Incidental Mutation 'R1560:Hmbs'
| ID |
170557 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Hmbs
|
| Ensembl Gene |
ENSMUSG00000032126 |
| Gene Name |
hydroxymethylbilane synthase |
| Synonyms |
Uros1, Ups, porphobilinogen deaminase, PBGD |
| MMRRC Submission |
039599-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1560 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
9 |
| Chromosomal Location |
44247645-44255525 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 44248657 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Histidine to Arginine
at position 72
(H72R)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000052686]
[ENSMUST00000054708]
[ENSMUST00000077353]
[ENSMUST00000097558]
[ENSMUST00000216852]
[ENSMUST00000215050]
[ENSMUST00000215091]
|
| 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: H256R
PolyPhen 2
Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
|
| SMART Domains |
Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126
AA Change: H256R
| 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 |
possibly damaging
Transcript: ENSMUST00000097558
AA Change: H239R
PolyPhen 2
Score 0.468 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126
AA Change: H239R
| 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: ENSMUST00000213709
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000214012
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000216658
AA Change: H72R
PolyPhen 2
Score 0.706 (Sensitivity: 0.86; Specificity: 0.92)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000216852
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000215050
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000215091
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000214967
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000215859
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000215934
|
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.3%
- 10x: 96.3%
- 20x: 92.6%
|
| 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: 49 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2610021A01Rik |
A |
G |
7: 41,275,466 (GRCm39) |
T390A |
probably benign |
Het |
| Adamts8 |
T |
A |
9: 30,867,963 (GRCm39) |
C596S |
probably damaging |
Het |
| Avl9 |
T |
A |
6: 56,702,113 (GRCm39) |
Y89* |
probably null |
Het |
| Cacna1e |
G |
A |
1: 154,296,850 (GRCm39) |
R18* |
probably null |
Het |
| Cacng2 |
A |
G |
15: 77,897,518 (GRCm39) |
F97S |
probably benign |
Het |
| Calu |
A |
G |
6: 29,361,657 (GRCm39) |
D107G |
probably benign |
Het |
| Capns2 |
G |
A |
8: 93,628,771 (GRCm39) |
R220Q |
probably damaging |
Het |
| Catsperb |
C |
T |
12: 101,591,985 (GRCm39) |
T1105I |
probably benign |
Het |
| Cep350 |
T |
C |
1: 155,804,825 (GRCm39) |
N753D |
possibly damaging |
Het |
| D6Ertd527e |
C |
G |
6: 87,088,506 (GRCm39) |
T223S |
unknown |
Het |
| Dnah5 |
G |
T |
15: 28,420,149 (GRCm39) |
V3816F |
probably damaging |
Het |
| Dzip3 |
T |
C |
16: 48,771,903 (GRCm39) |
|
probably null |
Het |
| Ep400 |
A |
T |
5: 110,818,972 (GRCm39) |
|
probably null |
Het |
| Epb41l2 |
T |
A |
10: 25,371,334 (GRCm39) |
|
probably null |
Het |
| Fetub |
T |
C |
16: 22,758,117 (GRCm39) |
V300A |
probably benign |
Het |
| Gabrb3 |
A |
T |
7: 57,466,043 (GRCm39) |
M308L |
probably damaging |
Het |
| Galnt16 |
A |
T |
12: 80,648,566 (GRCm39) |
D546V |
possibly damaging |
Het |
| Gimap8 |
G |
T |
6: 48,633,068 (GRCm39) |
G296W |
probably damaging |
Het |
| Gpr158 |
A |
G |
2: 21,831,125 (GRCm39) |
K742E |
probably damaging |
Het |
| Krt16 |
A |
G |
11: 100,137,475 (GRCm39) |
I410T |
probably damaging |
Het |
| Lamb3 |
G |
A |
1: 193,021,710 (GRCm39) |
A971T |
probably benign |
Het |
| Lilra6 |
A |
C |
7: 3,914,407 (GRCm39) |
|
probably null |
Het |
| Mroh7 |
A |
T |
4: 106,568,451 (GRCm39) |
M418K |
possibly damaging |
Het |
| Myh11 |
T |
A |
16: 14,044,484 (GRCm39) |
K640* |
probably null |
Het |
| Nsd1 |
T |
A |
13: 55,394,533 (GRCm39) |
C711* |
probably null |
Het |
| Or1j17 |
T |
A |
2: 36,578,155 (GRCm39) |
L47Q |
probably damaging |
Het |
| Or2ak5 |
A |
T |
11: 58,611,513 (GRCm39) |
Y120* |
probably null |
Het |
| Or3a10 |
A |
G |
11: 73,935,441 (GRCm39) |
S220P |
probably damaging |
Het |
| Or4c111 |
T |
C |
2: 88,843,550 (GRCm39) |
Y286C |
probably damaging |
Het |
| Otop3 |
A |
T |
11: 115,235,289 (GRCm39) |
H307L |
possibly damaging |
Het |
| Plekhm3 |
T |
C |
1: 64,976,976 (GRCm39) |
T165A |
probably benign |
Het |
| Poldip3 |
G |
A |
15: 83,022,527 (GRCm39) |
R86W |
probably damaging |
Het |
| Rif1 |
A |
T |
2: 52,001,143 (GRCm39) |
R1532S |
probably damaging |
Het |
| Sf3b1 |
C |
G |
1: 55,058,554 (GRCm39) |
E12Q |
possibly damaging |
Het |
| Slc27a6 |
T |
A |
18: 58,712,904 (GRCm39) |
L242* |
probably null |
Het |
| Spata45 |
T |
C |
1: 190,772,017 (GRCm39) |
S80P |
probably benign |
Het |
| Taf4 |
A |
G |
2: 179,577,746 (GRCm39) |
V525A |
probably benign |
Het |
| Tbck |
A |
G |
3: 132,543,809 (GRCm39) |
T887A |
probably damaging |
Het |
| Tnrc6c |
C |
T |
11: 117,650,463 (GRCm39) |
T1571I |
probably damaging |
Het |
| Trim38 |
A |
G |
13: 23,966,685 (GRCm39) |
Y44C |
probably benign |
Het |
| Tsg101 |
A |
T |
7: 46,542,208 (GRCm39) |
|
probably null |
Het |
| Tsku |
T |
A |
7: 98,002,151 (GRCm39) |
D60V |
probably damaging |
Het |
| Ttc28 |
G |
A |
5: 111,373,543 (GRCm39) |
S962N |
probably damaging |
Het |
| Upf1 |
G |
A |
8: 70,791,092 (GRCm39) |
P550L |
probably damaging |
Het |
| Vipr2 |
A |
G |
12: 116,058,401 (GRCm39) |
D106G |
probably benign |
Het |
| Vps13c |
T |
C |
9: 67,843,745 (GRCm39) |
|
probably null |
Het |
| Washc4 |
T |
C |
10: 83,391,973 (GRCm39) |
Y220H |
probably damaging |
Het |
| Wdr81 |
C |
T |
11: 75,342,449 (GRCm39) |
W939* |
probably null |
Het |
| Zfp512b |
T |
C |
2: 181,230,472 (GRCm39) |
T473A |
probably benign |
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 |
|
|
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 |
|
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'- ATGGAAATGACAGTCCCTCCCCTC -3'
(R):5'- TGGTTCATAACCTTTGGCACCTGC -3'
Sequencing Primer
(F):5'- TATGCACTGCTACGGGCAC -3'
(R):5'- GGCACCTGCTATCCATCAAATAAG -3'
|
| Posted On |
2014-04-13 |
Incidental Mutation