Mutagenetix > Incidental Mutation

Incidental Mutation 'R0578:Hadhb'

56301

Institutional Source

Beutler Lab

Gene Symbol

Hadhb

Ensembl Gene

ENSMUSG00000059447

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta

Synonyms

Mtpb, 4930479F15Rik

MMRRC Submission

038768-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.781) question?

Stock #

R0578 (G1)

Quality Score

150

Status

Validated

Chromosome

Chromosomal Location

30360251-30389591 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 30383804 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 342 (I342M)

Ref Sequence

ENSEMBL: ENSMUSP00000110434 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026841] [ENSMUST00000114783] [ENSMUST00000114786] [ENSMUST00000123980] [ENSMUST00000197109]

AlphaFold

Q99JY0

Predicted Effect

probably benign
Transcript: ENSMUST00000026841
AA Change: I342M

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000026841
Gene: ENSMUSG00000059447
AA Change: I342M

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	325	4.6e-96	PFAM
Pfam:ketoacyl-synt	86	193	1.8e-10	PFAM
Pfam:Thiolase_C	332	472	1.5e-51	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000114783
AA Change: I342M

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000110431
Gene: ENSMUSG00000059447
AA Change: I342M

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	55	325	1.4e-90	PFAM
Pfam:ketoacyl-synt	90	194	1.4e-10	PFAM
Pfam:Thiolase_C	332	472	1.3e-51	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000114786
AA Change: I342M

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000110434
Gene: ENSMUSG00000059447
AA Change: I342M

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	325	4.6e-96	PFAM
Pfam:ketoacyl-synt	86	193	1.8e-10	PFAM
Pfam:Thiolase_C	332	472	1.5e-51	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000122934

Predicted Effect

probably benign
Transcript: ENSMUST00000123980

SMART Domains

Protein: ENSMUSP00000118296
Gene: ENSMUSG00000059447

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	129	3.7e-20	PFAM
Pfam:Thiolase_N	119	173	3.3e-17	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133414

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141236

Predicted Effect

probably benign
Transcript: ENSMUST00000197109

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.5%
20x: 95.0%

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 the beta subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the beta subunit catalyzing the 3-ketoacyl-CoA thiolase activity. The encoded protein can also bind RNA and decreases the stability of some mRNAs. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. Mutations in this gene result in trifunctional protein deficiency. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
PHENOTYPE: Mice homozygous for an ENU-induced mutation display reduced postnatal weight gain, multifocal cardiac fibrosis and hepatic steatosis, and develop cardiac arrhythmias that range from a prolonged PR interval to complete atrioventricular dissociation and lead to sudden between 9 and 16 months of age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930407I10Rik	A	G	15: 81,943,556 (GRCm39)	Y56C	possibly damaging	Het
Abca5	A	T	11: 110,167,315 (GRCm39)	C1500*	probably null	Het
Acr	C	G	15: 89,453,678 (GRCm39)	H72Q	probably damaging	Het
Adam18	T	C	8: 25,131,863 (GRCm39)	D416G	possibly damaging	Het
Afap1l2	T	A	19: 56,904,214 (GRCm39)	Y691F	probably benign	Het
Akna	A	G	4: 63,289,147 (GRCm39)	S1259P	probably benign	Het
Atad2	G	A	15: 57,968,964 (GRCm39)	T525I	probably damaging	Het
Atp2a1	T	G	7: 126,049,315 (GRCm39)	M576L	probably benign	Het
B4galt6	T	C	18: 20,861,013 (GRCm39)		probably benign	Het
Best3	A	G	10: 116,844,904 (GRCm39)	D353G	probably benign	Het
Btg3	A	T	16: 78,161,834 (GRCm39)	D125E	probably benign	Het
Cabin1	A	T	10: 75,549,444 (GRCm39)	D1320E	probably damaging	Het
Cachd1	A	C	4: 100,852,039 (GRCm39)		probably benign	Het
Cad	T	C	5: 31,216,120 (GRCm39)	V151A	probably benign	Het
Capns1	A	T	7: 29,893,453 (GRCm39)		probably benign	Het
Catsperg2	T	A	7: 29,404,116 (GRCm39)	T860S	possibly damaging	Het
Ccdc61	T	C	7: 18,637,400 (GRCm39)	T76A	probably benign	Het
Cdipt	T	A	7: 126,578,702 (GRCm39)		probably null	Het
Cyp2d12	G	A	15: 82,440,584 (GRCm39)		probably benign	Het
Dennd4c	C	A	4: 86,730,659 (GRCm39)	P852Q	probably damaging	Het
Dsg2	G	A	18: 20,727,291 (GRCm39)	V613I	probably benign	Het
Dusp16	G	C	6: 134,695,284 (GRCm39)	L516V	probably damaging	Het
Eif2ak4	T	G	2: 118,305,472 (GRCm39)		probably benign	Het
Faf2	C	T	13: 54,769,658 (GRCm39)	A2V	possibly damaging	Het
Gas2l3	A	G	10: 89,252,937 (GRCm39)	I236T	probably damaging	Het
Gm6605	C	A	7: 38,147,699 (GRCm39)		noncoding transcript	Het
Got1	G	T	19: 43,504,222 (GRCm39)	S66R	probably benign	Het
Gpr149	T	A	3: 62,510,110 (GRCm39)	H335L	possibly damaging	Het
Helz	T	A	11: 107,577,226 (GRCm39)	V1859D	unknown	Het
Htr1a	T	A	13: 105,581,595 (GRCm39)	N278K	probably damaging	Het
Inppl1	T	C	7: 101,480,795 (GRCm39)	E355G	probably damaging	Het
Isl2	A	G	9: 55,452,319 (GRCm39)	Y297C	probably damaging	Het
Kat7	T	C	11: 95,182,350 (GRCm39)	H250R	probably benign	Het
Klhl30	A	T	1: 91,282,074 (GRCm39)	D225V	probably benign	Het
Mtch2	T	C	2: 90,683,174 (GRCm39)		probably benign	Het
Muc4	C	A	16: 32,755,690 (GRCm38)		probably benign	Het
Ncoa7	A	C	10: 30,577,913 (GRCm39)		probably null	Het
Nuf2	T	A	1: 169,338,118 (GRCm39)		probably benign	Het
Or5ak24	T	C	2: 85,261,017 (GRCm39)	D52G	probably benign	Het
Or6c8	A	G	10: 128,915,062 (GRCm39)	Y257H	probably damaging	Het
Pced1a	T	A	2: 130,261,763 (GRCm39)	S297C	probably damaging	Het
Pi15	A	T	1: 17,673,073 (GRCm39)	K91*	probably null	Het
Pla2g4e	C	T	2: 120,075,162 (GRCm39)		probably benign	Het
Plce1	A	T	19: 38,766,383 (GRCm39)	H2136L	probably damaging	Het
Plec	A	G	15: 76,061,084 (GRCm39)	L2973P	probably damaging	Het
Poln	A	G	5: 34,171,682 (GRCm39)	I695T	probably damaging	Het
Pramel32	T	A	4: 88,552,376 (GRCm39)	I2F	probably benign	Het
R3hdm1	C	T	1: 128,159,174 (GRCm39)	Q950*	probably null	Het
Rxra	C	T	2: 27,649,582 (GRCm39)	A429V	probably damaging	Het
Scnn1a	G	A	6: 125,299,207 (GRCm39)	G96S	probably damaging	Het
Senp5	T	A	16: 31,808,163 (GRCm39)	T337S	possibly damaging	Het
Smg9	A	G	7: 24,114,468 (GRCm39)	D269G	probably damaging	Het
Srsf11	C	T	3: 157,717,704 (GRCm39)		probably benign	Het
Tmtc1	C	T	6: 148,256,716 (GRCm39)		probably benign	Het
Vmn2r19	T	C	6: 123,312,931 (GRCm39)	V667A	probably damaging	Het

Other mutations in Hadhb

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02306:Hadhb	APN	5	30,371,747 (GRCm39)	missense	probably null	0.99
IGL02472:Hadhb	APN	5	30,389,061 (GRCm39)	missense	possibly damaging	0.68
R0110:Hadhb	UTSW	5	30,374,483 (GRCm39)	splice site	probably benign
R0481:Hadhb	UTSW	5	30,373,543 (GRCm39)	missense	probably damaging	1.00
R1483:Hadhb	UTSW	5	30,374,492 (GRCm39)	critical splice acceptor site	probably null
R1552:Hadhb	UTSW	5	30,381,931 (GRCm39)	missense	probably null	0.66
R1616:Hadhb	UTSW	5	30,371,713 (GRCm39)	missense	probably damaging	1.00
R1926:Hadhb	UTSW	5	30,385,935 (GRCm39)	missense	possibly damaging	0.94
R2064:Hadhb	UTSW	5	30,378,796 (GRCm39)	splice site	probably null
R5066:Hadhb	UTSW	5	30,369,094 (GRCm39)	intron	probably benign
R5298:Hadhb	UTSW	5	30,382,009 (GRCm39)	critical splice donor site	probably null
R6216:Hadhb	UTSW	5	30,379,929 (GRCm39)	missense	probably benign	0.00
R6787:Hadhb	UTSW	5	30,360,247 (GRCm39)	unclassified	probably benign
R8480:Hadhb	UTSW	5	30,373,568 (GRCm39)	critical splice donor site	probably null
R8802:Hadhb	UTSW	5	30,378,831 (GRCm39)	nonsense	probably null
R9481:Hadhb	UTSW	5	30,368,711 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- GCGATGCTAATCATGTCAGAGGACAG -3'
(R):5'- TCAAGGTTATAATGGAAGCCAGTGGTG -3'

Sequencing Primer
(F):5'- CTCTGGCCATGGGTTATAAACC -3'
(R):5'- ggttagggatgaagcccag -3'

Posted On

2013-07-11