ADI1
protein-codingacireductone dioxygenase 1
Gene summary
This gene encodes an enzyme that belongs to the aci-reductone dioxygenase family of metal-binding enzymes, which are involved in methionine salvage. This enzyme may regulate mRNA processing in the nucleus, and may carry out different functions depending on its localization. Related pseudogenes have been defined on chromosomes 8 and 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.2 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 ADI1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018269.4. 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 | 1 | ||||
| missense | 28 | 3 | 31 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 29 | 3 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060739.2 | 4 | MANE Select | |
| Ensembl | ENSP00000333666.3 | 4 | MANE Select | |
| RefSeq | NP_001293006.1 | 4 | Standard | |
| Ensembl | ENSP00000371525.5 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cysteine and methionine metabolism - Homo sapiens (human)
- Methionine De Novo and Salvage Pathway
- Metabolism of polyamines
- Metabolism of amino acids and derivatives
- Methionine salvage pathway
Biological Process
- methionine metabolic process
- L-methionine salvage from methylthioadenosine
- oxidation-reduction process
Molecular Function
- iron ion binding
- protein binding
- acireductone dioxygenase [iron(II)-requiring] activity
- oxidoreductase activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000327435
- Coding exons
- 4
- Length
- 22376
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125747
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.199 | 99 | 105 | 0.945 | 0.00000682 | 1175 |
| Missense (PolyPhen) | 41 | 45.456 | 0.90197 | 491 | ||
| Synonymous | 0.897 | 36 | 43.5 | 0.827 | 0.00000325 | 318 |
| Loss of Function | 0.147 | 7 | 7.43 | 0.942 | 4.00e-7 | 96 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of formate and 2-keto-4- methylthiobutyrate (KMTB) from 1,2-dihydroxy-3-keto-5- methylthiopentene (DHK-MTPene). Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line. {ECO:0000255|HAMAP- Rule:MF_03154, ECO:0000269|PubMed:11602742, ECO:0000269|PubMed:15938715}.;
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- LoFtool
- 0.293
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |