GCHFR

GTP cyclohydrolase I feedback regulator

Basic information

Region (hg38): 15:40764067-40767708

Links

ENSG00000137880 ∙ NCBI:2644 ∙ OMIM:602437 ∙ HGNC:4194 ∙ Uniprot:P30047 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GCHFR gene.

• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCHFR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			1			1
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	1	0	0

Variants in GCHFR

This is a list of pathogenic ClinVar variants found in the GCHFR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-40767279-G-A		not specified	Uncertain significance (Dec 19, 2023)
15-40767332-T-C		not specified	Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCHFR	protein_coding	protein_coding	ENST00000260447	3	3689

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0483	0.699	124102	0	2	124104	0.00000806

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.331	42	48.5	0.866	0.00000305	534
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000635	0.0000559
Finnish	0.00	0.00
European (Non-Finnish)	0.00000909	0.00000889
Middle Eastern	0.0000635	0.0000559
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine. {ECO:0000269|PubMed:16778797}.
• Pathway: Sepiapterin reductase deficiency;Segawa syndrome;Pterine Biosynthesis;Dopa-responsive dystonia;Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency;Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps);Hyperphenylalaninemia due to dhpr-deficiency;Metabolism;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;Metabolism of cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.428
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.400
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.700

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Gchfr

Gene ontology

• Biological process: nitric oxide biosynthetic process;negative regulation of biosynthetic process;neurotransmitter metabolic process;negative regulation of GTP cyclohydrolase I activity;cofactor metabolic process;protein heterooligomerization
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;dendrite;nuclear membrane;protein-containing complex;melanosome
• Molecular function: enzyme inhibitor activity;protein binding;amino acid binding;GTP-dependent protein binding;GTP cyclohydrolase binding