ALDOB

aldolase, fructose-bisphosphate B, the group of Aldolases

Basic information

Region (hg38): 9:101420560-101449664

Links

ENSG00000136872 ∙ NCBI:229 ∙ OMIM:612724 ∙ HGNC:417 ∙ Uniprot:P05062 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary fructose intolerance (Definitive), mode of inheritance: AR
• hereditary fructose intolerance (Strong), mode of inheritance: AR
• hereditary fructose intolerance (Definitive), mode of inheritance: AR
• hereditary fructose intolerance (Strong), mode of inheritance: AR
• hereditary fructose intolerance (Supportive), mode of inheritance: AR
• complex neurodevelopmental disorder (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fructose intolerance, hereditary	AR	Biochemical; Gastrointestinal	Clinical manifestations, which can be severe/fatal, occur with the dietary introduction of fructose or sucrose, and dietary measures (fructose restriction) can be effective	Biochemical; Gastrointestinal; Neurologic; Renal	13358219; 14060577; 13942402; 13959929; 4166890; 5637008; 4212946; 213970; 491970; 6888454; 3383242; 2916618; 2349937; 1967768 ; 2314976; 2122082; 8535439; 9610797; 18541450; 20848650; 20882353; 22375183

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDOB gene.

• Hereditary fructosuria (31 variants)
• not provided (3 variants)
• ALDOB-related disorder (2 variants)
• Inborn genetic diseases (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDOB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				141		141
missense	4	4	73	2	1	84
nonsense	11	19	1			31
start loss		4				4
frameshift	12	15				27
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	4	20				24
splice region		1	3	18	1	23
non coding			15	69	19	103
Total	31	63	91	212	20

Highest pathogenic variant AF is 0.000328

Variants in ALDOB

This is a list of pathogenic ClinVar variants found in the ALDOB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-101420658-T-C		Hereditary fructosuria	Benign (Jan 13, 2018)
9-101420690-G-A		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101420806-T-C		Hereditary fructosuria	Benign (Jan 13, 2018)
9-101420911-A-G		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101420912-C-T		Hereditary fructosuria	Benign (Jan 13, 2018)
9-101420960-A-G		Hereditary fructosuria	Likely benign (Jan 12, 2018)
9-101420990-T-G		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421007-T-C		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421057-G-C		Hereditary fructosuria	Likely benign (Jan 13, 2018)
9-101421080-C-G		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421095-T-C		Hereditary fructosuria	Uncertain significance (Jan 12, 2018)
9-101421126-A-G		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421197-T-C		Hereditary fructosuria	Benign (Jan 12, 2018)
9-101421241-C-T		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421242-G-A		Hereditary fructosuria	Likely benign (Jan 13, 2018)
9-101421257-A-T		Hereditary fructosuria	Benign (Jan 13, 2018)
9-101421293-A-T		Hereditary fructosuria	Likely pathogenic (Mar 18, 2021)
9-101421296-C-T		ALDOB-related disorder	Likely benign (Jun 21, 2022)
9-101421304-G-T		Hereditary fructosuria	Benign (Jan 12, 2018)
9-101421306-A-G		Hereditary fructosuria	Uncertain significance (Jan 12, 2018)
9-101421520-G-C		Hereditary fructosuria	Uncertain significance (Jun 14, 2016)
9-101421523-G-A		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421541-A-G		Hereditary fructosuria	Uncertain significance (Jan 12, 2018)
9-101421600-G-A		Hereditary fructosuria	Uncertain significance (Jan 13, 2018)
9-101421603-G-T		Hereditary fructosuria	Benign (Jun 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDOB	protein_coding	protein_coding	ENST00000374855	8	15246

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.88e-7	0.745	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.42	255	199	1.28	0.0000119	2368
Missense in Polyphen		125	91.645	1.364		1024
Synonymous	-1.68	94	75.5	1.25	0.00000442	733
Loss of Function	1.25	12	17.7	0.679	9.59e-7	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000506	0.000506
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000435	0.000435
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

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.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Fructose and mannose metabolism - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Warburg Effect;Fructose intolerance, hereditary;Fructose and Mannose Degradation;Fructosuria;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Polyol Pathway;Fructose metabolism;Metabolism of carbohydrates;Fructose Mannose metabolism;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;Pentose phosphate cycle;Glycolysis;Fructose and mannose metabolism;Pentose phosphate pathway;Glycerophospholipid metabolism;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Gluconeogenesis;Glucose metabolism;Fructose catabolism;sucrose degradation;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.728

Intolerance Scores

• loftool: 0.133
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.74

Haploinsufficiency Scores

• pHI: 0.248
• hipred: Y
• hipred_score: 0.685
• ghis: 0.474

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.800

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aldob
• Phenotype: hearing/vestibular/ear phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: fructose metabolic process;gluconeogenesis;glycolytic process;NADH oxidation;fructose 1,6-bisphosphate metabolic process;positive regulation of ATPase activity;canonical glycolysis;fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate;vacuolar proton-transporting V-type ATPase complex assembly
• Cellular component: microtubule organizing center;cytosol;centriolar satellite;extracellular exosome
• Molecular function: fructose-bisphosphate aldolase activity;protein binding;cytoskeletal protein binding;identical protein binding;ATPase binding;fructose-1-phosphate aldolase activity;fructose binding