ALDOA

aldolase, fructose-bisphosphate A, the group of Aldolases

Basic information

Region (hg38): 16:30064163-30070457

Links

ENSG00000149925 ∙ NCBI:226 ∙ OMIM:103850 ∙ HGNC:414 ∙ Uniprot:P04075 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to aldolase A deficiency (Definitive), mode of inheritance: AR
• glycogen storage disease due to aldolase A deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to aldolase A deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to aldolase A deficiency (Supportive), mode of inheritance: AR
• glycogen storage disease due to aldolase A deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease XII	AR	Biochemical; Hematologic; Renal	Individuals can have rhabdomyolysis from stressors such as febrile illness, and appropriate precautions and management may be beneficial; Aldolase A deficiency is also asociated with hereditary hemolytic anemia, and transfusions and splenectomy have been described in treatment	Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal	4788792; 7331996; 3688035; 2825199; 8598869; 14615364

ClinVar

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

• HNSHA due to aldolase A deficiency (185 variants)
• not provided (39 variants)
• not specified (26 variants)
• Inborn genetic diseases (11 variants)
• ALDOA-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDOA 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			3	48		51
missense		2	93	1		96
nonsense						0
start loss						0
frameshift			2			2
inframe indel			3			3
splice donor/acceptor (+/-2bp)			1			1
splice region			5	6		11
non coding			8	35	8	51
Total	0	2	110	84	8

Variants in ALDOA

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

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

Position	Type	Phenotype	Significance	ClinVar
16-30064419-C-T		not specified	Likely benign (Jul 26, 2016)
16-30064439-T-G		not specified	Likely benign (Aug 25, 2016)
16-30064516-A-C			Likely benign (Apr 13, 2020)
16-30064516-A-AG		not specified	Likely benign (Jan 02, 2018)
16-30066927-C-T		ALDOA-related disorder	Likely benign (Sep 17, 2019)
16-30066961-T-C		ALDOA-related disorder	Uncertain significance (Oct 05, 2023)
16-30066996-C-G		See cases	Uncertain significance (Jun 19, 2019)
16-30067126-G-A			Likely benign (Aug 15, 2018)
16-30067171-G-C		HNSHA due to aldolase A deficiency	Benign (Feb 01, 2024)
16-30067266-A-G		HNSHA due to aldolase A deficiency	Uncertain significance (Mar 18, 2020)
16-30067273-G-A		HNSHA due to aldolase A deficiency	Uncertain significance (Apr 25, 2022)
16-30067276-C-T		HNSHA due to aldolase A deficiency	Likely benign (Dec 01, 2023)
16-30067281-C-T		HNSHA due to aldolase A deficiency	Likely benign (Apr 14, 2023)
16-30067284-G-A		not specified	Likely benign (May 19, 2016)
16-30067294-A-G			Uncertain significance (Sep 26, 2022)
16-30067309-A-G		HNSHA due to aldolase A deficiency	Uncertain significance (Aug 14, 2021)
16-30067311-C-T		HNSHA due to aldolase A deficiency	Uncertain significance (Jun 14, 2016)
16-30067312-G-A		HNSHA due to aldolase A deficiency	Uncertain significance (Mar 18, 2022)
16-30067315-C-T		HNSHA due to aldolase A deficiency • Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
16-30067317-C-T		not specified	Likely benign (Aug 10, 2016)
16-30067318-C-T		HNSHA due to aldolase A deficiency	Uncertain significance (Aug 22, 2022)
16-30067319-G-A		Inborn genetic diseases	Uncertain significance (May 17, 2023)
16-30067331-C-T		HNSHA due to aldolase A deficiency	Uncertain significance (Dec 24, 2021)
16-30067365-T-G		HNSHA due to aldolase A deficiency	Uncertain significance (Jun 15, 2021)
16-30067370-C-T		HNSHA due to aldolase A deficiency • ALDOA-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDOA	protein_coding	protein_coding	ENST00000395248	9	17368

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00132	0.992	125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.259	235	246	0.954	0.0000161	2705
Missense in Polyphen		36	61.135	0.58886		817
Synonymous	-2.52	136	103	1.32	0.00000707	861
Loss of Function	2.36	8	19.1	0.418	0.00000101	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein (By similarity). {ECO:0000250}.
• Disease: DISEASE: Glycogen storage disease 12 (GSD12) [MIM:611881]: A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis. {ECO:0000269|PubMed:14615364, ECO:0000269|PubMed:14766013, ECO:0000269|PubMed:2229018, ECO:0000269|PubMed:2825199, ECO:0000269|PubMed:8598869}. 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);HIF-1 signaling pathway - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Pentose Phosphate Pathway;Fructose intolerance, hereditary;Glycolysis;Glycogenosis, Type VII. Tarui disease;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Fanconi-bickel syndrome;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Transaldolase deficiency;Fructose and Mannose Degradation;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Fructosuria;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neutrophil degranulation;downregulated of mta-3 in er-negative breast tumors;Metabolism of carbohydrates;Fructose Mannose metabolism;Glycolysis Gluconeogenesis;Innate Immune System;Immune System;Metabolism;Pentose phosphate cycle;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Glycolysis;EGFR1;Hemostasis;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Gluconeogenesis;Glucose metabolism;sucrose degradation;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.571

Intolerance Scores

• loftool: 0.0383
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.59

Haploinsufficiency Scores

• pHI: 0.303
• hipred: Y
• hipred_score: 0.630
• ghis: 0.580

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldoa

Zebrafish Information Network

• Gene name: aldoaa
• Affected structure: pigment cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: platelet degranulation;fructose metabolic process;gluconeogenesis;glycolytic process;ATP biosynthetic process;striated muscle contraction;actin filament organization;binding of sperm to zona pellucida;regulation of cell shape;fructose 1,6-bisphosphate metabolic process;neutrophil degranulation;muscle cell cellular homeostasis;protein homotetramerization;canonical glycolysis
• Cellular component: extracellular region;extracellular space;nucleus;cytosol;actin cytoskeleton;membrane;integral component of membrane;platelet alpha granule lumen;M band;I band;secretory granule lumen;sperm head;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: RNA binding;actin binding;fructose-bisphosphate aldolase activity;protein binding;cytoskeletal protein binding;tubulin binding;identical protein binding;cadherin binding;fructose binding