Incidental Mutation 'R0158:Cdkn2a'
ID 22963
Institutional Source Beutler Lab
Gene Symbol Cdkn2a
Ensembl Gene ENSMUSG00000044303
Gene Name cyclin dependent kinase inhibitor 2A
Synonyms p16, Ink4a/Arf, MTS1, p19ARF, p16INK4a, p19, Pctr1, Arf, INK4a-ARF, ARF-INK4a
MMRRC Submission 038438-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0158 (G1)
Quality Score 225
Status Validated (trace)
Chromosome 4
Chromosomal Location 89192710-89212856 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 89195004 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Glutamine at position 115 (H115Q)
Ref Sequence ENSEMBL: ENSMUSP00000061847 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000060501] [ENSMUST00000107131]
AlphaFold Q64364
Predicted Effect probably benign
Transcript: ENSMUST00000030237
AA Change: S137T

PolyPhen 2 Score 0.177 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000030237
Gene: ENSMUSG00000044303
AA Change: S137T

DomainStartEndE-ValueType
Pfam:P19Arf_N 4 54 4.6e-26 PFAM
low complexity region 70 76 N/A INTRINSIC
low complexity region 105 121 N/A INTRINSIC
transmembrane domain 142 159 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000060501
AA Change: H115Q

PolyPhen 2 Score 0.918 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000061847
Gene: ENSMUSG00000044303
AA Change: H115Q

DomainStartEndE-ValueType
ANK 3 32 1.53e3 SMART
ANK 36 64 4.07e-1 SMART
ANK 69 98 4.44e2 SMART
ANK 102 131 1.01e2 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000107131
AA Change: S137T

PolyPhen 2 Score 0.177 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000102748
Gene: ENSMUSG00000044303
AA Change: S137T

DomainStartEndE-ValueType
Blast:ANK 1 21 2e-6 BLAST
ANK 26 55 2.8e0 SMART
ANK 59 88 6.3e-1 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000127174
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129527
Meta Mutation Damage Score 0.2315 question?
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 97.9%
  • 10x: 95.3%
  • 20x: 89.1%
Validation Efficiency 93% (79/85)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
PHENOTYPE: Null mutants of p16INK4a or p19ARF proteins each show increased tumor susceptibility and sensitivity to carcinogens. Loss of both gives very early onset. p19ARF nulls also show thymic hyperplasia and the eye's hyaloid vascular system fails to regress. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 67 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcf3 C T 16: 20,371,316 (GRCm39) R437C probably damaging Het
Abhd3 A G 18: 10,647,840 (GRCm39) Y315H possibly damaging Het
Adam19 C T 11: 46,033,861 (GRCm39) P891L probably damaging Het
Ampd1 T A 3: 102,999,046 (GRCm39) Y400* probably null Het
Ap1g1 T C 8: 110,582,267 (GRCm39) S724P probably benign Het
Bst2 T A 8: 71,989,861 (GRCm39) T71S possibly damaging Het
C3 A G 17: 57,531,851 (GRCm39) probably null Het
Cacna2d1 C A 5: 16,566,815 (GRCm39) probably benign Het
Cacna2d4 C T 6: 119,213,709 (GRCm39) H43Y possibly damaging Het
Ccdc71 T G 9: 108,341,336 (GRCm39) V383G probably benign Het
Cd109 A T 9: 78,596,214 (GRCm39) Q849L possibly damaging Het
Ces1e T C 8: 93,946,057 (GRCm39) E161G probably benign Het
Cggbp1 C T 16: 64,676,201 (GRCm39) S89L possibly damaging Het
Crocc A T 4: 140,769,553 (GRCm39) probably benign Het
Cspg4b T A 13: 113,505,687 (GRCm39) L2272* probably null Het
Eef1akmt3 G A 10: 126,869,142 (GRCm39) Q111* probably null Het
Exoc7 T C 11: 116,186,118 (GRCm39) N361S probably benign Het
Fat2 G T 11: 55,187,011 (GRCm39) S1278R probably benign Het
Fbxo42 A G 4: 140,927,640 (GRCm39) N640S probably benign Het
Fbxw25 A G 9: 109,483,720 (GRCm39) V164A possibly damaging Het
Fcgbpl1 A G 7: 27,854,917 (GRCm39) I1848V probably damaging Het
Foxs1 T C 2: 152,774,330 (GRCm39) E241G probably damaging Het
Fras1 A T 5: 96,924,493 (GRCm39) I3645F possibly damaging Het
Gm14496 T A 2: 181,639,206 (GRCm39) V432E probably benign Het
H3c2 T A 13: 23,936,693 (GRCm39) C111S probably damaging Het
Herc1 T A 9: 66,403,203 (GRCm39) L4374* probably null Het
Ift122 T C 6: 115,901,445 (GRCm39) probably benign Het
Itgav C A 2: 83,622,381 (GRCm39) N654K probably benign Het
Itih5 T C 2: 10,239,803 (GRCm39) probably benign Het
Jak2 C A 19: 29,289,157 (GRCm39) T1103K probably benign Het
Kcnc4 C A 3: 107,365,920 (GRCm39) C96F probably benign Het
Med13l C A 5: 118,880,514 (GRCm39) S1202Y unknown Het
Mefv T C 16: 3,533,320 (GRCm39) E317G possibly damaging Het
Ncoa2 T C 1: 13,222,608 (GRCm39) T1226A probably benign Het
Nktr C T 9: 121,579,757 (GRCm39) probably benign Het
Nudt5 G A 2: 5,867,114 (GRCm39) V61M probably damaging Het
Or51a39 C T 7: 102,363,162 (GRCm39) A153T probably benign Het
Pakap A G 4: 57,709,649 (GRCm39) D198G possibly damaging Het
Pcdhb2 A C 18: 37,430,283 (GRCm39) Y752S probably damaging Het
Pcnx4 A G 12: 72,603,076 (GRCm39) D446G probably benign Het
Pnp2 G A 14: 51,201,761 (GRCm39) R249H probably damaging Het
Rgs3 A T 4: 62,542,121 (GRCm39) I32F probably damaging Het
Rnf139 A G 15: 58,770,727 (GRCm39) T251A probably benign Het
Rnf41 A G 10: 128,274,104 (GRCm39) E252G probably damaging Het
Rxfp2 T A 5: 149,975,093 (GRCm39) F220Y probably benign Het
Sdcbp A G 4: 6,379,042 (GRCm39) D43G possibly damaging Het
Serpina3f A G 12: 104,183,267 (GRCm39) D43G probably damaging Het
Sftpc T C 14: 70,758,887 (GRCm39) K154R probably null Het
Simc1 A G 13: 54,672,530 (GRCm39) T293A probably benign Het
Skint6 A T 4: 113,042,011 (GRCm39) probably benign Het
Slc6a15 T C 10: 103,225,208 (GRCm39) probably benign Het
Spata31e2 T G 1: 26,723,032 (GRCm39) H716P probably damaging Het
Ston2 A T 12: 91,707,376 (GRCm39) I78N probably damaging Het
Taok3 T C 5: 117,355,307 (GRCm39) probably null Het
Tent4b G A 8: 88,977,371 (GRCm39) G391D probably damaging Het
Tiam1 C T 16: 89,589,889 (GRCm39) probably benign Het
Tnfsf15 T C 4: 63,648,229 (GRCm39) H137R possibly damaging Het
Tpte G A 8: 22,817,755 (GRCm39) R247H possibly damaging Het
Trim2 T C 3: 84,117,476 (GRCm39) probably benign Het
Ulk1 A T 5: 110,936,810 (GRCm39) probably benign Het
Utp4 T G 8: 107,640,018 (GRCm39) H442Q probably null Het
Vmn1r193 T A 13: 22,403,798 (GRCm39) I65F probably damaging Het
Vps54 A T 11: 21,256,962 (GRCm39) Q690L probably damaging Het
Ybx2 T C 11: 69,831,145 (GRCm39) probably benign Het
Zbtb38 C T 9: 96,568,993 (GRCm39) G697D possibly damaging Het
Zfp202 C T 9: 40,120,212 (GRCm39) Q218* probably null Het
Zfp820 G A 17: 22,038,800 (GRCm39) T176I probably benign Het
Other mutations in Cdkn2a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01936:Cdkn2a APN 4 89,212,569 (GRCm39) critical splice donor site probably null 0.00
R2073:Cdkn2a UTSW 4 89,212,730 (GRCm39) missense possibly damaging 0.71
R4787:Cdkn2a UTSW 4 89,194,955 (GRCm39) missense unknown
R5679:Cdkn2a UTSW 4 89,195,098 (GRCm39) missense possibly damaging 0.88
R6863:Cdkn2a UTSW 4 89,193,003 (GRCm39) missense probably benign
R8344:Cdkn2a UTSW 4 89,194,987 (GRCm39) missense probably benign 0.17
R8348:Cdkn2a UTSW 4 89,200,291 (GRCm39) missense possibly damaging 0.58
R8448:Cdkn2a UTSW 4 89,200,291 (GRCm39) missense possibly damaging 0.58
R8490:Cdkn2a UTSW 4 89,212,759 (GRCm39) start codon destroyed probably null 0.02
Predicted Primers PCR Primer
(F):5'- TGTCCATGTTCTCAGGCTCATTTGG -3'
(R):5'- GCAACGTTCACGTAGCAGCTCTTC -3'

Sequencing Primer
(F):5'- CTCAGGCTCATTTGGGTTGC -3'
(R):5'- TGCTCAACTACGGTGCAG -3'
Posted On 2013-04-16