Incidental Mutation 'R4128:Pam'
| ID |
315461 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pam
|
| Ensembl Gene |
ENSMUSG00000026335 |
| Gene Name |
peptidylglycine alpha-amidating monooxygenase |
| Synonyms |
PHM |
| MMRRC Submission |
041635-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4128 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
1 |
| Chromosomal Location |
97748816-98023578 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 97762193 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Histidine
at position 691
(Y691H)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000125418
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000058762]
[ENSMUST00000097625]
[ENSMUST00000161567]
|
| AlphaFold |
P97467 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000058762
AA Change: Y797H
PolyPhen 2
Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: Y797H
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
24 |
N/A |
INTRINSIC |
|
Pfam:Cu2_monooxygen
|
62 |
178 |
7.8e-27 |
PFAM |
|
Pfam:Cu2_monoox_C
|
199 |
346 |
6.2e-47 |
PFAM |
|
Pfam:NHL
|
633 |
662 |
2.1e-8 |
PFAM |
|
low complexity region
|
673 |
680 |
N/A |
INTRINSIC |
|
Pfam:NHL
|
686 |
714 |
2.7e-8 |
PFAM |
|
Pfam:NHL
|
782 |
809 |
2.8e-7 |
PFAM |
|
transmembrane domain
|
870 |
892 |
N/A |
INTRINSIC |
|
low complexity region
|
908 |
930 |
N/A |
INTRINSIC |
|
low complexity region
|
950 |
969 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000097625
AA Change: Y797H
PolyPhen 2
Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: Y797H
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
24 |
N/A |
INTRINSIC |
|
Pfam:Cu2_monooxygen
|
60 |
183 |
3.7e-34 |
PFAM |
|
Pfam:Cu2_monoox_C
|
198 |
349 |
1.4e-54 |
PFAM |
|
Pfam:NHL
|
581 |
608 |
9.4e-9 |
PFAM |
|
Pfam:NHL
|
633 |
662 |
2.1e-8 |
PFAM |
|
low complexity region
|
673 |
680 |
N/A |
INTRINSIC |
|
Pfam:NHL
|
686 |
714 |
2.2e-8 |
PFAM |
|
Pfam:NHL
|
782 |
809 |
3.6e-8 |
PFAM |
|
transmembrane domain
|
869 |
891 |
N/A |
INTRINSIC |
|
low complexity region
|
907 |
929 |
N/A |
INTRINSIC |
|
low complexity region
|
949 |
968 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000159041
|
| SMART Domains |
Protein: ENSMUSP00000124284
Gene: ENSMUSG00000026335
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
37 |
44 |
N/A |
INTRINSIC |
|
Pfam:NHL
|
50 |
78 |
4.2e-9 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000159131
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000159585
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161567
AA Change: Y691H
PolyPhen 2
Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: Y691H
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
24 |
N/A |
INTRINSIC |
|
Pfam:Cu2_monooxygen
|
60 |
183 |
3.2e-34 |
PFAM |
|
Pfam:Cu2_monoox_C
|
198 |
349 |
1.2e-54 |
PFAM |
|
Pfam:NHL
|
475 |
502 |
8.3e-9 |
PFAM |
|
Pfam:NHL
|
527 |
556 |
1.9e-8 |
PFAM |
|
low complexity region
|
567 |
574 |
N/A |
INTRINSIC |
|
Pfam:NHL
|
580 |
608 |
1.9e-8 |
PFAM |
|
Pfam:NHL
|
676 |
703 |
3.2e-8 |
PFAM |
|
transmembrane domain
|
764 |
786 |
N/A |
INTRINSIC |
|
low complexity region
|
802 |
824 |
N/A |
INTRINSIC |
|
low complexity region
|
844 |
863 |
N/A |
INTRINSIC |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000162681
AA Change: Y92H
|
| SMART Domains |
Protein: ENSMUSP00000125133
Gene: ENSMUSG00000026335
AA Change: Y92H
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:NHL
|
78 |
105 |
6.2e-8 |
PFAM |
|
low complexity region
|
160 |
179 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000162803
|
| Meta Mutation Damage Score |
0.5819 |
| Coding Region Coverage |
- 1x: 99.4%
- 3x: 98.6%
- 10x: 97.1%
- 20x: 94.5%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
PHENOTYPE: Homozygous mutation of this gene results in embryonic lethality during fetal growth and development, edema, abnormal yolk sac vasculature, thin arterial walls, and abnormal bronchial epithelial morphology. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 34 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adamtsl4 |
C |
T |
3: 95,588,982 (GRCm39) |
R483Q |
probably benign |
Het |
| Bbox1 |
A |
G |
2: 110,100,525 (GRCm39) |
V224A |
probably benign |
Het |
| Cavin2 |
A |
G |
1: 51,340,581 (GRCm39) |
*419W |
probably null |
Het |
| Cdk19 |
A |
G |
10: 40,270,391 (GRCm39) |
I67V |
probably benign |
Het |
| Cds2 |
A |
G |
2: 132,139,191 (GRCm39) |
T145A |
probably benign |
Het |
| Chn2 |
G |
T |
6: 54,249,963 (GRCm39) |
R24M |
probably damaging |
Het |
| Csl |
T |
C |
10: 99,594,462 (GRCm39) |
D201G |
probably benign |
Het |
| Erap1 |
T |
C |
13: 74,814,315 (GRCm39) |
I33T |
probably damaging |
Het |
| Ermap |
T |
C |
4: 119,044,308 (GRCm39) |
T163A |
possibly damaging |
Het |
| Gnas |
A |
G |
2: 174,141,958 (GRCm39) |
N709S |
possibly damaging |
Het |
| Hsd17b14 |
G |
A |
7: 45,212,432 (GRCm39) |
V155M |
probably damaging |
Het |
| Igf2bp2 |
C |
T |
16: 21,897,371 (GRCm39) |
V281I |
probably benign |
Het |
| Ighj4 |
T |
C |
12: 113,392,176 (GRCm39) |
|
probably benign |
Het |
| Ireb2 |
T |
A |
9: 54,788,716 (GRCm39) |
D63E |
probably benign |
Het |
| Jarid2 |
T |
C |
13: 45,055,732 (GRCm39) |
S313P |
probably damaging |
Het |
| Kcnj11 |
A |
G |
7: 45,749,143 (GRCm39) |
F60S |
probably damaging |
Het |
| Lyplal1 |
A |
G |
1: 185,821,736 (GRCm39) |
C129R |
possibly damaging |
Het |
| Mertk |
C |
T |
2: 128,619,358 (GRCm39) |
Q539* |
probably null |
Het |
| Myrip |
C |
A |
9: 120,293,764 (GRCm39) |
S753* |
probably null |
Het |
| Narf |
G |
A |
11: 121,141,261 (GRCm39) |
|
probably null |
Het |
| Neb |
C |
A |
2: 52,182,712 (GRCm39) |
L1051F |
probably damaging |
Het |
| Nid1 |
T |
C |
13: 13,650,957 (GRCm39) |
V498A |
probably damaging |
Het |
| Or10ab5 |
T |
C |
7: 108,245,633 (GRCm39) |
N50S |
probably benign |
Het |
| Or14j8 |
A |
G |
17: 38,263,681 (GRCm39) |
I78T |
probably benign |
Het |
| Poln |
A |
G |
5: 34,261,295 (GRCm39) |
S561P |
probably benign |
Het |
| Rab39 |
T |
A |
9: 53,597,804 (GRCm39) |
I154L |
probably benign |
Het |
| Rnf187 |
A |
T |
11: 58,824,883 (GRCm39) |
S220T |
probably benign |
Het |
| Stac |
C |
A |
9: 111,433,126 (GRCm39) |
|
probably null |
Het |
| Stxbp3 |
T |
C |
3: 108,702,147 (GRCm39) |
Q553R |
probably benign |
Het |
| Tmem179 |
A |
T |
12: 112,477,461 (GRCm39) |
F8I |
possibly damaging |
Het |
| Trip11 |
G |
A |
12: 101,861,957 (GRCm39) |
Q203* |
probably null |
Het |
| Ubash3a |
T |
C |
17: 31,456,249 (GRCm39) |
Y506H |
probably damaging |
Het |
| Unc13c |
C |
A |
9: 73,641,819 (GRCm39) |
A1225S |
probably damaging |
Het |
| Zranb1 |
C |
A |
7: 132,568,281 (GRCm39) |
S313* |
probably null |
Het |
|
| Other mutations in Pam |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00467:Pam
|
APN |
1 |
97,852,152 (GRCm39) |
splice site |
probably benign |
|
|
IGL00485:Pam
|
APN |
1 |
97,750,678 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
IGL00597:Pam
|
APN |
1 |
97,762,169 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL01585:Pam
|
APN |
1 |
97,792,197 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01776:Pam
|
APN |
1 |
97,813,325 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL01981:Pam
|
APN |
1 |
97,762,166 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02152:Pam
|
APN |
1 |
97,768,474 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02605:Pam
|
APN |
1 |
97,768,064 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
IGL02882:Pam
|
APN |
1 |
97,768,092 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03142:Pam
|
APN |
1 |
97,822,111 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03409:Pam
|
APN |
1 |
97,792,054 (GRCm39) |
missense |
probably benign |
0.04 |
|
R0084:Pam
|
UTSW |
1 |
97,823,774 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0200:Pam
|
UTSW |
1 |
97,822,126 (GRCm39) |
splice site |
probably null |
|
|
R0520:Pam
|
UTSW |
1 |
97,811,920 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0734:Pam
|
UTSW |
1 |
97,792,087 (GRCm39) |
nonsense |
probably null |
|
|
R1881:Pam
|
UTSW |
1 |
97,850,876 (GRCm39) |
missense |
probably benign |
0.06 |
|
R2040:Pam
|
UTSW |
1 |
97,792,167 (GRCm39) |
missense |
possibly damaging |
0.55 |
|
R2106:Pam
|
UTSW |
1 |
97,759,215 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2913:Pam
|
UTSW |
1 |
97,850,854 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3148:Pam
|
UTSW |
1 |
97,823,403 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R3618:Pam
|
UTSW |
1 |
97,762,157 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3619:Pam
|
UTSW |
1 |
97,762,157 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3847:Pam
|
UTSW |
1 |
97,782,481 (GRCm39) |
intron |
probably benign |
|
|
R3848:Pam
|
UTSW |
1 |
97,782,481 (GRCm39) |
intron |
probably benign |
|
|
R3849:Pam
|
UTSW |
1 |
97,782,481 (GRCm39) |
intron |
probably benign |
|
|
R4231:Pam
|
UTSW |
1 |
97,811,849 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4233:Pam
|
UTSW |
1 |
97,792,119 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R4404:Pam
|
UTSW |
1 |
97,782,446 (GRCm39) |
intron |
probably benign |
|
|
R4536:Pam
|
UTSW |
1 |
97,772,424 (GRCm39) |
nonsense |
probably null |
|
|
R4738:Pam
|
UTSW |
1 |
97,850,857 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5054:Pam
|
UTSW |
1 |
97,749,642 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5501:Pam
|
UTSW |
1 |
97,768,090 (GRCm39) |
nonsense |
probably null |
|
|
R5572:Pam
|
UTSW |
1 |
97,782,469 (GRCm39) |
intron |
probably benign |
|
|
R5654:Pam
|
UTSW |
1 |
97,792,123 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5659:Pam
|
UTSW |
1 |
97,770,024 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6112:Pam
|
UTSW |
1 |
97,762,193 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6513:Pam
|
UTSW |
1 |
97,765,752 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
R6696:Pam
|
UTSW |
1 |
97,813,452 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R6743:Pam
|
UTSW |
1 |
97,823,774 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6833:Pam
|
UTSW |
1 |
97,765,717 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6834:Pam
|
UTSW |
1 |
97,765,717 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7098:Pam
|
UTSW |
1 |
97,826,072 (GRCm39) |
missense |
probably benign |
|
|
R7117:Pam
|
UTSW |
1 |
97,904,841 (GRCm39) |
start gained |
probably benign |
|
|
R7152:Pam
|
UTSW |
1 |
97,813,465 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7172:Pam
|
UTSW |
1 |
97,762,203 (GRCm39) |
missense |
probably benign |
0.10 |
|
R7206:Pam
|
UTSW |
1 |
97,823,757 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7262:Pam
|
UTSW |
1 |
97,782,448 (GRCm39) |
missense |
|
|
|
R7434:Pam
|
UTSW |
1 |
97,903,515 (GRCm39) |
nonsense |
probably null |
|
|
R7466:Pam
|
UTSW |
1 |
97,769,972 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7513:Pam
|
UTSW |
1 |
97,780,910 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R7790:Pam
|
UTSW |
1 |
97,749,572 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8054:Pam
|
UTSW |
1 |
97,768,114 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8093:Pam
|
UTSW |
1 |
97,813,357 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8183:Pam
|
UTSW |
1 |
97,762,199 (GRCm39) |
missense |
probably benign |
0.08 |
|
R8404:Pam
|
UTSW |
1 |
97,823,358 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8734:Pam
|
UTSW |
1 |
97,762,127 (GRCm39) |
splice site |
probably benign |
|
|
R9092:Pam
|
UTSW |
1 |
97,791,976 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9229:Pam
|
UTSW |
1 |
97,753,660 (GRCm39) |
missense |
probably benign |
0.02 |
|
R9261:Pam
|
UTSW |
1 |
97,903,620 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9409:Pam
|
UTSW |
1 |
97,749,585 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9435:Pam
|
UTSW |
1 |
97,822,144 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9476:Pam
|
UTSW |
1 |
97,826,065 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9500:Pam
|
UTSW |
1 |
97,772,325 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9510:Pam
|
UTSW |
1 |
97,826,065 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9653:Pam
|
UTSW |
1 |
97,768,469 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
Z1176:Pam
|
UTSW |
1 |
97,862,448 (GRCm39) |
missense |
probably benign |
0.01 |
|
| Predicted Primers |
PCR Primer
(F):5'- TGAAGATGCCAGACACGTGC -3'
(R):5'- AATGAACAGCTGCCGTTGG -3'
Sequencing Primer
(F):5'- GATGCCAGACACGTGCTGAAC -3'
(R):5'- CCGTTGGCTGGAGTTGC -3'
|
| Posted On |
2015-05-14 |
Incidental Mutation