ALDH1L1
protein-codingaldehyde dehydrogenase 1 family member L1, the group of Aldehyde dehydrogenases
Gene summary
The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
- FTHFD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~94.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALDH1L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012190.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 4 | 9 | ||
| missense | 108 | 2 | 4 | 114 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 111 | 6 | 8 | 125 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036322.2 | 22 | MANE Select | |
| Ensembl | ENSP00000377083.3 | 22 | MANE Select | |
| RefSeq | NP_001257293.1 | 23 | Standard | |
| RefSeq | NP_001257294.1 | 20 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aldh1l1 | Danio rerio | Structure: blood cell Quality: accumulation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- One carbon pool by folate - Homo sapiens (human)
- Folate malabsorption, hereditary
- Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
- Methotrexate Action Pathway
- Folate Metabolism
Biological Process
- one-carbon metabolic process
- biosynthetic process
- 10-formyltetrahydrofolate catabolic process
- folic acid metabolic process
- oxidation-reduction process
Molecular Function
- catalytic activity
- aldehyde dehydrogenase (NAD) activity
- formyltetrahydrofolate dehydrogenase activity
- hydroxymethyl-, formyl- and related transferase activity
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000273450
- Coding exons
- 23
- Length
- 94426
- Individuals with no LoFs
- 125530
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 214
- Defined
- 125748
- p
- 0.000867
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.605 | 512 | 552 | 0.928 | 0.0000332 | 5937 |
| Missense (PolyPhen) | 228 | 247.55 | 0.92102 | 2559 | ||
| Synonymous | -0.290 | 241 | 235 | 1.02 | 0.0000161 | 1811 |
| Loss of Function | 2.76 | 25 | 45.0 | 0.556 | 0.00000226 | 524 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.0014 | 0.0014 | notable |
| Finnish | 0.0054 | 0.0049 | notable |
| European (Non-Finnish) | 0.00049 | 0.00047 | rare |
| South Asian | 0.00034 | 0.00033 | rare |
| Other | 0.00052 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.199
Intolerance Scores
- LoFtool
- 0.690
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 40.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |