Incidental Mutation 'R4637:Hmbs'
ID 350763
Institutional Source Beutler Lab
Gene Symbol Hmbs
Ensembl Gene ENSMUSG00000032126
Gene Name hydroxymethylbilane synthase
Synonyms Uros1, Ups, porphobilinogen deaminase, PBGD
MMRRC Submission 042010-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4637 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 44247645-44255525 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 44250834 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 130 (S130P)
Ref Sequence ENSEMBL: ENSMUSP00000095166 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000052686] [ENSMUST00000077353] [ENSMUST00000097558] [ENSMUST00000215091] [ENSMUST00000216852]
AlphaFold P22907
Predicted Effect probably benign
Transcript: ENSMUST00000052686
SMART Domains Protein: ENSMUSP00000051432
Gene: ENSMUSG00000049932

DomainStartEndE-ValueType
H2A 3 123 1.64e-81 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000077353
AA Change: S147P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126
AA Change: S147P

DomainStartEndE-ValueType
Pfam:Porphobil_deam 21 233 1.7e-79 PFAM
Pfam:Porphobil_deamC 244 323 6.8e-24 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000097558
AA Change: S130P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126
AA Change: S130P

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: ENSMUST00000196879
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214012
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214967
Predicted Effect probably benign
Transcript: ENSMUST00000215091
Predicted Effect probably benign
Transcript: ENSMUST00000216658
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215859
Predicted Effect probably benign
Transcript: ENSMUST00000216852
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215934
Meta Mutation Damage Score 0.9753 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.1%
Validation Efficiency 96% (27/28)
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: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Art1 T A 7: 101,755,544 (GRCm39) V12E probably damaging Het
Ccdc121 G A 5: 31,645,435 (GRCm39) R396Q probably benign Het
Ccdc180 A G 4: 45,914,443 (GRCm39) S653G probably benign Het
Clic6 T C 16: 92,293,949 (GRCm39) probably benign Het
Fras1 T A 5: 96,925,947 (GRCm39) L3717Q probably damaging Het
Gpat3 C T 5: 101,005,039 (GRCm39) P58L probably benign Het
Gtf2f1 G T 17: 57,311,534 (GRCm39) P292H probably benign Het
Hcn1 A T 13: 118,112,249 (GRCm39) T738S unknown Het
Hivep2 C A 10: 14,004,713 (GRCm39) T437K probably benign Het
Kif1b A T 4: 149,283,768 (GRCm39) I1299N probably damaging Het
Mrc2 G A 11: 105,239,257 (GRCm39) probably null Het
Muc17 A T 5: 137,175,502 (GRCm39) L56Q probably damaging Het
Myd88 G A 9: 119,167,175 (GRCm39) probably null Het
Nol6 G A 4: 41,121,788 (GRCm39) R249W probably damaging Het
Or4g17 C T 2: 111,209,927 (GRCm39) T194I probably benign Het
Pcdhb1 T C 18: 37,398,802 (GRCm39) V251A possibly damaging Het
Prkcd A G 14: 30,320,722 (GRCm39) S633P probably benign Het
Rarb T C 14: 16,574,875 (GRCm38) H47R possibly damaging Het
Slc16a14 A G 1: 84,885,003 (GRCm39) V512A possibly damaging Het
Slc34a3 C T 2: 25,119,473 (GRCm39) V466M possibly damaging Het
Stat3 A G 11: 100,784,056 (GRCm39) S623P probably damaging Het
Vmn2r16 T G 5: 109,478,280 (GRCm39) S12A probably benign Het
Zfhx4 C G 3: 5,468,464 (GRCm39) P2874R probably damaging Het
Zfp3 T C 11: 70,662,181 (GRCm39) S47P probably benign Het
Zfp791 T C 8: 85,836,514 (GRCm39) E450G possibly 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
R5549:Hmbs UTSW 9 44,250,774 (GRCm39) critical splice donor site probably null
R6611:Hmbs UTSW 9 44,252,988 (GRCm39) missense probably damaging 0.98
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'- AATTGTCCTCATTGCCAGGC -3'
(R):5'- GCTGTTGTCTTTCACCCAAAG -3'

Sequencing Primer
(F):5'- CAGCTTGGTCTACAAAGTGAGTTCC -3'
(R):5'- GTTTATTGGAAAGACCCTGGAAACC -3'
Posted On 2015-10-08