Incidental Mutation 'R7927:Gch1'
ID 643404
Institutional Source Beutler Lab
Gene Symbol Gch1
Ensembl Gene ENSMUSG00000037580
Gene Name GTP cyclohydrolase 1
Synonyms GTPCH, GTP-CH
MMRRC Submission 045974-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.913) question?
Stock # R7927 (G1)
Quality Score 999
Status Validated
Chromosome 14
Chromosomal Location 47391352-47426870 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 47393380 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Tyrosine at position 201 (H201Y)
Ref Sequence ENSEMBL: ENSMUSP00000087405 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089959]
AlphaFold Q05915
Predicted Effect probably damaging
Transcript: ENSMUST00000089959
AA Change: H201Y

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000087405
Gene: ENSMUSG00000037580
AA Change: H201Y

DomainStartEndE-ValueType
Pfam:GTP_cyclohydroI 62 240 4e-78 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.9%
  • 20x: 99.7%
Validation Efficiency 98% (56/57)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null mutation display bradycardia, reduced L-DOPA levels and embryonic lethality during organogenesis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921539E11Rik A G 4: 103,123,539 (GRCm39) M111T probably benign Het
Adprhl1 C T 8: 13,298,682 (GRCm39) V83I probably damaging Het
Agrn C T 4: 156,257,266 (GRCm39) G1188D probably damaging Het
Amz2 A G 11: 109,319,884 (GRCm39) K90R probably damaging Het
Arhgef4 G T 1: 34,846,334 (GRCm39) Q227H probably damaging Het
B4galt3 T A 1: 171,099,342 (GRCm39) C10* probably null Het
Banf2 T A 2: 143,915,718 (GRCm39) M53K probably benign Het
BC034090 A T 1: 155,117,371 (GRCm39) L249* probably null Het
Cftr A G 6: 18,267,970 (GRCm39) D673G possibly damaging Het
Cntnap2 G T 6: 47,072,621 (GRCm39) C1063F possibly damaging Het
Cstpp1 T A 2: 91,252,250 (GRCm39) D37V probably damaging Het
Dnah3 A G 7: 119,550,494 (GRCm39) I296T probably damaging Het
Dpy19l2 A G 9: 24,607,197 (GRCm39) V88A probably benign Het
Fbln5 T C 12: 101,784,647 (GRCm39) probably benign Het
Fbn1 T C 2: 125,225,656 (GRCm39) D532G possibly damaging Het
Fnta G A 8: 26,494,454 (GRCm39) R258* probably null Het
G530012D18Rik C G 1: 85,504,935 (GRCm39) D113E unknown Het
Grik2 A T 10: 49,116,890 (GRCm39) S624T probably damaging Het
Grm5 T A 7: 87,685,382 (GRCm39) S500T probably benign Het
Hmcn1 T A 1: 150,485,526 (GRCm39) I4359F probably damaging Het
Hrc T A 7: 44,985,477 (GRCm39) H209Q possibly damaging Het
Hsd17b14 T C 7: 45,215,395 (GRCm39) M164T probably damaging Het
Hydin T C 8: 111,307,476 (GRCm39) F3952L possibly damaging Het
Kti12 A C 4: 108,705,443 (GRCm39) E119A probably benign Het
Kti12 G T 4: 108,705,444 (GRCm39) E119D probably benign Het
Lig4 A T 8: 10,023,629 (GRCm39) H50Q possibly damaging Het
Lrp6 G T 6: 134,497,513 (GRCm39) R165S probably damaging Het
Muc4 A G 16: 32,592,011 (GRCm39) T958A Het
Myo19 A G 11: 84,791,046 (GRCm39) E419G probably damaging Het
Ndufa5 A G 6: 24,527,291 (GRCm39) V16A possibly damaging Het
Or10a2 T C 7: 106,673,496 (GRCm39) F154L probably benign Het
Phf24 A C 4: 42,934,774 (GRCm39) T137P probably damaging Het
Pkp4 A T 2: 59,142,098 (GRCm39) N467I probably damaging Het
Pramel25 T A 4: 143,519,536 (GRCm39) I99N probably benign Het
Rbm12b2 C T 4: 12,095,417 (GRCm39) R759C possibly damaging Het
Rftn1 G T 17: 50,354,408 (GRCm39) A318D probably damaging Het
Rnf34 T A 5: 122,988,288 (GRCm39) probably benign Het
Rsf1 GGCGGCGGC GGCGGCGGCAGCGGCGGC 7: 97,229,131 (GRCm39) probably benign Het
Scaf8 T A 17: 3,209,495 (GRCm39) S73T unknown Het
Scn4a T A 11: 106,233,209 (GRCm39) E454D probably damaging Het
Serpina1e A G 12: 103,917,450 (GRCm39) V73A probably benign Het
Sh3rf2 A G 18: 42,244,487 (GRCm39) T350A probably benign Het
Slc35a1 A G 4: 34,669,021 (GRCm39) V264A probably damaging Het
Slf2 A G 19: 44,923,740 (GRCm39) K185E probably damaging Het
Spmip8 T A 8: 96,039,786 (GRCm39) S68T probably benign Het
Spsb2 T C 6: 124,786,336 (GRCm39) F23S probably benign Het
Ssx2ip T G 3: 146,138,365 (GRCm39) L404R probably damaging Het
Strn4 T A 7: 16,560,556 (GRCm39) L236Q probably null Het
Tcp10b A G 17: 13,288,579 (GRCm39) T202A probably benign Het
Tdp1 G T 12: 99,878,555 (GRCm39) V448L probably damaging Het
Tecrl T C 5: 83,502,666 (GRCm39) E61G probably damaging Het
Trim50 T C 5: 135,382,465 (GRCm39) F106L probably benign Het
Usp5 G T 6: 124,801,192 (GRCm39) F224L probably benign Het
Vmn2r45 C A 7: 8,486,513 (GRCm39) M258I probably benign Het
Zfp574 T A 7: 24,779,572 (GRCm39) V198E probably benign Het
Zmym4 A G 4: 126,799,170 (GRCm39) I722T probably benign Het
Other mutations in Gch1
AlleleSourceChrCoordTypePredicted EffectPPH Score
BB004:Gch1 UTSW 14 47,393,380 (GRCm39) missense probably damaging 1.00
BB014:Gch1 UTSW 14 47,393,380 (GRCm39) missense probably damaging 1.00
R2251:Gch1 UTSW 14 47,426,798 (GRCm39) start gained probably benign
R2253:Gch1 UTSW 14 47,426,798 (GRCm39) start gained probably benign
R4201:Gch1 UTSW 14 47,393,260 (GRCm39) missense probably benign 0.00
R5422:Gch1 UTSW 14 47,394,906 (GRCm39) missense probably damaging 1.00
R6950:Gch1 UTSW 14 47,426,723 (GRCm39) start codon destroyed probably null
R7803:Gch1 UTSW 14 47,426,418 (GRCm39) missense probably benign 0.00
R9211:Gch1 UTSW 14 47,426,519 (GRCm39) missense probably damaging 1.00
R9568:Gch1 UTSW 14 47,426,637 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- TGAGACAGATAACAGCCGC -3'
(R):5'- TTGGATGTATCAAGGACTCAGCC -3'

Sequencing Primer
(F):5'- GACAGATAACAGCCGCAGCAG -3'
(R):5'- TGTATCAAGGACTCAGCCACGAATAG -3'
Posted On 2020-08-07