GLA

Summary

GLA (galactosidase alpha, HGNC:4296) is a protein-coding gene on chromosome Xq22.1, encoding Alpha-galactosidase A (P06280). Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This enzyme predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose. A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease, a rare lysosomal storage disorder that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.

Source: NCBI Gene 2717 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fabry disease (Definitive, ClinGen)
• Clinical variants (ClinVar): 1,973 total — 637 pathogenic, 307 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes — 62 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4296
Approved symbol	GLA
Name	galactosidase alpha
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	GALA
Ensembl gene	ENSG00000102393
Ensembl biotype	protein_coding
OMIM	300644
Entrez	2717

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 6 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron

ENST00000218516, ENST00000466414, ENST00000468823, ENST00000479445, ENST00000480513, ENST00000486121, ENST00000493905, ENST00000649178, ENST00000674127, ENST00000674142, ENST00000674634, ENST00000675592, ENST00000675799, ENST00000675968, ENST00000676156, ENST00000676372, ENST00000710365

RefSeq mRNA: 3 — MANE Select: NM_000169 NM_000169, NM_001406747, NM_001406748

CCDS: CCDS14484

Canonical transcript exons

ENST00000218516 — 7 exons

Exon	Start	End
ENSE00003554033	101397803	101398099
ENSE00003622743	101401632	101401809
ENSE00003671052	101398785	101398946
ENSE00003703124	101403811	101403985
ENSE00003710838	101400666	101400757
ENSE00003901070	101407710	101407925
ENSE00004011673	101398370	101398567

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 96.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.2066 / max 980.6723, expressed in 1815 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199956	36.3832	1805
199952	2.0904	989
199957	1.4582	971
199954	1.1128	457
199955	0.9667	379
199953	0.1953	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.03	gold quality
monocyte	CL:0000576	94.83	gold quality
mononuclear cell	CL:0000842	94.47	gold quality
leukocyte	CL:0000738	94.01	gold quality
seminal vesicle	UBERON:0000998	93.51	gold quality
amniotic fluid	UBERON:0000173	93.26	gold quality
stromal cell of endometrium	CL:0002255	92.57	gold quality
cervix squamous epithelium	UBERON:0006922	92.20	gold quality
islet of Langerhans	UBERON:0000006	91.79	gold quality
bone marrow	UBERON:0002371	91.06	gold quality
tongue squamous epithelium	UBERON:0006919	90.81	silver quality
granulocyte	CL:0000094	90.33	gold quality
blood	UBERON:0000178	90.33	gold quality
mucosa of transverse colon	UBERON:0004991	90.13	gold quality
bone marrow cell	CL:0002092	90.04	gold quality
duodenum	UBERON:0002114	90.02	gold quality
left adrenal gland	UBERON:0001234	89.91	gold quality
right adrenal gland cortex	UBERON:0035827	89.74	gold quality
cartilage tissue	UBERON:0002418	89.65	gold quality
tibia	UBERON:0000979	89.53	gold quality
right adrenal gland	UBERON:0001233	89.49	gold quality
trabecular bone tissue	UBERON:0002483	89.49	gold quality
left adrenal gland cortex	UBERON:0035825	89.47	gold quality
adrenal gland	UBERON:0002369	89.00	gold quality
adrenal cortex	UBERON:0001235	88.94	gold quality
jejunal mucosa	UBERON:0000399	88.43	gold quality
visceral pleura	UBERON:0002401	88.30	gold quality
endometrium	UBERON:0001295	88.26	gold quality
placenta	UBERON:0001987	88.24	gold quality
adrenal tissue	UBERON:0018303	87.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	17.46
E-MTAB-10137	no	1955.93
E-GEOD-109979	no	243.67
E-MTAB-5061	no	3.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• novel mutations in patients of European origin with Fabry disease (PMID:11668641)
• Missense mutation (1280A to G, N34S) was detected in exon 1 of alpha-galactosidase gene. (PMID:11775551)
• Alternative splicing in the alpha-galactosidase A gene: increased exon inclusion results in the Fabry cardiac phenotype. (PMID:11828341)
• Overexpression of human alpha-galactosidase A did not affect cellular morphology, which indicates that its overexpression in gene therapy endeavors should be safe. (PMID:12033283)
• Review. Alpha-galactosidase-A deficiency causes Fabry disease, transmitted as an X-linked recessive trait. As the gene shows various mutations, the establishment of phenotype-genotype correlations is limited. (PMID:12360742)
• Review. The GLA gene has been cloned and more than 200 mutations have been identified. (PMID:12360745)
• The adeno-associated virus (AAV) vector containing the alpha-gal A gene was injected into the right quadriceps muscles of Fabry knockout mice. (PMID:12370426)
• Occurrence of edited alpha-gal A transcripts in humans (PMID:12471562)
• Fifteen novel GLA mutations were identified in 22 Spanish Fabry disease patients. (PMID:12938095)
• A previously unreported deletion mutation (c.1072_1074delGAG) in exon 7 of alpha-Gal A gene on Xq22 in a Taiwanese family with Fabry disease is reported. (PMID:15339079)
• 2 new intronic polymorphisms, c.640-16A>G and c.1000-22C>T, were detected with frequencies of 0.14 and 0.25 in both normal individuals and Fabry patients, respectively. (PMID:15712228)
• analysis of mutations in the GLA gene in 121 patients with Fabry disease (PMID:15776423)
• Data show the usefulness of 1-deoxygalactonojirimycin for correction of the lysosomal storage in Fabry fibroblasts harboring different alpha-galactosidase A mutations with residual enzyme activity. (PMID:16531566)
• Studies further define the molecular heterogeneity of the alpha-Gal A mutations in classical Fabry disease, permit precise heterozygote detection and prenatal diagnosis. (PMID:16595074)
• DNA analysis of the alpha-galactosidase A gene confirmed the diagnosis of Fabry disease, showing a de novo point mutation at position 691 of exon 5. (PMID:16899426)
• results indicate that a large proportion of mutant GLA enzymes in Fabry disease patients with residual enzyme activity are kinetically active (PMID:17555407)
• Because of lack of functionality of rescued mutant alpha-galactosidase A, 4-phenylbutyrate seems to be of limited use as a chemical chaperone for Fabry disease. (PMID:17592721)
• There is a significant correlation between the types of mutations of GLA and total Gb3 excretion in Fabry patients. (PMID:18023222)
• 62 Fabry patients in Japan were examined and 24 GLA mutations were found, including 11 novel ones. (PMID:18205205)
• The negative effect of antibody formation in Fabry disease could be overcome by increasing the dose of enzyme administered to mice. (PMID:18456533)
• Two novel different deletions were detected using MLPA assay on two Fabry patients. (PMID:18472290)
• a correlation between this new intronic mutation and the unbalanced alpha-galactosidase A mRNAs ratio, which could therefore be responsible for the reduced enzyme activity causing Fabry disease. (PMID:18560446)
• Structural characterization of mutant alpha-galactosidases causing Fabry disease. (PMID:18633574)
• Mutated alpha-galactosidase A did not respond to a pharmacological chaperone (PMID:18698230)
• We report here a new mutation in Fabry disease. The hemizygote did not show corneal manifestations as opposed to heterozygotes in the described family. (PMID:18724168)
• Novel disease-causing mutations were found in 15 unrelated Hungarian families diagnosed with Fabry disease. (PMID:18849176)
• Case Report: suggest that the g.1170C>T SNP may be co-dominantly associated with a relatively decreased GLA expression at the transcription and/or translation level. (PMID:18979178)
• Mean alpha-Gal leukocyte activity was higher in subjects with the g.1170C or CC genotype than in those with the alternative genotypes. (PMID:18979223)
• Downregulation of alpha-galactosidase A upregulates CD77 (PMID:19037253)
• The results of this study suggest that the chemical chaperone 1-deoxygalactonojirimycin enhances GLA enzyme activity and protein expression in milder mutations associated with the atypical form of Fabry disease. (PMID:19287194)
• Fabry disease is marked by deficiency of this enzyme, and enzyme replacement therapy may stabilize kidney function in these patients. (PMID:19357250)
• identified a new intronic mutation, g.9273C>T, located 5 nucleotides upstream of the alternative 3’ splicing junction in Fabry disease (PMID:19404287)
• Results show that the unpredictable amino-acid pairs of human alpha-galactosidase A are more sensitive to mutation. (PMID:19468850)
• Data show that the high resolution structures of each step in the catalytic cycle will allow for improved drug design efforts on alpha-GAL. (PMID:19940122)
• Study in alpha galactosidase mutations that may be helpful in clarifying the consequences of the missense genetic lesions detected in Fabry disease. (PMID:19941952)
• Data show that alpha-Gal epitopes can be removed from the porcine aortic valve and pericardial tissue using recombinant human alpha-galactosidase A as effectively as using green coffee bean alpha-galactosidase. (PMID:19949670)
• Screening for GLA mutations should probably be considered in different types of stroke; restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young stroke patients. (PMID:20110537)
• The R118C mutation was present in 60% of unrelated patients with alpha-galactosidase A causal mutations. (PMID:20122163)
• the active sites of human lysosomal enzymes alpha-galactosidase and alpha-N-acetylgalactosaminidase have interconvertible specificites (PMID:20444686)
• Mutations of the GLA gene is associated with Fabry disease. (PMID:20505683)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gla	ENSDARG00000036155
mus_musculus	Gla	ENSMUSG00000031266
rattus_norvegicus	Gla	ENSRNOG00000011513
drosophila_melanogaster	CG5731	FBGN0032192
drosophila_melanogaster	CG7997	FBGN0034117
caenorhabditis_elegans		WBGENE00011095

Paralogs (1): NAGA (ENSG00000198951)

Protein

Protein identifiers

Alpha-galactosidase A — P06280 (reviewed: P06280)

Alternative names: Alpha-D-galactosidase A, Alpha-D-galactoside galactohydrolase, Galactosylgalactosylglucosylceramidase GLA, Melibiase

All UniProt accessions (11): P06280, A0A3B3IRU3, A0A3B3IUC4, A0A669KB83, A0A6Q8PFA9, A0A6Q8PGG0, A0A6Q8PHD1, A0A6Q8PHM8, A0AA34QW02, Q53Y83, V9GYN5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome.

Subunit / interactions. Homodimer.

Subcellular location. Lysosome.

Disease relevance. Fabry disease (FD) [MIM:301500] Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride.

Similarity. Belongs to the glycosyl hydrolase 27 family.

RefSeq proteins (3): NP_000160, NP_001393676, NP_001393677 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000111	Glyco_hydro_27/36_CS	Conserved_site
IPR002241	Glyco_hydro_27	Family
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR035373	Melibiase/NAGA_C	Domain

Pfam: PF16499, PF17450

Enzyme classification (BRENDA):

• EC 3.2.1.22 — alpha-galactosidase (BRENDA: 152 organisms, 313 substrates, 322 inhibitors, 389 Km, 119 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
RAFFINOSE	0.42–252	57
MELIBIOSE	0.0014–254	47
STACHYOSE	0.22–72	32
4-NITROPHENYL ALPHA-D-GALACTOPYRANOSIDE	0.04–8.7	28
P-NITROPHENYL ALPHA-D-GALACTOPYRANOSIDE	0.075–12	25
P-NITROPHENYL ALPHA-D-GALACTOSIDE	0.08–6	22
4-METHYLUMBELLIFERYL-ALPHA-D-GALACTOSIDE	1.8–16.3	17
4-NITROPHENYL-ALPHA-D-GALACTOPYRANOSIDE	0.2–4.5	15
4-NITROPHENYL ALPHA-D-GALACTOSIDE	0.08–1	13
4-METHYLUMBELLIFERYL ALPHA-D-GALACTOSIDE	0.45–4.5	10
O-NITROPHENYL ALPHA-D-GALACTOSIDE	0.33–3.8	7
P-NITROPHENYL-ALPHA-D-GALACTOSIDE	0.26–1.36	7
P-NITROPHENYL-ALPHA-D-GALACTOPYRANOSIDE	0.23–0.83	6
METHYL ALPHA-D-GALACTOSIDE	5.3–14.3	5
PHENYL ALPHA-D-GALACTOSIDE	0.176–5	5

Catalyzed reactions (Rhea), 2 shown:

• a globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose (RHEA:21112)
• a globoside Gb3Cer + H2O = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + D-galactose (RHEA:48020)

UniProt features (285 total): sequence variant 226, strand 22, helix 17, turn 7, disulfide bond 5, glycosylation site 3, active site 2, signal peptide 1, chain 1, binding site 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3HG3	X-RAY DIFFRACTION	1.9
8K7F	X-RAY DIFFRACTION	1.98
6IBK	X-RAY DIFFRACTION	1.99
8K7K	X-RAY DIFFRACTION	2
8K7L	X-RAY DIFFRACTION	2
3S5Z	X-RAY DIFFRACTION	2
8K7J	X-RAY DIFFRACTION	2.01
6IBR	X-RAY DIFFRACTION	2.02
3LX9	X-RAY DIFFRACTION	2.04
6IBT	X-RAY DIFFRACTION	2.04
6IBM	X-RAY DIFFRACTION	2.07
3S5Y	X-RAY DIFFRACTION	2.1
8K7I	X-RAY DIFFRACTION	2.12
3GXP	X-RAY DIFFRACTION	2.2
8K7E	X-RAY DIFFRACTION	2.2
8K7H	X-RAY DIFFRACTION	2.28
3HG2	X-RAY DIFFRACTION	2.3
3HG4	X-RAY DIFFRACTION	2.3
3HG5	X-RAY DIFFRACTION	2.3
8K7G	X-RAY DIFFRACTION	2.32
3LXC	X-RAY DIFFRACTION	2.35
4NXS	X-RAY DIFFRACTION	2.55
8K7D	X-RAY DIFFRACTION	2.61
3TV8	X-RAY DIFFRACTION	2.64
3GXT	X-RAY DIFFRACTION	2.7
3LXB	X-RAY DIFFRACTION	2.85
3GXN	X-RAY DIFFRACTION	3.01
3LXA	X-RAY DIFFRACTION	3.04
1R46	X-RAY DIFFRACTION	3.25
1R47	X-RAY DIFFRACTION	3.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06280-F1	94.45	0.90

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 (2): 170 (nucleophile); 231 (proton donor)

Ligand- & substrate-binding residues (1): 203–207

Disulfide bonds (5): 142–172, 202–223, 378–382, 52–94, 56–63

Glycosylation sites (3): 139, 192, 215

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 476 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_OXIDOREDUCTASE_ACTIVITY, KEGG_LYSOSOME, MODULE_16, GGGTGGRR_PAX4_03

GO Biological Process (9): oligosaccharide metabolic process (GO:0009311), glycoside catabolic process (GO:0016139), negative regulation of nitric oxide biosynthetic process (GO:0045019), glycosylceramide catabolic process (GO:0046477), glycosphingolipid catabolic process (GO:0046479), negative regulation of nitric-oxide synthase activity (GO:0051001), carbohydrate metabolic process (GO:0005975), lipid metabolic process (GO:0006629), glycolipid catabolic process (GO:0019377)

GO Molecular Function (8): catalytic activity (GO:0003824), alpha-galactosidase activity (GO:0004557), signaling receptor binding (GO:0005102), hydrolase activity (GO:0016787), protein homodimerization activity (GO:0042803), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), protein binding (GO:0005515), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (8): extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), Golgi apparatus (GO:0005794), membrane (GO:0016020), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Innate Immune System	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Immune System	1
Metabolism of lipids	1
Metabolism	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
carbohydrate metabolic process	1
glycoside metabolic process	1
glycosyl compound catabolic process	1
nitric oxide biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
glycosylceramide metabolic process	1
glycosphingolipid catabolic process	1
ceramide catabolic process	1
glycosphingolipid metabolic process	1
glycolipid catabolic process	1
sphingolipid catabolic process	1
nitric-oxide synthase activity	1
regulation of nitric-oxide synthase activity	1
negative regulation of oxidoreductase activity	1
glycolipid metabolic process	1
lipid catabolic process	1
carbohydrate derivative catabolic process	1
molecular_function	1
galactosidase activity	1
protein binding	1
catalytic activity	1
identical protein binding	1
protein dimerization activity	1
hydrolase activity, acting on glycosyl bonds	1
binding	1
hydrolase activity	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1

Protein interactions and networks

STRING

1568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLA	ASAH1	Q13510	815
GLA	GBA1	P04062	803
GLA	GLB1	P16278	801
GLA	GALC	P54803	771
GLA	PSAP	P07292	767
GLA	ARSA	P15289	754
GLA	MGAM	O43451	742
GLA	SI	P14410	737
GLA	CD1D	P15813	706
GLA	SMPD1	P17405	703
GLA	MANBA	O00462	699
GLA	SKP1	P34991	673
GLA	IDUA	P35475	672
GLA	GUSB	P08236	665
GLA	LRP2	P98164	632

IntAct

158 interactions, top by confidence:

A	B	Type	Score
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
SORT1	GLA	psi-mi:“MI:0407”(direct interaction)	0.590
SORT1	GLA	psi-mi:“MI:0915”(physical association)	0.590
GLA	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
rep	GLA	psi-mi:“MI:0914”(association)	0.530
ZNF764	IPO8	psi-mi:“MI:0914”(association)	0.530
NPRL2	ZBTB5	psi-mi:“MI:0914”(association)	0.530
TMEM205	RBP4	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
GLA	ALG11	psi-mi:“MI:0915”(physical association)	0.500
GLA	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	GLA	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	GLA	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
GLA	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (100): GLA (Affinity Capture-MS), CNOT2 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT6 (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS), GLA (Proximity Label-MS), GLA (Affinity Capture-MS), GLA (Affinity Capture-MS)

ESM2 similar proteins: A2VDP5, B0BND0, F1N5C8, O08912, O94323, P04058, P06280, P17050, P28843, P29119, P31430, P51569, P54793, P84039, Q07075, Q0II73, Q0VA77, Q32KH8, Q566N0, Q58D55, Q58D68, Q58DH9, Q5BKW7, Q5FYA8, Q5RAC0, Q5RB45, Q5RFP3, Q64319, Q66H12, Q6AX80, Q6DDP3, Q6P179, Q6UE39, Q6UWR7, Q8BGN3, Q8BTJ4, Q8C129, Q8CF93, Q8IUC8, Q8IVL8

Diamond homologs: A1C5D3, A1D0A3, A1D9S3, A1DDD8, A2QEJ9, A2R2S6, A4DA70, A7XZT2, B0Y224, B0YEK2, B3PGJ1, B8N306, B8N7Z0, O94221, P04824, P06280, P14749, P17050, P41945, P41946, P41947, P51569, Q03647, Q09187, Q0CVX4, Q11129, Q2UI87, Q2UJ97, Q42656, Q4WE86, Q4WVZ3, Q55B10, Q58DH9, Q5AVQ6, Q5AX28, Q66H12, Q8RX86, Q8VXZ7, Q90744, Q99172

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
migalastat	“down-regulates activity”	GLA	“chemical inhibition”
GLA	“up-regulates quantity by expression”	1,3-dichloro-7-hydroxy-9,9-dimethyl-9H-acridin-2-one	“chemical modification”
TFEB	“up-regulates quantity by expression”	GLA	“transcriptional regulation”
TFE3	“up-regulates quantity by expression”	GLA	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	28.0×	1e-04
Assembly and cell surface presentation of NMDA receptors	8	19.9×	3e-06
Neurexins and neuroligins	8	15.4×	1e-05
Protein-protein interactions at synapses	5	13.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	38.5×	9e-10
receptor clustering	6	27.5×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	6	21.9×	7e-05
cell-cell adhesion	10	7.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1973 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	637
Likely pathogenic	307
Uncertain significance	418
Likely benign	240
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027590	NM_000169.3(GLA):c.242G>C (p.Trp81Ser)	Pathogenic
1059587	NM_000169.3(GLA):c.547+3A>G	Pathogenic
1064716	NM_000169.3(GLA):c.453C>G (p.Tyr151Ter)	Pathogenic
1064717	NM_000169.3(GLA):c.835C>T (p.Gln279Ter)	Pathogenic
1069600	NM_000169.3(GLA):c.379A>T (p.Lys127Ter)	Pathogenic
1070568	NM_000169.3(GLA):c.437del (p.Pro146fs)	Pathogenic
10715	NM_000169.3(GLA):c.902G>A (p.Arg301Gln)	Pathogenic
10716	NM_000169.3(GLA):c.131G>A (p.Trp44Ter)	Pathogenic
10718	NM_000169.3(GLA):c.370-1G>A	Pathogenic
10719	NM_000169.3(GLA):c.118C>T (p.Pro40Ser)	Pathogenic
10720	NM_000169.3(GLA):c.999+1G>T	Pathogenic
10722	NM_000169.3(GLA):c.982G>A (p.Gly328Arg)	Pathogenic
10724	NM_000169.3(GLA):c.101A>G (p.Asn34Ser)	Pathogenic
10725	NM_000169.3(GLA):c.166T>G (p.Cys56Gly)	Pathogenic
10729	NM_000169.3(GLA):c.606T>G (p.Cys202Trp)	Pathogenic
10731	NM_000169.3(GLA):c.806T>C (p.Val269Ala)	Pathogenic
10732	NM_000169.3(GLA):c.680G>A (p.Arg227Gln)	Pathogenic
10733	NM_000169.3(GLA):c.679C>T (p.Arg227Ter)	Pathogenic
10735	NM_000169.3(GLA):c.797A>T (p.Asp266Val)	Pathogenic
10736	NM_000169.3(GLA):c.861G>A (p.Trp287Ter)	Pathogenic
10739	NM_000169.3(GLA):c.979C>A (p.Gln327Lys)	Pathogenic
10741	NM_000169.3(GLA):c.1020G>A (p.Trp340Ter)	Pathogenic
10742	NM_000169.3(GLA):c.1025G>A (p.Arg342Gln)	Pathogenic
10743	NM_000169.3(GLA):c.1024C>T (p.Arg342Ter)	Pathogenic
10744	NM_000169.3(GLA):c.1081G>C (p.Gly361Arg)	Pathogenic
10745	NM_000169.3(GLA):c.1192G>T (p.Glu398Ter)	Pathogenic
10746	NM_000169.3(GLA):c.369+2T>G	Pathogenic
10749	NM_000169.3(GLA):c.125_137del (p.Met42fs)	Pathogenic
10750	GLA, 1-BP DEL, NT716	Pathogenic
10751	NM_000169.3(GLA):c.774_775del (p.Pro259fs)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2850 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101407774:A:G	W44R	0.994
X:101407774:A:T	W44R	0.994
X:101403897:A:G	W95R	0.990
X:101403897:A:T	W95R	0.990
X:101398479:G:A	S297F	0.989
X:101398802:A:G	W262R	0.989
X:101398802:A:T	W262R	0.989
X:101401735:A:C	S148R	0.989
X:101401735:A:T	S148R	0.989
X:101401737:T:G	S148R	0.989
X:101398906:C:G	R227P	0.988
X:101403841:A:C	F113L	0.986
X:101403841:A:T	F113L	0.986
X:101403843:A:G	F113L	0.986
X:101407754:G:C	F50L	0.986
X:101407754:G:T	F50L	0.986
X:101407756:A:G	F50L	0.986
X:101407772:C:A	W44C	0.986
X:101407772:C:G	W44C	0.986
X:101398074:C:G	R342P	0.985
X:101398510:A:G	W287R	0.985
X:101398510:A:T	W287R	0.985
X:101398917:G:C	C223W	0.985
X:101400700:C:T	C202Y	0.985
X:101401682:A:G	L166P	0.985
X:101403895:C:A	W95C	0.984
X:101403895:C:G	W95C	0.984
X:101398918:C:T	C223Y	0.983
X:101401675:T:A	K168N	0.983
X:101401675:T:G	K168N	0.983

dbSNP variants (sampled 300 via entrez): RS1000182160 (X:101399058 C>A,G), RS1000333260 (X:101408605 G>A), RS1000623276 (X:101407125 C>T), RS1000685069 (X:101408911 C>T), RS1001078239 (X:101406427 C>G), RS1001403373 (X:101398406 C>T), RS1001460927 (X:101408174 G>A,T), RS1001754342 (X:101398923 C>G), RS1001798082 (X:101405664 T>C), RS1001850525 (X:101405321 A>G), RS1003528020 (X:101403191 T>C), RS1004641235 (X:101398236 T>C), RS1004802201 (X:101407663 C>G), RS1005188786 (X:101404822 G>C), RS1006882029 (X:101405185 G>A)

Disease associations

OMIM: gene MIM:300644 | disease phenotypes: MIM:301500, MIM:192600, MIM:300986, MIM:118220, MIM:121300, MIM:307200

GenCC curated gene-disease

Disease	Classification	Inheritance
Fabry disease	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Fabry disease	Definitive	XL

Mondo (11): Fabry disease (MONDO:0010526), familial hypertrophic cardiomyopathy (MONDO:0024573), cardiomyopathy (MONDO:0004994), hypertrophic cardiomyopathy (MONDO:0005045), nephrotic syndrome (MONDO:0005377), intellectual disability, X-linked, syndromic, Bain type (MONDO:0010512), hypertrophic cardiomyopathy 1 (MONDO:0008647), steroid-resistant nephrotic syndrome (MONDO:0044765), Charcot-Marie-Tooth disease (MONDO:0015626), hereditary coproporphyria (MONDO:0007369), isolated growth hormone deficiency type III (MONDO:0010615)

Orphanet (10): Fabry disease (Orphanet:324), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Rare cardiomyopathy (Orphanet:167848), Rare hypertrophic cardiomyopathy (Orphanet:217569), Neurodevelopmental delay-intellectual disability-skeletal defects syndrome (Orphanet:662198), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Hereditary coproporphyria (Orphanet:79273), Isolated growth hormone deficiency type III (Orphanet:231692), Non-acquired isolated growth hormone deficiency (Orphanet:631), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000083	Renal insufficiency
HP:0000091	Abnormal renal tubule morphology
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000179	Thick lower lip vermilion
HP:0000280	Coarse facial features
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000524	Conjunctival telangiectasia
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000873	Diabetes insipidus
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000975	Hyperhidrosis
HP:0001004	Lymphedema
HP:0001014	Angiokeratoma
HP:0001071	Angiokeratoma corporis diffusum
HP:0001131	Corneal dystrophy
HP:0001155	Abnormality of the hand
HP:0001250	Seizure
HP:0001297	Stroke

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D046349	Coproporphyria, Hereditary	C06.552.830.074; C16.320.850.742.074; C17.800.827.742.074; C18.452.811.400.074
D000795	Fabry Disease	C10.228.140.163.100.435.825.200; C10.228.140.300.275.374; C14.907.253.329.374; C16.320.322.124; C16.320.565.189.435.825.200; C16.320.565.398.641.803.300; C16.320.565.595.554.825.200; C18.452.132.100.435.825.200; C18.452.584.563.641.803.300; C18.452.648.189.435.825.200; C18.452.648.398.641.803.300; C18.452.648.595.554.825.200
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C537149	Hypogammaglobulinemia and Isolated growth hormone deficiency, X-linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2524 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

62 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,169,792 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL110458	MIGALASTAT	4	430
CHEMBL1159	PINACIDIL ANHYDROUS	4	6,303
CHEMBL1200561	DOXAZOSIN MESYLATE	4	11,917
CHEMBL1200758	AMPICILLIN SODIUM	4	5,602
CHEMBL1200787	PHENOXYBENZAMINE HYDROCHLORIDE	4	2,483
CHEMBL1200938	METHYSERGIDE MALEATE	4	4
CHEMBL1201038	ACRISORCIN	4	1,956
CHEMBL1256842	NOMIFENSINE MALEATE	4	630
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1398126	AMILORIDE HYDROCHLORIDE	4	2,101
CHEMBL14060	PHENOL	4	1,871,332
CHEMBL1448187	FLUPHENAZINE HYDROCHLORIDE	4	6,110
CHEMBL1558	PRAZOSIN HYDROCHLORIDE	4	11,347
CHEMBL1590	PSEUDOEPHEDRINE	4	25,626
CHEMBL1611	PHENYTOIN SODIUM	4	122
CHEMBL1643	RIBAVIRIN	4	78,049
CHEMBL1700	SOTALOL HYDROCHLORIDE	4	3,968
CHEMBL1751	DIGOXIN	4	67,342
CHEMBL2	PRAZOSIN	4
CHEMBL219916	DOMPERIDONE	4
CHEMBL30	CIMETIDINE	4
CHEMBL313972	MASOPROCOL	4
CHEMBL34259	METHOTREXATE	4
CHEMBL43	AMSACRINE	4
CHEMBL480	LANSOPRAZOLE	4
CHEMBL500	PINDOLOL	4
CHEMBL56367	NIMESULIDE	4
CHEMBL585	TRIAMTERENE	4

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

PharmGKB clinical annotations

19 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs104894827	Efficacy	3	migalastat	Fabry Disease
rs104894828	Efficacy	3	migalastat	Fabry Disease
rs1569304898	Efficacy	3	migalastat	Fabry Disease
rs190347120	Efficacy	3	migalastat	Fabry Disease
rs28935195	Efficacy	3	migalastat	Fabry Disease
rs28935490	Efficacy	3	migalastat	Fabry Disease
rs372966991	Efficacy	3	migalastat	Fabry Disease
rs397515870	Efficacy	3	migalastat	Fabry Disease
rs397515874	Efficacy	3	migalastat	Fabry Disease
rs398123212	Efficacy	3	migalastat	Fabry Disease
rs398123217	Efficacy	3	migalastat	Fabry Disease
rs398123223	Efficacy	3	migalastat	Fabry Disease
rs398123226	Efficacy	3	migalastat	Fabry Disease
rs727504348	Efficacy	3	migalastat	Fabry Disease
rs727505292	Efficacy	3	migalastat	Fabry Disease
rs869312136	Efficacy	3	migalastat	Fabry Disease
rs869312138	Efficacy	3	migalastat	Fabry Disease
rs869312146	Efficacy	3	migalastat	Fabry Disease
rs869312399	Efficacy	3	migalastat	Fabry Disease

PharmGKB variants

19 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs398123212	GLA	3	0.00	1	migalastat
rs398123217	GLA	3	0.00	1	migalastat
rs397515874	GLA	3	0.00	1	migalastat
rs727505292	GLA	3	0.00	1	migalastat
rs869312399	GLA	3	0.00	1	migalastat
rs104894828	GLA	3	0.00	1	migalastat
rs398123226	GLA	3	0.00	1	migalastat
rs727504348	GLA	3	0.00	1	migalastat
rs869312136	GLA, HNRNPH2	3	0.00	1	migalastat
rs28935195	GLA	3	0.00	1	migalastat
rs104894827	GLA	3	0.00	1	migalastat
rs869312138	GLA, HNRNPH2	3	0.00	1	migalastat
rs1569304898	GLA	3	0.00	1	migalastat
rs372966991	GLA	3	0.00	1	migalastat
rs869312146	GLA	3	0.00	1	migalastat
rs398123223	GLA	3	0.00	1	migalastat
rs190347120	GLA	3	0.00	1	migalastat
rs28935490	GLA	3	0.00	1	migalastat
rs397515870	GLA	3	0.00	1	migalastat

Binding affinities (BindingDB)

3 measured of 7 human assays (7 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(hydroxymethyl)piperidine-3,4,5-triol;hydrochloride	IC50	0.78 nM
DGJ-pMe SPhT	IC50	1.4 nM
DGJ-pMe OPhT	IC50	16 nM

ChEMBL bioactivities

423 potent at pChembl≥5 of 3000 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.25	Potency	5.6	nM	CHEMBL1509159
7.89	IC50	13	nM	MIGALASTAT
7.38	IC50	42	nM	MIGALASTAT
7.28	IC50	53	nM	CHEMBL3350086
7.20	Potency	63.1	nM	CHEMBL1506331
7.16	IC50	70	nM	MIGALASTAT
7.05	Potency	89.1	nM	CHEMBL1505819
7.00	Potency	100	nM	CHEMBL1898790
7.00	Potency	100	nM	CHEMBL1422806
7.00	Potency	100	nM	CHEMBL1591251
7.00	Potency	100	nM	CHEMBL1337610
7.00	Potency	100	nM	CHEMBL1544563
6.95	Potency	112.2	nM	NECROSTATIN
6.80	Potency	158.5	nM	CHEMBL1495385
6.80	Potency	158.5	nM	CHEMBL1468715
6.80	Potency	158.5	nM	CHEMBL1602568
6.75	Potency	177.8	nM	CHEMBL1361851
6.75	Potency	177.8	nM	CHEMBL1527829
6.75	Potency	177.8	nM	CHEMBL1414631
6.75	Potency	177.8	nM	CHEMBL1385184
6.75	Potency	177.8	nM	CHEMBL1503116
6.75	Potency	177.8	nM	CHEMBL1346258
6.75	Potency	177.8	nM	CHEMBL1581772
6.75	Potency	177.8	nM	CHEMBL1494572
6.75	Potency	177.8	nM	CHEMBL3208544
6.75	Potency	177.8	nM	CHEMBL1606610
6.75	Potency	177.8	nM	CHEMBL1256720
6.75	Potency	177.8	nM	CHEMBL1523038
6.75	Potency	177.8	nM	CHEMBL1326103
6.75	Potency	177.8	nM	CHEMBL1563819
6.75	Potency	177.8	nM	SOTALOL HYDROCHLORIDE
6.75	Potency	177.8	nM	CHEMBL1341217
6.70	Ki	200	nM	CHEMBL4792854
6.70	Potency	199.5	nM	CHEMBL1401427
6.70	Potency	199.5	nM	CHEMBL1306659
6.65	Potency	223.9	nM	CHEMBL1502697
6.65	Potency	223.9	nM	CHEMBL1600521
6.65	Potency	223.9	nM	CHEMBL1529604
6.60	Potency	251.2	nM	CHEMBL1568449
6.60	Potency	251.2	nM	CHEMBL3212680
6.55	Potency	281.8	nM	CHEMBL1546078
6.50	Potency	316.2	nM	CHEMBL1539061
6.50	Potency	316.2	nM	CHEMBL259018
6.50	Potency	316.2	nM	CHEMBL1601549
6.50	Potency	316.2	nM	CHEMBL1366740
6.50	Potency	316.2	nM	CHEMBL1352596
6.40	Potency	398.1	nM	CHEMBL1390842
6.40	Potency	398.1	nM	CHEMBL1394350
6.35	Potency	446.7	nM	CHEMBL1427581
6.35	Potency	446.7	nM	CHEMBL1429822

PubChem BioAssay actives

45 with measured affinity, of 393 total; 25 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-(hydroxymethyl)piperidine-3,4,5-triol	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	0.0008	uM
(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)-N-(4-methylsulfanylphenyl)piperidine-1-carbothioamide	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	0.0014	uM
Migalastat	1435345: Inhibition of recombinant human alpha GAL-A using 4-methylumbelliferyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	0.0130	uM
(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)-N-(4-methoxyphenyl)piperidine-1-carbothioamide	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	0.0160	uM
(2R,3S,4R,5S)-N-(4-fluorophenyl)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidine-1-carbothioamide	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	0.0430	uM
(2R,3R,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol	1330592: Inhibition of human recombinant lysosomal alpha GAL-A using 4-methylberiilyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	0.0530	uM
1-N,3-N,5-N-tris[1,3-bis[[1-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxy]-2-[[1-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxymethyl]propan-2-yl]benzene-1,3,5-tricarboxamide	1737127: Competitive inhibition of human recombinant lysosomal alpha-GalA using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate preincubated for 45 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometry based Lineweaver-Burk plot analysis	ki	0.2000	uM
(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)-N-naphthalen-1-ylpiperidine-1-carbothioamide	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	0.3700	uM
(2R,3S,4R,5R)-2,5-bis(hydroxymethyl)pyrrolidine-3,4-diol	488424: Competitive inhibition of human lysosome alpha-galactosidase by Lineweaver-Burke plot analysis	ki	0.5000	uM
(E)-N-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]methyl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide	1435345: Inhibition of recombinant human alpha GAL-A using 4-methylumbelliferyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	1.1000	uM
(E)-3-[4-(trifluoromethyl)phenyl]-N-[[(2R,3S,4R,5S)-3,4,5-trihydroxypiperidin-2-yl]methyl]prop-2-enamide	1351452: Inhibition of human recombinant alpha-galactosidase A using 4-MU-alpha-d-galactopyranoside as substrate by fluorescence assay	ic50	1.2000	uM
N,N’-bis[1,3-bis[[1-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxy]-2-[[1-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxymethyl]propan-2-yl]hexanediamide	1737127: Competitive inhibition of human recombinant lysosomal alpha-GalA using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate preincubated for 45 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometry based Lineweaver-Burk plot analysis	ki	1.5000	uM
5-cyclohexyl-N-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]methyl]pentanamide	1435366: Non-competitive inhibition of recombinant human alpha GAL-A using varying levels of 4-methylumbelliferyl alpha-D-galactopyranoside substrate at pH 7 Lineweaver-burk plot analysis	ki	2.0000	uM
(6S,7R,8S)-3-(4-fluorophenyl)imino-1,5,6,7,8,8a-hexahydro-[1,3]thiazolo[3,4-a]pyridine-6,7,8-triol	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	2.1800	uM
(E)-3-(5-bromo-2-methoxyphenyl)-N-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]methyl]prop-2-enamide	1435345: Inhibition of recombinant human alpha GAL-A using 4-methylumbelliferyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	3.0000	uM
5-cyclohexyl-N-[[(2R,3S,4R,5S)-3,4,5-trihydroxypiperidin-2-yl]methyl]pentanamide	1351452: Inhibition of human recombinant alpha-galactosidase A using 4-MU-alpha-d-galactopyranoside as substrate by fluorescence assay	ic50	3.1000	uM
(E)-3-(5-bromo-2-methoxyphenyl)-N-[[(2R,3S,4R,5S)-3,4,5-trihydroxypiperidin-2-yl]methyl]prop-2-enamide	1351452: Inhibition of human recombinant alpha-galactosidase A using 4-MU-alpha-d-galactopyranoside as substrate by fluorescence assay	ic50	3.5000	uM
(E)-3-(3-bromophenyl)-N-[[(2R,3S,4R,5S)-3,4,5-trihydroxypiperidin-2-yl]methyl]prop-2-enamide	1351444: Competitive inhibition of human recombinant alpha-galactosidase A using 4-MU-alpha-d-galactopyranoside as substrate by Lineweaver-Burk plot method	ki	3.5000	uM
1-N,3-N,5-N-tris[1,3-bis[[1-[3-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]propyl]triazol-4-yl]methoxy]-2-[[1-[3-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]propyl]triazol-4-yl]methoxymethyl]propan-2-yl]benzene-1,3,5-tricarboxamide	1737128: Non-competitive inhibition of human recombinant lysosomal alpha-GalA using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate preincubated for 45 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometry based Lineweaver-Burk plot analysis	ki	3.7000	uM
3-cyclopentyl-N-[[(2R,3S,4R,5S)-3,4,5-trihydroxypiperidin-2-yl]methyl]propanamide	1351452: Inhibition of human recombinant alpha-galactosidase A using 4-MU-alpha-d-galactopyranoside as substrate by fluorescence assay	ic50	4.1000	uM
(2R,3S,4R,5S)-N-benzyl-3,4,5-trihydroxy-2-(hydroxymethyl)piperidine-1-carbothioamide	1800326: α-Gal A Assay from Article 10.1021/cb500143h: “Molecular Basis of 1-Deoxygalactonojirimycin Arylthiourea Binding to Human a-Galactosidase A: Pharmacological Chaperoning Efficacy on Fabry Disease Mutants.”	ic50	4.4100	uM
(3R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol	73341: Inhibitory activity measured against alpha-galactosidase of coffee bean by colorimetric assay using the D-glucose oxidase-peroxidase method	ic50	6.4000	uM
(2R,3S,4R)-2-[[4-[4-[2-[2-[4-[[2-[[1-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxymethyl]-2-[[3-[2-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxy]ethyl]triazol-4-yl]methoxymethyl]-3-[[1-[2-[4-[1-[[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]methyl]triazol-4-yl]phenoxy]ethoxymethyl]triazol-4-yl]methoxy]propoxy]methyl]triazol-1-yl]ethoxy]ethoxy]phenyl]triazol-1-yl]methyl]pyrrolidine-3,4-diol	1737127: Competitive inhibition of human recombinant lysosomal alpha-GalA using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate preincubated for 45 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometry based Lineweaver-Burk plot analysis	ki	7.4000	uM
N-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]methyl]-3-(2,4,5-trimethoxyphenyl)propanamide	1435345: Inhibition of recombinant human alpha GAL-A using 4-methylumbelliferyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	7.7000	uM
(2R,3S,4R)-2-(hydroxymethyl)pyrrolidine-3,4-diol	1330592: Inhibition of human recombinant lysosomal alpha GAL-A using 4-methylberiilyl alpha-D-galactopyranoside as substrate at pH 7 after 15 mins by fluorescence assay	ic50	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	6
sodium arsenite	increases expression, affects expression, affects cotreatment, increases abundance	4
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Tetrachlorodibenzodioxin	increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
dicrotophos	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sulforaphane	increases expression	1
cobaltous chloride	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
cyfluthrin	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
migalastat	affects binding, decreases response to substance	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
elesclomol	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1

ChEMBL screening assays

114 unique, capped per target: 104 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1116479	Binding	Activation of purified alpha-galactosidase A using 4-methylumbelliferyl-alpha-D-galactoside as substrate after 45 mins relative to basal	Evaluation of 2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one analogues as GAA activators. — Eur J Med Chem
CHEMBL1613841	Functional	PUBCHEM_BIOASSAY: Counterscreen for Glucocerebrosidase Inhibitors: qHTS Assay for Coffee Bean alpha-Galactosidase at pH 4.5. (Class of assay: confirmatory) [Related pubchem assays: 348, 360 ]	PubChem BioAssay data set

Cellosaurus cell lines

40 cell lines: 21 induced pluripotent stem cell, 9 finite cell line, 5 cancer cell line, 2 transformed cell line, 2 embryonic stem cell, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0P99	GM00107	Finite cell line	Male
CVCL_0Q46	GM00882	Finite cell line	Male
CVCL_0Q51	GM02769	Finite cell line	Male
CVCL_0Q52	GM02775	Finite cell line	Male
CVCL_4N32	GM02771	Finite cell line	Female
CVCL_4N33	GM02772	Finite cell line	Female
CVCL_4N34	GM02774	Finite cell line	Female
CVCL_4N44	GM04391	Transformed cell line	Male
CVCL_7305	GM00881	Finite cell line	Male
CVCL_A4EP	CMCi007-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00074984	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease
NCT00081497	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00097890	PHASE4	COMPLETED	Replagal Enzyme Replacement Therapy for Adults With Fabry Disease
NCT00140621	PHASE4	COMPLETED	A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease
NCT00230607	PHASE4	TERMINATED	Study of the Effects of Fabrazyme Treatment on Lactation and Infants
NCT00312767	PHASE4	WITHDRAWN	A Study in Patients With Fabry Disease Who Are on Chronic Hemodialysis Therapy for Treatment of End-stage Renal Insufficiency.
NCT00487630	PHASE4	UNKNOWN	Evaluation of Efficacy and Safety of Agalsidase Beta in Heterozygous Females for Fabry Disease
NCT01650779	PHASE4	COMPLETED	A Study Evaluating Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta
NCT01997489	PHASE4	COMPLETED	Ophthalmic Findings During 10-year Enzyme Substitution of Danish Fabry Patients.
NCT04143958	PHASE4	WITHDRAWN	To Assess the Glycosphingolipid Clearance and Clinical Effects of Switching to Agalsidase Beta (Fabrazyme) Versus Continuing on Agalsidase Alfa (Replagal) in Male Patients With Classic Fabry Disease
NCT05054387	PHASE4	COMPLETED	China Post-marketing Surveillance (PMS) Study of Fabrazyme®
NCT05067868	PHASE4	RECRUITING	A Study of Replagal in Children and Adults With Fabry Disease in India
NCT06019728	PHASE4	COMPLETED	A Prospective Study to Investigate Safety and Tolerability of Shorter Infusion of Fabrazyme
NCT00074971	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00701415	PHASE3	COMPLETED	A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
NCT00864851	PHASE3	COMPLETED	Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease
NCT00925301	PHASE3	COMPLETED	Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
NCT01124643	PHASE3	COMPLETED	Extension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease
NCT01218659	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
NCT01298141	PHASE3	COMPLETED	A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
NCT01458119	PHASE3	TERMINATED	Open-Label Phase 3 Long-Term Safety Study of Migalastat
NCT02194985	PHASE3	COMPLETED	Open-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease
NCT02795676	PHASE3	COMPLETED	Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function
NCT02921620	PHASE3	WITHDRAWN	Study to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease
NCT03018730	PHASE3	COMPLETED	Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
NCT03180840	PHASE3	COMPLETED	Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks
NCT03425539	PHASE3	COMPLETED	Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease
NCT03500094	PHASE3	COMPLETED	Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)
NCT03566017	PHASE3	COMPLETED	Open Label Extension Study of 1 mg/kg Pegunigalsidase Alfa Every 2 Weeks in Patients With Fabry Disease
NCT03614234	PHASE3	COMPLETED	Open Label Extension of 2 mg/kg Pegunigalsidase Alfa (PRX-102) Every 4 Weeks in Adult Fabry Disease Patients
NCT03737214	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease
NCT04020055	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease
NCT04049760	PHASE3	COMPLETED	Safety, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged >12 Years) With Fabry Disease
NCT04840667	PHASE3	TERMINATED	A Study of Replagal in Treatment-naïve Adults With Fabry Disease
NCT04974749	PHASE3	COMPLETED	A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease
NCT05206773	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease
NCT05280548	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease
NCT05843916	PHASE3	COMPLETED	Switch Over Study of Biosimilar Agalsidase Beta for Fabry Disease
NCT06081062	PHASE3	RECRUITING	Evaluate the Safety and Efficacy of Fabagal® (Agalsidase Beta) in Patients With Fabry Disease
NCT06904261	PHASE3	RECRUITING	A Study of Migalastat in Pediatric Subjects (2 to <12 Yrs) With Fabry Disease and Amenable GLA Variants