Incidental Mutation 'R6611:Hmbs'
ID 523584
Institutional Source Beutler Lab
Gene Symbol Hmbs
Ensembl Gene ENSMUSG00000032126
Gene Name hydroxymethylbilane synthase
Synonyms Uros1, Ups, porphobilinogen deaminase, PBGD
MMRRC Submission 044734-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6611 (G1)
Quality Score 225.009
Status Not validated
Chromosome 9
Chromosomal Location 44247645-44255525 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 44252988 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Leucine at position 15 (R15L)
Ref Sequence ENSEMBL: ENSMUSP00000149522 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000077353] [ENSMUST00000097558] [ENSMUST00000215091] [ENSMUST00000216852]
AlphaFold P22907
Predicted Effect probably benign
Transcript: ENSMUST00000077353
AA Change: R32L

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126
AA Change: R32L

DomainStartEndE-ValueType
Pfam:Porphobil_deam 21 233 1.7e-79 PFAM
Pfam:Porphobil_deamC 244 323 6.8e-24 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000097558
AA Change: R15L

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126
AA Change: R15L

DomainStartEndE-ValueType
Pfam:Porphobil_deam 3 219 3.9e-95 PFAM
Pfam:Porphobil_deamC 227 327 4.7e-23 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214012
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214967
Predicted Effect probably damaging
Transcript: ENSMUST00000215091
AA Change: R15L

PolyPhen 2 Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215859
Predicted Effect probably benign
Transcript: ENSMUST00000216852
Predicted Effect probably benign
Transcript: ENSMUST00000216658
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215934
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.1%
  • 20x: 94.6%
Validation Efficiency
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 hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice heterozygous for one null allele and a functional allele with a milder mutation exhibit typical features of acute intermittent porphyria with massive urinary excretion of aminolevulinic acid after phenobarbital treatment, erythruria, ataxia, motor dysfunction, and neurologic muscle atrophy. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 37 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810009J06Rik A T 6: 40,943,713 (GRCm39) T126S probably benign Het
Bex6 A G 16: 32,005,483 (GRCm39) K97R probably benign Het
Brca2 T C 5: 150,459,658 (GRCm39) L311P probably damaging Het
Ccng2 C G 5: 93,421,202 (GRCm39) S237R probably benign Het
Cdc16 C A 8: 13,831,512 (GRCm39) P582T probably benign Het
Cep112 T C 11: 108,397,377 (GRCm39) I280T possibly damaging Het
Cfhr4 A G 1: 139,660,128 (GRCm39) Y666H probably damaging Het
Chd2 A G 7: 73,143,313 (GRCm39) F527L probably damaging Het
Drc3 G T 11: 60,255,773 (GRCm39) R120L probably damaging Het
Efcab6 T A 15: 83,777,036 (GRCm39) R1133S possibly damaging Het
Fer1l5 T C 1: 36,445,735 (GRCm39) V834A probably benign Het
Flnb A G 14: 7,915,318 (GRCm38) Y1483C probably damaging Het
Fstl4 A T 11: 53,077,552 (GRCm39) M770L probably benign Het
Gm10428 A T 11: 62,644,115 (GRCm39) probably benign Het
Irx3 T C 8: 92,526,631 (GRCm39) T358A probably damaging Het
Kmt2a T A 9: 44,760,569 (GRCm39) I460L probably damaging Het
Mob2 G T 7: 141,563,293 (GRCm39) F55L probably damaging Het
Muc6 G C 7: 141,226,700 (GRCm39) probably benign Het
Ntrk2 T C 13: 59,202,228 (GRCm39) L612P probably damaging Het
Obscn A G 11: 58,955,056 (GRCm39) probably null Het
Or4d5 T C 9: 40,012,316 (GRCm39) I157V probably benign Het
Or5j1 A T 2: 86,879,577 (GRCm39) M1K probably null Het
Or8b44 A T 9: 38,410,534 (GRCm39) T190S probably damaging Het
Oxct2a T C 4: 123,216,640 (GRCm39) E247G probably damaging Het
Phykpl G T 11: 51,489,181 (GRCm39) A336S probably damaging Het
Pik3r4 T G 9: 105,521,476 (GRCm39) L14R probably damaging Het
Pnpla1 A G 17: 29,100,021 (GRCm39) N296S probably benign Het
Pramel7 A G 2: 87,320,393 (GRCm39) I300T probably damaging Het
Rictor T G 15: 6,780,140 (GRCm39) C132G probably damaging Het
Rsf1 G GACGGCGGCT 7: 97,229,116 (GRCm39) probably benign Homo
Slc9a9 G T 9: 94,821,531 (GRCm39) R306L probably benign Het
Smc5 A G 19: 23,206,283 (GRCm39) V681A probably benign Het
Snap91 C T 9: 86,672,180 (GRCm39) S646N probably benign Het
Ssh3 T C 19: 4,314,450 (GRCm39) N368S probably damaging Het
Syne1 A T 10: 4,995,273 (GRCm39) N8326K probably benign Het
Traf3 T G 12: 111,204,074 (GRCm39) L21R possibly damaging Het
Ubxn11 C A 4: 133,850,910 (GRCm39) T254K probably damaging Het
Other mutations in Hmbs
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01526:Hmbs APN 9 44,250,845 (GRCm39) missense possibly damaging 0.91
IGL02312:Hmbs APN 9 44,252,510 (GRCm39) critical splice donor site probably null
R0386:Hmbs UTSW 9 44,248,305 (GRCm39) missense probably benign 0.06
R0411:Hmbs UTSW 9 44,252,949 (GRCm39) nonsense probably null
R0656:Hmbs UTSW 9 44,248,657 (GRCm39) missense probably benign 0.31
R1503:Hmbs UTSW 9 44,248,729 (GRCm39) missense probably benign 0.42
R1560:Hmbs UTSW 9 44,248,657 (GRCm39) missense possibly damaging 0.71
R1953:Hmbs UTSW 9 44,248,741 (GRCm39) missense probably damaging 1.00
R2127:Hmbs UTSW 9 44,252,004 (GRCm39) missense probably benign 0.09
R4637:Hmbs UTSW 9 44,250,834 (GRCm39) missense probably damaging 1.00
R5549:Hmbs UTSW 9 44,250,774 (GRCm39) critical splice donor site probably null
R7509:Hmbs UTSW 9 44,248,208 (GRCm39) missense
R7702:Hmbs UTSW 9 44,248,147 (GRCm39) splice site probably null
R8383:Hmbs UTSW 9 44,249,240 (GRCm39) missense probably damaging 1.00
R8506:Hmbs UTSW 9 44,252,921 (GRCm39) critical splice donor site probably null
R9069:Hmbs UTSW 9 44,248,102 (GRCm39) missense possibly damaging 0.79
R9149:Hmbs UTSW 9 44,252,983 (GRCm39) nonsense probably null
R9780:Hmbs UTSW 9 44,247,985 (GRCm39) missense probably damaging 1.00
X0024:Hmbs UTSW 9 44,249,265 (GRCm39) missense possibly damaging 0.89
Predicted Primers PCR Primer
(F):5'- TCTTACAAGGCAGGCTTTGACC -3'
(R):5'- CCCAAAGGCTAGCATTGAGC -3'

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