GALE

UDP-galactose-4-epimerase, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 1:23795599-23800781

Links

ENSG00000117308 ∙ NCBI:2582 ∙ OMIM:606953 ∙ HGNC:4116 ∙ Uniprot:Q14376 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• galactose epimerase deficiency (Definitive), mode of inheritance: AR
• galactose epimerase deficiency (Strong), mode of inheritance: AR
• galactose epimerase deficiency (Strong), mode of inheritance: AR
• galactose epimerase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galactosemia III; Thrombocytopenia, autosomal recessive 13	AR	Biochemical; Hematologic; Neurologic	The generalized form of Galactosemia III, which typically manifests clinically in infancy upon exposure to lactose-containing diet, can result in lethal sequelae, and can be treated or prevented through dietary means (galactose/lactose restriction); Though data are unclear, individuals with intermediate forms of Galactosemia III may also benefit from galactose restriction as well; Thrombocytopenia, autosomal recessive 13 may involve increased risk of bleeding, and awareness may allow preventative measures as well as management of bleeding episodes; Thrombocytopenia, autosomal recessive 13 may involve cardiovascular anomalies, and awareness may allow early identification and management	Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic; Renal	4644860; 4785150; 404274; 7305435; 7227386; 6408303; 3948246; 9700591; 3141714; 8295413; 9326324; 9700591; 9538513; 9973283; 10086948; 11117433; 14970742; 15639193; 16301867; 16302980; 16385452; 18188677; 19250319; 19904445; 20725869; 21290786; 23430501; 30247636; 33510604; 34159722; 36395340

ClinVar

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

• UDPglucose-4-epimerase_deficiency (349 variants)
• not_provided (57 variants)
• Thrombocytopenia_13,_syndromic (27 variants)
• not_specified (22 variants)
• Inborn_genetic_diseases (21 variants)
• GALE-related_disorder (12 variants)
• Galactosemia_III,_severe (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALE gene is commonly pathogenic or not. These statistics are base on transcript: NM_001008216.2. Only rare variants are included in the table.

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

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

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	109		111
missense	2	13	86	3		104
nonsense	2	4	1			7
start loss	2	1				3
frameshift	15	7	1			23
splice donor/acceptor (+/-2bp)		14	2			16
Total	21	39	92	112	0

Highest pathogenic variant AF is 0.0000619589

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALE	protein_coding	protein_coding	ENST00000374497	10	5183

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.48e-10	0.109	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.322	217	204	1.06	0.0000133	2244
Missense in Polyphen		89	97.481	0.913		1045
Synonymous	0.0148	85	85.2	0.998	0.00000562	704
Loss of Function	0.332	16	17.5	0.914	8.58e-7	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000347	0.000347
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000490	0.000489
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N- acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6- phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP- GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids. {ECO:0000269|PubMed:22654673, ECO:0000303|PubMed:23732289}.
• Disease: DISEASE: Epimerase-deficiency galactosemia (EDG) [MIM:230350]: Clinical features include early-onset cataracts, liver damage, deafness and mental retardation. There are two clinically distinct forms of EDG. (1) A benign, or 'peripheral' form with no detectable GALE activity in red blood cells and characterized by mild symptoms. Some patients may suffer no symptoms beyond raised levels of galactose-1-phosphate in the blood. (2) A much rarer 'generalized' form with undetectable levels of GALE activity in all tissues and resulting in severe features such as restricted growth and mental development. {ECO:0000269|PubMed:11279193, ECO:0000269|PubMed:11903335, ECO:0000269|PubMed:15639193, ECO:0000269|PubMed:16301867, ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9326324, ECO:0000269|PubMed:9538513, ECO:0000269|PubMed:9973283}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: UDP-<i>N</i>-acetyl-D-galactosamine biosynthesis II;Galactose metabolism - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Galactosemia III;Galactosemia II (GALK);Galactose Metabolism;Nucleotide Sugars Metabolism;Galactosemia;Metabolism of carbohydrates;Metabolism;UDP-<i>N</i>-acetyl-D-galactosamine biosynthesis I;D-galactose degradation V (Leloir pathway);Galactose catabolism;Galactose metabolism (Consensus)

Recessive Scores

• pRec: 0.569

Intolerance Scores

• loftool: 0.0621
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.435
• hipred: N
• hipred_score: 0.389
• ghis: 0.493

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.467

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gale

Gene ontology

• Biological process: galactose catabolic process;galactose catabolic process via UDP-galactose
• Cellular component: cytosol
• Molecular function: UDP-N-acetylglucosamine 4-epimerase activity;UDP-glucose 4-epimerase activity;identical protein binding;protein homodimerization activity