ALDOA

Chr 16AR

aldolase, fructose-bisphosphate A

Also known as: ALDA, GSD12, HEL-S-87p

NCBI Gene: 226ENSG00000149925UniProt: P04075

This gene encodes a member of the class I fructose-bisphosphate aldolase protein family. The encoded protein is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Three aldolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Mutations in this gene have been associated with Glycogen Storage Disease XII, an autosomal recessive disorder associated with hemolytic anemia. Disruption of this gene also plays a role in the progression of multiple types of cancers. Related pseudogenes have been identified on chromosomes 3 and 10. [provided by RefSeq, Sep 2017]

Primary Disease Associations & Inheritance

Glycogen storage disease XIIMIM #611881
AR
547
ClinVar variants
230
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALDOA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
230 Pathogenic / Likely Pathogenic· 163 VUS of 547 total submissions

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.
0.76LOEUF
pLI 0.001
Z-score 2.36
OE 0.42 (0.24–0.76)
Tolerant

Typical tolerance to LoF variation

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.
0.26Z-score
OE missense 0.95 (0.86–1.06)
235 obs / 246.4 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.0.42 (0.24–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.06)
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.1.32
0≤1.21.6
LoF obs/exp: 8 / 19.1Missense obs/exp: 235 / 246.4Syn Z: -2.52

ClinVar Variant Classifications

547 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic196
Likely Pathogenic34
VUS163
Likely Benign140
Benign9
Conflicting5
196
Pathogenic
34
Likely Pathogenic
163
VUS
140
Likely Benign
9
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
191
0
196
Likely Pathogenic
3
2
29
0
34
VUS
2
119
41
1
163
Likely Benign
0
2
69
69
140
Benign
0
0
9
0
9
Conflicting
—5
Total812533970547

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

View in ClinVar →

Protein Context — Lollipop Plot

ALDOA · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALDOA-related glycogen storage disease

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycogen storage disease XII

MIM #611881

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma.
Gao Q et al.·Cell
2019
A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE.
Lin J et al.·Cell
2025
Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.
Ma W et al.·Circ Res
2024
The m(6)A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis.
Zhou Y et al.·Cell Death Dis
2024
LIPH contributes to glycolytic phenotype in pancreatic ductal adenocarcinoma by activating LPA/LPAR axis and maintaining ALDOA stability.
Han L et al.·J Transl Med
2023
ANGPTL4 mediated mesothelial-mesenchymal transition in pulmonary fibrosis: a potential therapeutic target.
Xia Y et al.·J Transl Med
2024
Exosomal lncRNA Mir100hg from lung cancer stem cells activates H3K14 lactylation to enhance metastatic activity in non-stem lung cancer cells.
Shi L et al.·J Nanobiotechnology
2025
Compensatory cross-talk between autophagy and glycolysis regulates senescence and stemness in heterogeneous glioblastoma tumor subpopulations.
Martell E et al.·Acta Neuropathol Commun
2023
Comprehensive PTM profiling with SCASP-PTM uncovers mechanisms of p62 degradation and ALDOA-mediated tumor progression.
Lin ZP et al.·Cell Rep
2025Functional
Initial clinical and experimental analyses of ALDOA in gastric cancer, as a novel prognostic biomarker and potential therapeutic target.
Chen L et al.·Clin Exp Med
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools