Mutagenetix > Incidental Mutation

Incidental Mutation 'R7414:Hadha'

575283

Institutional Source

Beutler Lab

Gene Symbol

Hadha

Ensembl Gene

ENSMUSG00000025745

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha

Synonyms

Mtpa

MMRRC Submission

045494-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7414 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

30324421-30359978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 30331610 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 449 (F449L)

Ref Sequence

ENSEMBL: ENSMUSP00000120976 (fasta)

Gene Model

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

AlphaFold

Q8BMS1

Predicted Effect

possibly damaging
Transcript: ENSMUST00000156859
AA Change: F449L

PolyPhen 2 Score 0.946 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: F449L

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

Meta Mutation Damage Score

0.5929

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

97% (98/101)

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: 101 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110082I17Rik	G	A	5: 139,349,779 (GRCm39)	T90M	probably damaging	Het
Abca4	T	A	3: 121,896,387 (GRCm39)	S540T	probably benign	Het
Adcy4	G	A	14: 56,019,090 (GRCm39)	L156F	probably benign	Het
Adcyap1	T	A	17: 93,510,256 (GRCm39)	L95M	probably damaging	Het
Ahctf1	T	C	1: 179,611,670 (GRCm39)	T567A	probably benign	Het
Ankrd26	T	C	6: 118,485,741 (GRCm39)	I1378V	possibly damaging	Het
Ankrd44	T	A	1: 54,706,539 (GRCm39)	H639L	probably damaging	Het
Arfrp1	C	T	2: 181,001,307 (GRCm39)	R189Q	possibly damaging	Het
Astn2	T	C	4: 65,459,193 (GRCm39)	D1126G	possibly damaging	Het
Bap1	G	C	14: 30,975,572 (GRCm39)	G139R	probably benign	Het
Bms1	C	T	6: 118,360,706 (GRCm39)	R1254Q	possibly damaging	Het
Ceacam15	A	G	7: 16,407,235 (GRCm39)	V94A	probably benign	Het
Cfap57	C	T	4: 118,472,128 (GRCm39)	V84I	probably benign	Het
Cip2a	T	C	16: 48,821,998 (GRCm39)	F209L	probably benign	Het
Clec2m	T	C	6: 129,302,596 (GRCm39)	T144A	probably benign	Het
Clock	T	C	5: 76,410,611 (GRCm39)	T87A	probably benign	Het
Cntrl	A	T	2: 35,055,479 (GRCm39)	I1706L	probably benign	Het
Cr2	C	A	1: 194,832,344 (GRCm39)	V981L	probably benign	Het
Cxcr6	G	A	9: 123,639,287 (GRCm39)	W103*	probably null	Het
Dld	A	T	12: 31,385,525 (GRCm39)	F272Y	probably damaging	Het
Dmrt2	T	A	19: 25,650,950 (GRCm39)	D45E	probably benign	Het
Eif2a	T	A	3: 58,433,502 (GRCm39)	L8*	probably null	Het
Epg5	G	T	18: 78,026,747 (GRCm39)	R1246L	possibly damaging	Het
Ets1	T	A	9: 32,664,153 (GRCm39)	C350*	probably null	Het
Fam135b	C	T	15: 71,350,105 (GRCm39)	R345Q	probably damaging	Het
Fbn2	C	T	18: 58,229,122 (GRCm39)	R696H	probably damaging	Het
Gbf1	C	A	19: 46,271,797 (GRCm39)	Y159*	probably null	Het
Gcsam	T	C	16: 45,437,301 (GRCm39)		probably null	Het
Gmpr2	G	T	14: 55,910,259 (GRCm39)		probably null	Het
H2-T3	C	A	17: 36,498,275 (GRCm39)	V257L	not run	Het
Haus3	T	A	5: 34,323,477 (GRCm39)	I378L	probably benign	Het
Hdac7	T	A	15: 97,706,392 (GRCm39)	H272L	probably benign	Het
Icam5	T	C	9: 20,948,889 (GRCm39)	V747A	probably damaging	Het
Ifrd2	G	A	9: 107,467,370 (GRCm39)	V81M	possibly damaging	Het
Insyn2a	G	T	7: 134,519,738 (GRCm39)	A264D	probably benign	Het
Ipcef1	G	T	10: 6,840,673 (GRCm39)	C345*	probably null	Het
Ipmk	T	A	10: 71,217,124 (GRCm39)	F223I	probably damaging	Het
Itpr2	A	T	6: 146,274,706 (GRCm39)	N825K	probably benign	Het
Itprid2	A	G	2: 79,475,072 (GRCm39)	K344E	possibly damaging	Het
Kazn	G	A	4: 141,836,649 (GRCm39)	T530I		Het
Kmt2d	C	T	15: 98,737,737 (GRCm39)	V5120M	unknown	Het
Krt6b	T	G	15: 101,587,449 (GRCm39)	D215A	probably benign	Het
Lgals12	T	C	19: 7,581,335 (GRCm39)	K124R	probably damaging	Het
Lpar6	T	A	14: 73,476,240 (GRCm39)	V67D	probably damaging	Het
Lrch3	T	C	16: 32,818,883 (GRCm39)	Y661H	probably damaging	Het
Lrrc32	A	T	7: 98,149,201 (GRCm39)	Q660H	probably benign	Het
Lurap1l	T	A	4: 80,871,991 (GRCm39)	H161Q	probably benign	Het
Map3k19	A	G	1: 127,766,189 (GRCm39)	I245T	probably damaging	Het
Mcf2l	T	A	8: 13,069,022 (GRCm39)	*1119K	probably null	Het
Mertk	C	A	2: 128,571,313 (GRCm39)	A89E	possibly damaging	Het
Mical3	A	T	6: 121,011,074 (GRCm39)	Y375N	probably damaging	Het
Myo15a	T	A	11: 60,374,309 (GRCm39)	D121E		Het
N4bp2l1	T	A	5: 150,499,758 (GRCm39)	N116I	probably damaging	Het
Nbeal1	T	C	1: 60,233,756 (GRCm39)		probably null	Het
Nlrp12	A	T	7: 3,289,977 (GRCm39)	D178E	probably benign	Het
Nt5c2	C	A	19: 46,878,328 (GRCm39)	G444C	probably damaging	Het
Or10g7	T	A	9: 39,905,349 (GRCm39)	M81K	possibly damaging	Het
Or2f1b	T	A	6: 42,739,762 (GRCm39)	Y259N	probably damaging	Het
Or8b48	T	C	9: 38,492,764 (GRCm39)	F64L	probably benign	Het
Pdcl2	A	C	5: 76,460,359 (GRCm39)	S220A	possibly damaging	Het
Pip5kl1	T	C	2: 32,468,247 (GRCm39)	S138P	possibly damaging	Het
Pkd1l1	A	T	11: 8,866,267 (GRCm39)	N979K		Het
Prkcb	A	T	7: 122,167,450 (GRCm39)	T387S	possibly damaging	Het
Pxdc1	A	G	13: 34,821,135 (GRCm39)		probably benign	Het
Sbf2	C	T	7: 109,913,271 (GRCm39)	E1668K	possibly damaging	Het
Sec16a	T	G	2: 26,313,643 (GRCm39)	T455P		Het
Sec24b	C	A	3: 129,803,514 (GRCm39)	V412F	probably benign	Het
Serpina3b	A	G	12: 104,099,145 (GRCm39)	N220S	probably benign	Het
Sgip1	C	T	4: 102,824,821 (GRCm39)	Q581*	probably null	Het
Shf	A	T	2: 122,190,063 (GRCm39)	I175N	possibly damaging	Het
Slc16a10	G	A	10: 40,017,992 (GRCm39)	T14M	probably benign	Het
Slc22a4	A	T	11: 53,888,254 (GRCm39)	M258K	probably benign	Het
Slfn8	A	T	11: 82,907,618 (GRCm39)	Y308*	probably null	Het
Slfnl1	T	C	4: 120,392,451 (GRCm39)	Y249H	probably damaging	Het
Smchd1	T	C	17: 71,782,074 (GRCm39)	Y29C	probably damaging	Het
Snai1	C	A	2: 167,380,588 (GRCm39)		probably null	Het
Sntg1	T	C	1: 8,518,289 (GRCm39)	Y368C	probably damaging	Het
Snx33	C	T	9: 56,833,151 (GRCm39)	R306H	probably damaging	Het
Spop	G	A	11: 95,365,334 (GRCm39)	V126M	probably damaging	Het
Taar3	A	T	10: 23,825,715 (GRCm39)	Y87F	probably damaging	Het
Tarm1	C	A	7: 3,545,318 (GRCm39)	M177I	probably benign	Het
Tcerg1l	A	G	7: 137,819,786 (GRCm39)	F485L	probably damaging	Het
Thsd7b	A	T	1: 129,556,717 (GRCm39)	I435F	probably damaging	Het
Tiam2	A	G	17: 3,464,388 (GRCm39)	D39G	possibly damaging	Het
Tigd4	T	C	3: 84,501,128 (GRCm39)	V15A	probably benign	Het
Tll2	T	C	19: 41,092,268 (GRCm39)	D523G	probably damaging	Het
Tmem117	A	G	15: 94,612,776 (GRCm39)	D104G	probably damaging	Het
Tmem132b	T	C	5: 125,864,555 (GRCm39)	L887P	probably damaging	Het
Tnfrsf26	A	T	7: 143,168,642 (GRCm39)	V132D	probably damaging	Het
Tomt	T	A	7: 101,549,715 (GRCm39)	D191V	probably damaging	Het
Ttc39b	T	C	4: 83,160,459 (GRCm39)	M373V	probably damaging	Het
Ttn	G	A	2: 76,568,493 (GRCm39)	P27467S	possibly damaging	Het
Ttn	A	C	2: 76,573,130 (GRCm39)	V25921G	probably damaging	Het
Ubxn2a	A	C	12: 4,941,381 (GRCm39)	V75G	probably damaging	Het
Uchl5	A	T	1: 143,682,433 (GRCm39)	K319N	unknown	Het
Ugt2b1	T	C	5: 87,073,693 (GRCm39)	D222G	probably damaging	Het
Vmn1r213	A	G	13: 23,195,446 (GRCm39)	I10V	unknown	Het
Vps13b	T	C	15: 35,910,973 (GRCm39)	I3579T	probably damaging	Het
Xpo5	T	A	17: 46,532,295 (GRCm39)	H443Q	probably benign	Het
Zfp316	A	G	5: 143,250,407 (GRCm39)	M2T	unknown	Het
Zscan4-ps2	A	G	7: 11,251,359 (GRCm39)	T160A	possibly 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
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
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'- CTGAGCTTTCTGATATACACAGCATG -3'
(R):5'- ACACAGCAGCTGTCTTCTG -3'

Sequencing Primer
(F):5'- AGCCTGACAACCTGGATTTG -3'
(R):5'- TCTTCTGCTGTTCTGTTCTAAGAG -3'

Posted On

2019-10-07