AHRR
protein-codingaryl hydrocarbon receptor repressor, the group of Basic helix-loop-helix proteins|PAS domain containing
Gene summary
The protein encoded by this gene participates in the aryl hydrocarbon receptor (AhR) signaling cascade, which mediates dioxin toxicity, and is involved in regulation of cell growth and differentiation. It functions as a feedback modulator by repressing AhR-dependent gene expression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]
- AHH
- AHHR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.6 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 AHRR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001377236.1. 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 | 8 | 1 | 9 | |||
| missense | 132 | 11 | 1 | 144 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 135 | 19 | 2 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001364165.1 | 10 | MANE Select | |
| Ensembl | ENSP00000507476.1 | 10 | MANE Select | |
| RefSeq | NP_001364168.1 | 10 | Standard | |
| Ensembl | ENSP00000323816.6 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ahrrb | Danio rerio | Structure: regulation of transcription from RNA polymerase II promoter in response to stress Quality: disrupted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Aryl Hydrocarbon Receptor
- Aryl Hydrocarbon Receptor Pathway
- Nuclear Receptors Meta-Pathway
- Aryl hydrocarbon receptor signalling
- Phase I - Functionalization of compounds
Biological Process
- negative regulation of transcription by RNA polymerase II
- xenobiotic metabolic process
- response to xenobiotic stimulus
- positive regulation of transcription by RNA polymerase II
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
- protein dimerization activity
Cellular Component
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316418
- Coding exons
- 12
- Length
- 134116
- Individuals with no LoFs
- 124770
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 124797
- p
- 0.000108
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.485 | 427 | 456 | 0.936 | 0.0000295 | 4579 |
| Missense (PolyPhen) | 116 | 141.32 | 0.82081 | 1595 | ||
| Synonymous | -0.500 | 212 | 203 | 1.04 | 0.0000141 | 1509 |
| Loss of Function | 2.46 | 10 | 22.6 | 0.442 | 0.00000113 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000066 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00031 | 0.00030 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.00035 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site. {ECO:0000269|PubMed:17890447, ECO:0000269|PubMed:18172554}.;
Recessive Scores
- pRec
- 0.164
Intolerance Scores
- LoFtool
- 0.621
- RVIS EVS
- 1
- RVIS percentile EVS
- 90.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |