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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GALM
galactose mutarotase
Chromosome 2 · 2p22.1
NCBI Gene: 130589Ensembl: ENSG00000143891.18HGNC: HGNC:24063UniProt: A0A384MDW6
26PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein homodimerization activitycarbohydrate metabolic processgalactose catabolic process via UDP-galactose, Leloir pathwayaldose 1-epimerase activitygalactosemia 4Abnormality of the skeletal systemalcohol drinkingskin disease
✦AI Summary

GALM (galactose mutarotase) catalyzes the interconversion of β-D-galactose and α-D-galactose during galactose metabolism 1. As the first enzyme in the Leloir pathway, GALM maintains equilibrium between galactose anomers, ensuring sufficient α-anomer substrate for GALK1, the next pathway enzyme 1. The enzyme uses a catalytic mechanism involving histidine and glutamate residues that open the pyranose ring structure, enabling anomeric interconversion 2. GALM shows substrate preference for galactose over glucose 1. Biallelic GALM pathogenic variants cause Type IV galactosemia, characterized by elevated blood galactose levels and early-onset bilateral cataracts 3. Missense mutations (R78S, R82G, A163E, P210S, Y281C, E307G, F339C) impair enzyme function through reduced substrate binding, increased protein rigidity, and altered protein stability 4. Beyond galactosemia, emerging evidence suggests GALM participates in Alzheimer's disease pathology: GALM overexpression reduces amyloid-β deposition by increasing ADAM10 maturation and ameliorates cognitive deficits in AD model mice 5. Current treatment for GALM deficiency relies on galactose dietary restriction; however, β-galactosidase supplementation shows promise in mitigating blood galactose elevation after lactose exposure 6.

Sources cited
1
GALM catalyzes β-D-galactose to α-D-galactose interconversion and maintains anomeric equilibrium for GALK1 substrate availability; shows galactose preference over glucose
PMID: 12753898
2
Biallelic GALM variants cause Type IV galactosemia with elevated blood galactose and cataracts; GALM is first enzyme in Leloir pathway
PMID: 30451973
3
GALM structural mechanism uses histidine and glutamate residues to open pyranose ring enabling anomeric interconversion; monomeric structure composed largely of β-sheets
PMID: 33181226
4
Missense GALM mutations impair function through altered substrate binding, increased protein rigidity, and affected phosphorylation sites
PMID: 36591702
5
GALM overexpression reduces amyloid-β deposition by increasing ADAM10 maturation and ameliorates hippocampal LTP and spatial memory in AD model mice
PMID: 40128515
6
GALM deficiency treated with galactose restriction; β-galactosidase supplementation significantly mitigates blood galactose elevation after lactose loading
PMID: 34611916
Disease Associationsⓘ21
galactosemia 4Open Targets
0.78Strong
Abnormality of the skeletal systemOpen Targets
0.41Moderate
alcohol drinkingOpen Targets
0.32Weak
skin diseaseOpen Targets
0.32Weak
nerve plexus diseaseOpen Targets
0.31Weak
Alzheimer diseaseOpen Targets
0.31Weak
nutritional deficiency diseaseOpen Targets
0.27Weak
Genu valgumOpen Targets
0.27Weak
Genu varumOpen Targets
0.26Weak
sialolithiasisOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
schizophreniaOpen Targets
0.11Weak
gliomaOpen Targets
0.07Suggestive
smoking initiationOpen Targets
0.05Suggestive
galactosemiaOpen Targets
0.03Suggestive
Barrett's esophagusOpen Targets
0.03Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.03Suggestive
liver diseaseOpen Targets
0.02Suggestive
lung carcinomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Galactosemia 4UniProt
Pathogenic Variants5
NM_138801.3(GALM):c.244C>T (p.Arg82Ter)Pathogenic
Galactosemia 4|not provided
★☆☆☆2023→ Residue 82
NM_138801.3(GALM):c.577G>T (p.Glu193Ter)Pathogenic
not provided
★☆☆☆2023→ Residue 193
NM_138801.3(GALM):c.195C>A (p.Tyr65Ter)Pathogenic
not provided
★☆☆☆2022→ Residue 65
NM_138801.3(GALM):c.294del (p.Ile99fs)Pathogenic
Galactosemia 4
☆☆☆☆2020→ Residue 99
NM_138801.3(GALM):c.932G>A (p.Trp311Ter)Pathogenic
Galactosemia 4
☆☆☆☆2020→ Residue 311
View on ClinVar ↗
Related Genes
IL11RAProtein interaction100%AKR1B1Protein interaction92%GLAProtein interaction92%GLB1Protein interaction92%LCTProtein interaction92%AKR1B10Protein interaction92%
Tissue Expression6 tissues
Liver
100%
Heart
35%
Lung
26%
Ovary
23%
Bone Marrow
8%
Brain
4%
Gene Interaction Network
Click a node to explore
GALMIL11RAAKR1B1GLAGLB1LCTAKR1B10
PROTEIN STRUCTURE
Preparing viewer…
PDB1SNZ · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.42LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.07 [0.82–1.42]
RankingsWhere GALM stands among ~20K protein-coding genes
  • #12,796of 20,598
    Most Researched26
  • #3,626of 5,498
    Most Pathogenic Variants5
  • #14,652of 17,882
    Most Constrained (LOEUF)1.42
Genes detectedGALM
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Comprehensive analysis of non-synonymous missense SNPs of human galactose mutarotase (GALM) gene: an integrated computational approach.
PMID: 36591702
J Biomol Struct Dyn · 2023
1.00
2
GALM Alleviates Aβ Pathology and Cognitive Deficit Through Increasing ADAM10 Maturation in a Mouse Model of Alzheimer's Disease.
PMID: 40128515
Neurosci Bull · 2025
0.90
3
The structural and molecular biology of type IV galactosemia.
PMID: 33181226
Biochimie · 2021
0.80
4
Biallelic GALM pathogenic variants cause a novel type of galactosemia.
PMID: 30451973
Genet Med · 2019
0.70
5
Gallium Liquid Metal Nanoparticles as Agents to Treat Multidrug-Resistant Bacterial Infections.
PMID: 41128841
Microbiologyopen · 2025
0.60