Incidental Mutation 'R1552:Hadhb'
ID 169993
Institutional Source Beutler Lab
Gene Symbol Hadhb
Ensembl Gene ENSMUSG00000059447
Gene Name hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta
Synonyms Mtpb, 4930479F15Rik
MMRRC Submission 039591-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.781) question?
Stock # R1552 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 30360251-30389591 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 30381931 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 287 (L287Q)
Ref Sequence ENSEMBL: ENSMUSP00000110434 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000026841] [ENSMUST00000114783] [ENSMUST00000114786] [ENSMUST00000123980] [ENSMUST00000197109]
AlphaFold Q99JY0
Predicted Effect probably null
Transcript: ENSMUST00000026841
AA Change: L287Q

PolyPhen 2 Score 0.658 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000026841
Gene: ENSMUSG00000059447
AA Change: L287Q

DomainStartEndE-ValueType
Pfam:Thiolase_N 52 325 4.6e-96 PFAM
Pfam:ketoacyl-synt 86 193 1.8e-10 PFAM
Pfam:Thiolase_C 332 472 1.5e-51 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000114783
AA Change: L287Q

PolyPhen 2 Score 0.658 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000110431
Gene: ENSMUSG00000059447
AA Change: L287Q

DomainStartEndE-ValueType
Pfam:Thiolase_N 55 325 1.4e-90 PFAM
Pfam:ketoacyl-synt 90 194 1.4e-10 PFAM
Pfam:Thiolase_C 332 472 1.3e-51 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000114786
AA Change: L287Q

PolyPhen 2 Score 0.658 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000110434
Gene: ENSMUSG00000059447
AA Change: L287Q

DomainStartEndE-ValueType
Pfam:Thiolase_N 52 325 4.6e-96 PFAM
Pfam:ketoacyl-synt 86 193 1.8e-10 PFAM
Pfam:Thiolase_C 332 472 1.5e-51 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000122934
Predicted Effect probably benign
Transcript: ENSMUST00000123980
SMART Domains Protein: ENSMUSP00000118296
Gene: ENSMUSG00000059447

DomainStartEndE-ValueType
Pfam:Thiolase_N 52 129 3.7e-20 PFAM
Pfam:Thiolase_N 119 173 3.3e-17 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133414
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141236
Predicted Effect probably benign
Transcript: ENSMUST00000197109
Meta Mutation Damage Score 0.5967 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.3%
  • 10x: 96.1%
  • 20x: 91.7%
Validation Efficiency 97% (71/73)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the beta 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 beta subunit catalyzing the 3-ketoacyl-CoA thiolase activity. The encoded protein can also bind RNA and decreases the stability of some mRNAs. 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. Mutations in this gene result in trifunctional protein deficiency. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
PHENOTYPE: Mice homozygous for an ENU-induced mutation display reduced postnatal weight gain, multifocal cardiac fibrosis and hepatic steatosis, and develop cardiac arrhythmias that range from a prolonged PR interval to complete atrioventricular dissociation and lead to sudden between 9 and 16 months of age. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc5 T A 16: 20,217,617 (GRCm39) I365F probably damaging Het
Abhd15 T C 11: 77,406,233 (GRCm39) L70P probably damaging Het
Adam18 A C 8: 25,136,377 (GRCm39) H381Q probably benign Het
Ankfy1 T C 11: 72,645,321 (GRCm39) probably null Het
Arcn1 C T 9: 44,670,291 (GRCm39) A112T probably damaging Het
Bltp3a T C 17: 28,109,045 (GRCm39) F1088S possibly damaging Het
Calhm1 C T 19: 47,129,640 (GRCm39) R294H probably benign Het
Ccdc121rt1 A G 1: 181,338,556 (GRCm39) L132P probably damaging Het
Cdk5rap1 T C 2: 154,212,615 (GRCm39) E81G probably benign Het
Cep170 T C 1: 176,610,060 (GRCm39) probably benign Het
Cep350 C T 1: 155,786,484 (GRCm39) R1454Q possibly damaging Het
Chrna3 C A 9: 54,923,192 (GRCm39) E205D probably benign Het
Chst5 T C 8: 112,616,912 (GRCm39) D236G probably damaging Het
Coro1a T C 7: 126,299,124 (GRCm39) N367D probably benign Het
Cyp3a16 T C 5: 145,373,346 (GRCm39) I474V probably benign Het
Cyth3 G A 5: 143,683,505 (GRCm39) V87I probably benign Het
Dclk3 C A 9: 111,317,647 (GRCm39) T761K probably damaging Het
Dvl2 T A 11: 69,897,198 (GRCm39) M300K possibly damaging Het
Eefsec C T 6: 88,353,182 (GRCm39) probably benign Het
Exog T C 9: 119,274,176 (GRCm39) S54P unknown Het
Fasn A G 11: 120,709,384 (GRCm39) S519P probably damaging Het
Gas8 G A 8: 124,247,385 (GRCm39) A16T probably benign Het
Got2 A G 8: 96,596,122 (GRCm39) S333P probably benign Het
Ift57 A G 16: 49,579,716 (GRCm39) T211A probably benign Het
Il1rap A G 16: 26,541,184 (GRCm39) E475G possibly damaging Het
Ilkap A T 1: 91,312,316 (GRCm39) D11E probably damaging Het
Impact T C 18: 13,117,337 (GRCm39) S137P probably benign Het
Jarid2 T C 13: 45,064,675 (GRCm39) V920A probably damaging Het
Kcnk18 A T 19: 59,223,890 (GRCm39) H345L probably damaging Het
Kdm4d A T 9: 14,375,325 (GRCm39) Y178N probably damaging Het
Klk1b1 A G 7: 43,618,767 (GRCm39) Y48C probably damaging Het
Klra5 G T 6: 129,886,848 (GRCm39) T60K probably damaging Het
Kng2 A T 16: 22,806,270 (GRCm39) L643H probably damaging Het
Lamb3 A G 1: 193,013,067 (GRCm39) probably null Het
Lingo2 A G 4: 35,708,315 (GRCm39) V555A probably damaging Het
Mbd5 T C 2: 49,162,946 (GRCm39) S251P probably damaging Het
Mc4r T C 18: 66,992,766 (GRCm39) S116G probably benign Het
Mipol1 T C 12: 57,352,874 (GRCm39) V71A possibly damaging Het
Myo15b A C 11: 115,757,461 (GRCm39) S1104R probably benign Het
Nek1 T A 8: 61,459,771 (GRCm39) D26E probably damaging Het
Neu1 C T 17: 35,151,089 (GRCm39) probably benign Het
Npffr2 T C 5: 89,730,975 (GRCm39) S302P possibly damaging Het
Or8b48 T C 9: 38,492,675 (GRCm39) M34T probably benign Het
Palmd T A 3: 116,741,689 (GRCm39) probably benign Het
Pcdh8 A T 14: 80,008,047 (GRCm39) V172E probably benign Het
Pnpla6 C A 8: 3,572,403 (GRCm39) Q291K probably damaging Het
Pou2af2 T A 9: 51,202,870 (GRCm39) S95C probably damaging Het
Prkch T C 12: 73,749,320 (GRCm39) F357L probably benign Het
Ptprj A T 2: 90,301,497 (GRCm39) Y212N probably damaging Het
Reln G T 5: 22,165,376 (GRCm39) H2061N probably benign Het
Rint1 T A 5: 24,005,656 (GRCm39) S113T probably benign Het
Rnf38 G C 4: 44,142,468 (GRCm39) probably null Het
Slc30a4 T A 2: 122,527,936 (GRCm39) I374L probably benign Het
Slfn10-ps T C 11: 82,920,676 (GRCm39) noncoding transcript Het
Smcp A T 3: 92,491,710 (GRCm39) C46S unknown Het
Smu1 A C 4: 40,748,570 (GRCm39) V240G probably damaging Het
Srsf5 A G 12: 80,996,519 (GRCm39) probably benign Het
Stn1 T C 19: 47,524,812 (GRCm39) probably null Het
Stx18 A G 5: 38,262,335 (GRCm39) E63G probably damaging Het
Tas2r130 A G 6: 131,607,130 (GRCm39) Y222H probably benign Het
Tescl G T 7: 24,032,758 (GRCm39) P189Q probably benign Het
Tlr1 A G 5: 65,084,203 (GRCm39) S125P probably damaging Het
Ugt2a2 G T 5: 87,609,880 (GRCm39) D566E possibly damaging Het
Unc13b A T 4: 43,237,144 (GRCm39) T3405S probably damaging Het
Upf1 G A 8: 70,785,709 (GRCm39) Q1046* probably null Het
Wwox T A 8: 115,172,090 (GRCm39) Y61* probably null Het
Zfhx4 C T 3: 5,468,170 (GRCm39) T2776M probably damaging Het
Zranb3 G A 1: 127,888,488 (GRCm39) probably benign Het
Other mutations in Hadhb
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02306:Hadhb APN 5 30,371,747 (GRCm39) missense probably null 0.99
IGL02472:Hadhb APN 5 30,389,061 (GRCm39) missense possibly damaging 0.68
R0110:Hadhb UTSW 5 30,374,483 (GRCm39) splice site probably benign
R0481:Hadhb UTSW 5 30,373,543 (GRCm39) missense probably damaging 1.00
R0578:Hadhb UTSW 5 30,383,804 (GRCm39) missense probably benign
R1483:Hadhb UTSW 5 30,374,492 (GRCm39) critical splice acceptor site probably null
R1616:Hadhb UTSW 5 30,371,713 (GRCm39) missense probably damaging 1.00
R1926:Hadhb UTSW 5 30,385,935 (GRCm39) missense possibly damaging 0.94
R2064:Hadhb UTSW 5 30,378,796 (GRCm39) splice site probably null
R5066:Hadhb UTSW 5 30,369,094 (GRCm39) intron probably benign
R5298:Hadhb UTSW 5 30,382,009 (GRCm39) critical splice donor site probably null
R6216:Hadhb UTSW 5 30,379,929 (GRCm39) missense probably benign 0.00
R6787:Hadhb UTSW 5 30,360,247 (GRCm39) unclassified probably benign
R8480:Hadhb UTSW 5 30,373,568 (GRCm39) critical splice donor site probably null
R8802:Hadhb UTSW 5 30,378,831 (GRCm39) nonsense probably null
R9481:Hadhb UTSW 5 30,368,711 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- AGACTGCTGCTCAGGAAGGTCAAG -3'
(R):5'- TGTATTTTAAGCCTCCAACCACACGC -3'

Sequencing Primer
(F):5'- ccccagaaagagcagcag -3'
(R):5'- AGCAAATTTGCTGCAGGC -3'
Posted On 2014-04-13