Mutagenetix > Incidental Mutation

Incidental Mutation 'R7192:Ptrh2'

559669

Institutional Source

Beutler Lab

Gene Symbol

Ptrh2

Ensembl Gene

ENSMUSG00000072582

Gene Name

peptidyl-tRNA hydrolase 2

Synonyms

A230072I16Rik, Bit1

MMRRC Submission

045333-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.806) question?

Stock #

R7192 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

86574900-86583283 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 86580835 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 151 (T151A)

Ref Sequence

ENSEMBL: ENSMUSP00000103657 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000060766] [ENSMUST00000103186] [ENSMUST00000108021] [ENSMUST00000108022]

AlphaFold

Q8R2Y8

Predicted Effect

probably benign
Transcript: ENSMUST00000060766

SMART Domains

Protein: ENSMUSP00000050220
Gene: ENSMUSG00000047126

Domain	Start	End	E-Value	Type
Pfam:Clathrin_propel	19	56	5.3e-10	PFAM
Pfam:Clathrin_propel	152	191	1.5e-11	PFAM
Pfam:Clathrin_propel	202	238	1.2e-11	PFAM
Pfam:Clathrin_propel	257	292	2.2e-8	PFAM
Pfam:Clathrin_propel	300	334	8.6e-10	PFAM
Pfam:Clathrin-link	335	358	1.7e-17	PFAM
Pfam:Clathrin_H_link	360	425	7.1e-35	PFAM
low complexity region	449	462	N/A	INTRINSIC
CLH	541	683	1.65e-41	SMART
CLH	690	832	1.24e-45	SMART
CLH	837	976	6.68e-42	SMART
CLH	983	1128	7.21e-47	SMART
CLH	1132	1273	7.91e-44	SMART
CLH	1278	1424	1.59e-48	SMART
CLH	1427	1586	8.36e-43	SMART
low complexity region	1666	1677	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000103186

SMART Domains

Protein: ENSMUSP00000099475
Gene: ENSMUSG00000047126

Domain	Start	End	E-Value	Type
Pfam:Clathrin_propel	19	56	2e-7	PFAM
Pfam:Clathrin_propel	148	187	3.8e-9	PFAM
Pfam:Clathrin_propel	198	234	3.8e-9	PFAM
Pfam:Clathrin-link	331	354	3.5e-17	PFAM
Pfam:Clathrin_H_link	356	421	1.9e-35	PFAM
low complexity region	445	458	N/A	INTRINSIC
CLH	537	679	1.65e-41	SMART
CLH	686	828	1.24e-45	SMART
CLH	833	972	6.68e-42	SMART
CLH	979	1124	7.21e-47	SMART
CLH	1128	1269	7.91e-44	SMART
CLH	1274	1420	1.59e-48	SMART
CLH	1423	1582	8.36e-43	SMART
low complexity region	1662	1673	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000108021
AA Change: T151A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000103656
Gene: ENSMUSG00000072582
AA Change: T151A

Domain	Start	End	E-Value	Type
transmembrane domain	10	32	N/A	INTRINSIC
Pfam:PTH2	66	181	4.7e-53	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000108022
AA Change: T151A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000103657
Gene: ENSMUSG00000072582
AA Change: T151A

Domain	Start	End	E-Value	Type
transmembrane domain	10	32	N/A	INTRINSIC
Pfam:PTH2	67	181	1.9e-51	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

97% (72/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a mitochondrial protein with two putative domains, an N-terminal mitochondrial localization sequence, and a UPF0099 domain. In vitro assays suggest that this protein possesses peptidyl-tRNA hydrolase activity, to release the peptidyl moiety from tRNA, thereby preventing the accumulation of dissociated peptidyl-tRNA that could reduce the efficiency of translation. This protein also plays a role regulating cell survival and death. It promotes survival as part of an integrin-signaling pathway for cells attached to the extracellular matrix (ECM), but also promotes apoptosis in cells that have lost their attachment to the ECM, a process called anoikos. After loss of cell attachment to the ECM, this protein is phosphorylated, is released from the mitochondria into the cytosol, and promotes caspase-independent apoptosis through interactions with transcriptional regulators. This gene has been implicated in the development and progression of tumors, and mutations in this gene have been associated with an infantile multisystem neurologic, endocrine, and pancreatic disease (INMEPD) characterized by intellectual disability, postnatal microcephaly, progressive cerebellar atrophy, hearing impairment, polyneuropathy, failure to thrive, and organ fibrosis with exocrine pancreas insufficiency (PMID: 25574476). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]
PHENOTYPE: Mice homozygous for a knock-out allele display neutropenia, delayed kidney and muscle development, and postnatal death due to a runting syndrome associated with progressive muscle weakness, ataxia, and decreased weight. Cultured mouse embryonic fibroblasts show increased resistance to anoikis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700001O22Rik	G	A	2: 30,686,188 (GRCm39)	T329I	probably damaging	Het
Actl6a	C	A	3: 32,774,373 (GRCm39)	P290H	probably damaging	Het
Akap9	T	A	5: 4,055,723 (GRCm39)		probably null	Het
Anxa2r2	T	A	13: 120,488,241 (GRCm39)	K103*	probably null	Het
Bach1	C	T	16: 87,526,551 (GRCm39)	S671L	possibly damaging	Het
Cacna1c	T	C	6: 118,633,210 (GRCm39)	I1099V		Het
Cage1	G	T	13: 38,203,220 (GRCm39)	P615T	probably benign	Het
Caskin2	C	A	11: 115,692,202 (GRCm39)	R861L	probably damaging	Het
Cc2d2b	A	G	19: 40,762,881 (GRCm39)	T386A	unknown	Het
Ccndbp1	A	G	2: 120,843,424 (GRCm39)	D272G	probably damaging	Het
Cep192	T	A	18: 67,983,599 (GRCm39)	V1553E	probably damaging	Het
Cfhr4	T	A	1: 139,667,033 (GRCm39)	H414L	probably damaging	Het
Chrm5	C	T	2: 112,310,672 (GRCm39)	G148D	probably damaging	Het
Cntnap4	T	C	8: 113,608,432 (GRCm39)	V1284A	probably benign	Het
Cpd	T	C	11: 76,705,667 (GRCm39)	Y355C	probably damaging	Het
Csmd3	C	T	15: 47,567,633 (GRCm39)	V1266I		Het
Cyfip2	T	C	11: 46,145,493 (GRCm39)	E609G	probably benign	Het
Dbr1	T	C	9: 99,458,755 (GRCm39)		probably null	Het
Dmxl1	T	C	18: 50,088,920 (GRCm39)	Y2800H	probably damaging	Het
Dnajc6	G	T	4: 101,455,000 (GRCm39)	A64S	probably benign	Het
Dpp8	A	T	9: 64,953,068 (GRCm39)	N248I	possibly damaging	Het
Dsp	A	T	13: 38,379,569 (GRCm39)	I2105F	probably benign	Het
Edem1	G	A	6: 108,805,965 (GRCm39)	V89M	probably benign	Het
Eml4	A	G	17: 83,761,890 (GRCm39)	Q528R	probably benign	Het
Epb42	A	T	2: 120,854,578 (GRCm39)	V669D	unknown	Het
Fat4	A	T	3: 39,034,613 (GRCm39)	Q2755L	probably benign	Het
Gata6	A	G	18: 11,054,475 (GRCm39)	K135E	possibly damaging	Het
Gmeb1	A	T	4: 131,955,201 (GRCm39)	F325I	probably benign	Het
H2-M10.3	C	T	17: 36,677,451 (GRCm39)	E276K	probably damaging	Het
H4c17	A	T	13: 21,996,227 (GRCm39)	K92*	probably null	Het
Ifi207	T	C	1: 173,556,584 (GRCm39)	N718S	not run	Het
Il6st	A	G	13: 112,631,741 (GRCm39)	N427D	probably benign	Het
Kat7	T	A	11: 95,166,656 (GRCm39)	M509L	probably benign	Het
Klk1b4	T	C	7: 43,859,045 (GRCm39)	V21A	probably benign	Het
Malt1	T	A	18: 65,570,898 (GRCm39)	L78Q	probably benign	Het
Mertk	A	G	2: 128,635,028 (GRCm39)		probably null	Het
Myo1b	A	G	1: 51,796,376 (GRCm39)	L1016P	probably damaging	Het
Neu4	A	G	1: 93,952,863 (GRCm39)	I411V	probably benign	Het
Nutm2	A	T	13: 50,627,105 (GRCm39)	D420V	probably damaging	Het
Or10j3b	T	A	1: 173,043,575 (GRCm39)	M119K	probably damaging	Het
Or2w2	A	G	13: 21,758,539 (GRCm39)	L29P	probably damaging	Het
Or4k1	T	C	14: 50,377,577 (GRCm39)	E173G	possibly damaging	Het
Or5ac24	T	C	16: 59,165,542 (GRCm39)	D174G	probably benign	Het
Pcdha12	C	T	18: 37,153,316 (GRCm39)	R12W	probably benign	Het
Pdgfra	G	T	5: 75,343,767 (GRCm39)	D763Y	probably damaging	Het
Pkd2	T	C	5: 104,634,523 (GRCm39)	V518A	probably benign	Het
Prb1a	G	T	6: 132,184,335 (GRCm39)	P433T	unknown	Het
Qars1	T	A	9: 108,388,760 (GRCm39)	N273K	probably damaging	Het
Robo2	T	C	16: 73,717,638 (GRCm39)	Y1154C	probably benign	Het
Rps6kc1	T	A	1: 190,532,556 (GRCm39)	D482V	probably damaging	Het
Sec16b	T	C	1: 157,357,013 (GRCm39)	S74P	probably benign	Het
Serpinb2	A	T	1: 107,452,306 (GRCm39)	I295F	probably damaging	Het
Sh3pxd2b	T	A	11: 32,364,318 (GRCm39)	D301E	probably damaging	Het
Sipa1l2	G	A	8: 126,149,348 (GRCm39)	T1637I	probably benign	Het
Slc27a4	A	T	2: 29,695,941 (GRCm39)	N159Y	probably damaging	Het
Stat1	A	C	1: 52,174,780 (GRCm39)	K161Q	possibly damaging	Het
Stc2	T	C	11: 31,319,872 (GRCm39)		probably benign	Het
Strip1	A	G	3: 107,522,651 (GRCm39)	W681R	possibly damaging	Het
Sv2a	G	A	3: 96,101,062 (GRCm39)	G687S	probably damaging	Het
Thnsl2	C	T	6: 71,116,739 (GRCm39)	V138I	probably benign	Het
Tmco3	G	A	8: 13,369,605 (GRCm39)		probably null	Het
Tnfrsf1a	T	C	6: 125,338,559 (GRCm39)	S235P	unknown	Het
Tpbg	T	A	9: 85,726,085 (GRCm39)	L18*	probably null	Het
Trabd2b	A	T	4: 114,467,217 (GRCm39)	Q482L	possibly damaging	Het
Trim35	T	A	14: 66,534,895 (GRCm39)	F126Y	probably damaging	Het
Ttn	A	T	2: 76,658,288 (GRCm39)	V12364D	unknown	Het
Ubac2	A	G	14: 122,211,128 (GRCm39)	Y166C	probably damaging	Het
Unc13b	T	A	4: 43,258,519 (GRCm39)	V1320D	probably damaging	Het
Usp34	T	A	11: 23,410,571 (GRCm39)	Y2693N		Het
Utp20	A	T	10: 88,608,321 (GRCm39)	M1572K	probably benign	Het
Vmn1r7	C	T	6: 57,001,452 (GRCm39)	M269I	probably benign	Het
Vmn2r3	C	T	3: 64,167,364 (GRCm39)	G589D	probably benign	Het
Vrtn	A	T	12: 84,695,636 (GRCm39)	M129L	probably damaging	Het
Zfp273	A	T	13: 67,973,183 (GRCm39)	T104S	possibly damaging	Het
Zfp384	T	A	6: 125,010,275 (GRCm39)	N390K	probably damaging	Het
Znfx1	A	G	2: 166,884,110 (GRCm39)	M933T	probably benign	Het

Other mutations in Ptrh2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02008:Ptrh2	APN	11	86,580,592 (GRCm39)	missense	probably benign	0.05
R4774:Ptrh2	UTSW	11	86,580,833 (GRCm39)	missense	probably damaging	1.00
R4869:Ptrh2	UTSW	11	86,580,631 (GRCm39)	nonsense	probably null
R4928:Ptrh2	UTSW	11	86,580,862 (GRCm39)	missense	probably damaging	1.00
R7210:Ptrh2	UTSW	11	86,580,793 (GRCm39)	missense	probably benign
R8835:Ptrh2	UTSW	11	86,580,412 (GRCm39)	missense	probably damaging	0.97
R8992:Ptrh2	UTSW	11	86,580,907 (GRCm39)	missense	possibly damaging	0.56

Predicted Primers

PCR Primer
(F):5'- AGTGTTCTCATGCTGCCGTG -3'
(R):5'- ATGGTCTAGTACATGATAGAGGAAC -3'

Sequencing Primer
(F):5'- TGCCGTGTCTGCCTACAAG -3'
(R):5'- TCTAGTACATGATAGAGGAACATGGG -3'

Posted On

2019-06-26