Incidental Mutation 'R0386:Hmbs'
ID 31292
Institutional Source Beutler Lab
Gene Symbol Hmbs
Ensembl Gene ENSMUSG00000032126
Gene Name hydroxymethylbilane synthase
Synonyms Uros1, Ups, porphobilinogen deaminase, PBGD
MMRRC Submission 038592-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0386 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 44247645-44255525 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 44248305 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 260 (Y260C)
Ref Sequence ENSEMBL: ENSMUSP00000095166 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000052686] [ENSMUST00000054708] [ENSMUST00000077353] [ENSMUST00000097558] [ENSMUST00000215091] [ENSMUST00000216852] [ENSMUST00000215050]
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 benign
Transcript: ENSMUST00000054708
SMART Domains Protein: ENSMUSP00000056282
Gene: ENSMUSG00000032123

DomainStartEndE-ValueType
transmembrane domain 10 32 N/A INTRINSIC
transmembrane domain 60 82 N/A INTRINSIC
Pfam:Glycos_transf_4 100 272 1.1e-38 PFAM
transmembrane domain 277 299 N/A INTRINSIC
transmembrane domain 381 403 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000077353
AA Change: Y277C

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126
AA Change: Y277C

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: Y260C

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126
AA Change: Y260C

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: ENSMUST00000213461
Predicted Effect unknown
Transcript: ENSMUST00000216658
AA Change: Y93C
Predicted Effect probably benign
Transcript: ENSMUST00000215091
Predicted Effect noncoding transcript
Transcript: ENSMUST00000213709
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214967
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215859
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215934
Predicted Effect probably benign
Transcript: ENSMUST00000216852
Predicted Effect probably benign
Transcript: ENSMUST00000215050
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214012
Meta Mutation Damage Score 0.3465 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.1%
  • 10x: 95.5%
  • 20x: 90.3%
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 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: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aasdh A G 5: 77,044,308 (GRCm39) V194A probably damaging Het
Adamts13 G A 2: 26,876,691 (GRCm39) probably null Het
Ahnak T C 19: 8,988,508 (GRCm39) M3264T possibly damaging Het
Birc6 T A 17: 74,906,335 (GRCm39) C1409S probably damaging Het
Camta1 C A 4: 151,159,597 (GRCm39) R1614L probably damaging Het
Dnah2 A G 11: 69,338,687 (GRCm39) V3161A probably damaging Het
Dnah5 A T 15: 28,383,727 (GRCm39) Y2983F probably damaging Het
Dnah6 G A 6: 73,060,107 (GRCm39) L2774F probably damaging Het
Dst A T 1: 34,256,917 (GRCm39) T4398S probably damaging Het
Efcab5 G A 11: 77,031,749 (GRCm39) R42W probably damaging Het
Efcab5 A T 11: 77,063,204 (GRCm39) M96K probably benign Het
Elavl4 A G 4: 110,063,902 (GRCm39) probably benign Het
Flt4 G A 11: 49,535,213 (GRCm39) A1214T probably benign Het
Fn1 G T 1: 71,634,945 (GRCm39) T2127N probably damaging Het
Foxj1 A T 11: 116,222,629 (GRCm39) S391R possibly damaging Het
Gabrb1 A T 5: 72,266,150 (GRCm39) Y269F probably damaging Het
Ghitm A G 14: 36,847,868 (GRCm39) S259P possibly damaging Het
Gm16332 A G 1: 139,851,928 (GRCm39) noncoding transcript Het
Gm16380 T A 9: 53,791,727 (GRCm39) noncoding transcript Het
Gm9869 A T 9: 60,745,344 (GRCm39) probably benign Het
Gm9936 G A 5: 114,995,192 (GRCm39) Q142* probably null Het
Hoxc5 T A 15: 102,923,784 (GRCm39) C193* probably null Het
Idh2 C T 7: 79,748,005 (GRCm39) A232T probably damaging Het
Lce1j T C 3: 92,696,695 (GRCm39) K28E unknown Het
Lpgat1 C T 1: 191,451,460 (GRCm39) probably benign Het
Lyst T C 13: 13,882,799 (GRCm39) probably benign Het
Megf11 A G 9: 64,547,360 (GRCm39) N235D probably damaging Het
Mst1r T A 9: 107,794,003 (GRCm39) probably null Het
Nr2c2ap A G 8: 70,584,237 (GRCm39) D9G probably benign Het
Obscn T C 11: 59,027,165 (GRCm39) T13A probably damaging Het
Ofcc1 A C 13: 40,367,950 (GRCm39) L188* probably null Het
Oma1 A T 4: 103,182,398 (GRCm39) probably benign Het
Or10aa3 A T 1: 173,877,965 (GRCm39) T9S probably benign Het
Or5m11 A G 2: 85,782,217 (GRCm39) E270G probably damaging Het
Pcm1 T C 8: 41,769,060 (GRCm39) F1642S probably damaging Het
Pglyrp2 A G 17: 32,639,836 (GRCm39) M1T probably null Het
Pnpla5 G T 15: 84,004,920 (GRCm39) L144M probably damaging Het
Prdm10 C A 9: 31,227,596 (GRCm39) T67K probably damaging Het
Ralgapa1 A T 12: 55,754,852 (GRCm39) H1193Q probably benign Het
Sall1 A G 8: 89,759,232 (GRCm39) S291P probably damaging Het
Sdk2 T C 11: 113,784,290 (GRCm39) T150A probably damaging Het
Sel1l2 T A 2: 140,117,361 (GRCm39) Y170F probably benign Het
Sema4a C T 3: 88,344,107 (GRCm39) V715I possibly damaging Het
Smgc G A 15: 91,738,841 (GRCm39) A500T probably benign Het
Spef2 A G 15: 9,584,148 (GRCm39) V1639A probably damaging Het
Srrm4 A G 5: 116,620,437 (GRCm39) probably benign Het
Tbc1d23 G A 16: 57,009,636 (GRCm39) H418Y probably damaging Het
Tbk1 A G 10: 121,420,159 (GRCm39) L10P probably damaging Het
Thumpd3 G A 6: 113,042,621 (GRCm39) probably null Het
Trp53bp1 G T 2: 121,035,424 (GRCm39) T1609K probably damaging Het
Tut1 A G 19: 8,932,919 (GRCm39) N84S probably benign Het
Urb1 C T 16: 90,593,287 (GRCm39) G282R probably damaging Het
Usp19 A T 9: 108,376,910 (GRCm39) D1160V probably damaging Het
Usp9y A G Y: 1,316,933 (GRCm39) V1872A probably damaging Het
Zfp276 C A 8: 123,986,242 (GRCm39) Y386* probably null 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
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
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'- CTGGACCATCTTCTTGCTGGATGAC -3'
(R):5'- CTGAAACTCTGCTTCGCTGCATTG -3'

Sequencing Primer
(F):5'- ATCTTCTTGCTGGATGACAGGTTAC -3'
(R):5'- CTTCGCTGCATTGCTGAAAG -3'
Posted On 2013-04-24