Mutagenetix > Incidental Mutation

Incidental Mutation 'R5870:Hadha'

455113

Institutional Source

Beutler Lab

Gene Symbol

Hadha

Ensembl Gene

ENSMUSG00000025745

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha

Synonyms

Mtpa

MMRRC Submission

044078-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5870 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

30324421-30359978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 30349284 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Phenylalanine at position 109 (S109F)

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: S109F

PolyPhen 2 Score 0.605 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: S109F

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

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.9%
3x: 99.4%
10x: 97.2%
20x: 91.1%

Validation Efficiency

93% (84/90)

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
Adcy9	A	G	16: 4,236,232 (GRCm39)	V156A	probably damaging	Het
Ak6	C	A	13: 100,791,932 (GRCm39)	P125Q	probably damaging	Het
Aqp4	A	C	18: 15,532,946 (GRCm39)	V49G	probably damaging	Het
Arfgef1	A	G	1: 10,251,163 (GRCm39)	I874T	probably damaging	Het
Arid1a	T	C	4: 133,408,387 (GRCm39)	D2040G	unknown	Het
Atp1a3	T	G	7: 24,697,003 (GRCm39)	D220A	probably benign	Het
C2cd4c	A	T	10: 79,448,043 (GRCm39)	I368N	possibly damaging	Het
Ccnt1	G	A	15: 98,441,394 (GRCm39)	Q625*	probably null	Het
Cd177	T	A	7: 24,455,757 (GRCm39)	H255L	probably benign	Het
Cdipt	G	A	7: 126,578,094 (GRCm39)	V114M	probably benign	Het
Coro1b	T	A	19: 4,199,384 (GRCm39)	H14Q	probably damaging	Het
Ctdp1	T	A	18: 80,451,901 (GRCm39)	D158V	unknown	Het
Cts7	A	T	13: 61,503,545 (GRCm39)	S140T	probably damaging	Het
Dlgap3	T	A	4: 127,089,502 (GRCm39)	L366*	probably null	Het
Dnah9	C	T	11: 65,976,036 (GRCm39)	A1338T	probably benign	Het
Dock7	T	C	4: 98,952,199 (GRCm39)	I424V	probably benign	Het
Dock8	G	T	19: 25,109,490 (GRCm39)	A891S	probably benign	Het
Dync2i1	A	G	12: 116,219,865 (GRCm39)	S26P	possibly damaging	Het
Elmod3	A	G	6: 72,571,721 (GRCm39)		probably null	Het
Eps15	G	A	4: 109,218,507 (GRCm39)	E107K	probably damaging	Het
Esco1	A	T	18: 10,593,744 (GRCm39)		probably null	Het
Fuz	A	G	7: 44,549,742 (GRCm39)	T407A	probably damaging	Het
Galr1	A	T	18: 82,424,197 (GRCm39)	F27I	probably benign	Het
Glt1d1	A	G	5: 127,754,344 (GRCm39)	Y182C	probably damaging	Het
Gm37240	A	T	3: 84,597,828 (GRCm39)		probably benign	Het
Gm37610	A	G	6: 41,061,848 (GRCm39)		noncoding transcript	Het
Gm6658	G	T	8: 91,635,020 (GRCm39)		probably benign	Het
Gm9376	A	G	14: 118,504,789 (GRCm39)	T74A	possibly damaging	Het
Herc3	A	T	6: 58,893,435 (GRCm39)	Q899L	probably benign	Het
Ift172	C	T	5: 31,434,284 (GRCm39)	E485K	probably benign	Het
Lrrc8e	A	G	8: 4,285,725 (GRCm39)	K650R	possibly damaging	Het
Ly6d	A	T	15: 74,635,381 (GRCm39)	V10D	possibly damaging	Het
Med27	A	G	2: 29,279,823 (GRCm39)		probably null	Het
Med29	A	T	7: 28,091,922 (GRCm39)	V56E	probably damaging	Het
Mobp	A	G	9: 119,996,919 (GRCm39)	K17E	probably damaging	Het
Mrpl37	G	A	4: 106,923,919 (GRCm39)	T25I	probably benign	Het
Myh1	A	G	11: 67,092,805 (GRCm39)	D33G	possibly damaging	Het
Nrg3	T	A	14: 39,194,586 (GRCm39)	I58F	possibly damaging	Het
Or52e2	A	G	7: 102,804,948 (GRCm39)	I2T	probably benign	Het
Or7e176	A	G	9: 20,171,874 (GRCm39)	D246G	probably benign	Het
Padi1	T	A	4: 140,553,892 (GRCm39)	D359V	probably benign	Het
Pcdh7	T	C	5: 57,877,753 (GRCm39)	V436A	possibly damaging	Het
Pgm3	C	A	9: 86,452,414 (GRCm39)	K15N	probably damaging	Het
Phip	A	T	9: 82,790,730 (GRCm39)		probably benign	Het
Pot1a	G	A	6: 25,778,950 (GRCm39)	T48I	possibly damaging	Het
Ppic	T	C	18: 53,542,333 (GRCm39)	K125R	probably benign	Het
Ppm1j	T	C	3: 104,692,811 (GRCm39)	V440A	possibly damaging	Het
Prg4	T	A	1: 150,331,300 (GRCm39)	K458*	probably null	Het
Rd3	A	T	1: 191,717,261 (GRCm39)	M244L	probably benign	Het
Rflnb	A	G	11: 75,912,864 (GRCm39)	Y175H	probably benign	Het
Rnf157	T	A	11: 116,237,900 (GRCm39)	S574C	probably benign	Het
Sardh	A	G	2: 27,110,653 (GRCm39)		probably null	Het
Senp3	C	T	11: 69,569,048 (GRCm39)		probably null	Het
Siglec1	G	A	2: 130,914,767 (GRCm39)	R1450C	probably damaging	Het
Sim2	A	G	16: 93,924,193 (GRCm39)	H446R	probably damaging	Het
Spon1	T	C	7: 113,631,021 (GRCm39)	I444T	probably damaging	Het
Srebf1	T	A	11: 60,094,410 (GRCm39)	Q568H	possibly damaging	Het
Stxbp4	A	T	11: 90,428,782 (GRCm39)	I441N	possibly damaging	Het
Sugt1	G	A	14: 79,846,451 (GRCm39)	V163I	probably benign	Het
Surf1	G	T	2: 26,806,271 (GRCm39)		probably benign	Het
Synj2	A	G	17: 6,088,128 (GRCm39)	E1348G	probably benign	Het
Tc2n	A	T	12: 101,619,111 (GRCm39)	V349D	probably damaging	Het
Ten1	A	G	11: 116,105,751 (GRCm39)	R112G	possibly damaging	Het
Tm9sf4	A	G	2: 153,036,201 (GRCm39)	D321G	probably damaging	Het
Ttll12	A	T	15: 83,461,237 (GRCm39)	M594K	probably damaging	Het
Ttn	T	A	2: 76,703,058 (GRCm39)		probably benign	Het
Usp28	C	T	9: 48,937,285 (GRCm39)	Q185*	probably null	Het
Vmn2r112	A	G	17: 22,838,004 (GRCm39)	I822V	probably benign	Het
Zc3hc1	A	T	6: 30,382,682 (GRCm39)	L88*	probably null	Het
Zfr	T	A	15: 12,160,701 (GRCm39)	V758D	probably damaging	Het
Zfyve27	T	G	19: 42,160,110 (GRCm39)	L42R	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
R5523:Hadha	UTSW	5	30,350,252 (GRCm39)	missense	possibly damaging	0.78
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'- CCATTCAGGCATTTGACAGCTG -3'
(R):5'- GTGCTCAATAGTTTGTTACAGAGC -3'

Sequencing Primer
(F):5'- CTAAAGGGCTCTGGTGGCAG -3'
(R):5'- GCAAAGTAAATTGTGTAACCTGTTCC -3'

Posted On

2017-02-10