Incidental Mutation 'R6950:Gch1'
ID 541233
Institutional Source Beutler Lab
Gene Symbol Gch1
Ensembl Gene ENSMUSG00000037580
Gene Name GTP cyclohydrolase 1
Synonyms GTPCH, GTP-CH
MMRRC Submission 045062-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.913) question?
Stock # R6950 (G1)
Quality Score 94.0077
Status Validated
Chromosome 14
Chromosomal Location 47391352-47426870 bp(-) (GRCm39)
Type of Mutation start codon destroyed
DNA Base Change (assembly) A to T at 47426723 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Lysine at position 1 (M1K)
Ref Sequence ENSEMBL: ENSMUSP00000087405 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089959]
AlphaFold Q05915
Predicted Effect probably null
Transcript: ENSMUST00000089959
AA Change: M1K

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000087405
Gene: ENSMUSG00000037580
AA Change: M1K

DomainStartEndE-ValueType
Pfam:GTP_cyclohydroI 62 240 4e-78 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.4%
  • 20x: 98.4%
Validation Efficiency 98% (59/60)
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: 59 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc1 T A 16: 14,229,480 (GRCm39) V404D probably damaging Het
Adcy2 A G 13: 69,036,184 (GRCm39) M159T possibly damaging Het
Agtpbp1 T C 13: 59,598,080 (GRCm39) K674R probably benign Het
Atxn7 C A 14: 14,095,511 (GRCm38) P403H probably damaging Het
Cav3 C T 6: 112,449,171 (GRCm39) T63I probably damaging Het
Ccr6 T C 17: 8,475,898 (GRCm39) *368Q probably null Het
Cdh8 A T 8: 99,757,395 (GRCm39) N734K probably benign Het
Ces5a G T 8: 94,257,402 (GRCm39) N134K probably benign Het
Cisd3 T G 11: 97,576,986 (GRCm39) probably null Het
Cyp4f39 T G 17: 32,711,280 (GRCm39) C476G probably damaging Het
Dffb A T 4: 154,054,549 (GRCm39) M180K probably benign Het
Dock4 A G 12: 40,783,313 (GRCm39) E749G possibly damaging Het
Eogt A G 6: 97,111,343 (GRCm39) F173L possibly damaging Het
Ephb1 T A 9: 102,072,108 (GRCm39) T224S probably benign Het
Fam114a1 A T 5: 65,137,322 (GRCm39) E88D possibly damaging Het
Fbn2 A C 18: 58,168,993 (GRCm39) M2262R probably null Het
Fsip2 A G 2: 82,816,332 (GRCm39) I4022V probably benign Het
Gapvd1 A G 2: 34,574,257 (GRCm39) V1301A probably benign Het
Hes1 T C 16: 29,886,089 (GRCm39) F231S probably damaging Het
Hoxb2 A G 11: 96,242,727 (GRCm39) T31A probably benign Het
Ifngr1 T A 10: 19,483,041 (GRCm39) V265D probably damaging Het
Ifnl3 A T 7: 28,222,432 (GRCm39) I58F probably benign Het
Igf2r T C 17: 12,937,605 (GRCm39) T561A probably benign Het
Igfbpl1 T A 4: 45,815,494 (GRCm39) H214L probably damaging Het
Irf8 A G 8: 121,481,864 (GRCm39) T318A probably benign Het
Kmt2d T C 15: 98,737,901 (GRCm39) probably benign Het
Lratd2 T C 15: 60,695,563 (GRCm39) D61G probably benign Het
Lrrc36 G T 8: 106,152,021 (GRCm39) probably null Het
Msl2 C T 9: 100,979,174 (GRCm39) P516L possibly damaging Het
Naaladl1 A T 19: 6,156,011 (GRCm39) I62F probably damaging Het
Neto2 G T 8: 86,397,072 (GRCm39) P60Q probably damaging Het
Nipsnap3b A T 4: 53,015,136 (GRCm39) H61L possibly damaging Het
Npb T C 11: 120,499,473 (GRCm39) F47L probably benign Het
Nutm1 T A 2: 112,078,904 (GRCm39) T1004S probably benign Het
Or4a78 T A 2: 89,497,895 (GRCm39) I112F probably benign Het
Or4z4 A G 19: 12,076,754 (GRCm39) V83A probably benign Het
Or8c17 A T 9: 38,179,842 (GRCm39) N3I probably damaging Het
Oxr1 C A 15: 41,683,951 (GRCm39) A439E probably benign Het
Phf14 A T 6: 12,006,854 (GRCm39) K835N probably damaging Het
Prkdc T A 16: 15,633,850 (GRCm39) V3518E probably damaging Het
Ptpru T A 4: 131,503,663 (GRCm39) E1132D probably damaging Het
Rapgef6 T A 11: 54,567,206 (GRCm39) M1129K probably benign Het
Rgmb T C 17: 16,028,048 (GRCm39) K224E probably damaging Het
Ryr3 T C 2: 112,517,170 (GRCm39) I3318V possibly damaging Het
Slc9a4 A G 1: 40,642,045 (GRCm39) Y338C probably damaging Het
Smg5 T C 3: 88,256,576 (GRCm39) probably null Het
Tenm3 A T 8: 48,693,514 (GRCm39) Y1789* probably null Het
Tgm7 T C 2: 120,924,128 (GRCm39) E598G probably damaging Het
Tiam1 C T 16: 89,657,092 (GRCm39) probably null Het
Tmem175 A G 5: 108,790,948 (GRCm39) N166S probably benign Het
Trp73 G T 4: 154,146,510 (GRCm39) N368K probably benign Het
Trpc3 C T 3: 36,692,739 (GRCm39) R751H probably damaging Het
Trpm4 C A 7: 44,968,704 (GRCm39) A410S probably damaging Het
Ube2t T G 1: 134,899,095 (GRCm39) probably null Het
Vmn2r114 C T 17: 23,529,137 (GRCm39) A322T probably benign Het
Xylt2 C T 11: 94,558,455 (GRCm39) R567H probably benign Het
Zfp119b T C 17: 56,246,137 (GRCm39) K318E probably damaging Het
Zfp626 T G 7: 27,518,339 (GRCm39) L440R probably damaging Het
Zfp850 A G 7: 27,689,939 (GRCm39) S90P possibly damaging 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
R7803:Gch1 UTSW 14 47,426,418 (GRCm39) missense probably benign 0.00
R7927:Gch1 UTSW 14 47,393,380 (GRCm39) missense probably damaging 1.00
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'- TGGTGAAGTACTGCATGGCG -3'
(R):5'- AATGAAAATATCTCGCGGCGC -3'

Sequencing Primer
(F):5'- CCAGTTTGGGGAGGTTCACC -3'
(R):5'- GAGTCGCCCTGCCATAAAAAGAG -3'
Posted On 2018-11-28