Incidental Mutation 'R9409:Pam'
ID 711698
Institutional Source Beutler Lab
Gene Symbol Pam
Ensembl Gene ENSMUSG00000026335
Gene Name peptidylglycine alpha-amidating monooxygenase
Synonyms PHM
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9409 (G1)
Quality Score 225.009
Status Not validated
Chromosome 1
Chromosomal Location 97748816-98023578 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 97749585 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 964 (S964P)
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: S964P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: S964P

DomainStartEndE-ValueType
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: S963P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: S963P

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
low complexity region 37 44 N/A INTRINSIC
Pfam:NHL 50 78 4.2e-9 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000161567
AA Change: S858P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: S858P

DomainStartEndE-ValueType
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
SMART Domains Protein: ENSMUSP00000125133
Gene: ENSMUSG00000026335
AA Change: S173P

DomainStartEndE-ValueType
Pfam:NHL 78 105 6.2e-8 PFAM
low complexity region 160 179 N/A INTRINSIC
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.6%
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: 32 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700030K09Rik A T 8: 73,211,888 (GRCm39) I538F possibly damaging Het
Arih2 C G 9: 108,488,938 (GRCm39) R260P probably damaging Het
Ccdc138 A G 10: 58,374,135 (GRCm39) H385R probably damaging Het
Cep43 T C 17: 8,411,088 (GRCm39) V367A probably benign Het
Cfhr1 T C 1: 139,478,704 (GRCm39) D222G probably benign Het
Cpb2 A T 14: 75,505,522 (GRCm39) I173F probably damaging Het
Creb3l1 C T 2: 91,822,231 (GRCm39) probably null Het
Ebf2 T C 14: 67,472,665 (GRCm39) S28P probably damaging Het
Eomes A T 9: 118,314,069 (GRCm39) T705S probably benign Het
Fbxo15 T A 18: 84,977,246 (GRCm39) W98R possibly damaging Het
Gm12258 T C 11: 58,745,119 (GRCm39) F17L Het
Grin2c C T 11: 115,144,106 (GRCm39) R697H probably benign Het
Ighmbp2 C A 19: 3,318,832 (GRCm39) A415S possibly damaging Het
Il6st C G 13: 112,640,872 (GRCm39) Q883E probably benign Het
Med17 T C 9: 15,176,695 (GRCm39) M511V probably benign Het
Or2n1d A T 17: 38,646,320 (GRCm39) T91S possibly damaging Het
Or8b39 G A 9: 37,996,584 (GRCm39) G151R probably damaging Het
Pacrg A T 17: 10,996,065 (GRCm39) I67N probably damaging Het
Pcdh15 A G 10: 74,160,190 (GRCm39) T436A probably damaging Het
Pgap4 T A 4: 49,586,043 (GRCm39) E375V probably damaging Het
Rag1 A T 2: 101,473,192 (GRCm39) L650Q probably damaging Het
Rhobtb1 A T 10: 69,106,217 (GRCm39) T323S probably benign Het
Rhot2 T C 17: 26,060,085 (GRCm39) T299A probably benign Het
Rnf180 CGAGG CGAGGAGG 13: 105,386,781 (GRCm39) probably benign Het
Ryr2 C A 13: 11,695,973 (GRCm39) V2965F probably damaging Het
Serpina1b A T 12: 103,694,607 (GRCm39) M379K probably benign Het
Serpinb9 A G 13: 33,192,797 (GRCm39) Q118R probably benign Het
Slc16a14 G A 1: 84,907,116 (GRCm39) Q53* probably null Het
Tas2r130 T A 6: 131,607,660 (GRCm39) D45V probably damaging Het
Tie1 T C 4: 118,339,945 (GRCm39) N361D probably damaging Het
Tmtc2 G T 10: 105,159,419 (GRCm39) L560M probably damaging Het
Trav13-5 G T 14: 54,033,277 (GRCm39) R62L possibly damaging Het
Other mutations in Pam
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- TGTACAGTTCCACACGGACG -3'
(R):5'- CATCTGGTTCTGTAAGGGAAATCTC -3'

Sequencing Primer
(F):5'- TTCCACACGGACGAGTACAGTTTAC -3'
(R):5'- GCAGCGGCTTAAATCTAG -3'
Posted On 2022-05-16