Incidental Mutation 'R6577:Uros'
ID 523541
Institutional Source Beutler Lab
Gene Symbol Uros
Ensembl Gene ENSMUSG00000030979
Gene Name uroporphyrinogen III synthase
Synonyms uroporphyrinogen-III synthase, hydroxymethylbilane hydrolyase (cyclizing), URO-synthase, Uros3
MMRRC Submission 044701-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6577 (G1)
Quality Score 225.009
Status Validated
Chromosome 7
Chromosomal Location 133287972-133311801 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 133302569 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Phenylalanine at position 73 (C73F)
Ref Sequence ENSEMBL: ENSMUSP00000101750 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000033276] [ENSMUST00000106144] [ENSMUST00000106145] [ENSMUST00000106146] [ENSMUST00000124759] [ENSMUST00000209636] [ENSMUST00000151348] [ENSMUST00000153698]
AlphaFold P51163
Predicted Effect probably damaging
Transcript: ENSMUST00000033276
AA Change: C73F

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000033276
Gene: ENSMUSG00000030979
AA Change: C73F

DomainStartEndE-ValueType
Pfam:HEM4 17 253 1.2e-44 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000106144
AA Change: C73F

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000101750
Gene: ENSMUSG00000030979
AA Change: C73F

DomainStartEndE-ValueType
Pfam:HEM4 17 168 5.1e-20 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000106145
AA Change: C73F

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000101751
Gene: ENSMUSG00000030979
AA Change: C73F

DomainStartEndE-ValueType
Pfam:HEM4 17 253 2.9e-45 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000106146
AA Change: C73F

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000101752
Gene: ENSMUSG00000030979
AA Change: C73F

DomainStartEndE-ValueType
Pfam:HEM4 17 253 1.2e-44 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000124759
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135760
Predicted Effect noncoding transcript
Transcript: ENSMUST00000144789
Predicted Effect possibly damaging
Transcript: ENSMUST00000209636
AA Change: C45F

PolyPhen 2 Score 0.955 (Sensitivity: 0.79; Specificity: 0.95)
Predicted Effect probably benign
Transcript: ENSMUST00000151348
Predicted Effect probably benign
Transcript: ENSMUST00000153698
Meta Mutation Damage Score 0.7673 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.5%
  • 10x: 97.6%
  • 20x: 93.1%
Validation Efficiency 97% (38/39)
MGI Phenotype FUNCTION: The protein encoded by this gene is the fourth enzyme in the heme biosynthesis pathway. It converts hydroxymethylbilane to uroporphyrinogen III, a cyclic tetrapyrrole. This enzyme is defective in the autosomal recessive disorder congenital erythropoietic porphyria. Alternate promoter usage controls cell type-specific expression, including erythroid cell-specific expression. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit complete embryonic lethality before implantation. Knock-in mice with sufficient residual enzymatic activity for survival display hemolytic anemia, hepatosplenomegaly, increased porphyrin level, erythruria, porphyria, and skin photosensitivity. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Api5 T C 2: 94,252,726 (GRCm39) Y348C probably benign Het
Ark2n T C 18: 77,740,855 (GRCm39) T285A probably benign Het
Arl14 A G 3: 69,130,405 (GRCm39) E184G probably benign Het
Asap3 T C 4: 135,965,541 (GRCm39) probably null Het
Atp11b T A 3: 35,893,311 (GRCm39) V36E probably damaging Het
Atp13a4 C T 16: 29,298,659 (GRCm39) S100N probably benign Het
Cd27 T C 6: 125,213,756 (GRCm39) T34A probably benign Het
Clec10a T C 11: 70,061,436 (GRCm39) S274P probably benign Het
Cntnap2 C T 6: 46,147,206 (GRCm39) T484I probably benign Het
Cpsf1 CCCCTGCATGAGGCAGGTCCC CCCC 15: 76,481,655 (GRCm39) probably null Het
Cracd A T 5: 77,013,947 (GRCm39) probably benign Het
Def8 T C 8: 124,183,449 (GRCm39) S304P probably benign Het
Dgkd G A 1: 87,867,962 (GRCm39) V299M probably damaging Het
Ephb2 T C 4: 136,384,861 (GRCm39) D850G probably damaging Het
Gjd3 T C 11: 102,691,130 (GRCm39) N291S possibly damaging Het
Hc T C 2: 34,922,138 (GRCm39) I563V probably benign Het
Hells C T 19: 38,919,909 (GRCm39) Q20* probably null Het
Hid1 G C 11: 115,245,462 (GRCm39) P448A possibly damaging Het
Igkv8-24 C T 6: 70,193,947 (GRCm39) R87H possibly damaging Het
Irf6 A G 1: 192,851,662 (GRCm39) S418G probably damaging Het
Kcnv2 T A 19: 27,301,420 (GRCm39) C424S possibly damaging Het
Lmln T A 16: 32,927,370 (GRCm39) probably null Het
Myo1a A T 10: 127,551,189 (GRCm39) I678F possibly damaging Het
Nup98 A C 7: 101,778,053 (GRCm39) probably null Het
Papolg GGACTTGGGATACTTACGCTTTG GG 11: 23,829,857 (GRCm39) probably benign Het
Ppfibp1 T A 6: 146,901,153 (GRCm39) probably null Het
Sardh T C 2: 27,108,867 (GRCm39) T623A possibly damaging Het
Scml4 A G 10: 42,823,107 (GRCm39) N251D probably damaging Het
Skap1 T C 11: 96,416,870 (GRCm39) Y52H probably damaging Het
Srp68 G A 11: 116,156,290 (GRCm39) R113W probably damaging Het
Srsf12 T C 4: 33,209,196 (GRCm39) probably benign Het
Stat5b A G 11: 100,688,526 (GRCm39) M312T probably benign Het
Tma7 T C 9: 108,911,262 (GRCm39) probably benign Het
Tmem120b T G 5: 123,254,710 (GRCm39) F304V probably damaging Het
Tns3 G A 11: 8,499,057 (GRCm39) L9F probably damaging Het
Tns3 G T 11: 8,499,058 (GRCm39) D8E probably damaging Het
Tsc2 C T 17: 24,829,473 (GRCm39) A765T probably damaging Het
Tut7 C T 13: 59,955,975 (GRCm39) C45Y probably damaging Het
Uba1y A G Y: 825,465 (GRCm39) I276V probably benign Homo
Upb1 T G 10: 75,248,723 (GRCm39) L81R probably damaging Het
Zfp820 T C 17: 22,038,384 (GRCm39) I315V probably benign Het
Other mutations in Uros
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02135:Uros APN 7 133,288,734 (GRCm39) missense possibly damaging 0.87
R1960:Uros UTSW 7 133,288,735 (GRCm39) missense probably benign
R3722:Uros UTSW 7 133,304,120 (GRCm39) start codon destroyed probably null 1.00
R4065:Uros UTSW 7 133,304,057 (GRCm39) critical splice donor site probably null
R7982:Uros UTSW 7 133,294,278 (GRCm39) missense unknown
R9257:Uros UTSW 7 133,292,853 (GRCm39) missense probably damaging 0.96
Predicted Primers PCR Primer
(F):5'- CAGGTAAGAGTCTGCTGGAC -3'
(R):5'- GTAGAAGACCCAGTTGTCTGC -3'

Sequencing Primer
(F):5'- TGGACTCCAGAGCAGACC -3'
(R):5'- GAAGACCCAGTTGTCTGCTTCTTTG -3'
Posted On 2018-06-22