Mutagenetix > Incidental Mutation

Incidental Mutation 'R1614:Slc25a19'

177012

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

039651-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1614 (G1)

Quality Score

192

Status

Validated

Chromosome

Chromosomal Location

115505004-115519121 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

A to T at 115507449 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Stop codon at position 224 (C224*)

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 null
Transcript: ENSMUST00000021089
AA Change: C224*

SMART Domains

Protein: ENSMUSP00000021089
Gene: ENSMUSG00000020744
AA Change: C224*

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

possibly damaging
Transcript: ENSMUST00000106503
AA Change: V163E

PolyPhen 2 Score 0.564 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000102112
Gene: ENSMUSG00000020744
AA Change: V163E

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 null
Transcript: ENSMUST00000135552
AA Change: C141*

SMART Domains

Protein: ENSMUSP00000114566
Gene: ENSMUSG00000020744
AA Change: C141*

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 null
Transcript: ENSMUST00000178003
AA Change: C224*

SMART Domains

Protein: ENSMUSP00000137534
Gene: ENSMUSG00000020744
AA Change: C224*

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: ENSMUST00000129194

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146244

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142637

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

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

0.9755

Coding Region Coverage

1x: 99.0%
3x: 98.1%
10x: 95.4%
20x: 89.4%

Validation Efficiency

100% (53/53)

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arl9	A	G	5: 77,158,412 (GRCm39)	T165A	probably benign	Het
Atpaf1	A	T	4: 115,653,954 (GRCm39)	K201N	possibly damaging	Het
Cacna1b	G	T	2: 24,580,819 (GRCm39)	Q676K	possibly damaging	Het
Ccdc88c	A	T	12: 100,879,243 (GRCm39)	H1959Q	probably benign	Het
Cep162	T	C	9: 87,094,985 (GRCm39)	D808G	probably damaging	Het
Chct1	T	G	11: 85,063,690 (GRCm39)	S28A	possibly damaging	Het
Chtf18	A	G	17: 25,946,064 (GRCm39)	L42P	probably benign	Het
Cox7c	A	G	13: 86,193,904 (GRCm39)	F40L	probably benign	Het
Dock7	C	T	4: 98,949,517 (GRCm39)	V442I	probably benign	Het
Dst	T	C	1: 34,314,344 (GRCm39)	F4198S	probably damaging	Het
Fam13a	T	A	6: 58,917,169 (GRCm39)	D569V	probably damaging	Het
Gm6741	T	A	17: 91,544,424 (GRCm39)	H62Q	probably benign	Het
Gnptab	A	G	10: 88,250,451 (GRCm39)	T172A	probably benign	Het
Greb1	A	G	12: 16,751,172 (GRCm39)	S1013P	probably damaging	Het
Insl5	A	T	4: 102,883,846 (GRCm39)	L25*	probably null	Het
Ipo13	A	G	4: 117,761,815 (GRCm39)	S462P	probably benign	Het
Itgb1	G	A	8: 129,446,546 (GRCm39)	C401Y	probably damaging	Het
Kcnh7	G	T	2: 62,680,948 (GRCm39)	A213E	probably benign	Het
Kcnv1	G	A	15: 44,977,840 (GRCm39)	T66M	probably damaging	Het
Mesp2	T	C	7: 79,461,367 (GRCm39)	S231P	probably benign	Het
Nabp1	T	C	1: 51,510,511 (GRCm39)	N164D	possibly damaging	Het
Nop53	A	G	7: 15,679,890 (GRCm39)	V30A	probably benign	Het
Or1j17	T	G	2: 36,578,321 (GRCm39)	Y102*	probably null	Het
Or4a73	T	A	2: 89,421,040 (GRCm39)	I140L	possibly damaging	Het
Or4f54	T	A	2: 111,123,411 (GRCm39)	V266E	probably damaging	Het
Or4f62	T	A	2: 111,986,862 (GRCm39)	C189S	probably damaging	Het
Pcsk5	G	A	19: 17,492,620 (GRCm39)	R918C	probably damaging	Het
Pecam1	T	C	11: 106,571,905 (GRCm39)	D554G	probably benign	Het
Polr2a	T	C	11: 69,634,199 (GRCm39)	I744V	possibly damaging	Het
Pop1	C	A	15: 34,530,356 (GRCm39)	A918D	possibly damaging	Het
Ppp2r5e	C	G	12: 75,516,341 (GRCm39)	A239P	probably damaging	Het
Prmt3	A	T	7: 49,476,467 (GRCm39)	I359F	possibly damaging	Het
Proz	G	A	8: 13,116,904 (GRCm39)	C152Y	probably damaging	Het
Ptgfr	A	C	3: 151,507,416 (GRCm39)	Y316D	probably benign	Het
Ralgapa2	G	T	2: 146,230,532 (GRCm39)	S1011Y	probably damaging	Het
Rnf43	C	T	11: 87,622,485 (GRCm39)	R529*	probably null	Het
Slc17a6	G	A	7: 51,296,025 (GRCm39)		probably benign	Het
Smarcd3	A	G	5: 24,799,874 (GRCm39)	S299P	possibly damaging	Het
Stard9	T	C	2: 120,528,156 (GRCm39)	F1471S	possibly damaging	Het
Strada	A	C	11: 106,059,145 (GRCm39)	V211G	probably damaging	Het
Tom1l1	T	C	11: 90,574,080 (GRCm39)	E68G	probably damaging	Het
Vmn2r27	T	G	6: 124,200,893 (GRCm39)	I355L	probably benign	Het
Vmn2r68	A	T	7: 84,870,946 (GRCm39)	M779K	possibly damaging	Het
Zbtb18	T	C	1: 177,274,736 (GRCm39)	L23P	probably damaging	Het
Zfp112	G	T	7: 23,826,024 (GRCm39)	C664F	probably damaging	Het
Zfp955a	A	T	17: 33,461,306 (GRCm39)	N275K	possibly 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
R3775:Slc25a19	UTSW	11	115,506,285 (GRCm39)	missense	probably damaging	1.00
R3776: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'- ACAGCAGGGACAGGGTCACTAC -3'
(R):5'- GGCACAGTGATGTGCTGGCTAAC -3'

Sequencing Primer
(F):5'- GGTCACTACCGCCAGTTC -3'
(R):5'- agccacctctccagccc -3'

Posted On

2014-04-24