AFG1L
protein-codingAFG1 like ATPase
Gene summary
This gene encodes a mitochondrial integral membrane protein that plays a role in mitochondrial protein homeostasis. The protein contains a P-loop motif and a five-domain structure that is conserved in fly, yeast, and bacteria. It functions to mediate the degradation of nuclear-encoded complex IV subunits. Two conserved estrogen receptor binding sites are located within 2.5 kb of this gene. Polymorphisms in this gene have been associated with bipolar disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]
- LACE1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~231.8 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 AFG1L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145315.5. 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 | 2 | 2 | ||||
| missense | 76 | 1 | 77 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 79 | 1 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_660358.2 | 13 | MANE Select | |
| Ensembl | ENSP00000357973.3 | 13 | MANE Select | |
| RefSeq | NP_001309934.1 | 12 | Standard | |
| Ensembl | ENSP00000398225.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| afg1lb | Danio rerio | Structure: ventricular system Quality: hydrocephalic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mitochondrial electron transport, cytochrome c to oxygen
- mitochondrion organization
- mitochondrial protein catabolic process
Molecular Function
- protein binding
- ATP binding
- ATPase activity
Cellular Component
- cytoplasm
- mitochondrion
- mitochondrial membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368977
- Coding exons
- 13
- Length
- 231902
- Individuals with no LoFs
- 125569
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 179
- Defined
- 125748
- p
- 0.000712
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.805 | 228 | 265 | 0.861 | 0.0000140 | 3145 |
| Missense (PolyPhen) | 66 | 77.44 | 0.85228 | 898 | ||
| Synonymous | -1.35 | 117 | 99.9 | 1.17 | 0.00000565 | 899 |
| Loss of Function | 1.70 | 17 | 26.4 | 0.643 | 0.00000136 | 332 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0051 | 0.0051 | notable |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative mitochondrial ATPase. Plays a role in mitochondrial morphology and mitochondrial protein metabolism. Promotes degradation of excess nuclear-encoded complex IV subunits (COX4I1, COX5A and COX6A1) and normal activity of complexes III and IV of the respiratory chain (PubMed:26759378, PubMed:27323408). Mediates mitochondrial translocation of TP53 and its transcription-independent apoptosis in response to genotoxic stress (PubMed:27323408). {ECO:0000269|PubMed:26759378, ECO:0000269|PubMed:27323408}.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.96
Essentials
- Essential (gene trap)
- N