Mutagenetix > Incidental Mutations

Incidental Mutation 'R4231:Pam'

320818

Institutional Source

Beutler Lab

Gene Symbol

Pam

Ensembl Gene

ENSMUSG00000026335

Gene Name

peptidylglycine alpha-amidating monooxygenase

Synonyms

PHM

MMRRC Submission

041050-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4231 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

97795114-98095646 bp(-) (GRCm38)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

A to G at 97884124 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000125418 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000058762] [ENSMUST00000097625] [ENSMUST00000161567]

AlphaFold

P97467

Predicted Effect

probably null
Transcript: ENSMUST00000058762

SMART Domains

Protein: ENSMUSP00000057112
Gene: ENSMUSG00000026335

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 null
Transcript: ENSMUST00000097625

SMART Domains

Protein: ENSMUSP00000095228
Gene: ENSMUSG00000026335

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 null
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

probably null
Transcript: ENSMUST00000161567

SMART Domains

Protein: ENSMUSP00000125418
Gene: ENSMUSG00000026335

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

noncoding transcript
Transcript: ENSMUST00000192914

Meta Mutation Damage Score

0.9490

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.2%

Validation Efficiency

99% (75/76)

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
4930567H17Rik	C	T	X: 70,394,529	A53T	probably benign	Het
4932438A13Rik	C	T	3: 36,920,236	T663I	probably benign	Het
Ajuba	T	C	14: 54,569,526	R490G	probably damaging	Het
Akap6	A	T	12: 53,141,038	D1745V	probably damaging	Het
Aldh5a1	C	T	13: 24,911,653	G494R	probably damaging	Het
Ankar	T	C	1: 72,658,542	D1034G	probably benign	Het
Aox3	T	A	1: 58,114,885	N23K	probably benign	Het
Arhgef18	T	C	8: 3,450,317	I541T	possibly damaging	Het
Atg14	T	C	14: 47,551,345	K184E	probably benign	Het
Cacnb2	A	G	2: 14,981,440	K343E	probably damaging	Het
Casp8	T	C	1: 58,844,770	V432A	probably damaging	Het
Cd93	A	T	2: 148,442,960	H155Q	probably benign	Het
Cox6b2	T	C	7: 4,752,835	M1V	probably null	Het
Crat	T	C	2: 30,413,011	E88G	possibly damaging	Het
Ddx1	C	T	12: 13,223,857	V590I	possibly damaging	Het
Dip2a	G	A	10: 76,319,470	P94S	probably damaging	Het
Dtx3	A	G	10: 127,193,189	I60T	possibly damaging	Het
Fam196b	A	T	11: 34,403,143	E395V	probably benign	Het
Filip1l	T	C	16: 57,506,768	S54P	probably benign	Het
Gm12887	A	T	4: 121,622,102	M1K	probably null	Het
Gm26678	T	C	3: 54,633,083		noncoding transcript	Het
Impg1	A	G	9: 80,345,329	L523P	probably damaging	Het
Ip6k2	G	A	9: 108,805,648	R319Q	probably benign	Het
Irak2	A	G	6: 113,690,856	E466G	probably damaging	Het
Irgm2	C	T	11: 58,219,478		probably benign	Het
Jak3	T	A	8: 71,685,545	V880D	probably damaging	Het
Jmy	G	T	13: 93,498,925	P128T	probably benign	Het
Kif20a	A	G	18: 34,632,038	N775S	probably benign	Het
Kremen1	G	A	11: 5,243,881	Q50*	probably null	Het
Lrrc71	A	G	3: 87,740,991	I438T	probably benign	Het
Map3k1	T	C	13: 111,768,494	T374A	probably benign	Het
Med12l	T	G	3: 59,257,223		probably null	Het
Mrps30	T	C	13: 118,386,840	D132G	probably damaging	Het
Mta1	T	C	12: 113,135,827	M603T	possibly damaging	Het
Myo5a	A	G	9: 75,189,997	N1319S	possibly damaging	Het
Nalcn	T	A	14: 123,599,913	Q13L	probably benign	Het
Nbas	A	G	12: 13,393,343	N1133S	probably damaging	Het
Nsun2	A	G	13: 69,619,541	N205D	probably damaging	Het
Nxpe4	A	T	9: 48,398,837	T467S	probably damaging	Het
Olfr1293-ps	C	T	2: 111,528,201	R314C	probably damaging	Het
Olfr53	T	C	7: 140,652,740	Y254H	probably damaging	Het
Olfr849	T	A	9: 19,441,590	L226I	probably damaging	Het
Pcdh7	G	A	5: 57,719,289	G62D	possibly damaging	Het
Plxna2	C	T	1: 194,644,454	T232I	probably damaging	Het
Prkar1b	A	G	5: 139,108,621	S71P	probably benign	Het
Ptprq	A	T	10: 107,686,283	Y602*	probably null	Het
Rfx4	A	T	10: 84,814,694	M84L	probably benign	Het
Rfx7	A	T	9: 72,619,390	E1287D	possibly damaging	Het
Rin2	C	T	2: 145,860,446	T354I	probably benign	Het
Rnf216	A	T	5: 143,093,090	S35T	probably damaging	Het
Rps6kc1	A	G	1: 190,808,900	V402A	probably damaging	Het
Rufy4	T	C	1: 74,147,663	C537R	probably damaging	Het
Sart3	A	G	5: 113,771,418	M73T	probably benign	Het
Scn10a	G	T	9: 119,631,544	T1088K	probably damaging	Het
Senp2	T	C	16: 22,011,554		probably null	Het
Setd7	T	C	3: 51,542,730	N92D	probably benign	Het
Sipa1	A	T	19: 5,654,089	L735Q	probably damaging	Het
Skint11	C	A	4: 114,244,659	Q99K	probably benign	Het
Slitrk6	A	T	14: 110,751,388	S296T	probably benign	Het
Spc24	T	C	9: 21,756,202		probably null	Het
Tex15	T	C	8: 33,572,137	S806P	probably damaging	Het
Tgm3	A	T	2: 130,044,589	K577*	probably null	Het
Wscd2	A	G	5: 113,560,984	D200G	probably benign	Het
Xpo6	T	C	7: 126,174,182	T24A	possibly damaging	Het
Zfhx2	A	G	14: 55,073,534	C568R	possibly damaging	Het
Zfp599	T	A	9: 22,249,745	K375*	probably null	Het

Other mutations in Pam

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00467:Pam	APN	1	97924427	splice site	probably benign
IGL00485:Pam	APN	1	97822953	missense	possibly damaging	0.78
IGL00597:Pam	APN	1	97834444	missense	probably benign	0.02
IGL01585:Pam	APN	1	97864472	missense	probably damaging	0.99
IGL01776:Pam	APN	1	97885600	critical splice donor site	probably null
IGL01981:Pam	APN	1	97834441	missense	probably damaging	1.00
IGL02152:Pam	APN	1	97840749	missense	probably damaging	1.00
IGL02605:Pam	APN	1	97840339	missense	possibly damaging	0.85
IGL02882:Pam	APN	1	97840367	missense	probably damaging	1.00
IGL03142:Pam	APN	1	97894386	missense	probably damaging	1.00
IGL03409:Pam	APN	1	97864329	missense	probably benign	0.04
R0084:Pam	UTSW	1	97896049	missense	probably benign	0.01
R0200:Pam	UTSW	1	97894401	splice site	probably null
R0520:Pam	UTSW	1	97884195	missense	probably benign	0.00
R0734:Pam	UTSW	1	97864362	nonsense	probably null
R1881:Pam	UTSW	1	97923151	missense	probably benign	0.06
R2040:Pam	UTSW	1	97864442	missense	possibly damaging	0.55
R2106:Pam	UTSW	1	97831490	missense	probably damaging	1.00
R2913:Pam	UTSW	1	97923129	missense	probably damaging	1.00
R3148:Pam	UTSW	1	97895678	missense	possibly damaging	0.84
R3618:Pam	UTSW	1	97834432	missense	probably damaging	1.00
R3619:Pam	UTSW	1	97834432	missense	probably damaging	1.00
R3847:Pam	UTSW	1	97854756	intron	probably benign
R3848:Pam	UTSW	1	97854756	intron	probably benign
R3849:Pam	UTSW	1	97854756	intron	probably benign
R4128:Pam	UTSW	1	97834468	missense	probably damaging	0.99
R4233:Pam	UTSW	1	97864394	missense	possibly damaging	0.86
R4404:Pam	UTSW	1	97854721	intron	probably benign
R4536:Pam	UTSW	1	97844699	nonsense	probably null
R4738:Pam	UTSW	1	97923132	missense	probably damaging	1.00
R5054:Pam	UTSW	1	97821917	missense	probably damaging	1.00
R5501:Pam	UTSW	1	97840365	nonsense	probably null
R5572:Pam	UTSW	1	97854744	intron	probably benign
R5654:Pam	UTSW	1	97864398	missense	probably benign	0.00
R5659:Pam	UTSW	1	97842299	missense	probably damaging	1.00
R6112:Pam	UTSW	1	97834468	missense	probably damaging	0.99
R6513:Pam	UTSW	1	97838027	missense	possibly damaging	0.60
R6696:Pam	UTSW	1	97885727	missense	possibly damaging	0.79
R6743:Pam	UTSW	1	97896049	missense	probably benign	0.01
R6833:Pam	UTSW	1	97837992	missense	probably damaging	0.99
R6834:Pam	UTSW	1	97837992	missense	probably damaging	0.99
R7098:Pam	UTSW	1	97898347	missense	probably benign
R7117:Pam	UTSW	1	97977116	start gained	probably benign
R7152:Pam	UTSW	1	97885740	missense	probably damaging	1.00
R7172:Pam	UTSW	1	97834478	missense	probably benign	0.10
R7206:Pam	UTSW	1	97896032	missense	probably damaging	1.00
R7262:Pam	UTSW	1	97854723	missense
R7434:Pam	UTSW	1	97975790	nonsense	probably null
R7466:Pam	UTSW	1	97842247	missense	probably damaging	1.00
R7513:Pam	UTSW	1	97853185	missense	possibly damaging	0.88
R7790:Pam	UTSW	1	97821847	missense	probably damaging	1.00
R8054:Pam	UTSW	1	97840389	missense	probably damaging	1.00
R8093:Pam	UTSW	1	97885632	missense	probably damaging	1.00
R8183:Pam	UTSW	1	97834474	missense	probably benign	0.08
R8404:Pam	UTSW	1	97895633	missense	probably damaging	1.00
R8734:Pam	UTSW	1	97834402	splice site	probably benign
R9092:Pam	UTSW	1	97864251	missense	probably benign	0.00
R9229:Pam	UTSW	1	97825935	missense	probably benign	0.02
R9261:Pam	UTSW	1	97975895	missense	probably benign	0.00
R9409:Pam	UTSW	1	97821860
R9435:Pam	UTSW	1	97894419
Z1176:Pam	UTSW	1	97934723	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- GGTTAAGTGTGATAAATGGCCAC -3'
(R):5'- ACAAGACGGATGGTTGTGCTG -3'

Sequencing Primer
(F):5'- CAGTGAAGATATGGTCTGAGG -3'
(R):5'- CCAGTGTAATGAACATAAGGTCCTG -3'

Posted On

2015-06-12