GeneBe

ALDOB

protein-coding

aldolase, fructose-bisphosphate B, the group of Aldolases

Gene summary

Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a tetrameric glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Vertebrates have 3 aldolase isozymes which are distinguished by their electrophoretic and catalytic properties. Differences indicate that aldolases A, B, and C are distinct proteins, the products of a family of related 'housekeeping' genes exhibiting developmentally regulated expression of the different isozymes. The developing embryo produces aldolase A, which is produced in even greater amounts in adult muscle where it can be as much as 5% of total cellular protein. In adult liver, kidney and intestine, aldolase A expression is repressed and aldolase B is produced. In brain and other nervous tissue, aldolase A and C are expressed about equally. There is a high degree of homology between aldolase A and C. Defects in ALDOB cause hereditary fructose intolerance. [provided by RefSeq, Dec 2008]

MANE transcript

NM_000035.4

Inheritance

AR

ClinVar variants

P:145U:142B:172

Top phenotype

Fructose intolerance, hereditary

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr9:101,420,560-101,449,664

External References & Databases

Ensembl (ENSG00000136872)NCBI Gene (229)OMIM (612724)HGNC:417GenCCUniProt (P05062)AlphaFoldClinVar (ALDOB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~29.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary fructose intoleranceDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Ambry Genetics

hereditary fructose intoleranceSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Genomics England PanelApp

hereditary fructose intoleranceDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: ClinGen

*ALDOB* was first reported in relation to autosomal recessive hereditary fructose intolerance in 1988 (Cross et al., PMID: 3383242). Thirteen variants (missense, in-frame indel, nonsense, frameshift, splice), that have been reported in twelve probands in five publications (PMIDs: 3383242, 8071980, 1967768, 18541450, 25595217) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by a knockout mouse model (PMID: 25637246). In summary, there is definitive evidence supporting the relationship between *ALDOB* and autosomal recessive hereditary fructose intolerance. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. UNC and Myriad Women’s Health biocurators contributed to this curation. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date September 4, 2025 (SOP Version 11).

hereditary fructose intoleranceDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Natera

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

hereditary fructose intoleranceSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Orphanet

hereditary fructose intoleranceSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Labcorp Genetics (formerly Invitae)

hereditary fructose intoleranceSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: PanelApp Australia

hereditary fructose intoleranceDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009249

Submitter: Myriad Women's Health

Clinical Genomic Database (CGD)

Fructose intolerance, hereditaryAR

Manifestation: Biochemical; Gastrointestinal; Neurologic; Renal

Intervention: Biochemical; Gastrointestinal

Rationale: Clinical manifestations, which can be severe/fatal, occur with the dietary introduction of fructose or sucrose, and dietary measures (fructose restriction) can be effective

Refs: 13358219; 14060577; 13942402; 13959929; 4166890; 5637008; 4212946; 213970; 491970; 6888454; 3383242; 2916618; 2349937; 1967768 ; 2314976; 2122082; 8535439; 9610797; 18541450; 20848650; 20882353; 22375183Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALDOB variants in ClinVar

8 Conditions Cataloged
Hereditary fructosuriaTotal: 482
not providedTotal: 73
ALDOB-related disorderTotal: 67
Inborn genetic diseasesTotal: 64
not specifiedTotal: 29
Glycogen storage diseaseTotal: 3
See casesTotal: 3
Inborn errors of metabolismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000035.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
8
clinvar
165
clinvar
 174
missense
4
clinvar
17
clinvar
131
clinvar
7
clinvar
 159
nonsense
16
clinvar
19
clinvar
1
clinvar
 36
start loss
4
clinvar
 4
frameshift
16
clinvar
32
clinvar
 48
splice donor/acceptor (+/-2bp)
8
clinvar
28
clinvar
2
clinvar
 38
Total441011421720459

Highest pathogenic variant AF is 0.004390486

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000035.4RefSeqNP_000026.28MANE Select
ENST00000647789.2EnsemblENSP00000497767.18MANE Select
ENST00000648064.1EnsemblENSP00000497990.18Standard
ENST00000648423.1EnsemblENSP00000497985.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glycolysis / Gluconeogenesis - Homo sapiens (human)
  • Fructose and mannose metabolism - Homo sapiens (human)
  • Pentose phosphate pathway - Homo sapiens (human)
  • Warburg Effect
  • Fructose intolerance, hereditary

Biological Process

  • fructose metabolic process
  • gluconeogenesis
  • glycolytic process
  • NADH oxidation
  • fructose 1,6-bisphosphate metabolic process

Molecular Function

  • fructose-bisphosphate aldolase activity
  • protein binding
  • cytoskeletal protein binding
  • identical protein binding
  • ATPase binding

Cellular Component

  • microtubule organizing center
  • cytosol
  • centriolar satellite
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000374855
Coding exons
8
Length
15246
Individuals with no LoFs
125680
Homozygous LoFs
0
Heterozygous LoFs
68
Defined
125748
p
0.000270
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.422551991.280.00001192368
Missense (PolyPhen)12591.6451.3641024
Synonymous-1.689475.51.250.00000442733
Loss of Function1.251217.70.6799.59e-7202

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000260.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000430.00044rare
Finnish0.000320.00032rare
European (Non-Finnish)0.000270.00027rare
South Asian0.000230.00023rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease
DISEASE: Hereditary fructose intolerance (HFI) [MIM:229600]: Autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life. {ECO:0000269|PubMed:10024431, ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:15532022, ECO:0000269|PubMed:15880727, ECO:0000269|PubMed:1967768, ECO:0000269|PubMed:20848650, ECO:0000269|PubMed:2336380, ECO:0000269|PubMed:3383242, ECO:0000269|PubMed:8162030, ECO:0000269|PubMed:8299883}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.728

Intolerance Scores

LoFtool
0.133
RVIS EVS
0.06
RVIS percentile EVS
58.74

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.800

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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