Incidental Mutation 'R1381:Hadha'
ID 163005
Institutional Source Beutler Lab
Gene Symbol Hadha
Ensembl Gene ENSMUSG00000025745
Gene Name hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
Synonyms Mtpa
MMRRC Submission 039443-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1381 (G1)
Quality Score 89
Status Not validated
Chromosome 5
Chromosomal Location 30324421-30359978 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 30333834 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Lysine at position 395 (T395K)
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: ENSMUST00000126081
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130358
Predicted Effect probably benign
Transcript: ENSMUST00000156859
AA Change: T395K

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000120976
Gene: ENSMUSG00000025745
AA Change: T395K

DomainStartEndE-ValueType
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: ENSMUST00000196946
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197491
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 97.8%
  • 10x: 94.4%
  • 20x: 86.2%
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: 83 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4932414N04Rik C A 2: 68,561,430 (GRCm39) F252L probably benign Het
Aadac A T 3: 59,947,351 (GRCm39) M350L probably damaging Het
Agtrap G A 4: 148,168,422 (GRCm39) T19I probably damaging Het
Apba3 C T 10: 81,107,590 (GRCm39) T142M possibly damaging Het
Cd55b T A 1: 130,347,412 (GRCm39) K133I probably damaging Het
Cep295 A C 9: 15,233,861 (GRCm39) C2312G probably benign Het
Ces1a A G 8: 93,760,659 (GRCm39) V231A probably damaging Het
Chdh C A 14: 29,758,791 (GRCm39) L579I probably damaging Het
Cyb5r4 T A 9: 86,904,286 (GRCm39) S19T probably benign Het
Cyp2d22 C A 15: 82,256,709 (GRCm39) R355L probably benign Het
Dach2 T C X: 112,208,472 (GRCm39) Y117H probably damaging Het
Dennd4c G A 4: 86,692,769 (GRCm39) R93K probably benign Het
Dph2 G T 4: 117,746,865 (GRCm39) L452I probably damaging Het
Exoc6b T C 6: 84,812,099 (GRCm39) D634G probably benign Het
Fam217b G A 2: 178,062,218 (GRCm39) V61I probably benign Het
Fbln7 A C 2: 128,719,299 (GRCm39) Q32P probably damaging Het
Fgfr1op2 A G 6: 146,490,239 (GRCm39) Y46C probably damaging Het
Fhod3 T A 18: 25,223,528 (GRCm39) I958N probably damaging Het
Foxp2 T A 6: 15,409,765 (GRCm39) M455K possibly damaging Het
Gabrr2 G A 4: 33,081,420 (GRCm39) G152D probably damaging Het
Galntl6 G T 8: 58,925,989 (GRCm39) P92Q probably damaging Het
Gm5592 A T 7: 40,935,596 (GRCm39) T33S probably benign Het
Grid2ip A T 5: 143,348,406 (GRCm39) T166S probably benign Het
Grsf1 G A 5: 88,813,723 (GRCm39) S225L probably benign Het
Hars2 C T 18: 36,922,270 (GRCm39) A295V possibly damaging Het
Hsf5 T A 11: 87,528,995 (GRCm39) S577T probably benign Het
Ice2 A G 9: 69,307,809 (GRCm39) Y31C probably damaging Het
Ift80 A T 3: 68,822,116 (GRCm39) I643N possibly damaging Het
Iglon5 A T 7: 43,126,064 (GRCm39) D222E probably benign Het
Ilvbl C A 10: 78,412,430 (GRCm39) S50R probably damaging Het
Invs C A 4: 48,421,942 (GRCm39) S858* probably null Het
Ipo13 T G 4: 117,761,592 (GRCm39) T508P probably damaging Het
Itgb4 T C 11: 115,885,163 (GRCm39) I1015T probably benign Het
Kank4 A T 4: 98,668,175 (GRCm39) W91R probably damaging Het
Kansl1l C T 1: 66,760,063 (GRCm39) A906T probably benign Het
Klk4 G A 7: 43,534,706 (GRCm39) V222M probably damaging Het
Lipo4 T A 19: 33,476,741 (GRCm39) M336L probably benign Het
Lrig1 T C 6: 94,583,111 (GRCm39) N1002D probably benign Het
Lzts3 A G 2: 130,477,219 (GRCm39) S524P probably damaging Het
Maz A T 7: 126,622,324 (GRCm39) C409* probably null Het
Mmp24 A T 2: 155,656,047 (GRCm39) Q495L possibly damaging Het
Mrgpra9 C T 7: 46,885,050 (GRCm39) V206I possibly damaging Het
Myof A G 19: 37,983,933 (GRCm39) Y124H probably damaging Het
Nalcn A T 14: 123,551,517 (GRCm39) V1030D probably damaging Het
Neb T A 2: 52,150,544 (GRCm39) I2495F probably damaging Het
Nfix G A 8: 85,453,155 (GRCm39) R300C probably damaging Het
Nrbf2 G A 10: 67,103,605 (GRCm39) T166M probably damaging Het
Nup153 T C 13: 46,842,657 (GRCm39) D837G probably damaging Het
Nup210 C A 6: 91,052,942 (GRCm39) G331V probably damaging Het
Or5b97 T C 19: 12,878,320 (GRCm39) T275A probably benign Het
Or5w18 T C 2: 87,633,480 (GRCm39) L245P probably damaging Het
Or6z7 A G 7: 6,484,008 (GRCm39) probably null Het
Or8b56 T A 9: 38,739,634 (GRCm39) S210T probably benign Het
Pabpc4 T A 4: 123,182,852 (GRCm39) L163H probably damaging Het
Pcdh7 T A 5: 57,878,882 (GRCm39) Y126* probably null Het
Pdzd2 A G 15: 12,385,525 (GRCm39) S1082P probably benign Het
Pkd2l1 T C 19: 44,138,902 (GRCm39) I649M probably benign Het
Plcl2 G A 17: 50,914,757 (GRCm39) E589K probably damaging Het
Plppr1 C A 4: 49,337,674 (GRCm39) T325N possibly damaging Het
Prss8 GCTGCCCAAGTCCC GC 7: 127,529,021 (GRCm39) probably benign Het
Ptcd2 A G 13: 99,481,105 (GRCm39) S25P probably benign Het
Ptpro T A 6: 137,420,592 (GRCm39) V1007D probably damaging Het
Rusc2 T A 4: 43,416,137 (GRCm39) V481E probably damaging Het
Sephs2 G T 7: 126,872,139 (GRCm39) T318K probably damaging Het
Sf3b1 T A 1: 55,042,313 (GRCm39) I497L probably damaging Het
Slc30a7 C T 3: 115,750,519 (GRCm39) probably null Het
Slc66a2 T G 18: 80,326,529 (GRCm39) S126A probably benign Het
Smarca2 T C 19: 26,608,228 (GRCm39) S96P probably damaging Het
Spata31d1c A C 13: 65,184,368 (GRCm39) I637L probably benign Het
Ston2 A T 12: 91,707,266 (GRCm39) S115T probably damaging Het
Tal2 A C 4: 53,785,999 (GRCm39) E60A probably benign Het
Tdpoz3 A T 3: 93,733,447 (GRCm39) T41S probably benign Het
Tent4b T A 8: 88,969,937 (GRCm39) M203K possibly damaging Het
Tespa1 T C 10: 130,196,560 (GRCm39) I166T probably benign Het
Thsd7a A T 6: 12,555,438 (GRCm39) C149S probably damaging Het
Trav6-1 T A 14: 52,875,967 (GRCm39) probably benign Het
Txnl4a T C 18: 80,250,479 (GRCm39) V25A probably benign Het
Utp4 C A 8: 107,632,908 (GRCm39) P297Q probably benign Het
Vmn1r34 T C 6: 66,613,922 (GRCm39) Y272C probably damaging Het
Vmn2r112 A T 17: 22,837,467 (GRCm39) I643F probably damaging Het
Vmn2r121 C A X: 123,037,837 (GRCm39) G728W probably damaging Het
Vmn2r24 T A 6: 123,763,692 (GRCm39) S190T probably damaging Het
Zfp507 A G 7: 35,475,435 (GRCm39) V926A possibly damaging Het
Other mutations in Hadha
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- GCAGGTTCCATAATCCATTCCACGG -3'
(R):5'- AGTGTTTCCCAGCTAATCAGTGCC -3'

Sequencing Primer
(F):5'- GGCCAATGTCCTATGACATAATC -3'
(R):5'- CTGAGGTGTTCACCAGAACTG -3'
Posted On 2014-03-17