GALC

Protein identityUniProt · HPA

UniProt accession

P54803

Gene

GALC

Ensembl

ENSG00000054983

Chromosome

14

Canonical length

685 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

685 residues, UniProt reviewed canonical sequence.

>P54803|GALC
     1  MAEWLLSASW QRRAKAMTAA AGSAGRAAVP LLLCALLAPG GAYVLDDSDG LGREFDGIGA
    61  VSGGGATSRL LVNYPEPYRS QILDYLFKPN FGASLHILKV EIGGDGQTTD GTEPSHMHYA
   121  LDENYFRGYE WWLMKEAKKR NPNITLIGLP WSFPGWLGKG FDWPYVNLQL TAYYVVTWIV
   181  GAKRYHDLDI DYIGIWNERS YNANYIKILR KMLNYQGLQR VKIIASDNLW ESISASMLLD
   241  AELFKVVDVI GAHYPGTHSA KDAKLTGKKL WSSEDFSTLN SDMGAGCWGR ILNQNYINGY
   301  MTSTIAWNLV ASYYEQLPYG RCGLMTAQEP WSGHYVVESP VWVSAHTTQF TQPGWYYLKT
   361  VGHLEKGGSY VALTDGLGNL TIIIETMSHK HSKCIRPFLP YFNVSQQFAT FVLKGSFSEI
   421  PELQVWYTKL GKTSERFLFK QLDSLWLLDS DGSFTLSLHE DELFTLTTLT TGRKGSYPLP
   481  PKSQPFPSTY KDDFNVDYPF FSEAPNFADQ TGVFEYFTNI EDPGEHHFTL RQVLNQRPIT
   541  WAADASNTIS IIGDYNWTNL TIKCDVYIET PDTGGVFIAG RVNKGGILIR SARGIFFWIF
   601  ANGSYRVTGD LAGWIIYALG RVEVTAKKWY TLTLTIKGHF TSGMLNDKSL WTDIPVNFPK
   661  NGWAAIGTHS FEFAQFDNFL VEATR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GALC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GALC.

Disease | AllUniProt

Conditions GALC is implicated in, by any mechanism.

• Krabbe disease (KRB) MIM:245200

Disease | GeneticClinVar

373 pathogenic / likely-pathogenic of 1,595 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Galactosylceramide beta-galactosidase deficiency
• Inborn genetic diseases
• GALC-related disorder
• Spastic ataxia
• 19 conditions

Disease | AutoantibodyPubMed

Conditions in which antibodies against GALC are reported. Each links to that disease's full target list.

• Guillain-Barre Syndrome 8

Showing 1 of 2 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for GALC from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

0.19

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• galactosylceramide catabolic process
• glycosphingolipid catabolic process
• myelination

Molecular functions

• galactosylceramidase activity

Cellular components

• lysosomal lumen
• lysosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• Aldolase-type TIM barrel
• Glycoside hydrolase superfamily
• Glycoside hydrolase, family 59
• Glycosyl hydrolase family 59, central domain
• Glycosyl hydrolase family 59, catalytic domain
• Glycosyl hydrolase family 59, C-terminal lectin domain
• Glycosyl hydrolase family 59
• Glycosyl hydrolase family 59 central domain
• Galactocerebrosidase, C-terminal lectin domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Glycosidase
• Hydrolase
• Leukodystrophy
• Lipid degradation
• Lipid metabolism
• Lysosome
• Signal
• Sphingolipid metabolism