Incidental Mutation 'R6513:Pam'
ID 519978
Institutional Source Beutler Lab
Gene Symbol Pam
Ensembl Gene ENSMUSG00000026335
Gene Name peptidylglycine alpha-amidating monooxygenase
Synonyms PHM
MMRRC Submission 044640-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6513 (G1)
Quality Score 225.009
Status Validated
Chromosome 1
Chromosomal Location 97748816-98023578 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 97765752 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 759 (V759A)
Ref Sequence ENSEMBL: ENSMUSP00000057112 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000058762] [ENSMUST00000097625] [ENSMUST00000161567]
AlphaFold P97467
Predicted Effect possibly damaging
Transcript: ENSMUST00000058762
AA Change: V759A

PolyPhen 2 Score 0.599 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335
AA Change: V759A

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 benign
Transcript: ENSMUST00000097625
AA Change: V759A

PolyPhen 2 Score 0.117 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335
AA Change: V759A

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 unknown
Transcript: ENSMUST00000159041
AA Change: V122A
SMART Domains Protein: ENSMUSP00000124284
Gene: ENSMUSG00000026335
AA Change: V122A

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000161567
AA Change: V653A

PolyPhen 2 Score 0.234 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335
AA Change: V653A

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 unknown
Transcript: ENSMUST00000162681
AA Change: V54A
SMART Domains Protein: ENSMUSP00000125133
Gene: ENSMUSG00000026335
AA Change: V54A

DomainStartEndE-ValueType
Pfam:NHL 78 105 6.2e-8 PFAM
low complexity region 160 179 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000162803
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 97.8%
  • 20x: 93.4%
Validation Efficiency 98% (62/63)
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: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4932438H23Rik T C 16: 90,852,654 (GRCm39) S161G probably benign Het
Ankfy1 G A 11: 72,621,308 (GRCm39) R198Q possibly damaging Het
Ankrd11 A G 8: 123,616,919 (GRCm39) V2290A probably benign Het
Aox4 A G 1: 58,252,212 (GRCm39) N29S probably benign Het
Arhgap17 T C 7: 122,891,379 (GRCm39) R592G possibly damaging Het
Caap1 A T 4: 94,389,640 (GRCm39) D231E possibly damaging Het
Cabp1 T A 5: 115,307,193 (GRCm39) M165L possibly damaging Het
Calhm4 T A 10: 33,917,630 (GRCm39) R274* probably null Het
Cep72 A T 13: 74,206,582 (GRCm39) L73H probably damaging Het
Cfap74 A G 4: 155,525,743 (GRCm39) S731G probably null Het
Dsc2 T C 18: 20,179,295 (GRCm39) I258V probably benign Het
Dsg1c T G 18: 20,407,687 (GRCm39) N344K probably benign Het
Enah A G 1: 181,841,920 (GRCm39) probably benign Het
Fbn1 T A 2: 125,225,591 (GRCm39) S554C probably damaging Het
Fkrp C A 7: 16,545,037 (GRCm39) R275L possibly damaging Het
Gbp4 C T 5: 105,270,986 (GRCm39) G215D possibly damaging Het
Gli2 G A 1: 118,783,284 (GRCm39) L239F probably damaging Het
Gpr146 A G 5: 139,378,573 (GRCm39) D125G probably damaging Het
Hectd4 C A 5: 121,494,259 (GRCm39) probably null Het
Invs G A 4: 48,397,534 (GRCm39) V370I possibly damaging Het
Kdm2b A G 5: 123,018,302 (GRCm39) V1040A probably damaging Het
Kidins220 T A 12: 25,088,434 (GRCm39) V1059D possibly damaging Het
Kif26a T A 12: 112,141,926 (GRCm39) S727T probably damaging Het
Kifbp T C 10: 62,410,813 (GRCm39) probably null Het
Klk1b27 A G 7: 43,705,169 (GRCm39) H112R probably benign Het
Krt72 T G 15: 101,685,187 (GRCm39) probably null Het
Lactb C T 9: 66,878,172 (GRCm39) R219H probably damaging Het
Lrig2 A T 3: 104,373,045 (GRCm39) I612N probably damaging Het
Meaf6 A C 4: 124,983,697 (GRCm39) N51T probably damaging Het
Mtap A G 4: 89,066,498 (GRCm39) T36A possibly damaging Het
Myo3a G A 2: 22,412,143 (GRCm39) G713S probably damaging Het
Nr4a3 C T 4: 48,083,255 (GRCm39) T596I probably damaging Het
Or10ak14 A T 4: 118,611,224 (GRCm39) C172* probably null Het
Or4f14 C G 2: 111,743,228 (GRCm39) G16R possibly damaging Het
Pcare T A 17: 72,051,701 (GRCm39) E1217V probably damaging Het
Pds5a T A 5: 65,772,944 (GRCm39) I1220F probably benign Het
Phldb2 T A 16: 45,568,240 (GRCm39) M1222L possibly damaging Het
Phospho1 C T 11: 95,721,513 (GRCm39) A61V possibly damaging Het
Pnpla7 G A 2: 24,906,550 (GRCm39) V638I possibly damaging Het
Pramel34 C A 5: 93,785,391 (GRCm39) probably null Het
Ptf1a T A 2: 19,451,848 (GRCm39) D282E probably damaging Het
Ptgs2 A T 1: 149,975,879 (GRCm39) probably benign Het
Racgap1 T C 15: 99,522,156 (GRCm39) R471G probably damaging Het
Rptn T C 3: 93,303,419 (GRCm39) S251P possibly damaging Het
Shcbp1 T C 8: 4,794,507 (GRCm39) M429V probably benign Het
Shprh T C 10: 11,062,637 (GRCm39) L1248P probably damaging Het
Son T C 16: 91,456,835 (GRCm39) probably benign Het
Sppl3 T C 5: 115,233,995 (GRCm39) L355P probably damaging Het
Tbc1d31 A T 15: 57,818,778 (GRCm39) R794W probably damaging Het
Telo2 T C 17: 25,320,386 (GRCm39) Y766C probably damaging Het
Tfr2 A G 5: 137,572,793 (GRCm39) probably null Het
Tle4 T C 19: 14,429,056 (GRCm39) D722G probably damaging Het
Tprg1l A G 4: 154,243,862 (GRCm39) V98A probably benign Het
Trak1 C T 9: 121,272,822 (GRCm39) R237C probably benign Het
Vmn2r113 T C 17: 23,177,715 (GRCm39) I833T probably damaging Het
Vmn2r118 T A 17: 55,915,093 (GRCm39) S518C probably damaging Het
Vmn2r49 A G 7: 9,710,524 (GRCm39) I736T probably damaging Het
Wdr38 T A 2: 38,889,970 (GRCm39) probably null Het
Wee2 A G 6: 40,429,553 (GRCm39) E180G probably benign Het
Zbtb1 T C 12: 76,432,604 (GRCm39) S197P possibly damaging Het
Zc3h7a T C 16: 10,976,629 (GRCm39) probably null Het
Zfp516 T A 18: 82,973,835 (GRCm39) L11Q probably damaging Het
Zfp623 G A 15: 75,819,317 (GRCm39) R91H probably benign Het
Zkscan7 G A 9: 122,725,170 (GRCm39) R713Q probably benign 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
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'- ATATGACTGTCCACTCAGCTAAG -3'
(R):5'- TCTGTTTGGCCCAGATCTGATAAC -3'

Sequencing Primer
(F):5'- CTGTCCACTCAGCTAAGAAAGTTGTC -3'
(R):5'- TTGGCCCAGATCTGATAACTCACTAC -3'
Posted On 2018-06-06