Mutagenetix > Incidental Mutation

Incidental Mutation 'R7215:Hadha'

561376

Institutional Source

Beutler Lab

Gene Symbol

Hadha

Ensembl Gene

ENSMUSG00000025745

Gene Name

hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit

Synonyms

Mtpa

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7215 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

30118304-30155162 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 30119842 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Lysine at position 755 (N755K)

Ref Sequence

ENSEMBL: ENSMUSP00000120976 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000058045] [ENSMUST00000156859]

AlphaFold

Q8BMS1

Predicted Effect

probably benign
Transcript: ENSMUST00000058045

SMART Domains

Protein: ENSMUSP00000054208
Gene: ENSMUSG00000044576

Domain	Start	End	E-Value	Type
Pfam:CABIT	29	337	1.2e-77	PFAM
low complexity region	379	405	N/A	INTRINSIC
low complexity region	464	486	N/A	INTRINSIC
low complexity region	524	534	N/A	INTRINSIC
low complexity region	538	553	N/A	INTRINSIC
low complexity region	569	588	N/A	INTRINSIC
low complexity region	640	663	N/A	INTRINSIC
low complexity region	674	684	N/A	INTRINSIC
low complexity region	686	696	N/A	INTRINSIC
PDB:2DKZ\|A	794	878	3e-30	PDB
Blast:SAM	812	879	6e-35	BLAST
SCOP:d1kw4a_	816	877	1e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000156859
AA Change: N755K

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: N755K

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

98% (79/81)

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210408I21Rik	G	A	13: 77,323,571	V1032M	possibly damaging	Het
Abca13	T	A	11: 9,288,405		probably null	Het
Adamts14	T	A	10: 61,211,596	H739L	possibly damaging	Het
Adgrl3	A	G	5: 81,693,550	E758G	probably damaging	Het
Ano3	T	A	2: 110,665,932	T826S	probably damaging	Het
Arhgap45	C	T	10: 80,025,482	T493I	possibly damaging	Het
Atg9b	A	C	5: 24,388,041	W455G	probably damaging	Het
Atp4a	A	G	7: 30,717,360	N496S	possibly damaging	Het
Bckdk	T	A	7: 127,905,110	D60E	possibly damaging	Het
Blmh	A	T	11: 76,965,899	K244*	probably null	Het
Btbd17	T	C	11: 114,791,465	I474V	possibly damaging	Het
C87436	A	G	6: 86,462,680	E451G	possibly damaging	Het
Camta1	T	C	4: 151,144,737	E546G	probably damaging	Het
Casp1	A	G	9: 5,298,523		probably null	Het
Ccdc114	C	T	7: 45,936,622	R148C	probably damaging	Het
Ccdc116	A	G	16: 17,139,928	Y456H	probably damaging	Het
Cep350	A	C	1: 155,894,707	S1812R	possibly damaging	Het
Chrna10	A	G	7: 102,112,208	L392P	possibly damaging	Het
Col22a1	A	T	15: 71,970,332	C434*	probably null	Het
Cxcl9	G	A	5: 92,323,888	Q98*	probably null	Het
Cyp2c54	G	A	19: 40,046,182	T348I	probably damaging	Het
Dnah7a	G	A	1: 53,618,350	R756C	probably damaging	Het
Dnajc18	T	C	18: 35,681,981	T239A	probably benign	Het
Dnase2a	A	T	8: 84,909,770		probably null	Het
Dpyd	A	G	3: 119,266,032	T793A	probably benign	Het
E430018J23Rik	A	G	7: 127,391,523	S431P	probably benign	Het
Edil3	T	C	13: 88,822,050		probably null	Het
Ehd1	T	A	19: 6,297,642	I342N	possibly damaging	Het
Erbb4	A	T	1: 68,339,460	S341T	probably benign	Het
Ezh1	T	A	11: 101,215,299	T87S	probably benign	Het
Fam20b	A	T	1: 156,690,553	W224R	probably damaging	Het
Galns	A	T	8: 122,599,348		probably null	Het
Gm13283	C	T	4: 88,760,730		probably benign	Het
Gm15448	C	T	7: 3,822,311	C444Y	unknown	Het
Gm49342	A	T	14: 50,944,583	M23L	probably benign	Het
Gm5114	T	A	7: 39,411,371	H18L	probably benign	Het
Gpr89	A	G	3: 96,880,088	W299R	probably damaging	Het
Inpp5d	A	T	1: 87,701,218	H620L	probably benign	Het
Klk1b3	T	A	7: 44,200,404		probably null	Het
Macf1	T	C	4: 123,507,304	T663A	probably damaging	Het
Man1b1	A	G	2: 25,350,390	N601S	probably benign	Het
Mbtps1	A	G	8: 119,524,568	V605A	possibly damaging	Het
Med23	C	G	10: 24,888,429	D311E	probably benign	Het
Myo3a	G	T	2: 22,245,567	D82Y	possibly damaging	Het
Nsd1	T	A	13: 55,247,641	D1121E	probably benign	Het
Olfr1042	C	T	2: 86,159,456	V305I	probably benign	Het
Olfr1221	G	A	2: 89,112,501	Q4*	probably null	Het
Olfr918	A	G	9: 38,673,447	I12T	probably benign	Het
Otoa	T	C	7: 121,118,572	V19A	unknown	Het
Pcdhb20	A	T	18: 37,505,386	T322S	probably benign	Het
Pecam1	T	C	11: 106,695,919	T257A	probably benign	Het
Pi16	G	T	17: 29,319,098		probably benign	Het
Pik3c2g	C	T	6: 139,754,863	T293M		Het
Pkhd1l1	T	A	15: 44,528,163	C1542S	possibly damaging	Het
Prrc2b	G	A	2: 32,229,297	G2172R	probably damaging	Het
Prrt1	A	T	17: 34,629,703		probably null	Het
Ptprb	T	A	10: 116,338,776	N784K	possibly damaging	Het
Rem1	C	A	2: 152,628,149	S18R	probably damaging	Het
Ripk4	G	A	16: 97,747,323		probably null	Het
Scn8a	G	A	15: 101,029,830	V1397I	possibly damaging	Het
Setbp1	T	A	18: 78,856,837	H1205L	probably damaging	Het
Shmt1	T	C	11: 60,801,535	I132V	probably damaging	Het
Slc24a1	T	A	9: 64,928,503	T781S	unknown	Het
Sncaip	C	T	18: 52,907,343	Q870*	probably null	Het
Stab1	A	T	14: 31,160,797	N416K	possibly damaging	Het
Tcea1	A	G	1: 4,867,483	D26G	probably damaging	Het
Tcf20	A	T	15: 82,853,489	S1254T	probably benign	Het
Tead4	T	A	6: 128,228,678	I354F	probably damaging	Het
Tex36	G	A	7: 133,587,418	R142*	probably null	Het
Trav6d-3	T	A	14: 52,725,342	L12Q	probably damaging	Het
Trpc4	A	G	3: 54,194,896	T72A	possibly damaging	Het
Trrap	G	A	5: 144,797,135	A933T	probably benign	Het
Tspoap1	T	A	11: 87,770,489	I589N	probably benign	Het
Ttll5	T	A	12: 85,933,396	V918E	probably benign	Het
Txn2	A	G	15: 77,927,686		probably null	Het
Ucn3	T	G	13: 3,941,365	T96P	probably benign	Het
Usp36	T	C	11: 118,265,154	E764G	possibly damaging	Het
Vmn2r23	A	T	6: 123,704,364	H77L	probably benign	Het
Vmn2r57	T	C	7: 41,400,286	T680A	probably benign	Het
Vwa3a	T	C	7: 120,795,630	I891T	possibly damaging	Het
Zcchc11	T	C	4: 108,527,008	Y1091H	probably damaging	Het
Zhx2	A	G	15: 57,823,643	I803V	probably benign	Het

Other mutations in Hadha

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00430:Hadha	APN	5	30120147	missense	possibly damaging	0.94
IGL00435:Hadha	APN	5	30122173	missense	probably benign	0.12
IGL01413:Hadha	APN	5	30141027	missense	probably benign	0.01
IGL01715:Hadha	APN	5	30120084	missense	probably damaging	1.00
IGL02065:Hadha	APN	5	30142845	splice site	probably benign
IGL02316:Hadha	APN	5	30126567	missense	probably benign	0.04
IGL02366:Hadha	APN	5	30135050	missense	probably benign	0.01
IGL02453:Hadha	APN	5	30144306	splice site	probably benign
IGL02611:Hadha	APN	5	30128943	splice site	probably benign
IGL03127:Hadha	APN	5	30134186	splice site	probably benign
IGL03181:Hadha	APN	5	30121526	missense	probably benign	0.20
R1381:Hadha	UTSW	5	30128836	missense	probably benign
R1501:Hadha	UTSW	5	30128806	missense	probably benign	0.02
R2060:Hadha	UTSW	5	30128836	missense	probably benign	0.30
R3764:Hadha	UTSW	5	30144209	missense	probably damaging	1.00
R3778:Hadha	UTSW	5	30120129	missense	probably damaging	0.98
R5025:Hadha	UTSW	5	30154961	unclassified	probably benign
R5523:Hadha	UTSW	5	30145254	missense	possibly damaging	0.78
R5870:Hadha	UTSW	5	30144286	missense	possibly damaging	0.61
R6054:Hadha	UTSW	5	30123684	missense	probably benign	0.00
R6144:Hadha	UTSW	5	30140996	missense	probably benign	0.04
R6245:Hadha	UTSW	5	30120044	critical splice donor site	probably null
R6495:Hadha	UTSW	5	30120050	missense	probably benign	0.03
R6862:Hadha	UTSW	5	30147979	critical splice donor site	probably null
R7038:Hadha	UTSW	5	30120000	splice site	probably null
R7200:Hadha	UTSW	5	30145317	missense	probably benign	0.25
R7267:Hadha	UTSW	5	30122757	missense	probably damaging	1.00
R7414:Hadha	UTSW	5	30126612	missense	possibly damaging	0.95
R8172:Hadha	UTSW	5	30145287	missense	probably damaging	0.97
R8429:Hadha	UTSW	5	30144257	missense	probably benign	0.00
R8494:Hadha	UTSW	5	30142812	missense	probably damaging	1.00
R8516:Hadha	UTSW	5	30126584	missense	probably damaging	1.00
R9180:Hadha	UTSW	5	30135040	missense	probably benign
R9618:Hadha	UTSW	5	30134167	missense	possibly damaging	0.73

Predicted Primers

PCR Primer
(F):5'- CAGAAGGCACTCTGATGGAG -3'
(R):5'- ACATCGGAGCTGTCTTTGG -3'

Sequencing Primer
(F):5'- CACTCTGATGGAGGAGCAAGCC -3'
(R):5'- CCCTTGTCTCGGAGGTCAGTG -3'

Posted On

2019-06-26