Mutagenetix > Incidental Mutation

Incidental Mutation 'R3776:Slc25a19'

273604

Institutional Source

Beutler Lab

Gene Symbol

Slc25a19

Ensembl Gene

ENSMUSG00000020744

Gene Name

solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19

Synonyms

2900089E13Rik, DNC, MUP1, TPC

MMRRC Submission

040874-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3776 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

115505004-115519121 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 115506285 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 303 (Y303H)

Ref Sequence

ENSEMBL: ENSMUSP00000137534 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021087] [ENSMUST00000021089] [ENSMUST00000106503] [ENSMUST00000106506] [ENSMUST00000106507] [ENSMUST00000135552] [ENSMUST00000178003] [ENSMUST00000148574]

AlphaFold

Q9DAM5

Predicted Effect

probably benign
Transcript: ENSMUST00000021087

SMART Domains

Protein: ENSMUSP00000021087
Gene: ENSMUSG00000020743

Domain	Start	End	E-Value	Type
Pfam:MIF4G	4	205	1.4e-14	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000021089
AA Change: Y303H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000021089
Gene: ENSMUSG00000020744
AA Change: Y303H

Domain	Start	End	E-Value	Type
Pfam:Mito_carr	12	111	5.7e-20	PFAM
Pfam:Mito_carr	114	205	5.3e-24	PFAM
Pfam:Mito_carr	212	313	5.2e-23	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000106503

SMART Domains

Protein: ENSMUSP00000102112
Gene: ENSMUSG00000020744

Domain	Start	End	E-Value	Type
Pfam:Mito_carr	11	111	1.7e-22	PFAM
Pfam:Mito_carr	114	172	9.7e-9	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000106506

SMART Domains

Protein: ENSMUSP00000102115
Gene: ENSMUSG00000020743

Domain	Start	End	E-Value	Type
Pfam:MIF4G	4	186	1.1e-9	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000106507

SMART Domains

Protein: ENSMUSP00000102116
Gene: ENSMUSG00000020743

Domain	Start	End	E-Value	Type
Pfam:MIF4G	4	204	3.5e-15	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124407

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127132

Predicted Effect

probably damaging
Transcript: ENSMUST00000135552
AA Change: Y220H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000114566
Gene: ENSMUSG00000020744
AA Change: Y220H

Domain	Start	End	E-Value	Type
Pfam:Mito_carr	31	122	1.1e-25	PFAM
Pfam:Mito_carr	129	226	4.7e-25	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000178003
AA Change: Y303H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000137534
Gene: ENSMUSG00000020744
AA Change: Y303H

Domain	Start	End	E-Value	Type
Pfam:Mito_carr	11	111	1.1e-21	PFAM
Pfam:Mito_carr	114	205	7e-25	PFAM
Pfam:Mito_carr	212	313	1e-24	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137304

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000180919

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144083

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139556

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142637

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129194

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146244

Predicted Effect

probably benign
Transcript: ENSMUST00000148574

SMART Domains

Protein: ENSMUSP00000119643
Gene: ENSMUSG00000020743

Domain	Start	End	E-Value	Type
Pfam:MIF4G	4	162	1.3e-7	PFAM

Meta Mutation Damage Score

0.7410

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.3%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutation of this gene results in lethality by E12, neural tube closure defects resulting in exencephaly and microcephaly, growth arrest, anemia, elevated alpha-ketoglutarate in amniotic fluid, and reduced thiamine pyrophosphate content in mitochondria. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 44 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acer1	C	T	17: 57,262,111 (GRCm39)	V264M	probably damaging	Het
Adgrg1	C	T	8: 95,736,283 (GRCm39)	S479F	probably damaging	Het
Ank2	T	A	3: 126,735,911 (GRCm39)		probably benign	Het
Atp2b1	CTTTTT	CTTTTTT	10: 98,815,731 (GRCm39)		probably null	Het
Ccdc88c	G	A	12: 100,913,438 (GRCm39)	T529M	probably damaging	Het
Cdc27	T	G	11: 104,406,263 (GRCm39)	E617D	probably damaging	Het
Cfap54	A	G	10: 92,880,962 (GRCm39)	V367A	probably damaging	Het
Col6a4	G	A	9: 105,928,900 (GRCm39)	Q1445*	probably null	Het
Crispld2	T	C	8: 120,756,005 (GRCm39)	S325P	probably damaging	Het
Dll1	T	C	17: 15,588,786 (GRCm39)	S630G	probably benign	Het
Ednra	A	G	8: 78,401,724 (GRCm39)	S189P	probably damaging	Het
Eif6	T	A	2: 155,668,296 (GRCm39)	T20S	possibly damaging	Het
Fbxl5	A	G	5: 43,915,618 (GRCm39)	V555A	possibly damaging	Het
Gdpd5	G	A	7: 99,103,779 (GRCm39)	R422Q	probably benign	Het
Glt1d1	T	A	5: 127,771,375 (GRCm39)	F289I	probably damaging	Het
Gm5565	T	A	5: 146,095,419 (GRCm39)	E192V	probably benign	Het
Gpc5	T	C	14: 115,607,472 (GRCm39)	M358T	probably benign	Het
Helz2	G	A	2: 180,882,182 (GRCm39)	R204*	probably null	Het
Hhex	A	T	19: 37,425,718 (GRCm39)	Q149L	probably damaging	Het
Kat2b	A	G	17: 53,874,609 (GRCm39)		probably null	Het
Kif23	G	A	9: 61,832,274 (GRCm39)	S623L	probably benign	Het
Klra2	A	T	6: 131,219,926 (GRCm39)	L85H	probably benign	Het
Krt32	A	G	11: 99,978,947 (GRCm39)	C36R	probably benign	Het
Megf10	G	A	18: 57,410,177 (GRCm39)	G653S	probably damaging	Het
Mpp3	G	T	11: 101,914,193 (GRCm39)	S134*	probably null	Het
Mttp	T	C	3: 137,820,024 (GRCm39)		probably null	Het
Mxi1	C	A	19: 53,360,160 (GRCm39)	A294E	probably benign	Het
Nin	G	T	12: 70,085,456 (GRCm39)	Q1592K	possibly damaging	Het
Nlrc5	A	G	8: 95,199,467 (GRCm39)	E26G	possibly damaging	Het
Nup160	G	T	2: 90,552,420 (GRCm39)	C1132F	probably benign	Het
Or4a15	A	T	2: 89,193,108 (GRCm39)	S222T	possibly damaging	Het
Pdgfc	A	G	3: 81,048,858 (GRCm39)	T89A	probably damaging	Het
Pdgfrb	A	G	18: 61,214,992 (GRCm39)	D1007G	probably benign	Het
Pgbd1	A	G	13: 21,612,543 (GRCm39)	L98P	probably benign	Het
Pkhd1l1	G	A	15: 44,378,371 (GRCm39)		probably null	Het
Plod1	A	G	4: 148,015,734 (GRCm39)	V105A	possibly damaging	Het
Polg2	G	T	11: 106,670,110 (GRCm39)	F53L	probably benign	Het
Ptprc	T	G	1: 137,992,511 (GRCm39)	Q1205H	probably damaging	Het
Rab3gap2	T	C	1: 185,009,402 (GRCm39)	L1086P	probably damaging	Het
Rnf19a	T	A	15: 36,266,058 (GRCm39)	N13I	probably benign	Het
Tnrc6c	C	T	11: 117,614,355 (GRCm39)	R838W	probably damaging	Het
Trpm3	T	C	19: 22,955,966 (GRCm39)	F1143L	possibly damaging	Het
Ubxn11	C	T	4: 133,835,605 (GRCm39)	P4S	probably damaging	Het
Zg16	T	A	7: 126,649,704 (GRCm39)	I86F	probably damaging	Het

Other mutations in Slc25a19

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
Baggins	UTSW	11	115,508,386 (GRCm39)	missense	possibly damaging	0.91
rings	UTSW	11	115,506,377 (GRCm39)	missense	probably benign	0.14
BB001:Slc25a19	UTSW	11	115,506,376 (GRCm39)	missense	unknown
BB011:Slc25a19	UTSW	11	115,506,376 (GRCm39)	missense	unknown
PIT4498001:Slc25a19	UTSW	11	115,514,781 (GRCm39)	missense	possibly damaging	0.80
R0335:Slc25a19	UTSW	11	115,515,032 (GRCm39)	missense	probably damaging	1.00
R0398:Slc25a19	UTSW	11	115,508,401 (GRCm39)	missense	probably damaging	1.00
R0454:Slc25a19	UTSW	11	115,508,423 (GRCm39)	nonsense	probably null
R1614:Slc25a19	UTSW	11	115,507,449 (GRCm39)	nonsense	probably null
R3775:Slc25a19	UTSW	11	115,506,285 (GRCm39)	missense	probably damaging	1.00
R5000:Slc25a19	UTSW	11	115,507,497 (GRCm39)	splice site	probably null
R5593:Slc25a19	UTSW	11	115,507,418 (GRCm39)	missense	probably damaging	1.00
R5738:Slc25a19	UTSW	11	115,515,060 (GRCm39)	missense	probably benign	0.24
R6167:Slc25a19	UTSW	11	115,506,377 (GRCm39)	missense	probably benign	0.14
R6306:Slc25a19	UTSW	11	115,508,386 (GRCm39)	missense	possibly damaging	0.91
R7014:Slc25a19	UTSW	11	115,511,792 (GRCm39)	missense	probably damaging	1.00
R7161:Slc25a19	UTSW	11	115,507,373 (GRCm39)	missense	possibly damaging	0.66
R7924:Slc25a19	UTSW	11	115,506,376 (GRCm39)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- AGCTCCGGATGACTTCATGC -3'
(R):5'- TTAGAAAGAGTGAGGAGCTCCC -3'

Sequencing Primer
(F):5'- GATGACTTCATGCTCCCGG -3'
(R):5'- CAGGCAGTTACAGGAGCTGC -3'

Posted On

2015-03-25