GALK1

Chr 17AR

galactokinase 1

Also known as: GALK, GK1, HEL-S-19

NCBI Gene: 2584ENSG00000108479UniProt: P51570

Galactokinase is a major enzyme for the metabolism of galactose and its deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Galactokinase deficiency with cataractsMIM #230200
AR
UniProtGalactosemia 2
0
Active trials
62
Pathogenic / LP
481
ClinVar variants
2
Pubs (1 yr)
0.6
Missense Z
1.09
LOEUF
Clinical Summary— GALK1
🧬
Gene-Disease Validity (ClinGen)
galactokinase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 188 VUS of 481 total submissions
📖
GeneReview available — GALK1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.09LOEUF
pLI 0.000
Z-score 1.30
OE 0.64 (0.40–1.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.59Z-score
OE missense 0.89 (0.80–1.00)
221 obs / 247.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.40–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.80–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 10 / 15.5Missense obs/exp: 221 / 247.3Syn Z: -0.00

ClinVar Variant Classifications

481 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic32
VUS188
Likely Benign213
Benign4
Conflicting14
30
Pathogenic
32
Likely Pathogenic
188
VUS
213
Likely Benign
4
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
3
10
0
30
Likely Pathogenic
20
1
11
0
32
VUS
1
165
15
7
188
Likely Benign
0
0
78
135
213
Benign
0
0
3
1
4
Conflicting
—14
Total38169117143481

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GALK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GALK1-related galactokinase deficiency with cataracts

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
GALACTOKINASE 1; GALK1
MIM #604313 · *

Galactokinase deficiency with cataracts

MIM #230200

Molecular basis of disorder known

Autosomal recessive

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Reshaping the Treatment Landscape of a Galactose Metabolism Disorder.
Rubio-Gozalbo ME et al.·J Inherit Metab Dis
2025Review
Proteomics Profiling of Bladder Cancer Tissues from Early to Advanced Stages Reveals NNMT and GALK1 as Biomarkers for Early Detection and Prognosis of BCa.
Davalieva K et al.·Int J Mol Sci
2023
Identifying novel risk targets in inflammatory skin diseases by comprehensive proteome-wide Mendelian randomization study.
Li Y et al.·Postgrad Med J
2025
A Novel Homozygous GALK1 Variant Combined With Cataract and Prolonged Jaundice.
Ozler O et al.·Clin Pediatr (Phila)
2023
HEK293T cell lines defective for O-linked glycosylation.
Termini JM et al.·PLoS One
2017
Galactokinase deficiency: lessons from the GalNet registry.
Rubio-Gozalbo ME et al.·Genet Med
2021
Biallelic GALM pathogenic variants cause a novel type of galactosemia.
Wada Y et al.·Genet Med
2019
A novel c.-22T>C mutation in GALK1 promoter is associated with elevated galactokinase phenotype.
Park HD et al.·BMC Med Genet
2009
Novel mutations in the GALK1 gene in patients with galactokinase deficiency.
Hunter M et al.·Hum Mutat
2001Cohort
The molecular basis of galactosemia - Past, present and future.
Timson DJ·Gene
2016Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Isobaric Tags for Relative and Absolute Quantification-Based Proteomics Reveals Candidate Proteins of Fat Deposition in Chinese Indigenous Sheep With Morphologically Different Tails
Zhu C et al.·Front Genet
2021
Identification and prognostic value of a glycolysis-related gene signature in patients with bladder cancer
Wu Z et al.·Medicine (Baltimore)
2021Cohort
A metabolic reprogramming-related gene signature correlates with prognosis and proliferation of BLCA
Wu Y et al.·Discov Oncol
2024
Current and Future Treatments for Classic Galactosemia
Delnoy B et al.·J Pers Med
2021
Galactokinase deficiency: a treatable cause of bilateral cataracts.
Cordeiro C et al.·BMJ Case Rep
2021
Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.
Liu L et al.·J Med Chem
2021
The Discovery of GALM Deficiency (Type IV Galactosemia) and Newborn Screening System for Galactosemia in Japan
Kikuchi A et al.·Int J Neonatal Screen
2021
Top 7 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients