GCHFR
protein-codingGTP cyclohydrolase I feedback regulator
Gene summary
GTP cyclohydrolase I feedback regulatory protein binds to and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. The regulatory protein, GCHFR, consists of a homodimer. It is postulated that GCHFR may play a role in regulating phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.6 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 GCHFR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005258.3. 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 | 0 | |||||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 12 | 0 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005249.1 | 3 | MANE Select | |
| Ensembl | ENSP00000260447.4 | 3 | MANE Select | |
| Ensembl | ENSP00000453640.1 | 2 | Standard | |
| Ensembl | ENSP00000453640.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sepiapterin reductase deficiency
- Segawa syndrome
- Pterine Biosynthesis
- Dopa-responsive dystonia
- Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
Biological Process
- nitric oxide biosynthetic process
- negative regulation of biosynthetic process
- neurotransmitter metabolic process
- negative regulation of GTP cyclohydrolase I activity
- cofactor metabolic process
Molecular Function
- enzyme inhibitor activity
- protein binding
- amino acid binding
- GTP-dependent protein binding
- GTP cyclohydrolase binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260447
- Coding exons
- 3
- Length
- 3689
- Individuals with no LoFs
- 124102
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124104
- p
- 0.00000806
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.331 | 42 | 48.5 | 0.866 | 0.00000305 | 534 |
| Missense (PolyPhen) | 16 | 22.194 | 0.72092 | 258 | ||
| Synonymous | -0.808 | 25 | 20.4 | 1.23 | 0.00000134 | 167 |
| Loss of Function | 0.632 | 2 | 3.22 | 0.620 | 1.36e-7 | 47 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000063 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000091 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine. {ECO:0000269|PubMed:16778797}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.428
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.700
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |