Incidental Mutation 'R8093:Pam'
| ID |
629969 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pam
|
| Ensembl Gene |
ENSMUSG00000026335 |
| Gene Name |
peptidylglycine alpha-amidating monooxygenase |
| Synonyms |
PHM |
| MMRRC Submission |
067525-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R8093 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
97748816-98023578 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 97813357 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Tyrosine
at position 358
(D358Y)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000057112
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000058762]
[ENSMUST00000097625]
[ENSMUST00000161567]
|
| AlphaFold |
P97467 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000058762
AA Change: D358Y
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: D358Y
| 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: D358Y
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: D358Y
| 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 |
|
| SMART Domains |
Protein: ENSMUSP00000124479
Gene: ENSMUSG00000026335
AA Change: D64Y
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Cu2_monoox_C
|
1 |
53 |
4.3e-15 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161567
AA Change: D358Y
PolyPhen 2
Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: D358Y
| 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: 99.9%
- 3x: 99.7%
- 10x: 99.2%
- 20x: 98.3%
|
| Validation Efficiency |
100% (60/60) |
| 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: 66 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930562C15Rik |
A |
T |
16: 4,669,368 (GRCm39) |
T745S |
possibly damaging |
Het |
| Abca12 |
T |
C |
1: 71,319,552 (GRCm39) |
I1777V |
probably benign |
Het |
| Abhd6 |
T |
C |
14: 8,028,353 (GRCm38) |
L28P |
probably damaging |
Het |
| Angpt1 |
T |
A |
15: 42,339,873 (GRCm39) |
E279D |
probably benign |
Het |
| Arfgef2 |
A |
G |
2: 166,736,577 (GRCm39) |
M1750V |
probably benign |
Het |
| Atrn |
T |
C |
2: 130,817,908 (GRCm39) |
F821L |
probably benign |
Het |
| Cbx3 |
A |
G |
6: 51,458,748 (GRCm39) |
E71G |
possibly damaging |
Het |
| Ccdc14 |
G |
A |
16: 34,530,022 (GRCm39) |
A482T |
probably damaging |
Het |
| Cdh15 |
G |
T |
8: 123,593,574 (GRCm39) |
A723S |
probably damaging |
Het |
| Cyp2a12 |
A |
G |
7: 26,736,054 (GRCm39) |
S488G |
probably damaging |
Het |
| Ddx55 |
C |
A |
5: 124,694,883 (GRCm39) |
H104N |
possibly damaging |
Het |
| Det1 |
G |
T |
7: 78,493,257 (GRCm39) |
T249N |
possibly damaging |
Het |
| Disp3 |
A |
G |
4: 148,354,973 (GRCm39) |
S348P |
possibly damaging |
Het |
| Dnah6 |
T |
G |
6: 73,137,896 (GRCm39) |
N936T |
probably damaging |
Het |
| Dnajc11 |
A |
T |
4: 152,054,357 (GRCm39) |
N188Y |
probably damaging |
Het |
| Etaa1 |
G |
A |
11: 17,897,559 (GRCm39) |
T186I |
possibly damaging |
Het |
| Fhip1a |
T |
C |
3: 85,580,111 (GRCm39) |
D698G |
probably benign |
Het |
| Ftl1-ps1 |
T |
A |
13: 74,555,138 (GRCm39) |
V139E |
probably benign |
Het |
| Fzd10 |
A |
G |
5: 128,679,303 (GRCm39) |
K341R |
probably benign |
Het |
| Galnt7 |
A |
G |
8: 57,985,739 (GRCm39) |
Y544H |
probably benign |
Het |
| Gm21190 |
T |
A |
5: 15,730,814 (GRCm39) |
I181F |
possibly damaging |
Het |
| Gm3604 |
T |
C |
13: 62,517,363 (GRCm39) |
N332D |
probably damaging |
Het |
| Gm47996 |
G |
T |
1: 151,086,055 (GRCm39) |
E45D |
possibly damaging |
Het |
| Gm5475 |
T |
A |
15: 100,321,893 (GRCm39) |
L14Q |
unknown |
Het |
| Gmcl1 |
G |
T |
6: 86,698,408 (GRCm39) |
A163E |
probably damaging |
Het |
| Gpr137b |
T |
C |
13: 13,533,991 (GRCm39) |
Y355C |
|
Het |
| Gpr182 |
T |
C |
10: 127,586,783 (GRCm39) |
Y56C |
probably damaging |
Het |
| Gxylt2 |
T |
A |
6: 100,710,188 (GRCm39) |
W110R |
probably damaging |
Het |
| Hivep3 |
G |
T |
4: 119,952,632 (GRCm39) |
R316L |
possibly damaging |
Het |
| Hnf1a |
T |
C |
5: 115,093,336 (GRCm39) |
T310A |
probably benign |
Het |
| Igkv6-32 |
A |
G |
6: 70,051,547 (GRCm39) |
F8L |
probably benign |
Het |
| Kcnq1 |
A |
G |
7: 142,916,389 (GRCm39) |
N550D |
probably damaging |
Het |
| Lrrc40 |
T |
G |
3: 157,757,419 (GRCm39) |
Y249* |
probably null |
Het |
| Lrrc43 |
T |
A |
5: 123,639,192 (GRCm39) |
M407K |
probably benign |
Het |
| Map2k6 |
A |
C |
11: 110,373,411 (GRCm39) |
E21D |
probably benign |
Het |
| Mcoln1 |
T |
A |
8: 3,558,740 (GRCm39) |
I246N |
possibly damaging |
Het |
| Msantd5f6 |
A |
T |
4: 73,321,759 (GRCm39) |
V92E |
probably damaging |
Het |
| Myh2 |
A |
G |
11: 67,079,536 (GRCm39) |
K998E |
probably damaging |
Het |
| Myo1b |
C |
T |
1: 51,797,034 (GRCm39) |
|
probably null |
Het |
| Numbl |
T |
A |
7: 26,980,461 (GRCm39) |
M481K |
possibly damaging |
Het |
| Nxpe4 |
G |
T |
9: 48,307,852 (GRCm39) |
V319F |
probably benign |
Het |
| Papola |
A |
G |
12: 105,775,836 (GRCm39) |
M251V |
probably damaging |
Het |
| Pcnx1 |
C |
T |
12: 81,965,593 (GRCm39) |
R59* |
probably null |
Het |
| Prelid2 |
A |
G |
18: 42,065,700 (GRCm39) |
S112P |
probably damaging |
Het |
| Ptgfrn |
T |
C |
3: 100,963,753 (GRCm39) |
T620A |
probably benign |
Het |
| Ptgfrn |
C |
T |
3: 100,980,257 (GRCm39) |
R361Q |
probably benign |
Het |
| Pygm |
T |
A |
19: 6,436,072 (GRCm39) |
M148K |
probably damaging |
Het |
| Ren1 |
T |
A |
1: 133,287,812 (GRCm39) |
I382N |
probably damaging |
Het |
| Rev1 |
T |
C |
1: 38,114,097 (GRCm39) |
|
probably benign |
Het |
| Sdsl |
T |
C |
5: 120,598,017 (GRCm39) |
K159E |
probably benign |
Het |
| Serinc4 |
T |
C |
2: 121,285,434 (GRCm39) |
N203S |
possibly damaging |
Het |
| Slc12a2 |
A |
G |
18: 58,012,423 (GRCm39) |
H182R |
probably benign |
Het |
| Sned1 |
C |
A |
1: 93,202,387 (GRCm39) |
T677K |
possibly damaging |
Het |
| Ston2 |
G |
A |
12: 91,710,460 (GRCm39) |
T3I |
probably damaging |
Het |
| Tnf |
T |
C |
17: 35,420,072 (GRCm39) |
T77A |
probably benign |
Het |
| Trav6-2 |
G |
A |
14: 52,905,126 (GRCm39) |
G49E |
probably benign |
Het |
| Trav7-4 |
A |
T |
14: 53,699,140 (GRCm39) |
I96F |
probably damaging |
Het |
| Trmu |
T |
A |
15: 85,766,921 (GRCm39) |
D43E |
probably benign |
Het |
| Uggt1 |
T |
A |
1: 36,266,566 (GRCm39) |
Q136L |
probably damaging |
Het |
| Ugt1a5 |
T |
A |
1: 88,094,304 (GRCm39) |
Y177* |
probably null |
Het |
| Vmn1r126 |
T |
C |
7: 21,034,516 (GRCm39) |
R293G |
probably damaging |
Het |
| Vmn2r89 |
A |
G |
14: 51,693,699 (GRCm39) |
I350V |
probably benign |
Het |
| Vps11 |
A |
T |
9: 44,267,529 (GRCm39) |
L361Q |
probably damaging |
Het |
| Zfp467 |
A |
G |
6: 48,420,366 (GRCm39) |
L5P |
possibly damaging |
Het |
| Zfp652 |
A |
G |
11: 95,640,288 (GRCm39) |
H71R |
probably damaging |
Het |
| Zfp804b |
T |
C |
5: 6,820,082 (GRCm39) |
K994E |
probably benign |
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 |
|
|
R4128:Pam
|
UTSW |
1 |
97,762,193 (GRCm39) |
missense |
probably damaging |
0.99 |
|
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 |
|
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'- AATGTCAGGGAGTGGAGATTGTAT -3'
(R):5'- CGAGCACTTTCGATGTCCTGT -3'
Sequencing Primer
(F):5'- CAGGGAGTGGAGATTGTATATGAAAG -3'
(R):5'- GCACTTTCGATGTCCTGTCTACTTTC -3'
|
| Posted On |
2020-06-30 |
Incidental Mutation