Incidental Mutation 'R4044:Itih4'
ID 314000
Institutional Source Beutler Lab
Gene Symbol Itih4
Ensembl Gene ENSMUSG00000021922
Gene Name inter alpha-trypsin inhibitor, heavy chain 4
Synonyms Itih-4
MMRRC Submission 040967-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R4044 (G1)
Quality Score 225
Status Validated
Chromosome 14
Chromosomal Location 30608433-30623943 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 30616995 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Isoleucine at position 517 (N517I)
Ref Sequence ENSEMBL: ENSMUSP00000125920 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006703] [ENSMUST00000078490] [ENSMUST00000120269] [ENSMUST00000168782]
AlphaFold A6X935
Predicted Effect probably damaging
Transcript: ENSMUST00000006703
AA Change: N517I

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000006703
Gene: ENSMUSG00000021922
AA Change: N517I

DomainStartEndE-ValueType
VIT 19 148 3.22e-80 SMART
VWA 272 456 5.97e-30 SMART
coiled coil region 552 584 N/A INTRINSIC
low complexity region 662 690 N/A INTRINSIC
Pfam:ITI_HC_C 781 941 2e-11 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000078490
AA Change: N517I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000077580
Gene: ENSMUSG00000021922
AA Change: N517I

DomainStartEndE-ValueType
VIT 19 148 3.22e-80 SMART
VWA 272 456 5.97e-30 SMART
coiled coil region 552 584 N/A INTRINSIC
low complexity region 662 690 N/A INTRINSIC
Pfam:ITI_HC_C 777 941 2.2e-45 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000120269
AA Change: N517I

PolyPhen 2 Score 0.896 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000112798
Gene: ENSMUSG00000021922
AA Change: N517I

DomainStartEndE-ValueType
VIT 19 148 3.22e-80 SMART
VWA 272 456 5.97e-30 SMART
coiled coil region 552 584 N/A INTRINSIC
low complexity region 662 690 N/A INTRINSIC
Pfam:ITI_HC_C 738 902 6.5e-46 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000134988
Predicted Effect probably damaging
Transcript: ENSMUST00000168782
AA Change: N517I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000125920
Gene: ENSMUSG00000021922
AA Change: N517I

DomainStartEndE-ValueType
VIT 19 148 3.22e-80 SMART
VWA 272 456 5.97e-30 SMART
coiled coil region 552 584 N/A INTRINSIC
low complexity region 662 690 N/A INTRINSIC
Pfam:ITI_HC_C 761 925 2.2e-45 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227899
Meta Mutation Damage Score 0.1181 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 94.5%
Validation Efficiency 100% (45/45)
MGI Phenotype FUNCTION: This gene encodes a member of the inter-alpha trypsin inhibitor (IaI) family of plasma serine protease inhibitors with diverse functions as anti-apoptotic and matrix stabilizing molecules during development. This gene is predominantly expressed in the liver and the encoded protein was found to be a plasma kallikrein-sensitive glycoprotein. This gene is located in a cluster of related inter alpha trypsin inhibitor genes on chromosome 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
PHENOTYPE: Mice homozygous for a knock-out allele are viable, fertile and overtly normal. Surprisingly, IL-6/STAT3 signaling is significantly suppressed in mutant liver tissues but hepatocytes remain well differentiated. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 43 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930579C12Rik T A 9: 89,044,347 (GRCm39) noncoding transcript Het
Ada A T 2: 163,577,380 (GRCm39) I36N probably damaging Het
Armh3 A T 19: 45,808,763 (GRCm39) Y643N probably damaging Het
Atg7 T C 6: 114,678,939 (GRCm39) V384A probably benign Het
Ccl1 T A 11: 82,070,519 (GRCm39) I18L probably benign Het
Cep70 T A 9: 99,144,662 (GRCm39) C66S possibly damaging Het
D16Ertd472e A T 16: 78,372,894 (GRCm39) D14E probably damaging Het
Dnah9 T C 11: 66,024,461 (GRCm39) K278E probably benign Het
Dsg1a C A 18: 20,457,087 (GRCm39) N153K probably damaging Het
Galnt5 T A 2: 57,888,472 (GRCm39) I24N probably damaging Het
Grid1 A T 14: 35,172,358 (GRCm39) probably benign Het
Gtf2a1 T C 12: 91,542,441 (GRCm39) H47R probably benign Het
Igf1r A G 7: 67,839,810 (GRCm39) T706A possibly damaging Het
Jam3 C A 9: 27,013,159 (GRCm39) probably null Het
Katnip A G 7: 125,467,913 (GRCm39) I1366V probably benign Het
Klk1b4 A G 7: 43,860,179 (GRCm39) M98V probably benign Het
Kndc1 A G 7: 139,504,044 (GRCm39) E1116G probably benign Het
Ksr2 C T 5: 117,693,127 (GRCm39) R192* probably null Het
L3mbtl4 T C 17: 69,084,909 (GRCm39) S607P possibly damaging Het
Map6 T C 7: 98,917,256 (GRCm39) C10R probably damaging Het
Myo3a A G 2: 22,467,712 (GRCm39) E322G probably damaging Het
Nell1 A G 7: 49,869,367 (GRCm39) N214S probably damaging Het
Npm3 T C 19: 45,736,692 (GRCm39) E149G possibly damaging Het
Or4k35 C T 2: 111,099,927 (GRCm39) V262I probably benign Het
Or5h24 G A 16: 58,919,124 (GRCm39) T77I unknown Het
Orc3 G A 4: 34,587,055 (GRCm39) Q345* probably null Het
Otol1 A G 3: 69,935,112 (GRCm39) D368G probably damaging Het
Pals1 G A 12: 78,871,613 (GRCm39) E398K probably benign Het
Pramel26 T A 4: 143,538,170 (GRCm39) N267I probably benign Het
Prss40 G T 1: 34,599,960 (GRCm39) S9* probably null Het
Radx C T X: 138,407,752 (GRCm39) S364L probably damaging Het
Reln A T 5: 22,333,630 (GRCm39) V264D possibly damaging Het
Rpp40 A G 13: 36,082,549 (GRCm39) C275R probably benign Het
Scaf1 G A 7: 44,655,798 (GRCm39) probably benign Het
Sncaip A G 18: 53,040,475 (GRCm39) T890A probably benign Het
Spata6l A T 19: 28,923,183 (GRCm39) C80S possibly damaging Het
Thada A G 17: 84,749,135 (GRCm39) V612A probably benign Het
Tsnaxip1 G A 8: 106,560,177 (GRCm39) probably null Het
Vcan T A 13: 89,840,662 (GRCm39) L1627F probably benign Het
Vrtn T C 12: 84,695,844 (GRCm39) I198T probably damaging Het
Wnt9b T C 11: 103,622,824 (GRCm39) D193G probably damaging Het
Znrd2 T C 19: 5,780,431 (GRCm39) E189G probably damaging Het
Zswim5 A G 4: 116,843,899 (GRCm39) D979G probably damaging Het
Other mutations in Itih4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00094:Itih4 APN 14 30,617,426 (GRCm39) missense probably damaging 0.97
IGL00776:Itih4 APN 14 30,611,561 (GRCm39) missense probably benign 0.03
IGL01309:Itih4 APN 14 30,613,706 (GRCm39) missense probably damaging 1.00
IGL01433:Itih4 APN 14 30,617,405 (GRCm39) missense probably benign 0.01
IGL01598:Itih4 APN 14 30,609,774 (GRCm39) missense possibly damaging 0.92
IGL02332:Itih4 APN 14 30,609,817 (GRCm39) missense probably damaging 1.00
IGL03075:Itih4 APN 14 30,614,240 (GRCm39) missense probably benign 0.02
IGL03304:Itih4 APN 14 30,620,006 (GRCm39) missense probably damaging 0.98
IGL03353:Itih4 APN 14 30,609,801 (GRCm39) missense probably damaging 1.00
IGL03396:Itih4 APN 14 30,609,906 (GRCm39) missense probably damaging 1.00
PIT4453001:Itih4 UTSW 14 30,623,127 (GRCm39) missense probably benign 0.29
R0304:Itih4 UTSW 14 30,612,051 (GRCm39) splice site probably null
R0477:Itih4 UTSW 14 30,611,631 (GRCm39) missense probably damaging 1.00
R0783:Itih4 UTSW 14 30,617,380 (GRCm39) missense possibly damaging 0.84
R0882:Itih4 UTSW 14 30,614,231 (GRCm39) missense probably damaging 1.00
R1118:Itih4 UTSW 14 30,618,124 (GRCm39) splice site probably benign
R1126:Itih4 UTSW 14 30,611,918 (GRCm39) critical splice donor site probably null
R1238:Itih4 UTSW 14 30,609,906 (GRCm39) missense probably damaging 1.00
R1456:Itih4 UTSW 14 30,614,610 (GRCm39) missense probably benign 0.31
R1573:Itih4 UTSW 14 30,619,504 (GRCm39) missense probably benign 0.00
R1695:Itih4 UTSW 14 30,613,456 (GRCm39) critical splice donor site probably null
R2085:Itih4 UTSW 14 30,614,280 (GRCm39) missense possibly damaging 0.91
R2093:Itih4 UTSW 14 30,613,694 (GRCm39) missense probably damaging 1.00
R2213:Itih4 UTSW 14 30,612,670 (GRCm39) missense probably damaging 0.99
R2249:Itih4 UTSW 14 30,621,351 (GRCm39) nonsense probably null
R2267:Itih4 UTSW 14 30,614,385 (GRCm39) missense probably damaging 1.00
R2268:Itih4 UTSW 14 30,614,385 (GRCm39) missense probably damaging 1.00
R2508:Itih4 UTSW 14 30,617,435 (GRCm39) missense probably damaging 1.00
R3724:Itih4 UTSW 14 30,614,541 (GRCm39) missense possibly damaging 0.60
R3859:Itih4 UTSW 14 30,614,286 (GRCm39) missense probably damaging 1.00
R4042:Itih4 UTSW 14 30,616,995 (GRCm39) missense probably damaging 1.00
R4246:Itih4 UTSW 14 30,613,359 (GRCm39) missense probably damaging 1.00
R4422:Itih4 UTSW 14 30,611,821 (GRCm39) missense probably damaging 1.00
R4553:Itih4 UTSW 14 30,622,910 (GRCm39) missense probably damaging 1.00
R4581:Itih4 UTSW 14 30,622,925 (GRCm39) missense probably benign 0.01
R4608:Itih4 UTSW 14 30,623,626 (GRCm39) missense probably damaging 1.00
R4609:Itih4 UTSW 14 30,623,626 (GRCm39) missense probably damaging 1.00
R4726:Itih4 UTSW 14 30,611,792 (GRCm39) missense probably damaging 1.00
R4790:Itih4 UTSW 14 30,611,867 (GRCm39) missense probably damaging 1.00
R4975:Itih4 UTSW 14 30,614,244 (GRCm39) missense probably damaging 1.00
R5004:Itih4 UTSW 14 30,614,629 (GRCm39) missense probably damaging 1.00
R5911:Itih4 UTSW 14 30,612,612 (GRCm39) missense possibly damaging 0.90
R6014:Itih4 UTSW 14 30,614,586 (GRCm39) missense probably benign 0.01
R6957:Itih4 UTSW 14 30,614,560 (GRCm39) missense probably damaging 1.00
R7012:Itih4 UTSW 14 30,612,706 (GRCm39) missense probably benign 0.16
R7075:Itih4 UTSW 14 30,614,560 (GRCm39) missense probably damaging 1.00
R7195:Itih4 UTSW 14 30,621,432 (GRCm39) missense probably damaging 1.00
R7231:Itih4 UTSW 14 30,618,571 (GRCm39) missense probably benign 0.17
R7509:Itih4 UTSW 14 30,617,404 (GRCm39) missense probably benign 0.08
R7819:Itih4 UTSW 14 30,623,620 (GRCm39) missense probably benign 0.00
R7967:Itih4 UTSW 14 30,614,370 (GRCm39) missense probably damaging 1.00
R8084:Itih4 UTSW 14 30,621,400 (GRCm39) missense possibly damaging 0.95
R8257:Itih4 UTSW 14 30,609,825 (GRCm39) missense possibly damaging 0.93
R8534:Itih4 UTSW 14 30,622,979 (GRCm39) missense probably benign 0.13
R8797:Itih4 UTSW 14 30,618,529 (GRCm39) missense probably benign 0.00
R8886:Itih4 UTSW 14 30,617,482 (GRCm39) nonsense probably null
R9006:Itih4 UTSW 14 30,612,086 (GRCm39) missense probably damaging 1.00
R9035:Itih4 UTSW 14 30,618,650 (GRCm39) missense probably benign 0.00
R9377:Itih4 UTSW 14 30,608,533 (GRCm39) missense probably damaging 1.00
Z1176:Itih4 UTSW 14 30,621,419 (GRCm39) frame shift probably null
Predicted Primers PCR Primer
(F):5'- TACACAGCTGTCTTGCGAC -3'
(R):5'- CACTAAAAGGGCTCAATGGTG -3'

Sequencing Primer
(F):5'- GATCAGCTGCTAACATTTACCTGAC -3'
(R):5'- CTCAATGGTGTCACGTGAAAGCC -3'
Posted On 2015-04-30