Incidental Mutation 'R0845:Comt'
| ID |
77343 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Comt
|
| Ensembl Gene |
ENSMUSG00000000326 |
| Gene Name |
catechol-O-methyltransferase |
| Synonyms |
D16Wsu103e, Comt1, D330014B15Rik |
| MMRRC Submission |
039024-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R0845 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
16 |
| Chromosomal Location |
18225636-18245602 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 18226711 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 225
(Y225C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000130077
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000000335]
[ENSMUST00000090103]
[ENSMUST00000115609]
[ENSMUST00000115610]
[ENSMUST00000115612]
[ENSMUST00000115613]
[ENSMUST00000115614]
[ENSMUST00000165430]
[ENSMUST00000232025]
[ENSMUST00000232241]
[ENSMUST00000150253]
[ENSMUST00000147720]
|
| AlphaFold |
O88587 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000000335
AA Change: Y225C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000000335
Gene: ENSMUSG00000000326
AA Change: Y225C
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
2 |
24 |
N/A |
INTRINSIC |
|
Pfam:Methyltransf_3
|
63 |
224 |
3.5e-24 |
PFAM |
|
Pfam:Methyltransf_26
|
102 |
224 |
3.3e-9 |
PFAM |
|
Pfam:Methyltransf_24
|
106 |
214 |
1.2e-13 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000090103
|
| SMART Domains |
Protein: ENSMUSP00000087562
Gene: ENSMUSG00000000325
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
11 |
46 |
N/A |
INTRINSIC |
|
low complexity region
|
89 |
99 |
N/A |
INTRINSIC |
|
low complexity region
|
117 |
138 |
N/A |
INTRINSIC |
|
low complexity region
|
141 |
157 |
N/A |
INTRINSIC |
|
low complexity region
|
208 |
227 |
N/A |
INTRINSIC |
|
ARM
|
391 |
431 |
4.48e-7 |
SMART |
|
ARM
|
434 |
475 |
3.31e-10 |
SMART |
|
Blast:ARM
|
476 |
533 |
2e-20 |
BLAST |
|
ARM
|
536 |
582 |
2.1e1 |
SMART |
|
ARM
|
652 |
693 |
9.55e1 |
SMART |
|
ARM
|
699 |
739 |
4.05e-5 |
SMART |
|
ARM
|
790 |
832 |
3.03e0 |
SMART |
|
low complexity region
|
927 |
945 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000115609
AA Change: Y225C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000111272
Gene: ENSMUSG00000000326
AA Change: Y225C
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
2 |
24 |
N/A |
INTRINSIC |
|
Pfam:Methyltransf_3
|
63 |
224 |
3.5e-24 |
PFAM |
|
Pfam:Methyltransf_26
|
102 |
224 |
3.3e-9 |
PFAM |
|
Pfam:Methyltransf_24
|
106 |
214 |
1.2e-13 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000115610
|
| SMART Domains |
Protein: ENSMUSP00000111273
Gene: ENSMUSG00000000325
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
25 |
35 |
N/A |
INTRINSIC |
|
low complexity region
|
53 |
74 |
N/A |
INTRINSIC |
|
low complexity region
|
77 |
93 |
N/A |
INTRINSIC |
|
low complexity region
|
144 |
163 |
N/A |
INTRINSIC |
|
ARM
|
327 |
367 |
4.48e-7 |
SMART |
|
ARM
|
370 |
411 |
3.31e-10 |
SMART |
|
Blast:ARM
|
412 |
469 |
1e-20 |
BLAST |
|
ARM
|
472 |
518 |
2.1e1 |
SMART |
|
low complexity region
|
555 |
563 |
N/A |
INTRINSIC |
|
ARM
|
582 |
623 |
9.55e1 |
SMART |
|
ARM
|
629 |
669 |
4.05e-5 |
SMART |
|
ARM
|
720 |
762 |
3.03e0 |
SMART |
|
low complexity region
|
857 |
875 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000115612
|
| SMART Domains |
Protein: ENSMUSP00000111275
Gene: ENSMUSG00000000325
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
11 |
46 |
N/A |
INTRINSIC |
|
low complexity region
|
89 |
99 |
N/A |
INTRINSIC |
|
low complexity region
|
117 |
138 |
N/A |
INTRINSIC |
|
low complexity region
|
141 |
157 |
N/A |
INTRINSIC |
|
low complexity region
|
208 |
227 |
N/A |
INTRINSIC |
|
ARM
|
391 |
431 |
4.48e-7 |
SMART |
|
ARM
|
434 |
475 |
3.31e-10 |
SMART |
|
Blast:ARM
|
476 |
533 |
2e-20 |
BLAST |
|
ARM
|
536 |
582 |
2.1e1 |
SMART |
|
low complexity region
|
619 |
627 |
N/A |
INTRINSIC |
|
ARM
|
646 |
687 |
9.55e1 |
SMART |
|
ARM
|
693 |
733 |
4.05e-5 |
SMART |
|
ARM
|
784 |
826 |
3.03e0 |
SMART |
|
low complexity region
|
921 |
939 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000115613
|
| SMART Domains |
Protein: ENSMUSP00000111276
Gene: ENSMUSG00000000325
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
11 |
46 |
N/A |
INTRINSIC |
|
low complexity region
|
89 |
99 |
N/A |
INTRINSIC |
|
low complexity region
|
117 |
138 |
N/A |
INTRINSIC |
|
low complexity region
|
141 |
157 |
N/A |
INTRINSIC |
|
low complexity region
|
208 |
227 |
N/A |
INTRINSIC |
|
ARM
|
391 |
431 |
4.48e-7 |
SMART |
|
ARM
|
434 |
475 |
3.31e-10 |
SMART |
|
Blast:ARM
|
476 |
533 |
2e-20 |
BLAST |
|
ARM
|
536 |
582 |
2.1e1 |
SMART |
|
ARM
|
652 |
693 |
9.55e1 |
SMART |
|
ARM
|
699 |
739 |
4.05e-5 |
SMART |
|
ARM
|
790 |
832 |
3.03e0 |
SMART |
|
low complexity region
|
927 |
945 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000115614
|
| SMART Domains |
Protein: ENSMUSP00000111278
Gene: ENSMUSG00000000325
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
11 |
46 |
N/A |
INTRINSIC |
|
low complexity region
|
89 |
99 |
N/A |
INTRINSIC |
|
low complexity region
|
117 |
138 |
N/A |
INTRINSIC |
|
low complexity region
|
141 |
157 |
N/A |
INTRINSIC |
|
low complexity region
|
208 |
227 |
N/A |
INTRINSIC |
|
ARM
|
391 |
431 |
4.48e-7 |
SMART |
|
ARM
|
434 |
475 |
3.31e-10 |
SMART |
|
Blast:ARM
|
476 |
533 |
2e-20 |
BLAST |
|
ARM
|
536 |
582 |
2.1e1 |
SMART |
|
low complexity region
|
619 |
627 |
N/A |
INTRINSIC |
|
ARM
|
646 |
687 |
9.55e1 |
SMART |
|
ARM
|
693 |
733 |
4.05e-5 |
SMART |
|
ARM
|
784 |
826 |
3.03e0 |
SMART |
|
low complexity region
|
921 |
939 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000165430
AA Change: Y225C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000130077
Gene: ENSMUSG00000000326
AA Change: Y225C
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
2 |
24 |
N/A |
INTRINSIC |
|
Pfam:Methyltransf_3
|
57 |
221 |
1.1e-22 |
PFAM |
|
Pfam:Methyltransf_24
|
106 |
214 |
6.2e-14 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000152132
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150484
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000232025
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000232241
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000150253
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000147720
|
| SMART Domains |
Protein: ENSMUSP00000121810
Gene: ENSMUSG00000000326
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
2 |
24 |
N/A |
INTRINSIC |
|
Pfam:Methyltransf_3
|
62 |
171 |
4.1e-18 |
PFAM |
|
Pfam:Methyltransf_24
|
106 |
171 |
4.4e-9 |
PFAM |
|
| Meta Mutation Damage Score |
0.6467 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.6%
- 10x: 96.9%
- 20x: 93.2%
|
| Validation Efficiency |
96% (45/47) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. [provided by RefSeq, Sep 2008]
PHENOTYPE: Mice homozygous for disruption of this gene are viable, fertile, and show no gross or histological abnormalities. However dopamine levels in the frontal cortex of males are increased. Also, males show increased aggression and females show increased anxiety. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 44 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Actn4 |
G |
T |
7: 28,612,855 (GRCm39) |
A116E |
probably damaging |
Het |
| Adamtsl3 |
A |
G |
7: 82,225,204 (GRCm39) |
I338V |
probably damaging |
Het |
| Akap13 |
T |
G |
7: 75,375,128 (GRCm39) |
V1920G |
probably damaging |
Het |
| Atp6v0d2 |
C |
T |
4: 19,880,055 (GRCm39) |
V281I |
probably benign |
Het |
| AW209491 |
T |
G |
13: 14,811,607 (GRCm39) |
S153R |
probably damaging |
Het |
| Brd7 |
A |
T |
8: 89,069,395 (GRCm39) |
Y433* |
probably null |
Het |
| Bub1b |
A |
G |
2: 118,440,457 (GRCm39) |
H187R |
probably damaging |
Het |
| Clstn2 |
T |
A |
9: 97,452,681 (GRCm39) |
Q242L |
probably benign |
Het |
| Col1a2 |
G |
A |
6: 4,518,822 (GRCm39) |
|
probably benign |
Het |
| Ctbs |
T |
A |
3: 146,160,862 (GRCm39) |
L143Q |
probably damaging |
Het |
| Ctsw |
T |
C |
19: 5,515,489 (GRCm39) |
|
probably benign |
Het |
| Dhx16 |
T |
C |
17: 36,194,194 (GRCm39) |
I435T |
probably damaging |
Het |
| Dmxl1 |
T |
C |
18: 50,026,469 (GRCm39) |
F1859S |
probably damaging |
Het |
| Glud1 |
A |
G |
14: 34,051,351 (GRCm39) |
|
probably benign |
Het |
| Gm8220 |
A |
G |
14: 44,524,248 (GRCm39) |
H71R |
probably damaging |
Het |
| Gnb1l |
A |
G |
16: 18,371,223 (GRCm39) |
E238G |
probably benign |
Het |
| H2-T23 |
T |
C |
17: 36,341,475 (GRCm39) |
H332R |
probably benign |
Het |
| Itga5 |
T |
A |
15: 103,259,196 (GRCm39) |
T744S |
probably benign |
Het |
| Larp1 |
A |
G |
11: 57,938,576 (GRCm39) |
E453G |
probably benign |
Het |
| Lrrk2 |
C |
A |
15: 91,640,165 (GRCm39) |
P1570Q |
probably benign |
Het |
| Lrsam1 |
C |
T |
2: 32,843,455 (GRCm39) |
R150Q |
possibly damaging |
Het |
| Mroh2a |
A |
G |
1: 88,186,386 (GRCm39) |
S64G |
probably benign |
Het |
| Msln |
T |
C |
17: 25,969,770 (GRCm39) |
Y320C |
probably damaging |
Het |
| Mtbp |
T |
C |
15: 55,426,486 (GRCm39) |
|
probably null |
Het |
| Muc5b |
A |
G |
7: 141,404,183 (GRCm39) |
|
probably null |
Het |
| Mup21 |
A |
G |
4: 62,068,547 (GRCm39) |
S40P |
probably damaging |
Het |
| Myh8 |
T |
C |
11: 67,177,090 (GRCm39) |
V414A |
probably damaging |
Het |
| P2rx5 |
T |
C |
11: 73,056,400 (GRCm39) |
I108T |
probably damaging |
Het |
| Paqr9 |
T |
C |
9: 95,442,793 (GRCm39) |
L261P |
probably damaging |
Het |
| Pde5a |
A |
G |
3: 122,522,980 (GRCm39) |
D29G |
probably benign |
Het |
| Phf11d |
A |
T |
14: 59,590,793 (GRCm39) |
M188K |
possibly damaging |
Het |
| Pih1d1 |
A |
G |
7: 44,809,106 (GRCm39) |
D230G |
probably benign |
Het |
| Pik3r1 |
G |
T |
13: 101,822,772 (GRCm39) |
D643E |
probably benign |
Het |
| Rnf207 |
A |
G |
4: 152,396,521 (GRCm39) |
|
probably benign |
Het |
| Septin9 |
T |
C |
11: 117,247,151 (GRCm39) |
|
probably benign |
Het |
| Serinc1 |
A |
T |
10: 57,401,479 (GRCm39) |
S105T |
probably benign |
Het |
| Slc8a1 |
A |
G |
17: 81,745,177 (GRCm39) |
S676P |
probably benign |
Het |
| Srrm4 |
C |
T |
5: 116,582,944 (GRCm39) |
|
probably null |
Het |
| Tcn2 |
T |
A |
11: 3,869,349 (GRCm39) |
D391V |
probably benign |
Het |
| Tmem131 |
T |
C |
1: 36,855,303 (GRCm39) |
T808A |
probably damaging |
Het |
| Ubqln3 |
G |
T |
7: 103,791,275 (GRCm39) |
Q272K |
probably damaging |
Het |
| Unc79 |
T |
C |
12: 103,139,703 (GRCm39) |
|
probably benign |
Het |
| Xpo6 |
G |
A |
7: 125,728,715 (GRCm39) |
|
probably benign |
Het |
| Zfp667 |
A |
T |
7: 6,309,091 (GRCm39) |
K586N |
possibly damaging |
Het |
|
| Other mutations in Comt |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02363:Comt
|
APN |
16 |
18,229,881 (GRCm39) |
missense |
probably benign |
0.21 |
|
IGL02568:Comt
|
APN |
16 |
18,230,454 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03286:Comt
|
APN |
16 |
18,230,490 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1318:Comt
|
UTSW |
16 |
18,226,641 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1541:Comt
|
UTSW |
16 |
18,230,565 (GRCm39) |
missense |
probably benign |
0.20 |
|
R4496:Comt
|
UTSW |
16 |
18,230,437 (GRCm39) |
splice site |
probably null |
|
|
R5619:Comt
|
UTSW |
16 |
18,230,469 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6753:Comt
|
UTSW |
16 |
18,226,771 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7286:Comt
|
UTSW |
16 |
18,229,440 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8061:Comt
|
UTSW |
16 |
18,230,040 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8419:Comt
|
UTSW |
16 |
18,230,637 (GRCm39) |
nonsense |
probably null |
|
|
R8872:Comt
|
UTSW |
16 |
18,245,239 (GRCm39) |
unclassified |
probably benign |
|
|
| Predicted Primers |
PCR Primer
(F):5'- GCCTCAATGCAGCCTTTGATGCAC -3'
(R):5'- TGGCGAACCTCCAAACCTTCACTG -3'
Sequencing Primer
(F):5'- TGTATGACAATCTGGAGCCAC -3'
(R):5'- CAAACCTTCACTGTGTGGC -3'
|
| Posted On |
2013-10-16 |
Incidental Mutation