Galactose epimerase deficiency

Summary

Galactose epimerase deficiency (MONDO:0009257) is a disease caused by GALE (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: GALE (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 368
• Phenotypes (HPO): 13

Clinical features

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000952	Jaundice	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0003355	Aminoaciduria	Very frequent (80-99%)
HP:0004915	Impairment of galactose metabolism	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	galactose epimerase deficiency
Mondo ID	MONDO:0009257
OMIM	230350
Orphanet	79238
DOID	DOID:0111458
SNOMED CT	8849004
UMLS	C0751161
MedGen	199598
GARD	0005392
Is cancer (heuristic)	no

Also known as: epimerase deficiency galactosemia · galactose epimerase deficiency · galactosemia type 3 · GALE deficiency · GALE-D · UDP-galactose-4-epimerase deficiency · uridine diphosphate galactose-4-epimerase deficiency

Data availability: 368 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › galactosemia › galactose epimerase deficiency

Related subtypes (3): galactokinase deficiency, classic galactosemia, galactosemia 4

Subtypes (2): erythrocyte galactose epimerase deficiency, generalized galactose epimerase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

368 retrieved; paginated sample, class counts are floors:

207 likely benign, 72 uncertain significance, 23 likely pathogenic, 22 conflicting classifications of pathogenicity, 22 pathogenic, 11 pathogenic/likely pathogenic, 5 benign, 4 benign/likely benign, 2 conflicting classifications of pathogenicity; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029823	NM_001008216.2(GALE):c.449C>T (p.Thr150Met)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2019974	NM_001008216.2(GALE):c.563_564del (p.Pro188fs)	GALE	Pathogenic	criteria provided, single submitter
2059872	NM_001008216.2(GALE):c.933del (p.Ser312fs)	GALE	Pathogenic	criteria provided, single submitter
21171	NM_001008216.2(GALE):c.505C>T (p.Arg169Trp)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21172	NM_001008216.2(GALE):c.715C>T (p.Arg239Trp)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2693656	NM_001008216.2(GALE):c.534G>A (p.Trp178Ter)	GALE	Pathogenic	criteria provided, single submitter
2696158	NM_001008216.2(GALE):c.634_635del (p.Val212fs)	GALE	Pathogenic	criteria provided, single submitter
2749215	NM_001008216.2(GALE):c.700del (p.Asp234fs)	GALE	Pathogenic	criteria provided, single submitter
2801209	NM_001008216.2(GALE):c.689_690del (p.Asp229_Tyr230insTer)	GALE	Pathogenic	criteria provided, single submitter
281922	NM_001008216.2(GALE):c.796-1G>T	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2822494	NM_001008216.2(GALE):c.196dup (p.Asp66fs)	GALE	Pathogenic	criteria provided, single submitter
2837803	NM_001008216.2(GALE):c.517del (p.Gln173fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2843503	NM_001008216.2(GALE):c.152_155del (p.Arg51fs)	GALE	Pathogenic	criteria provided, single submitter
2866226	NM_001008216.2(GALE):c.1A>G (p.Met1Val)	GALE	Pathogenic	criteria provided, single submitter
2873958	NM_001008216.2(GALE):c.773dup (p.Lys259fs)	GALE	Pathogenic	criteria provided, single submitter
2876476	NM_001008216.2(GALE):c.151_154del (p.Arg51fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2993130	NM_001008216.2(GALE):c.695_696del (p.Thr232fs)	GALE	Pathogenic	criteria provided, single submitter
2999805	NM_001008216.2(GALE):c.815del (p.Gly272fs)	GALE	Pathogenic	criteria provided, single submitter
3002671	NM_001008216.2(GALE):c.3G>A (p.Met1Ile)	GALE	Pathogenic	criteria provided, single submitter
3009976	NM_001008216.2(GALE):c.655C>T (p.Arg219Ter)	GALE	Pathogenic	criteria provided, single submitter
3012577	NM_001008216.2(GALE):c.2T>C (p.Met1Thr)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3247673	NC_000001.10:g.(?24125085)(24151905_?)del	GALE	Pathogenic	criteria provided, single submitter
3247677	NC_000001.10:g.(?24122439)(24144093_?)del	GALE	Pathogenic	criteria provided, single submitter
3384691	NM_001008216.2(GALE):c.264del (p.Phe88fs)	GALE	Pathogenic	criteria provided, single submitter
3582025	NM_001008216.2(GALE):c.315_316del (p.Tyr105_Arg106delinsTer)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582055	NM_001008216.2(GALE):c.142_143del (p.Ser48fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3646597	NM_001008216.2(GALE):c.370del (p.Gly123_Val124insTer)	GALE	Pathogenic	criteria provided, single submitter
3677	NM_001008216.2(GALE):c.269G>A (p.Gly90Glu)	GALE	Pathogenic	no assertion criteria provided
3680	NM_001008216.2(GALE):c.937C>A (p.Leu313Met)	GALE	Pathogenic	no assertion criteria provided
3682	NM_001008216.2(GALE):c.280G>A (p.Val94Met)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GALE	Definitive	Autosomal recessive	galactose epimerase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GALE	Orphanet:308473	Erythrocyte galactose epimerase deficiency
GALE	Orphanet:308487	Generalized galactose epimerase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GALE	HGNC:4116	ENSG00000117308	Q14376	UDP-glucose 4-epimerase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GALE	UDP-glucose 4-epimerase	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GALE	Enzyme (other)	yes	5.1.3.2	UDP_G4E, NAD(P)-bd_dom, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	1
mucosa of transverse colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GALE	248	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GALE	2,133

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALE	Q14376	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective GALE causes EDG	1	11420.0×	2e-04	GALE
Galactose catabolism	1	1631.4×	6e-04	GALE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	3370.4×	4e-04	GALE
galactose catabolic process	1	2808.7×	4e-04	GALE

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GALE	HALOPROGIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GALE	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
HALOPROGIN	4	GALE
DIETHYLSTILBESTROL	4	GALE
ETHACRYNIC ACID	4	GALE
EBSELEN	3	GALE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GALE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALE	5.1.3.2, 5.1.3.7	UDP-glucose 4-epimerase, UDP-N-acetylglucosamine 4-epimerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
HALOPROGIN	4	GALE
DIETHYLSTILBESTROL	4	GALE
ETHACRYNIC ACID	4	GALE
EBSELEN	3	GALE

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GALE
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.