Incidental Mutation 'R5054:Pam'
| ID |
390682 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pam
|
| Ensembl Gene |
ENSMUSG00000026335 |
| Gene Name |
peptidylglycine alpha-amidating monooxygenase |
| Synonyms |
PHM |
| MMRRC Submission |
042644-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5054 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
97748816-98023578 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 97749642 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Tyrosine
at position 839
(D839Y)
|
| 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: D945Y
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: D945Y
| 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: D944Y
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: D944Y
| 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: ENSMUST00000159585
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000160210
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161567
AA Change: D839Y
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: D839Y
| 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: D154Y
|
| SMART Domains |
Protein: ENSMUSP00000125133
Gene: ENSMUSG00000026335
AA Change: D154Y
| 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 |
0.4095 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.1%
|
| Validation Efficiency |
94% (67/71) |
| 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: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4921517D22Rik |
A |
G |
13: 59,837,315 (GRCm39) |
Y257H |
probably damaging |
Het |
| Adam28 |
C |
T |
14: 68,855,164 (GRCm39) |
C659Y |
probably damaging |
Het |
| Adamtsl2 |
G |
A |
2: 26,991,732 (GRCm39) |
E627K |
probably damaging |
Het |
| Atad5 |
T |
A |
11: 79,985,502 (GRCm39) |
S196R |
probably benign |
Het |
| Bcam |
T |
A |
7: 19,490,785 (GRCm39) |
|
probably benign |
Het |
| Birc6 |
A |
G |
17: 74,962,320 (GRCm39) |
H3978R |
probably damaging |
Het |
| Btbd7 |
T |
C |
12: 102,804,471 (GRCm39) |
I190V |
probably benign |
Het |
| Ccdc8 |
T |
C |
7: 16,728,970 (GRCm39) |
V153A |
probably damaging |
Het |
| Cyp2a5 |
C |
G |
7: 26,540,529 (GRCm39) |
R68G |
probably damaging |
Het |
| Dock3 |
T |
C |
9: 106,815,105 (GRCm39) |
Y1254C |
probably damaging |
Het |
| Dync2h1 |
T |
C |
9: 7,085,007 (GRCm39) |
E2794G |
possibly damaging |
Het |
| Dytn |
C |
A |
1: 63,700,318 (GRCm39) |
V271L |
possibly damaging |
Het |
| Eif1ad15 |
T |
C |
12: 88,288,071 (GRCm39) |
I61V |
probably benign |
Het |
| Eif2s2 |
A |
C |
2: 154,734,590 (GRCm39) |
|
probably null |
Het |
| Fndc7 |
A |
G |
3: 108,788,663 (GRCm39) |
S193P |
probably damaging |
Het |
| Fzr1 |
G |
A |
10: 81,207,253 (GRCm39) |
|
probably benign |
Het |
| Gm17472 |
T |
C |
6: 42,957,938 (GRCm39) |
I69T |
probably damaging |
Het |
| Gmppa |
C |
A |
1: 75,416,015 (GRCm39) |
Y137* |
probably null |
Het |
| Gpr45 |
A |
G |
1: 43,071,809 (GRCm39) |
I151V |
probably benign |
Het |
| H1f0 |
G |
A |
15: 78,912,973 (GRCm39) |
A18T |
probably damaging |
Het |
| Hbb-bh1 |
C |
T |
7: 103,491,063 (GRCm39) |
V114I |
probably benign |
Het |
| Impa2 |
C |
A |
18: 67,439,797 (GRCm39) |
P98Q |
probably damaging |
Het |
| Kazn |
T |
C |
4: 141,835,957 (GRCm39) |
N573D |
unknown |
Het |
| Kcna2 |
A |
T |
3: 107,011,656 (GRCm39) |
D79V |
probably damaging |
Het |
| Kcna7 |
G |
A |
7: 45,056,015 (GRCm39) |
R77H |
probably damaging |
Het |
| Kif13a |
A |
G |
13: 46,956,122 (GRCm39) |
Y561H |
probably damaging |
Het |
| Klk14 |
G |
A |
7: 43,341,501 (GRCm39) |
C51Y |
probably damaging |
Het |
| Klra1 |
T |
A |
6: 130,352,247 (GRCm39) |
Q165L |
probably damaging |
Het |
| Mat2b |
T |
A |
11: 40,570,869 (GRCm39) |
R318S |
probably damaging |
Het |
| Mgat4d |
G |
A |
8: 84,094,837 (GRCm39) |
|
probably null |
Het |
| Mtor |
T |
A |
4: 148,641,312 (GRCm39) |
|
probably null |
Het |
| Nostrin |
A |
T |
2: 69,006,057 (GRCm39) |
Q247L |
possibly damaging |
Het |
| Obi1 |
C |
T |
14: 104,745,466 (GRCm39) |
G70E |
probably damaging |
Het |
| Obscn |
T |
C |
11: 58,964,443 (GRCm39) |
E3033G |
probably damaging |
Het |
| Pds5a |
A |
G |
5: 65,795,157 (GRCm39) |
V693A |
probably damaging |
Het |
| Pigo |
A |
T |
4: 43,021,337 (GRCm39) |
L535Q |
probably damaging |
Het |
| Ppp1r12b |
G |
T |
1: 134,883,471 (GRCm39) |
A17E |
probably benign |
Het |
| Ptar1 |
G |
T |
19: 23,671,729 (GRCm39) |
R44L |
probably damaging |
Het |
| Rad51c |
T |
C |
11: 87,288,580 (GRCm39) |
H201R |
probably benign |
Het |
| Rims2 |
A |
T |
15: 39,381,265 (GRCm39) |
|
probably null |
Het |
| Rpl22l1 |
T |
G |
3: 28,860,985 (GRCm39) |
S67A |
possibly damaging |
Het |
| Rps10 |
A |
G |
17: 27,849,454 (GRCm39) |
S143P |
probably damaging |
Het |
| Rundc1 |
T |
C |
11: 101,315,967 (GRCm39) |
V13A |
probably benign |
Het |
| Sephs2 |
C |
A |
7: 126,872,564 (GRCm39) |
M176I |
probably benign |
Het |
| Serpina16 |
C |
T |
12: 103,641,189 (GRCm39) |
V179I |
probably benign |
Het |
| Serpini2 |
T |
A |
3: 75,166,784 (GRCm39) |
T158S |
probably damaging |
Het |
| Slc12a3 |
A |
G |
8: 95,072,979 (GRCm39) |
R701G |
probably damaging |
Het |
| Slc1a6 |
A |
G |
10: 78,650,436 (GRCm39) |
E558G |
probably damaging |
Het |
| Ssx2ip |
T |
C |
3: 146,136,672 (GRCm39) |
|
probably benign |
Het |
| Tbr1 |
A |
T |
2: 61,636,346 (GRCm39) |
I241F |
possibly damaging |
Het |
| Tgfa |
G |
C |
6: 86,247,064 (GRCm39) |
|
probably null |
Het |
| Tlr12 |
T |
A |
4: 128,511,063 (GRCm39) |
K396* |
probably null |
Het |
| Tmppe |
A |
G |
9: 114,235,026 (GRCm39) |
I442V |
probably benign |
Het |
| Tubb3 |
T |
C |
8: 124,147,607 (GRCm39) |
V180A |
probably damaging |
Het |
| Vmn1r222 |
A |
G |
13: 23,416,901 (GRCm39) |
V104A |
probably damaging |
Het |
| Vmn2r95 |
G |
T |
17: 18,671,708 (GRCm39) |
V482L |
possibly damaging |
Het |
| Zfp184 |
G |
T |
13: 22,143,452 (GRCm39) |
R386L |
possibly damaging |
Het |
| Zfp444 |
T |
A |
7: 6,192,792 (GRCm39) |
V270E |
probably damaging |
Het |
| Zfp985 |
A |
T |
4: 147,667,438 (GRCm39) |
Y102F |
probably damaging |
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 |
|
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'- ATGCACAGAACTTTACACGCG -3'
(R):5'- TCTGGTTCTGTAAGGGAAATCTC -3'
Sequencing Primer
(F):5'- CAGAACTTTACACGCGTTAAAGG -3'
(R):5'- CTACTGTGGCATTCGATC -3'
|
| Posted On |
2016-06-06 |
Incidental Mutation