Mutagenetix > Incidental Mutation

Incidental Mutation 'R5523:Hadha'

431657

Institutional Source

Beutler Lab

Gene Symbol

Hadha

Ensembl Gene

ENSMUSG00000025745

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha

Synonyms

Mtpa

MMRRC Submission

043265-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5523 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

30324421-30359978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 30350252 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Phenylalanine at position 99 (V99F)

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

possibly damaging
Transcript: ENSMUST00000156859
AA Change: V99F

PolyPhen 2 Score 0.784 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: V99F

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000199559

Coding Region Coverage

1x: 98.3%
3x: 97.3%
10x: 95.4%
20x: 91.4%

Validation Efficiency

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acadm	G	A	3: 153,644,273 (GRCm39)	T70M	probably benign	Het
Adamtsl3	G	A	7: 82,223,650 (GRCm39)	A218T	possibly damaging	Het
Ahnak2	T	C	12: 112,741,642 (GRCm39)	D810G	probably damaging	Het
Ak7	T	A	12: 105,707,341 (GRCm39)	L315*	probably null	Het
Apoa5	T	C	9: 46,181,887 (GRCm39)	F321S	possibly damaging	Het
Baiap2l1	G	C	5: 144,212,768 (GRCm39)	P416A	probably damaging	Het
Bco1	A	G	8: 117,835,432 (GRCm39)	I128V	possibly damaging	Het
Bpifb2	T	C	2: 153,717,905 (GRCm39)		probably benign	Het
Cdt1	G	A	8: 123,294,832 (GRCm39)	R13H	possibly damaging	Het
Cenpj	A	G	14: 56,789,880 (GRCm39)	V723A	probably benign	Het
Chl1	T	A	6: 103,685,675 (GRCm39)	W849R	probably damaging	Het
Cpne9	A	G	6: 113,267,192 (GRCm39)	D169G	probably damaging	Het
Cyp2d22	A	G	15: 82,256,772 (GRCm39)	V334A	probably damaging	Het
Cyp4f39	C	A	17: 32,689,807 (GRCm39)	N84K	probably benign	Het
Cyp4f40	T	A	17: 32,888,796 (GRCm39)	F192I	probably damaging	Het
Disp3	T	C	4: 148,342,554 (GRCm39)	D632G	probably benign	Het
Dnhd1	G	A	7: 105,352,416 (GRCm39)	R2523Q	probably damaging	Het
Echs1	G	T	7: 139,692,426 (GRCm39)	T107K	probably benign	Het
Ehmt2	C	T	17: 35,118,067 (GRCm39)	R40*	probably null	Het
Ergic1	G	A	17: 26,843,580 (GRCm39)	V17I	probably damaging	Het
Fank1	G	T	7: 133,478,569 (GRCm39)	C210F	probably damaging	Het
Fbxo15	T	G	18: 84,978,194 (GRCm39)	M136R	probably damaging	Het
Ggcx	C	A	6: 72,401,017 (GRCm39)	P240H	probably damaging	Het
Gpr179	T	C	11: 97,227,608 (GRCm39)	R1516G	probably benign	Het
Gprin3	G	A	6: 59,330,931 (GRCm39)	Q459*	probably null	Het
Hirip3	A	G	7: 126,463,034 (GRCm39)	D330G	possibly damaging	Het
Irx2	T	C	13: 72,779,714 (GRCm39)	W333R	probably damaging	Het
Kansl1l	T	C	1: 66,841,271 (GRCm39)	T10A	probably benign	Het
Kcnd2	T	C	6: 21,723,211 (GRCm39)	I467T	probably benign	Het
Klc3	A	T	7: 19,130,932 (GRCm39)	I215N	probably damaging	Het
Kmt2c	A	G	5: 25,504,337 (GRCm39)	V3657A	probably benign	Het
Lin28b	A	T	10: 45,345,164 (GRCm39)	L54*	probably null	Het
Mgll	T	C	6: 88,702,743 (GRCm39)	V14A	probably benign	Het
Mrc2	A	G	11: 105,234,408 (GRCm39)	N976S	probably benign	Het
Myh8	C	A	11: 67,196,788 (GRCm39)	A1807E	possibly damaging	Het
Nalcn	G	A	14: 123,647,155 (GRCm39)	P573S	probably damaging	Het
Ncam2	C	T	16: 81,231,766 (GRCm39)	R77*	probably null	Het
Neb	T	C	2: 52,168,827 (GRCm39)	S1903G	probably benign	Het
Nfe2	T	A	15: 103,157,556 (GRCm39)	D145V	probably damaging	Het
Or52a20	T	A	7: 103,366,687 (GRCm39)	Y295*	probably null	Het
Padi1	A	T	4: 140,542,164 (GRCm39)	V586D	probably damaging	Het
Pcdh12	T	C	18: 38,416,192 (GRCm39)	D311G	probably damaging	Het
Pcdha11	A	T	18: 37,145,439 (GRCm39)	H510L	probably damaging	Het
Plcb1	C	A	2: 135,102,486 (GRCm39)	P221H	probably benign	Het
Plekhg2	A	T	7: 28,069,856 (GRCm39)	V58E	probably damaging	Het
Pparg	A	C	6: 115,467,032 (GRCm39)	Q435P	probably damaging	Het
Ppp1r36	A	G	12: 76,484,892 (GRCm39)	T282A	possibly damaging	Het
Prcd	T	C	11: 116,559,110 (GRCm39)		probably benign	Het
Pygo1	A	T	9: 72,852,266 (GRCm39)	H151L	possibly damaging	Het
Rnmt	A	G	18: 68,446,773 (GRCm39)	Y266C	probably benign	Het
Rxrb	T	C	17: 34,255,411 (GRCm39)	V246A	probably damaging	Het
Sart1	A	G	19: 5,433,704 (GRCm39)	S378P	probably damaging	Het
Sema4d	T	C	13: 51,865,390 (GRCm39)	N318S	possibly damaging	Het
Sis	C	T	3: 72,798,754 (GRCm39)	V1765I	probably benign	Het
Slc17a6	A	T	7: 51,276,598 (GRCm39)	K116*	probably null	Het
Smc6	T	A	12: 11,341,540 (GRCm39)	H519Q	probably benign	Het
Sowahc	T	A	10: 59,058,785 (GRCm39)	M307K	probably benign	Het
Sptbn1	A	G	11: 30,087,560 (GRCm39)	Y960H	probably damaging	Het
Tmem270	A	C	5: 134,931,636 (GRCm39)	V102G	probably benign	Het
Tmprss11d	A	G	5: 86,486,729 (GRCm39)	F54L	probably benign	Het
Top1	T	A	2: 160,544,695 (GRCm39)	Y270*	probably null	Het
Trpm2	A	G	10: 77,771,795 (GRCm39)	F615L	probably benign	Het
Ttf2	A	G	3: 100,866,558 (GRCm39)	S525P	probably damaging	Het
Ttn	A	T	2: 76,777,241 (GRCm39)	M1387K	possibly damaging	Het
Upk3bl	A	T	5: 136,088,954 (GRCm39)	R156W	probably damaging	Het
Usp34	G	T	11: 23,299,198 (GRCm39)	R290L	probably benign	Het
Vwf	T	C	6: 125,620,005 (GRCm39)	V1561A		Het
Zan	A	G	5: 137,420,155 (GRCm39)	I2834T	unknown	Het
Zfp105	A	G	9: 122,755,454 (GRCm39)	Y90C	probably benign	Het
Zfp804a	T	C	2: 82,089,339 (GRCm39)	V1056A	probably damaging	Het
Zfp956	A	T	6: 47,930,455 (GRCm39)		probably benign	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
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
R6144:Hadha	UTSW	5	30,345,994 (GRCm39)	missense	probably benign	0.04
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'- GTCTGATGGATGAAGACTAGGC -3'
(R):5'- TCTGCTGCATAAACAGACTTGAC -3'

Sequencing Primer
(F):5'- CTAGGCAGTCATTCTTGGTTAAC -3'
(R):5'- GCATAAACAGACTTGACAGTGATTG -3'

Posted On

2016-10-05