Mutagenetix > Incidental Mutation

Incidental Mutation 'R6144:Hadha'

488730

Institutional Source

Beutler Lab

Gene Symbol

Hadha

Ensembl Gene

ENSMUSG00000025745

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha

Synonyms

Mtpa

MMRRC Submission

044291-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6144 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

30324421-30359978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 30345994 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 210 (D210G)

Ref Sequence

ENSEMBL: ENSMUSP00000120976 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000156859]

AlphaFold

Q8BMS1

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000026843

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130358

Predicted Effect

probably benign
Transcript: ENSMUST00000156859
AA Change: D210G

PolyPhen 2 Score 0.035 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: D210G

Domain	Start	End	E-Value	Type
Pfam:ECH_1	44	297	3.6e-42	PFAM
Pfam:ECH_2	49	225	8.6e-27	PFAM
Pfam:3HCDH_N	363	542	1e-54	PFAM
Pfam:3HCDH	544	639	7.7e-29	PFAM
low complexity region	706	720	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000197491

Meta Mutation Damage Score

0.1675

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.4%
20x: 95.6%

Validation Efficiency

96% (65/68)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the alpha 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 alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. 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. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die within 36 hours with hypoglycemia and liver steatosis. Liver steatosis and insulin resistance develop in heterozygotes with age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3300002I08Rik	A	T	2: 150,186,564 (GRCm39)	D40E	possibly damaging	Het
4921517D22Rik	C	T	13: 59,837,347 (GRCm39)	R246H	probably damaging	Het
Agbl1	A	G	7: 76,069,832 (GRCm39)	T203A	probably benign	Het
Alms1	T	A	6: 85,600,056 (GRCm39)	D2096E	probably damaging	Het
Ankrd53	T	C	6: 83,739,639 (GRCm39)		probably benign	Het
Arap3	C	A	18: 38,118,486 (GRCm39)	G814C	probably damaging	Het
Armc9	T	G	1: 86,172,301 (GRCm39)	I5S	probably benign	Het
Catsperg1	T	C	7: 28,910,120 (GRCm39)	T74A	probably damaging	Het
Cdca7l	T	A	12: 117,837,446 (GRCm39)		probably null	Het
Cfhr2	T	A	1: 139,733,153 (GRCm39)		probably benign	Het
Chpt1	A	G	10: 88,288,955 (GRCm39)		probably benign	Het
Cntrl	A	C	2: 35,055,745 (GRCm39)	D1213A	possibly damaging	Het
Col7a1	C	T	9: 108,803,148 (GRCm39)	R2149C	unknown	Het
Cpa4	T	C	6: 30,585,082 (GRCm39)	S289P	probably damaging	Het
Cpsf3	G	A	12: 21,356,887 (GRCm39)		probably null	Het
Creb3l1	T	C	2: 91,822,350 (GRCm39)	H212R	possibly damaging	Het
Cybb	C	G	X: 9,316,989 (GRCm39)	D246H	probably benign	Het
Cyp2c29	A	G	19: 39,310,053 (GRCm39)	D254G	possibly damaging	Het
Dennd1b	A	G	1: 139,008,993 (GRCm39)	H232R	probably damaging	Het
Dhx29	T	C	13: 113,101,105 (GRCm39)	L1216P	probably damaging	Het
Dsg1b	T	C	18: 20,529,476 (GRCm39)	I307T	possibly damaging	Het
Ep300	A	G	15: 81,485,435 (GRCm39)	S141G	unknown	Het
Evl	A	C	12: 108,619,290 (GRCm39)	K101T	probably damaging	Het
Exph5	G	A	9: 53,284,328 (GRCm39)	G470R	probably benign	Het
Flg	A	T	3: 93,190,515 (GRCm39)		probably benign	Het
Gm45704	T	A	8: 73,510,920 (GRCm39)			Het
Grm1	T	C	10: 10,955,640 (GRCm39)	M215V	probably benign	Het
Hmcn1	T	C	1: 150,598,175 (GRCm39)	Y1709C	probably damaging	Het
Hrc	A	T	7: 44,986,157 (GRCm39)	H436L	possibly damaging	Het
Hycc1	T	C	5: 24,171,367 (GRCm39)	S352G	possibly damaging	Het
Ido1	T	A	8: 25,075,306 (GRCm39)	T259S	possibly damaging	Het
Itgb7	C	A	15: 102,131,917 (GRCm39)	R222L	probably benign	Het
Khnyn	T	C	14: 56,125,296 (GRCm39)	V485A	probably damaging	Het
Kifc5b	T	C	17: 27,140,826 (GRCm39)	V100A	probably benign	Het
Lsm10	T	C	4: 125,991,794 (GRCm39)	M50T	probably damaging	Het
Map3k6	T	G	4: 132,972,986 (GRCm39)	W382G	probably damaging	Het
Mink1	T	A	11: 70,501,478 (GRCm39)	F922I	possibly damaging	Het
Mrap2	T	C	9: 87,057,871 (GRCm39)	V53A	probably damaging	Het
Mrps7	C	A	11: 115,495,000 (GRCm39)	A5E	probably benign	Het
Muc4	A	G	16: 32,587,298 (GRCm39)	N2713S	possibly damaging	Het
Nckipsd	T	C	9: 108,689,585 (GRCm39)	S249P	probably damaging	Het
Neil3	T	C	8: 54,052,447 (GRCm39)	T384A	probably benign	Het
Noc3l	A	T	19: 38,787,399 (GRCm39)	I504K	probably damaging	Het
Nudt13	A	G	14: 20,357,839 (GRCm39)	N107S	probably benign	Het
Or11h4b	C	A	14: 50,918,392 (GRCm39)	R233L	probably benign	Het
Or2n1	T	A	17: 38,486,116 (GRCm39)	L47H	probably damaging	Het
Or5c1	T	A	2: 37,222,125 (GRCm39)	M122K	probably damaging	Het
Otub1	G	T	19: 7,176,518 (GRCm39)	Y205*	probably null	Het
Pals1	T	C	12: 78,871,563 (GRCm39)	V381A	possibly damaging	Het
Pierce2	C	A	9: 72,887,270 (GRCm39)	C79F	probably damaging	Het
Plpp7	T	A	2: 31,986,100 (GRCm39)	S93T	probably damaging	Het
Pxk	T	G	14: 8,138,011 (GRCm38)	Y188D	probably damaging	Het
Rigi	T	C	4: 40,229,551 (GRCm39)	I78V	probably benign	Het
Rnd2	C	T	11: 101,359,825 (GRCm39)	L57F	probably damaging	Het
Rpap1	A	T	2: 119,603,128 (GRCm39)	C602*	probably null	Het
Sbds	T	C	5: 130,275,185 (GRCm39)	K248E	probably benign	Het
Serpina10	A	T	12: 103,595,092 (GRCm39)	N42K	probably benign	Het
Slc7a8	A	G	14: 54,966,797 (GRCm39)	L368P	probably damaging	Het
Srrm1	T	C	4: 135,065,184 (GRCm39)		probably benign	Het
Sun2	C	T	15: 79,614,533 (GRCm39)	V288I	probably benign	Het
Tas2r107	C	A	6: 131,636,966 (GRCm39)	A28S	possibly damaging	Het
Tbc1d9b	T	C	11: 50,037,155 (GRCm39)	I268T	probably benign	Het
Tjp2	A	G	19: 24,097,437 (GRCm39)	F495L	probably damaging	Het
Top2b	T	C	14: 16,423,740 (GRCm38)	L1434P	possibly damaging	Het
Top3b	A	G	16: 16,697,005 (GRCm39)		probably null	Het
Trdv2-2	A	T	14: 54,198,761 (GRCm39)	E17V	possibly damaging	Het
Ttc6	T	A	12: 57,719,886 (GRCm39)	L819Q	possibly damaging	Het
Txlnb	A	G	10: 17,718,914 (GRCm39)	T582A	probably benign	Het
Zfp788	T	C	7: 41,299,193 (GRCm39)	S558P	probably damaging	Het

Other mutations in Hadha

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00430:Hadha	APN	5	30,325,145 (GRCm39)	missense	possibly damaging	0.94
IGL00435:Hadha	APN	5	30,327,171 (GRCm39)	missense	probably benign	0.12
IGL01413:Hadha	APN	5	30,346,025 (GRCm39)	missense	probably benign	0.01
IGL01715:Hadha	APN	5	30,325,082 (GRCm39)	missense	probably damaging	1.00
IGL02065:Hadha	APN	5	30,347,843 (GRCm39)	splice site	probably benign
IGL02316:Hadha	APN	5	30,331,565 (GRCm39)	missense	probably benign	0.04
IGL02366:Hadha	APN	5	30,340,048 (GRCm39)	missense	probably benign	0.01
IGL02453:Hadha	APN	5	30,349,304 (GRCm39)	splice site	probably benign
IGL02611:Hadha	APN	5	30,333,941 (GRCm39)	splice site	probably benign
IGL03127:Hadha	APN	5	30,339,184 (GRCm39)	splice site	probably benign
IGL03181:Hadha	APN	5	30,326,524 (GRCm39)	missense	probably benign	0.20
R1381:Hadha	UTSW	5	30,333,834 (GRCm39)	missense	probably benign
R1501:Hadha	UTSW	5	30,333,804 (GRCm39)	missense	probably benign	0.02
R2060:Hadha	UTSW	5	30,333,834 (GRCm39)	missense	probably benign	0.30
R3764:Hadha	UTSW	5	30,349,207 (GRCm39)	missense	probably damaging	1.00
R3778:Hadha	UTSW	5	30,325,127 (GRCm39)	missense	probably damaging	0.98
R5025:Hadha	UTSW	5	30,359,959 (GRCm39)	unclassified	probably benign
R5523:Hadha	UTSW	5	30,350,252 (GRCm39)	missense	possibly damaging	0.78
R5870:Hadha	UTSW	5	30,349,284 (GRCm39)	missense	possibly damaging	0.61
R6054:Hadha	UTSW	5	30,328,682 (GRCm39)	missense	probably benign	0.00
R6245:Hadha	UTSW	5	30,325,042 (GRCm39)	critical splice donor site	probably null
R6495:Hadha	UTSW	5	30,325,048 (GRCm39)	missense	probably benign	0.03
R6862:Hadha	UTSW	5	30,352,977 (GRCm39)	critical splice donor site	probably null
R7038:Hadha	UTSW	5	30,324,998 (GRCm39)	splice site	probably null
R7200:Hadha	UTSW	5	30,350,315 (GRCm39)	missense	probably benign	0.25
R7215:Hadha	UTSW	5	30,324,840 (GRCm39)	missense	probably benign	0.00
R7267:Hadha	UTSW	5	30,327,755 (GRCm39)	missense	probably damaging	1.00
R7414:Hadha	UTSW	5	30,331,610 (GRCm39)	missense	possibly damaging	0.95
R8172:Hadha	UTSW	5	30,350,285 (GRCm39)	missense	probably damaging	0.97
R8429:Hadha	UTSW	5	30,349,255 (GRCm39)	missense	probably benign	0.00
R8494:Hadha	UTSW	5	30,347,810 (GRCm39)	missense	probably damaging	1.00
R8516:Hadha	UTSW	5	30,331,582 (GRCm39)	missense	probably damaging	1.00
R9180:Hadha	UTSW	5	30,340,038 (GRCm39)	missense	probably benign
R9618:Hadha	UTSW	5	30,339,165 (GRCm39)	missense	possibly damaging	0.73

Predicted Primers

PCR Primer
(F):5'- AAATGTCACTCCTGGTTGGTTG -3'
(R):5'- TGACCCGCTAAGCATCTCTC -3'

Sequencing Primer
(F):5'- AGGCCAACATGGTTTGCG -3'
(R):5'- GCTAAGCATCTCTCCAGCC -3'

Posted On

2017-10-10