ALDOA

Chr 16AR

aldolase, fructose-bisphosphate A

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

NCBI Gene: 226 ENSG00000149925 UniProt: P04075 OMIM: 103850

The protein is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate in cellular energy metabolism. Mutations cause Glycogen Storage Disease XII, an autosomal recessive disorder associated with hemolytic anemia. The pathogenic mechanism appears to be dominant negative.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.761 OMIM phenotype

Clinical Summary— ALDOA

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 unique Pathogenic / Likely Pathogenic· 159 VUS of 373 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.001

Z-score 2.36

OE 0.42 (0.24–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.26Z-score

OE missense 0.95 (0.86–1.06)

235 obs / 246.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.24–0.76)

0≤0.351.4

Missense OE?0.95 (0.86–1.06)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 8 / 19.1Missense obs/exp: 235 / 246.4Syn Z: -2.52

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALDOA-related glycogen storage diseaseOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7229th %ile

GOF

0.5759th %ile

LOF

0.2580th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

373 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic7

VUS159

Likely Benign168

Benign13

Conflicting6

Pathogenic

Likely Pathogenic

159

VUS

168

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	2	0	0	6
Likely Pathogenic	4	3	0	0	7
VUS	2	126	30	1	159
Likely Benign	0	2	83	83	168
Benign	0	0	12	1	13
Conflicting	—				6
Total	10	133	125	85	359

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

View in ClinVar →

284 pathogenic / likely-pathogenic (of 304) ClinVar copy-number / structural variants overlap ALDOA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →