Incidental Mutation 'R3148:Pam'
| ID | 264310 |
|---|
| Institutional Source |
Beutler Lab
|
|---|
| Gene Symbol |
Pam
|
|---|
| Ensembl Gene |
ENSMUSG00000026335 |
|---|
| Gene Name | peptidylglycine alpha-amidating monooxygenase |
|---|
| Synonyms | PHM |
|---|
| MMRRC Submission |
040600-MU
|
|---|
| Accession Numbers | |
|---|
| Is this an essential gene? |
Essential (E-score: 1.000)
|
|---|
| Stock # | R3148 (G1)
|
|---|
| Quality Score | 225 |
|---|
| Status |
Not validated
|
|---|
| Chromosome | 1 |
|---|
| Chromosomal Location | 97795114-98095646 bp(-) (GRCm38) |
|---|
| Type of Mutation | missense |
|---|
| DNA Base Change (assembly) |
T to A
at 97895678 bp
|
|---|
| Zygosity | Heterozygous |
|---|
| Amino Acid Change |
Asparagine to Isoleucine
at position 256
(N256I)
|
|---|
| Ref Sequence |
ENSEMBL: ENSMUSP00000095228
(fasta)
|
|---|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000058762]
[ENSMUST00000097625]
[ENSMUST00000161567]
|
|---|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000058762
AA Change: N256I
PolyPhen 2
Score 0.838 (Sensitivity: 0.84; Specificity: 0.93)
|
|---|
| SMART Domains |
Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: N256I
| 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 |
possibly damaging
Transcript: ENSMUST00000097625
AA Change: N256I
PolyPhen 2
Score 0.838 (Sensitivity: 0.84; Specificity: 0.93)
|
|---|
| SMART Domains |
Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: N256I
| 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: ENSMUST00000159841
|
|---|
| SMART Domains |
Protein: ENSMUSP00000124479
Gene: ENSMUSG00000026335
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Cu2_monoox_C
|
1 |
53 |
4.3e-15 |
PFAM |
|
|---|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000161567
AA Change: N256I
PolyPhen 2
Score 0.697 (Sensitivity: 0.86; Specificity: 0.92)
|
|---|
| SMART Domains |
Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: N256I
| 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 |
|
|---|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.7%
- 10x: 97.6%
- 20x: 95.9%
|
|---|
| 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: 26 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4933436I01Rik |
T |
C |
X: 67,921,378 |
D12G |
probably benign |
Het |
| Adamts18 |
C |
A |
8: 113,738,858 |
V701L |
probably damaging |
Het |
| Alg2 |
A |
T |
4: 47,472,259 |
V183D |
probably damaging |
Het |
| Ank2 |
T |
C |
3: 126,933,075 |
I857V |
probably benign |
Het |
| Asb15 |
G |
T |
6: 24,566,259 |
A404S |
probably damaging |
Het |
| Baalc |
A |
T |
15: 38,949,173 |
E106V |
possibly damaging |
Het |
| Catsperd |
G |
T |
17: 56,664,039 |
C701F |
possibly damaging |
Het |
| Cc2d2a |
T |
A |
5: 43,709,155 |
I769N |
probably damaging |
Het |
| Cntnap4 |
A |
G |
8: 112,757,439 |
T375A |
probably damaging |
Het |
| Col7a1 |
A |
G |
9: 108,961,405 |
T974A |
unknown |
Het |
| Ehbp1 |
T |
C |
11: 22,100,465 |
Y502C |
probably damaging |
Het |
| Gm13083 |
A |
T |
4: 143,617,477 |
D449V |
probably benign |
Het |
| Kcnj11 |
C |
T |
7: 46,099,120 |
V260I |
probably benign |
Het |
| Klk14 |
G |
A |
7: 43,692,077 |
C51Y |
probably damaging |
Het |
| Marf1 |
A |
G |
16: 14,125,979 |
V1380A |
possibly damaging |
Het |
| Olfr1280 |
T |
C |
2: 111,316,288 |
F270L |
possibly damaging |
Het |
| Otog |
T |
C |
7: 46,290,169 |
L2124P |
probably damaging |
Het |
| Pcbp1 |
C |
T |
6: 86,525,489 |
E143K |
probably damaging |
Het |
| Prrx1 |
T |
C |
1: 163,257,848 |
D171G |
probably benign |
Het |
| Rasal2 |
A |
T |
1: 157,243,764 |
|
probably benign |
Het |
| Serpinb5 |
T |
A |
1: 106,881,825 |
H320Q |
probably damaging |
Het |
| Snx4 |
A |
C |
16: 33,287,724 |
D296A |
probably benign |
Het |
| Sorcs2 |
T |
C |
5: 36,035,788 |
Q778R |
probably benign |
Het |
| Spata16 |
T |
C |
3: 26,878,712 |
|
probably null |
Het |
| Tcerg1l |
G |
T |
7: 138,259,867 |
Q378K |
probably benign |
Het |
| Trpm1 |
T |
C |
7: 64,235,012 |
Y814H |
probably benign |
Het |
|
|---|
| Other mutations in Pam |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00467:Pam
|
APN |
1 |
97924427 |
splice site |
probably benign |
|
|
IGL00485:Pam
|
APN |
1 |
97822953 |
missense |
possibly damaging |
0.78 |
|
IGL00597:Pam
|
APN |
1 |
97834444 |
missense |
probably benign |
0.02 |
|
IGL01585:Pam
|
APN |
1 |
97864472 |
missense |
probably damaging |
0.99 |
|
IGL01776:Pam
|
APN |
1 |
97885600 |
critical splice donor site |
probably null |
|
|
IGL01981:Pam
|
APN |
1 |
97834441 |
missense |
probably damaging |
1.00 |
|
IGL02152:Pam
|
APN |
1 |
97840749 |
missense |
probably damaging |
1.00 |
|
IGL02605:Pam
|
APN |
1 |
97840339 |
missense |
possibly damaging |
0.85 |
|
IGL02882:Pam
|
APN |
1 |
97840367 |
missense |
probably damaging |
1.00 |
|
IGL03142:Pam
|
APN |
1 |
97894386 |
missense |
probably damaging |
1.00 |
|
IGL03409:Pam
|
APN |
1 |
97864329 |
missense |
probably benign |
0.04 |
|
R0084:Pam
|
UTSW |
1 |
97896049 |
missense |
probably benign |
0.01 |
|
R0200:Pam
|
UTSW |
1 |
97894401 |
splice site |
probably null |
|
|
R0520:Pam
|
UTSW |
1 |
97884195 |
missense |
probably benign |
0.00 |
|
R0734:Pam
|
UTSW |
1 |
97864362 |
nonsense |
probably null |
|
|
R1881:Pam
|
UTSW |
1 |
97923151 |
missense |
probably benign |
0.06 |
|
R2040:Pam
|
UTSW |
1 |
97864442 |
missense |
possibly damaging |
0.55 |
|
R2106:Pam
|
UTSW |
1 |
97831490 |
missense |
probably damaging |
1.00 |
|
R2913:Pam
|
UTSW |
1 |
97923129 |
missense |
probably damaging |
1.00 |
|
R3618:Pam
|
UTSW |
1 |
97834432 |
missense |
probably damaging |
1.00 |
|
R3619:Pam
|
UTSW |
1 |
97834432 |
missense |
probably damaging |
1.00 |
|
R3847:Pam
|
UTSW |
1 |
97854756 |
intron |
probably benign |
|
|
R3848:Pam
|
UTSW |
1 |
97854756 |
intron |
probably benign |
|
|
R3849:Pam
|
UTSW |
1 |
97854756 |
intron |
probably benign |
|
|
R4128:Pam
|
UTSW |
1 |
97834468 |
missense |
probably damaging |
0.99 |
|
R4231:Pam
|
UTSW |
1 |
97884124 |
critical splice donor site |
probably null |
|
|
R4233:Pam
|
UTSW |
1 |
97864394 |
missense |
possibly damaging |
0.86 |
|
R4404:Pam
|
UTSW |
1 |
97854721 |
intron |
probably benign |
|
|
R4536:Pam
|
UTSW |
1 |
97844699 |
nonsense |
probably null |
|
|
R4738:Pam
|
UTSW |
1 |
97923132 |
missense |
probably damaging |
1.00 |
|
R5054:Pam
|
UTSW |
1 |
97821917 |
missense |
probably damaging |
1.00 |
|
R5501:Pam
|
UTSW |
1 |
97840365 |
nonsense |
probably null |
|
|
R5572:Pam
|
UTSW |
1 |
97854744 |
intron |
probably benign |
|
|
R5654:Pam
|
UTSW |
1 |
97864398 |
missense |
probably benign |
0.00 |
|
R5659:Pam
|
UTSW |
1 |
97842299 |
missense |
probably damaging |
1.00 |
|
R6112:Pam
|
UTSW |
1 |
97834468 |
missense |
probably damaging |
0.99 |
|
R6513:Pam
|
UTSW |
1 |
97838027 |
missense |
possibly damaging |
0.60 |
|
R6696:Pam
|
UTSW |
1 |
97885727 |
missense |
possibly damaging |
0.79 |
|
R6743:Pam
|
UTSW |
1 |
97896049 |
missense |
probably benign |
0.01 |
|
R6833:Pam
|
UTSW |
1 |
97837992 |
missense |
probably damaging |
0.99 |
|
R6834:Pam
|
UTSW |
1 |
97837992 |
missense |
probably damaging |
0.99 |
|
R7098:Pam
|
UTSW |
1 |
97898347 |
missense |
probably benign |
|
|
R7117:Pam
|
UTSW |
1 |
97977116 |
start gained |
probably benign |
|
|
R7152:Pam
|
UTSW |
1 |
97885740 |
missense |
probably damaging |
1.00 |
|
R7172:Pam
|
UTSW |
1 |
97834478 |
missense |
probably benign |
0.10 |
|
R7206:Pam
|
UTSW |
1 |
97896032 |
missense |
probably damaging |
1.00 |
|
R7262:Pam
|
UTSW |
1 |
97854723 |
missense |
|
|
|
R7434:Pam
|
UTSW |
1 |
97975790 |
nonsense |
probably null |
|
|
R7466:Pam
|
UTSW |
1 |
97842247 |
missense |
probably damaging |
1.00 |
|
R7513:Pam
|
UTSW |
1 |
97853185 |
missense |
possibly damaging |
0.88 |
|
R7790:Pam
|
UTSW |
1 |
97821847 |
missense |
probably damaging |
1.00 |
|
R8054:Pam
|
UTSW |
1 |
97840389 |
missense |
probably damaging |
1.00 |
|
R8093:Pam
|
UTSW |
1 |
97885632 |
missense |
probably damaging |
1.00 |
|
R8183:Pam
|
UTSW |
1 |
97834474 |
missense |
probably benign |
0.08 |
|
R8404:Pam
|
UTSW |
1 |
97895633 |
missense |
probably damaging |
1.00 |
|
Z1176:Pam
|
UTSW |
1 |
97934723 |
missense |
probably benign |
0.01 |
|
|---|
| Predicted Primers |
PCR Primer
(F):5'- AACTGCCACCATATCGAGAG -3'
(R):5'- CGAATTCCTTGAACTCTTATGATGC -3'
Sequencing Primer
(F):5'- TCGAGAGAACCGATGAAGTATTAAAC -3'
(R):5'- GATGCTTCATTAAGATAGGCAACAG -3'
|
|---|
| Posted On | 2015-02-05 |
|---|
