Mutagenetix > Incidental Mutation

Incidental Mutation 'R3148:Pam'

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

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3148 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

97748816-98023578 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 97823403 bp (GRCm39)

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]

AlphaFold

P97467

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: 66,964,984 (GRCm39)	D12G	probably benign	Het
Adamts18	C	A	8: 114,465,490 (GRCm39)	V701L	probably damaging	Het
Alg2	A	T	4: 47,472,259 (GRCm39)	V183D	probably damaging	Het
Ank2	T	C	3: 126,726,724 (GRCm39)	I857V	probably benign	Het
Asb15	G	T	6: 24,566,258 (GRCm39)	A404S	probably damaging	Het
Baalc	A	T	15: 38,812,568 (GRCm39)	E106V	possibly damaging	Het
Catsperd	G	T	17: 56,971,039 (GRCm39)	C701F	possibly damaging	Het
Cc2d2a	T	A	5: 43,866,497 (GRCm39)	I769N	probably damaging	Het
Cntnap4	A	G	8: 113,484,071 (GRCm39)	T375A	probably damaging	Het
Col7a1	A	G	9: 108,790,473 (GRCm39)	T974A	unknown	Het
Ehbp1	T	C	11: 22,050,465 (GRCm39)	Y502C	probably damaging	Het
Kcnj11	C	T	7: 45,748,544 (GRCm39)	V260I	probably benign	Het
Klk14	G	A	7: 43,341,501 (GRCm39)	C51Y	probably damaging	Het
Marf1	A	G	16: 13,943,843 (GRCm39)	V1380A	possibly damaging	Het
Or4k36	T	C	2: 111,146,633 (GRCm39)	F270L	possibly damaging	Het
Otog	T	C	7: 45,939,593 (GRCm39)	L2124P	probably damaging	Het
Pcbp1	C	T	6: 86,502,471 (GRCm39)	E143K	probably damaging	Het
Pramel21	A	T	4: 143,344,047 (GRCm39)	D449V	probably benign	Het
Prrx1	T	C	1: 163,085,417 (GRCm39)	D171G	probably benign	Het
Rasal2	A	T	1: 157,071,334 (GRCm39)		probably benign	Het
Serpinb5	T	A	1: 106,809,555 (GRCm39)	H320Q	probably damaging	Het
Snx4	A	C	16: 33,108,094 (GRCm39)	D296A	probably benign	Het
Sorcs2	T	C	5: 36,193,132 (GRCm39)	Q778R	probably benign	Het
Spata16	T	C	3: 26,932,861 (GRCm39)		probably null	Het
Tcerg1l	G	T	7: 137,861,596 (GRCm39)	Q378K	probably benign	Het
Trpm1	T	C	7: 63,884,760 (GRCm39)	Y814H	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
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
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'- AACTGCCACCATATCGAGAG -3'
(R):5'- CGAATTCCTTGAACTCTTATGATGC -3'

Sequencing Primer
(F):5'- TCGAGAGAACCGATGAAGTATTAAAC -3'
(R):5'- GATGCTTCATTAAGATAGGCAACAG -3'

Posted On

2015-02-05