC_000001.10:g.(?24191961)(24194776_?)del	Pathogenic
2627143	NM_000147.5(FUCA1):c.699G>A (p.Trp233Ter)	Pathogenic
265438	NM_000147.5(FUCA1):c.393T>A (p.Tyr131Ter)	Pathogenic
2706835	NM_000147.5(FUCA1):c.1057G>T (p.Glu353Ter)	Pathogenic
2709717	NM_000147.5(FUCA1):c.610_614del (p.Gln204fs)	Pathogenic
2711635	NM_000147.5(FUCA1):c.1131_1132delinsTT (p.Gln378Ter)	Pathogenic
2745354	NM_000147.5(FUCA1):c.679_683dup (p.Trp228Ter)	Pathogenic
2745555	NM_000147.5(FUCA1):c.355_364del (p.Glu119fs)	Pathogenic
2749012	NM_000147.5(FUCA1):c.969+1G>T	Pathogenic
2757124	NM_000147.5(FUCA1):c.293dup (p.Pro99fs)	Pathogenic
2791475	NM_000147.5(FUCA1):c.679_683del (p.Ile227fs)	Pathogenic
2824353	NM_000147.5(FUCA1):c.80C>A (p.Ser27Ter)	Pathogenic
2838100	NM_000147.5(FUCA1):c.563G>A (p.Trp188Ter)	Pathogenic
2839403	NM_000147.5(FUCA1):c.291C>G (p.Tyr97Ter)	Pathogenic
2849047	NM_000147.5(FUCA1):c.23C>A (p.Ser8Ter)	Pathogenic
2873243	NM_000147.5(FUCA1):c.1260+2T>A	Pathogenic
2878433	NM_000147.5(FUCA1):c.607del (p.Thr203fs)	Pathogenic
2885817	NM_000147.5(FUCA1):c.557T>A (p.Leu186Ter)	Pathogenic
2910847	NM_000147.5(FUCA1):c.460_475del (p.Asn154fs)	Pathogenic

SpliceAI

1111 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23848644:CTCA:C	donor_loss	1.0000
1:23848645:TCACC:T	donor_loss	1.0000
1:23848646:CACCA:C	donor_loss	1.0000
1:23848647:A:AC	donor_gain	1.0000
1:23848647:A:C	donor_loss	1.0000
1:23848648:C:CC	donor_gain	1.0000
1:23848648:CCATA:C	donor_gain	1.0000
1:23848836:GTTC:G	acceptor_gain	1.0000
1:23848838:TC:T	acceptor_gain	1.0000
1:23848839:CC:C	acceptor_gain	1.0000
1:23848840:C:A	acceptor_loss	1.0000
1:23848840:C:CC	acceptor_gain	1.0000
1:23848841:T:A	acceptor_loss	1.0000
1:23854354:TCTTA:T	donor_loss	1.0000
1:23854355:CTTA:C	donor_loss	1.0000
1:23854356:TTACC:T	donor_loss	1.0000
1:23854357:TA:T	donor_loss	1.0000
1:23854358:A:AC	donor_gain	1.0000
1:23854359:C:CC	donor_gain	1.0000
1:23854359:CCGAA:C	donor_gain	1.0000
1:23854557:CATC:C	acceptor_gain	1.0000
1:23854558:ATCC:A	acceptor_loss	1.0000
1:23854559:TC:T	acceptor_gain	1.0000
1:23854560:CC:C	acceptor_gain	1.0000
1:23854560:CCTA:C	acceptor_loss	1.0000
1:23854561:C:CA	acceptor_loss	1.0000
1:23854561:C:CC	acceptor_gain	1.0000
1:23854562:T:C	acceptor_loss	1.0000
1:23863128:TCTTA:T	donor_loss	1.0000
1:23863129:CTTA:C	donor_loss	1.0000

AlphaMissense

3050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23859877:T:A	D230V	0.998
1:23854536:A:G	W265R	0.997
1:23854536:A:T	W265R	0.997
1:23854538:C:G	R264P	0.997
1:23859876:A:C	D230E	0.996
1:23859876:A:T	D230E	0.996
1:23854452:A:G	W293R	0.995
1:23854452:A:T	W293R	0.995
1:23854441:G:C	C296W	0.994
1:23854534:C:A	W265C	0.994
1:23854534:C:G	W265C	0.994
1:23854543:A:C	N262K	0.994
1:23854543:A:T	N262K	0.994
1:23859877:T:G	D230A	0.994
1:23859884:A:G	W228R	0.994
1:23859884:A:T	W228R	0.994
1:23865604:C:A	K137N	0.994
1:23865604:C:G	K137N	0.994
1:23848802:A:G	L336P	0.993
1:23854450:C:A	W293C	0.993
1:23854450:C:G	W293C	0.993
1:23859807:G:C	S253R	0.993
1:23859807:G:T	S253R	0.993
1:23859809:T:G	S253R	0.993
1:23859878:C:G	D230H	0.993
1:23868097:A:G	W64R	0.993
1:23868097:A:T	W64R	0.993
1:23868164:C:A	W41C	0.993
1:23868164:C:G	W41C	0.993
1:23848728:A:G	W361R	0.992

dbSNP variants (sampled 300 via entrez): RS1000046142 (1:23862861 C>T), RS1000149563 (1:23869702 A>G), RS1000254774 (1:23850384 C>A,T), RS1000462567 (1:23857756 C>T), RS1000868644 (1:23863315 C>T), RS1000884400 (1:23869930 A>G), RS1000915319 (1:23870137 C>T), RS1001071310 (1:23856739 C>A), RS1001094466 (1:23850260 A>G,T), RS1001127786 (1:23854702 G>A), RS1001300700 (1:23863710 A>C,T), RS1001407879 (1:23847136 A>T), RS1001456710 (1:23864668 C>A,G), RS1001692763 (1:23853551 G>A,C), RS1001754383 (1:23847636 A>G)

Disease associations

OMIM: gene MIM:612280 | disease phenotypes: MIM:230000, MIM:246450

GenCC curated gene-disease

Disease	Classification	Inheritance
fucosidosis	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
fucosidosis	Definitive	AR

Mondo (4): fucosidosis (MONDO:0009254), 3-hydroxy-3-methylglutaric aciduria (MONDO:0009520), intellectual disability (MONDO:0001071), congenital nervous system disorder (MONDO:0002320)

Orphanet (3): Fucosidosis (Orphanet:349), 3-hydroxy-3-methylglutaric aciduria (Orphanet:20), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

83 total (30 of 83 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000164	Abnormality of the dentition
HP:0000179	Thick lower lip vermilion
HP:0000240	Abnormality of skull size
HP:0000248	Brachycephaly
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000503	Tortuosity of conjunctival vessels
HP:0000574	Thick eyebrow
HP:0000821	Hypothyroidism
HP:0000914	Shield chest
HP:0000943	Dysostosis multiplex
HP:0000958	Dry skin
HP:0000967	Petechiae
HP:0000970	Anhidrosis
HP:0000975	Hyperhidrosis
HP:0000978	Bruising susceptibility
HP:0001014	Angiokeratoma
HP:0001063	Acrocyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001271	Polyneuropathy

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008403_21	Arterial stiffness index	4.000000e-07
GCST90002385_604	High light scatter reticulocyte count	3.000000e-27
GCST90002386_309	High light scatter reticulocyte percentage of red cells	3.000000e-32
GCST90002387_192	Immature fraction of reticulocytes	1.000000e-21
GCST90002390_590	Mean corpuscular hemoglobin	3.000000e-11
GCST90002405_594	Reticulocyte count	4.000000e-21
GCST90002406_132	Reticulocyte fraction of red cells	8.000000e-25

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004517	arterial stiffness measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005645	Fucosidosis	C10.228.140.163.100.435.295; C16.320.565.189.435.295; C16.320.565.202.303; C16.320.565.595.554.295; C18.452.132.100.435.295; C18.452.648.189.435.295; C18.452.648.202.303; C18.452.648.595.554.295
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C538324	3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4176 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,739 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL307429	DUVOGLUSTAT	2	4,739

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[[(2R,3R,4S,5R,6R)-6-(fluoromethyl)-3,4,5-trihydroxypiperidin-2-yl]methyl]-9-oxofluorene-1-carboxamide	IC50	16 nM	US-10308607: Fucosidase inhibitors
N-[[(2S,3R,4S,5R,6R)-6-(fluoromethyl)-3,4,5-trihydroxypiperidin-2-yl]methyl]-9-oxofluorene-1-carboxamide	IC50	59 nM	US-10308607: Fucosidase inhibitors
(2Z)-N-(9-oxofluoren-1-yl)-2-[(3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-ylidene]acetamide	IC50	1500 nM	US-10308607: Fucosidase inhibitors

ChEMBL bioactivities

133 potent at pChembl≥5 of 178 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.82	Ki	1.5	nM	CHEMBL114103
8.40	IC50	4	nM	CHEMBL114103
8.30	Ki	5	nM	CHEMBL87463
8.24	Ki	5.8	nM	CHEMBL69294
8.22	Ki	6	nM	CHEMBL87463
8.21	Ki	6.2	nM	DEOXYFUCONOJIRIMYCIN
8.15	Ki	7	nM	CHEMBL85773
8.10	Ki	8	nM	CHEMBL114103
8.10	IC50	7.9	nM	CHEMBL2442786
8.00	Ki	10	nM	CHEMBL84647
8.00	Ki	10	nM	DEOXYFUCONOJIRIMYCIN
7.96	IC50	11	nM	CHEMBL114103
7.96	Ki	11	nM	CHEMBL114103
7.92	Ki	12	nM	CHEMBL2115269
7.92	Ki	12	nM	CHEMBL2114287
7.85	IC50	14	nM	CHEMBL2442788
7.82	IC50	15	nM	CHEMBL2442783
7.80	Ki	16	nM	CHEMBL85218
7.80	IC50	16	nM	CHEMBL5982231
7.80	Ki	16	nM	CHEMBL314757
7.72	Ki	19	nM	CHEMBL539176
7.72	IC50	19	nM	CHEMBL2442784
7.70	IC50	20	nM	CHEMBL539176
7.58	IC50	26	nM	CHEMBL2442779
7.54	Ki	29	nM	DEOXYFUCONOJIRIMYCIN
7.52	Ki	30	nM	CHEMBL539176
7.52	IC50	30	nM	CHEMBL2442782
7.52	IC50	30	nM	CHEMBL2442777
7.51	IC50	31	nM	CHEMBL2442787
7.51	Ki	31	nM	DEOXYFUCONOJIRIMYCIN
7.50	Ki	32	nM	CHEMBL316609
7.46	IC50	35	nM	CHEMBL2442773
7.40	IC50	40	nM	CHEMBL539176
7.40	IC50	40	nM	CHEMBL115930
7.33	Ki	47	nM	CHEMBL539176
7.32	Ki	48	nM	CHEMBL95110
7.30	IC50	50	nM	CHEMBL115828
7.25	IC50	56	nM	CHEMBL539176
7.24	IC50	58	nM	CHEMBL2442781
7.23	IC50	59	nM	CHEMBL5986730
7.16	Ki	69	nM	CHEMBL96392
7.13	Ki	74	nM	CHEMBL319008
7.12	IC50	75	nM	CHEMBL114487
7.10	IC50	80	nM	CHEMBL326403
7.10	Ki	80	nM	CHEMBL87474
7.10	Ki	80	nM	DEOXYFUCONOJIRIMYCIN
7.07	IC50	86	nM	CHEMBL2442776
6.96	IC50	110	nM	CHEMBL114487
6.96	Ki	110	nM	CHEMBL95106
6.96	IC50	110	nM	CHEMBL314757

PubChem BioAssay actives

121 with measured affinity, of 238 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[3,4,5-trihydroxy-2-(hydroxymethyl)-6-methylpiperidin-1-yl]acetaldehyde	218795: Compound was tested for inhibitory activity against alpha-1,2-Fucosidase obtained from Arthrobacter oxidans F1	ki	0.0015	uM
(4S,5R)-2-methylpiperidine-3,4,5-triol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.0050	uM
(3R,4S,5R)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol	218950: Inhibitory activity against alpha-L-fucosidase in bovine epididymis; Competitive Inhibition type	ki	0.0058	uM
(2S,3R,4S,5R)-2-methylpiperidine-3,4,5-triol	218950: Inhibitory activity against alpha-L-fucosidase in bovine epididymis; Competitive Inhibition type	ki	0.0062	uM
(4R,5R)-6-(hydroxymethyl)-2-methyl-2,3,4,5-tetrahydropyridine-3,4,5-triol	36834: Inhibitory activity against alpha-L-fucosidase of bovine epididymis expressed as Ki	ki	0.0070	uM
N-(2-fluorophenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0079	uM
3,4-dihydroxy-5-methylpyrrolidine-2-sulfonic acid	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.0100	uM
(1R,2R,3R,4S,6R)-4-amino-6-methylcyclohexane-1,2,3-triol	36811: The compound was tested for the inhibitory activity against alpha-L-Fucosidase in bovine kidney	ki	0.0120	uM
(1R,2R,3R,4R,6R)-4-amino-6-methylcyclohexane-1,2,3-triol	36811: The compound was tested for the inhibitory activity against alpha-L-Fucosidase in bovine kidney	ki	0.0120	uM
N-(4-fluorophenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0140	uM
N-(4-methylphenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0150	uM
(2R,3S)-2-amino-5-methylpiperidine-3,4-diol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.0160	uM
4-methyl-6-(octylamino)cyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.0160	uM
(2S)-2-amino-3-hydroxy-N-[[3,4,5-trihydroxy-2-(hydroxymethyl)-6-methylpiperidin-2-yl]methyl]propanamide	218940: Compound was tested for inhibitory activity against alpha-Fucosidase obtained from Bovine epididymis	ki	0.0190	uM
N-(2,4-dimethylphenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0190	uM
N-(4-methoxyphenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0260	uM
N-phenyl-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0300	uM
N-(3-methylphenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0300	uM
N-(3-fluorophenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0310	uM
4-methyl-6-(2-phenylethylamino)cyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.0320	uM
N-(2,4-difluorophenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0350	uM
benzyl N-[2-oxo-2-[[3,4,5-trihydroxy-2-(hydroxymethyl)-6-methylpiperidin-2-yl]methylamino]ethyl]carbamate	218830: Compound was tested for inhibitory activity against alpha-Fucosidase obtained from Bovine epididymis	ic50	0.0400	uM
4-(heptylamino)-6-methylcyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.0480	uM
2-amino-N-[[3,4,5-trihydroxy-2-(hydroxymethyl)-6-methylpiperidin-2-yl]methyl]acetamide	218939: Compound was tested for inhibitory activity against alpha-Fucosidase obtained from Bovine kidney	ic50	0.0500	uM
N-(2-methylphenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0580	uM
4-(benzylamino)-6-methylcyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.0690	uM
4-(butylamino)-6-methylcyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.0740	uM
3,4,5-trihydroxy-2-(hydroxymethyl)-6-methylpiperidine-2-carbonitrile	218939: Compound was tested for inhibitory activity against alpha-Fucosidase obtained from Bovine kidney	ic50	0.0750	uM
2-(aminomethyl)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol	218793: Compound was tested for inhibitory activity against alpha-1,2-Fucosidase obtained from Arthrobacter oxidans F1	ic50	0.0800	uM
(2R,3R,4R,5R,6S)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol	36836: Inhibitory activity measured against alpha-L-fucosidase of bovine epididymis by colorimetric assay using the D-glucose oxidase-peroxidase method	ki	0.0800	uM
(2S,3R,4R,5R,6R)-2-methyl-6-(3-phenylpropyl)piperidine-3,4,5-triol	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.0860	uM
4-methyl-6-(nonylamino)cyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.1100	uM
N-butyl-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.1300	uM
2-methyl-3,4-dihydro-2H-pyrrole-3,4-diol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.1600	uM
4-(ethylamino)-6-methylcyclohexane-1,2,3-triol	36827: Binding affinity against alpha-L-fucosidase in bovine kidney was determined	ki	0.1800	uM
N-(2,4,6-trifluorophenyl)-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.1800	uM
N-benzyl-2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.1900	uM
2-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methylpiperidin-2-yl]-N-(2,4,6-trimethylphenyl)acetamide	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.2000	uM
(4R)-2-[(3R)-4,5-dihydroxy-6-(hydroxymethyl)-2-prop-2-enoxyoxan-3-yl]oxy-6-methylthiane-3,4,5-triol	36812: Inhibitory activity against alpha-L-fucosidase of bacillus species (K40T) expressed as Ki	ki	0.2100	uM
trans-(2R,3R)-4-amino-6-methylcyclohexane-1,2,3-triol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.2300	uM
5-(dimethylamino)-N-[6-[(2S,3R,4S,5R)-3,4,5-trihydroxy-2-methylpiperidin-1-yl]hexyl]naphthalene-1-sulfonamide	263091: Inhibition of human liver alpha-L-fucosidase	ki	0.5000	uM
(2R)-4-(benzylamino)-5-methylcyclopentane-1,2,3-triol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.6800	uM
(1R,3R,4S)-4-(decylamino)-6-methylcyclohexane-1,2,3-triol	36694: Inhibitory activity against alpha-Fucosidase in bovine kidney	ic50	0.7000	uM
(4R,5R)-6-hydrazinyl-2-methyl-2,3,4,5-tetrahydropyridine-3,4,5-triol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	0.8200	uM
(2R,3R,4R,5R,6S)-2-hexyl-6-methylpiperidine-3,4,5-triol	779302: Inhibition of human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	ic50	0.8900	uM
(1R,3R,4S)-4-(dodecylamino)-6-methylcyclohexane-1,2,3-triol	36694: Inhibitory activity against alpha-Fucosidase in bovine kidney	ic50	1.2000	uM
(1R,3R,6S)-4-methyl-6-(4-phenylbutylamino)cyclohexane-1,2,3-triol	36694: Inhibitory activity against alpha-Fucosidase in bovine kidney	ic50	1.2000	uM
(2S,3S,4R,5S)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	1.4000	uM
(1R,3R,6S)-4-methyl-6-(octylamino)cyclohexane-1,2,3-triol	36694: Inhibitory activity against alpha-Fucosidase in bovine kidney	ic50	1.8000	uM
2-methylpyrrolidine-3,4-diol	36835: In vitro inhibition of alpha-L-fucosidase isolated from bovine kidney.	ki	2.0000	uM

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
Tretinoin	increases expression	3
Valproic Acid	affects expression, increases expression	3
Acetaminophen	affects expression, increases expression	2
Benzo(a)pyrene	affects reaction, increases expression, affects methylation	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
deoxynivalenol	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
zinc chromate	increases abundance, increases expression	1
doxifluridine	increases response to substance	1
ochratoxin A	increases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
nickel sulfate	decreases expression	1
1-UFT protocol	increases response to substance	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
S 1 (combination)	increases response to substance	1
K 7174	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
gardiquimod	decreases expression, decreases reaction	1
PP242	increases expression	1
Capecitabine	increases response to substance	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	increases expression	1
Decitabine	affects expression	1

ChEMBL screening assays

83 unique, capped per target: 79 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2444881	Binding	Ratio of deoxyfuconojirimycin IC50 to compound IC50 for human lysosome alpha-L-fucosidase using 4-methylumbelliferyl-alpha-L-fucopyranoside by spectrophotometry	Synthesis and biological evaluation of N-(2-fluorophenyl)-2β-deoxyfuconojirimycin acetamide as a potent inhibitor for α-l-fucosidases. — Bioorg Med Chem
CHEMBL4824547	ADMET	Substrate activity at recombinant N-terminal GFP tagged human alpha L-fucosidase expressed in HEK293T cells assessed as formation of p-nitrophenyl products at 5 mM measured by UV spectrometer assay	Comparative studies on the substrate specificity and defucosylation activity of three α-l-fucosidases using synthetic fucosylated glycopeptides and glycoproteins as substrates. — Bioorg Med Chem

Cellosaurus cell lines

8 cell lines: 4 finite cell line, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_V761	GM00289	Finite cell line	Male
CVCL_V762	GM00290	Finite cell line	Female
CVCL_V763	GM00291	Finite cell line	Male
CVCL_V764	GM00292	Finite cell line	Male
CVCL_V791	GM01023	Transformed cell line	Male
CVCL_V792	GM01024	Transformed cell line	Male
CVCL_V793	GM01025	Transformed cell line	Male
CVCL_V794	GM01026	Transformed cell line	Female

Clinical trials (associated diseases)

208 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00668564	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism
NCT01043640	PHASE2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00176904	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Inborn Errors of Metabolism
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT00005900	Not specified	UNKNOWN	Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
NCT01891422	Not specified	COMPLETED	Longitudinal Studies of the Glycoproteinoses
NCT07615400	Not specified	RECRUITING	A Long-Term Observational Study of Patients With Fucosidosis
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability