ALDH7A1
aldehyde dehydrogenase 7 family member A1, the group of Aldehyde dehydrogenases
Basic information
Region (hg38): 5:126531199-126595362
Previous symbols: [ "ATQ1" ]
Links
Phenotypes
GenCC
Source:
- pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (Definitive), mode of inheritance: AR
- pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (Strong), mode of inheritance: AR
- pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (Definitive), mode of inheritance: AD
- pyridoxine-dependent epilepsy (Definitive), mode of inheritance: AR
- pyridoxine-dependent epilepsy (Supportive), mode of inheritance: AR
- pyridoxine-dependent epilepsy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Epilepsy, early-onset, 4, vitamin B6-dependent | AR | Neurologic | Individuals frequently present in the neonatal period with seizures (neonatal lactic acidosis and hypoglycemia have also been described), and the seizures, though otherwise refractory to other anti-epileptics, can typically be controlled via medical management (daily pyridoxine monotherapy), though the condition may still impact longer-term developmental manifestations | Neurologic | 13133562; 14131641; 3977296; 16159904; 16075246; 16491085; 17068770; 17721876; 21704546; 20301659; 22529283; 22728861; 22804844; 23054014; 28331464 |
ClinVar
This is a list of variants' phenotypes submitted to
- Pyridoxine-dependent epilepsy (759 variants)
- not provided (241 variants)
- Inborn genetic diseases (84 variants)
- not specified (74 variants)
- Seizure (3 variants)
- Neonatal epileptic spasm (2 variants)
- See cases (2 variants)
- Ventriculomegaly;Seizure (2 variants)
- Intellectual disability (2 variants)
- ALDH7A1-related condition (2 variants)
- Developmental and epileptic encephalopathy, 1 (2 variants)
- Abnormal brain morphology (1 variants)
- Leukoencephalopathy (1 variants)
- Developmental and epileptic encephalopathy, 13 (1 variants)
- Abnormality of the nervous system (1 variants)
- Intractable seizure (1 variants)
- neonatal seizures (1 variants)
- Pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH7A1 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 | 115 | 129 | ||||
| missense | 25 | 23 | 229 | 284 | ||
| nonsense | 16 | 24 | ||||
| start loss | 2 | |||||
| frameshift | 16 | 24 | ||||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 12 | 15 | 27 | |||
| splice region ? | 3 | 2 | 21 | 38 | 64 | |
| non coding ? | 64 | 134 | 76 | 274 | ||
| Total | 71 | 51 | 312 | 255 | 79 |
Highest pathogenic variant AF is 0.0000986
Variants in ALDH7A1
This is a list of pathogenic ClinVar variants found in the ALDH7A1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-126541841-T-C | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126541884-G-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126541943-A-G | Pyridoxine-dependent epilepsy | Benign (Jan 13, 2018) | ||
| 5-126541967-G-GA | Pyridoxine-dependent epilepsy | Benign (Jun 14, 2016) | ||
| 5-126541967-G-GAA | Pyridoxine-dependent epilepsy | Uncertain significance (Jun 14, 2016) | ||
| 5-126541998-A-G | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542051-T-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 13, 2018) | ||
| 5-126542144-T-TA | Pyridoxine-dependent epilepsy | Uncertain significance (Jun 14, 2016) | ||
| 5-126542147-A-G | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 13, 2018) | ||
| 5-126542184-G-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542265-T-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 13, 2018) | ||
| 5-126542362-C-T | Pyridoxine-dependent epilepsy | Likely benign (Jan 12, 2018) | ||
| 5-126542381-G-T | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542390-A-G | Pyridoxine-dependent epilepsy | Benign (Jan 12, 2018) | ||
| 5-126542395-G-GGC | Pyridoxine-dependent epilepsy | Uncertain significance (Jun 14, 2016) | ||
| 5-126542401-C-T | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 13, 2018) | ||
| 5-126542416-C-G | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 13, 2018) | ||
| 5-126542453-C-T | Pyridoxine-dependent epilepsy | Benign (Jan 13, 2018) | ||
| 5-126542466-C-T | Pyridoxine-dependent epilepsy | Benign (Jan 13, 2018) | ||
| 5-126542467-G-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542471-A-G | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542473-G-A | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) | ||
| 5-126542500-C-CA | Pyridoxine-dependent epilepsy | Uncertain significance (Jun 14, 2016) | ||
| 5-126542542-G-A | Pyridoxine-dependent epilepsy | Benign (Jan 13, 2018) | ||
| 5-126542556-T-G | Pyridoxine-dependent epilepsy | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ALDH7A1 | protein_coding | protein_coding | ENST00000409134 | 18 | 53578 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.39e-22 | 0.00241 | 125652 | 0 | 96 | 125748 | 0.000382 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.368 | 278 | 296 | 0.940 | 0.0000149 | 3497 |
| Missense in Polyphen | 95 | 119.14 | 0.7974 | 1449 | ||
| Synonymous | -0.185 | 108 | 106 | 1.02 | 0.00000571 | 1051 |
| Loss of Function | 0.369 | 35 | 37.4 | 0.935 | 0.00000216 | 400 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000322 | 0.000322 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000220 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000414 | 0.000413 |
| Middle Eastern | 0.000220 | 0.000217 |
| South Asian | 0.000987 | 0.000980 |
| Other | 0.000502 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735}.;
- Pathway
- Tryptophan metabolism - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Glycerolipid metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);Ascorbate and aldarate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Lysine Degradation;Hyperlysinemia I, Familial;2-aminoadipic 2-oxoadipic aciduria;Betaine Metabolism;Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;sarcosine oncometabolite pathway ;Glutaric Aciduria Type I;Hyperlysinemia II or Saccharopinuria;Amino Acid metabolism;Vitamin B6-dependent and responsive disorders;choline degradation;Lysine catabolism;Glutamate Glutamine metabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Glycolysis and Gluconeogenesis;Leukotriene metabolism;Metabolism;Lysine degradation;Choline catabolism;Propanoate metabolism;superpathway of choline degradation to L-serine;Histidine metabolism;Lysine metabolism;Tryptophan metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Valine, leucine and isoleucine degradation;Butanoate metabolism;Propanoate metabolism;Bile acid biosynthesis;Glycerophospholipid metabolism;lysine degradation II (pipecolate pathway);Arginine Proline metabolism;Pyruvate metabolism;lysine degradation I (saccharopine pathway);Tryptophan degradation;Valine Leucine Isoleucine degradation;Histidine degradation
(Consensus)
Recessive Scores
- pRec
- 0.378
Intolerance Scores
- loftool
- 0.398
- rvis_EVS
- -0.47
- rvis_percentile_EVS
- 23.43
Haploinsufficiency Scores
- pHI
- 0.465
- hipred
- N
- hipred_score
- 0.352
- ghis
- 0.557
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.687
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Aldh7a1
- Phenotype
- normal phenotype;
Zebrafish Information Network
- Gene name
- aldh7a1
- Affected structure
- pharyngeal arch cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- cellular aldehyde metabolic process;lysine catabolic process;sensory perception of sound;glycine betaine biosynthetic process from choline;choline catabolic process;oxidation-reduction process
- Cellular component
- nucleus;mitochondrion;mitochondrial matrix;cytosol;extracellular exosome
- Molecular function
- aldehyde dehydrogenase (NAD) activity;L-aminoadipate-semialdehyde dehydrogenase activity;protein binding;betaine-aldehyde dehydrogenase activity;glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity