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)
|
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
Domain | Start | End | E-Value | Type |
H2A
|
3 |
123 |
1.64e-81 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000054708
|
SMART Domains |
Protein: ENSMUSP00000056282 Gene: ENSMUSG00000032123
Domain | Start | End | E-Value | Type |
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
Domain | Start | End | E-Value | Type |
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
Domain | Start | End | E-Value | Type |
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 |
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
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
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 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |