Incidental Mutation 'R0092:Hipk2'
ID 20273
Institutional Source Beutler Lab
Gene Symbol Hipk2
Ensembl Gene ENSMUSG00000061436
Gene Name homeodomain interacting protein kinase 2
Synonyms B230339E18Rik, 1110014O20Rik, Stank
MMRRC Submission 038379-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.958) question?
Stock # R0092 (G1)
Quality Score 225
Status Validated (trace)
Chromosome 6
Chromosomal Location 38671325-38853099 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 38720164 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 482 (D482G)
Ref Sequence ENSEMBL: ENSMUSP00000125572 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000160360] [ENSMUST00000160962] [ENSMUST00000161779] [ENSMUST00000162359]
AlphaFold Q9QZR5
Predicted Effect noncoding transcript
Transcript: ENSMUST00000159307
Predicted Effect noncoding transcript
Transcript: ENSMUST00000159894
Predicted Effect probably damaging
Transcript: ENSMUST00000160360
AA Change: D489G

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000125500
Gene: ENSMUSG00000061436
AA Change: D489G

low complexity region 94 104 N/A INTRINSIC
low complexity region 156 180 N/A INTRINSIC
S_TKc 199 527 3.05e-78 SMART
low complexity region 895 909 N/A INTRINSIC
low complexity region 963 992 N/A INTRINSIC
low complexity region 998 1018 N/A INTRINSIC
low complexity region 1057 1072 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000160962
AA Change: D482G

PolyPhen 2 Score 0.971 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000125572
Gene: ENSMUSG00000061436
AA Change: D482G

low complexity region 87 97 N/A INTRINSIC
low complexity region 149 173 N/A INTRINSIC
S_TKc 192 520 3.05e-78 SMART
low complexity region 888 902 N/A INTRINSIC
low complexity region 956 985 N/A INTRINSIC
low complexity region 991 1011 N/A INTRINSIC
low complexity region 1050 1065 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000161779
AA Change: D489G

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000124133
Gene: ENSMUSG00000061436
AA Change: D489G

low complexity region 94 104 N/A INTRINSIC
low complexity region 156 180 N/A INTRINSIC
S_TKc 199 527 3.05e-78 SMART
low complexity region 923 937 N/A INTRINSIC
low complexity region 991 1020 N/A INTRINSIC
low complexity region 1026 1046 N/A INTRINSIC
low complexity region 1085 1100 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000162359
AA Change: D489G

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000125150
Gene: ENSMUSG00000061436
AA Change: D489G

low complexity region 94 104 N/A INTRINSIC
low complexity region 156 180 N/A INTRINSIC
S_TKc 199 527 3.05e-78 SMART
low complexity region 896 910 N/A INTRINSIC
low complexity region 964 993 N/A INTRINSIC
low complexity region 999 1019 N/A INTRINSIC
low complexity region 1058 1073 N/A INTRINSIC
Meta Mutation Damage Score 0.3128 question?
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 97.9%
  • 10x: 95.1%
  • 20x: 88.6%
Validation Efficiency 99% (112/113)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a conserved serine/threonine kinase that is a member of the homeodomain-interacting protein kinase family. The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53, and can function as both a corepressor and a coactivator depending on the transcription factor and its subcellular localization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
PHENOTYPE: Homozygous null mice display decreased apoptosis and increased neuron numbers in the trigeminal ganglion. [provided by MGI curators]
Allele List at MGI

All alleles(10) : Targeted(7) Gene trapped(3)

Other mutations in this stock
Total: 94 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcg2 T A 6: 58,662,762 (GRCm39) S535T probably benign Het
Acad11 A T 9: 103,967,540 (GRCm39) probably benign Het
Acadm A T 3: 153,647,512 (GRCm39) probably benign Het
Acot12 T A 13: 91,889,684 (GRCm39) M12K probably damaging Het
Actr2 A T 11: 20,044,308 (GRCm39) N99K probably benign Het
Adam2 G A 14: 66,291,336 (GRCm39) A314V probably damaging Het
Agl C T 3: 116,587,453 (GRCm39) R34Q probably damaging Het
Agrn C T 4: 156,263,410 (GRCm39) R338H probably damaging Het
AI661453 A G 17: 47,778,440 (GRCm39) probably benign Het
Alpk3 A G 7: 80,742,301 (GRCm39) D706G probably benign Het
Apbb1 T C 7: 105,208,361 (GRCm39) E648G probably damaging Het
Astn2 C A 4: 66,322,219 (GRCm39) A127S unknown Het
Asxl2 T C 12: 3,546,313 (GRCm39) S366P probably benign Het
Bdh1 A T 16: 31,266,380 (GRCm39) K92* probably null Het
Bltp1 A G 3: 37,082,308 (GRCm39) D3790G probably benign Het
Cacna1g C T 11: 94,348,090 (GRCm39) S666N probably damaging Het
Ces2b A G 8: 105,563,144 (GRCm39) T361A possibly damaging Het
Col6a4 T A 9: 105,890,513 (GRCm39) E1927V probably benign Het
Ctnnb1 T G 9: 120,781,929 (GRCm39) I314S possibly damaging Het
Cyp2c66 T C 19: 39,172,224 (GRCm39) probably benign Het
Dennd4c T A 4: 86,699,844 (GRCm39) F232I probably damaging Het
Dennd5a T C 7: 109,499,013 (GRCm39) N950S possibly damaging Het
Dhx30 T C 9: 109,914,078 (GRCm39) N14S possibly damaging Het
Dip2b T A 15: 100,100,146 (GRCm39) V1004D probably damaging Het
Dnah1 A C 14: 30,993,566 (GRCm39) S2872A probably benign Het
Dnajc10 T C 2: 80,156,026 (GRCm39) V233A probably damaging Het
E230025N22Rik A G 18: 36,822,277 (GRCm39) L162P probably damaging Het
Elmod3 T C 6: 72,543,792 (GRCm39) D333G probably benign Het
Epb41l3 T A 17: 69,593,745 (GRCm39) M846K probably damaging Het
Frem2 A G 3: 53,497,217 (GRCm39) Y1766H probably benign Het
Fxr2 T C 11: 69,532,972 (GRCm39) probably benign Het
Gmpr2 A G 14: 55,915,402 (GRCm39) R258G probably benign Het
Helb T C 10: 119,925,713 (GRCm39) Y888C probably damaging Het
Hephl1 TTCCAGATGTCC TTCC 9: 15,001,899 (GRCm39) probably null Het
Itgb4 G T 11: 115,869,950 (GRCm39) R44L probably damaging Het
Itih1 T C 14: 30,662,820 (GRCm39) probably benign Het
Kit T A 5: 75,808,414 (GRCm39) S719R possibly damaging Het
Krt13 G A 11: 100,012,258 (GRCm39) Q22* probably null Het
L3mbtl4 A C 17: 68,732,698 (GRCm39) R59S probably benign Het
Lpp A G 16: 24,580,352 (GRCm39) S23G probably benign Het
Magi3 G A 3: 103,958,280 (GRCm39) Q602* probably null Het
Man2a1 A G 17: 64,966,079 (GRCm39) probably benign Het
Muc5ac A G 7: 141,372,367 (GRCm39) E2667G possibly damaging Het
Myef2l G A 3: 10,153,633 (GRCm39) C134Y possibly damaging Het
Myo15b C G 11: 115,753,812 (GRCm39) S842C possibly damaging Het
Naf1 T A 8: 67,341,760 (GRCm39) S462T probably benign Het
Necab3 T C 2: 154,400,659 (GRCm39) D34G possibly damaging Het
Nisch C A 14: 30,913,410 (GRCm39) probably benign Het
Nlrc5 T C 8: 95,216,222 (GRCm39) probably benign Het
Nmt1 T C 11: 102,937,319 (GRCm39) F119L probably damaging Het
Nod1 T G 6: 54,921,526 (GRCm39) D264A probably damaging Het
Nol8 C T 13: 49,815,923 (GRCm39) A677V possibly damaging Het
Nt5e T A 9: 88,252,338 (GRCm39) F567I probably benign Het
Obscn A T 11: 58,942,073 (GRCm39) M4434K possibly damaging Het
Opa1 A T 16: 29,444,412 (GRCm39) D866V probably damaging Het
Or10a3m T C 7: 108,313,031 (GRCm39) V145A probably benign Het
Or10al3 T G 17: 38,011,696 (GRCm39) L45R probably damaging Het
Or10p1 A G 10: 129,444,090 (GRCm39) S87P probably damaging Het
Or1j21 A G 2: 36,683,508 (GRCm39) T87A probably benign Het
Or51ai2 T C 7: 103,586,934 (GRCm39) S116P probably damaging Het
Otop1 T A 5: 38,457,174 (GRCm39) V311E probably damaging Het
Pcsk2 A G 2: 143,642,944 (GRCm39) D407G probably damaging Het
Pdcd1 A G 1: 93,980,149 (GRCm39) W23R possibly damaging Het
Pigp A G 16: 94,166,321 (GRCm39) V129A probably damaging Het
Pik3r5 A G 11: 68,383,629 (GRCm39) R483G probably benign Het
Pink1 A G 4: 138,047,309 (GRCm39) V225A probably benign Het
Plcl1 C G 1: 55,735,924 (GRCm39) Q422E probably damaging Het
Plec T C 15: 76,067,943 (GRCm39) E1222G probably benign Het
Polr1a T C 6: 71,944,439 (GRCm39) probably benign Het
Prokr2 C T 2: 132,215,517 (GRCm39) V154M probably damaging Het
Rasgrp4 A G 7: 28,844,557 (GRCm39) R280G possibly damaging Het
Rmnd5b T C 11: 51,520,419 (GRCm39) E8G possibly damaging Het
Sbf2 T A 7: 109,920,013 (GRCm39) probably benign Het
Sec23b A G 2: 144,408,830 (GRCm39) M172V probably benign Het
Setx T C 2: 29,036,305 (GRCm39) V930A probably benign Het
Sft2d2 G A 1: 165,006,829 (GRCm39) A159V possibly damaging Het
Sh3gl1 G T 17: 56,325,088 (GRCm39) R250S probably benign Het
Skor1 C A 9: 63,053,277 (GRCm39) D231Y probably damaging Het
Slc24a1 T G 9: 64,856,034 (GRCm39) E291A unknown Het
Slc28a2b G T 2: 122,348,078 (GRCm39) probably benign Het
Smc1b A T 15: 84,951,925 (GRCm39) probably benign Het
Tbccd1 A T 16: 22,644,844 (GRCm39) N177K possibly damaging Het
Tdp1 T A 12: 99,921,248 (GRCm39) Y595N probably damaging Het
Tle5 G A 10: 81,397,054 (GRCm39) G10D possibly damaging Het
Tmem108 T C 9: 103,366,504 (GRCm39) K496E possibly damaging Het
Tmprss7 T C 16: 45,487,959 (GRCm39) D490G probably damaging Het
Tnrc6b A T 15: 80,802,729 (GRCm39) N1511Y probably damaging Het
Top2b G A 14: 16,409,263 (GRCm38) R802Q probably damaging Het
Trip10 A T 17: 57,557,798 (GRCm39) K27N possibly damaging Het
Txlnb A G 10: 17,718,503 (GRCm39) N445D possibly damaging Het
Txnrd1 T A 10: 82,715,636 (GRCm39) I159N probably damaging Het
Ulk1 C A 5: 110,944,193 (GRCm39) A164S probably null Het
Vmn2r83 T C 10: 79,327,798 (GRCm39) V802A probably damaging Het
Zbtb4 A G 11: 69,670,177 (GRCm39) I967V probably benign Het
Other mutations in Hipk2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00582:Hipk2 APN 6 38,796,257 (GRCm39) splice site probably benign
IGL00814:Hipk2 APN 6 38,795,484 (GRCm39) missense probably damaging 1.00
IGL00907:Hipk2 APN 6 38,795,208 (GRCm39) missense probably damaging 1.00
IGL01350:Hipk2 APN 6 38,795,250 (GRCm39) missense probably damaging 1.00
IGL01714:Hipk2 APN 6 38,796,117 (GRCm39) missense probably damaging 1.00
IGL01893:Hipk2 APN 6 38,795,330 (GRCm39) missense probably benign 0.05
IGL02028:Hipk2 APN 6 38,795,691 (GRCm39) missense possibly damaging 0.67
IGL02133:Hipk2 APN 6 38,796,069 (GRCm39) missense probably benign
IGL02135:Hipk2 APN 6 38,795,934 (GRCm39) missense possibly damaging 0.90
IGL02543:Hipk2 APN 6 38,680,436 (GRCm39) missense possibly damaging 0.95
IGL02630:Hipk2 APN 6 38,795,456 (GRCm39) missense possibly damaging 0.48
IGL02896:Hipk2 APN 6 38,675,382 (GRCm39) missense probably damaging 1.00
IGL02900:Hipk2 APN 6 38,706,879 (GRCm39) missense probably damaging 0.96
IGL03345:Hipk2 APN 6 38,724,937 (GRCm39) splice site probably benign
R0070:Hipk2 UTSW 6 38,795,919 (GRCm39) nonsense probably null
R0070:Hipk2 UTSW 6 38,795,919 (GRCm39) nonsense probably null
R0184:Hipk2 UTSW 6 38,695,866 (GRCm39) missense possibly damaging 0.77
R0494:Hipk2 UTSW 6 38,706,924 (GRCm39) missense probably benign 0.03
R0617:Hipk2 UTSW 6 38,724,420 (GRCm39) missense possibly damaging 0.70
R0720:Hipk2 UTSW 6 38,675,491 (GRCm39) missense probably damaging 1.00
R1812:Hipk2 UTSW 6 38,675,098 (GRCm39) missense probably benign 0.14
R1864:Hipk2 UTSW 6 38,695,870 (GRCm39) critical splice acceptor site probably null
R1919:Hipk2 UTSW 6 38,795,919 (GRCm39) nonsense probably null
R1995:Hipk2 UTSW 6 38,692,909 (GRCm39) missense probably damaging 1.00
R2079:Hipk2 UTSW 6 38,795,720 (GRCm39) missense probably damaging 1.00
R2238:Hipk2 UTSW 6 38,706,850 (GRCm39) splice site probably benign
R2384:Hipk2 UTSW 6 38,795,306 (GRCm39) missense probably damaging 0.99
R3775:Hipk2 UTSW 6 38,720,029 (GRCm39) missense probably damaging 0.99
R3792:Hipk2 UTSW 6 38,675,491 (GRCm39) missense probably damaging 1.00
R3841:Hipk2 UTSW 6 38,795,861 (GRCm39) missense probably damaging 1.00
R3883:Hipk2 UTSW 6 38,676,200 (GRCm39) missense probably damaging 1.00
R4471:Hipk2 UTSW 6 38,713,857 (GRCm39) intron probably benign
R4724:Hipk2 UTSW 6 38,675,327 (GRCm39) missense probably benign 0.10
R4838:Hipk2 UTSW 6 38,795,339 (GRCm39) missense possibly damaging 0.94
R4843:Hipk2 UTSW 6 38,796,192 (GRCm39) missense possibly damaging 0.94
R5040:Hipk2 UTSW 6 38,707,816 (GRCm39) missense possibly damaging 0.82
R5044:Hipk2 UTSW 6 38,795,814 (GRCm39) missense probably benign 0.06
R5320:Hipk2 UTSW 6 38,795,212 (GRCm39) missense probably damaging 1.00
R5409:Hipk2 UTSW 6 38,706,977 (GRCm39) missense probably damaging 1.00
R5682:Hipk2 UTSW 6 38,714,408 (GRCm39) missense possibly damaging 0.50
R5695:Hipk2 UTSW 6 38,795,810 (GRCm39) missense possibly damaging 0.64
R5876:Hipk2 UTSW 6 38,707,802 (GRCm39) critical splice donor site probably null
R6309:Hipk2 UTSW 6 38,675,446 (GRCm39) missense probably damaging 1.00
R6612:Hipk2 UTSW 6 38,795,808 (GRCm39) missense probably benign 0.04
R6815:Hipk2 UTSW 6 38,795,777 (GRCm39) missense probably damaging 1.00
R7104:Hipk2 UTSW 6 38,795,579 (GRCm39) missense probably damaging 0.98
R7124:Hipk2 UTSW 6 38,795,413 (GRCm39) nonsense probably null
R7238:Hipk2 UTSW 6 38,692,992 (GRCm39) missense probably benign 0.45
R7712:Hipk2 UTSW 6 38,680,569 (GRCm39) missense probably benign 0.02
R7994:Hipk2 UTSW 6 38,795,403 (GRCm39) missense possibly damaging 0.94
R8190:Hipk2 UTSW 6 38,795,728 (GRCm39) missense possibly damaging 0.88
R8388:Hipk2 UTSW 6 38,722,630 (GRCm39) missense probably damaging 1.00
R8796:Hipk2 UTSW 6 38,675,158 (GRCm39) missense probably damaging 0.99
R9041:Hipk2 UTSW 6 38,724,909 (GRCm39) nonsense probably null
R9388:Hipk2 UTSW 6 38,707,956 (GRCm39) missense probably damaging 1.00
R9480:Hipk2 UTSW 6 38,680,377 (GRCm39) missense probably benign 0.37
R9485:Hipk2 UTSW 6 38,680,445 (GRCm39) missense possibly damaging 0.94
R9562:Hipk2 UTSW 6 38,724,390 (GRCm39) missense probably damaging 0.99
R9565:Hipk2 UTSW 6 38,724,390 (GRCm39) missense probably damaging 0.99
Predicted Primers PCR Primer

Sequencing Primer
Protein Function and Prediction

Homeodomain interacting protein kinase 2 (Hipk2) is a conserved serine/threonine kinase that interacts with and phosphorylates homeodomain transcription factors to regulate transcription during development and in response to DNA damage (1). Hipk2 has a conserved N-terminal kinase domain with a DYRK motif, a nuclear localization sequence, a PEST domain, and C-terminal region that contains speckle-retention signal, an autoinhibitory domain, and a ubiquitylation site (1;2).

Northern blot analysis detected ubiquitous expression of a 11.0-kb HIPK2 transcript, with strongest expression in human neuronal tissue; a 7.8-kb transcript was detected in the uterus and a 1.4-kb transcript was detected in the pancreas (3). Hipk2 is detectable in postnatal day (P) 15 mouse embryos and is strong by P17 (4).  In situ hybridization detected expression in neural retina, telencephalon, and muscle at P16.5 (4). Similar to human HIPK2, mouse Hipk2 is ubiquitously expressed in the adult, Pierantoni et al. detected highest expression in the heart, muscle and kidney by RT-PCR (4).

Hipk2tm1Hko/tm1Hko; MGI:3624127

involves: C57BL/6

Embyronic fibroblasts from null mice are slightly resistant to UV radiation (5). Also, there are more frequent instances of neural tube defects in these mice (5).

Hipk2tm1Ejh/tm1Ejh; MGI:3487301

involves: 129X1/SvJ * C57BL/6

Homozygous mice exhibit diminished locomotor activity response to amphetamine compared with wild-type mice as well as abnormal limb grasping, impaired coordination, abnormal voluntary movement, and abnormal gait (6).  There is also decreased neuron apoptosis in dopaminergic neurons at E17.5 and P0 (6). Homozygotes have decreased dopaminergic neuron number throughout life (6).

Hipk2tm1Ejh/tm1Ejh; MGI:3487301

involves: 129X1/SvJ * C57BL/6J

In this genetic background, homozygotes have more neurons in the trigeminal ganglion at E13.5 and P0 due to a reduction in apoptotic neurons (7).

Hipk2tm1Afus/tm1Afus; MGI:4429497

involves: 129X1/SvJ * C57BL/6

Homozygotes in this model have abnormal motor capabilities/coordination/movement as well as an increase in the number of mouse embryonic fibroblasts in the G0/G1 phase of the cell cycle and reduced proliferation (8). Homozygotes have decreased birth and body weight over their life (8).

Posted On 2013-04-11
Science Writer Anne Murray