Incidental Mutation 'F6893:Zc3hc1'
ID226
Institutional Source Beutler Lab
Gene Symbol Zc3hc1
Ensembl Gene ENSMUSG00000039130
Gene Namezinc finger, C3HC type 1
Synonyms1110054L24Rik, Nipa, HSPC216
Accession Numbers

Genbank: NM_172735; MGI: 1916023

Is this an essential gene? Possibly non essential (E-score: 0.383) question?
Stock #F6893 (G3) of strain busy
Quality Score
Status Validated
Chromosome6
Chromosomal Location30366380-30391028 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to T at 30387526 bp
ZygosityHomozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 51 (D51E)
Ref Sequence ENSEMBL: ENSMUSP00000110838 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000080812] [ENSMUST00000102992] [ENSMUST00000115184] [ENSMUST00000136255] [ENSMUST00000152391]
Predicted Effect probably benign
Transcript: ENSMUST00000080812
AA Change: D51E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000079627
Gene: ENSMUSG00000039130
AA Change: D51E

DomainStartEndE-ValueType
Pfam:zf-C3HC 72 201 2e-38 PFAM
low complexity region 216 231 N/A INTRINSIC
Pfam:Rsm1 248 343 6.8e-14 PFAM
low complexity region 406 420 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000102992
AA Change: D51E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000100057
Gene: ENSMUSG00000039130
AA Change: D51E

DomainStartEndE-ValueType
Pfam:zf-C3HC 72 201 2.4e-37 PFAM
low complexity region 216 231 N/A INTRINSIC
Pfam:Rsm1 248 343 2.2e-13 PFAM
low complexity region 406 420 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000115184
AA Change: D51E

PolyPhen 2 Score 0.069 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000110838
Gene: ENSMUSG00000039130
AA Change: D51E

DomainStartEndE-ValueType
Pfam:zf-C3HC 72 201 5.9e-38 PFAM
low complexity region 216 231 N/A INTRINSIC
Pfam:Rsm1 248 339 8.6e-14 PFAM
Pfam:Rsm1 331 394 4.6e-8 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126945
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129796
Predicted Effect probably benign
Transcript: ENSMUST00000136255
Predicted Effect probably benign
Transcript: ENSMUST00000147990
Predicted Effect noncoding transcript
Transcript: ENSMUST00000152101
Predicted Effect probably benign
Transcript: ENSMUST00000152391
AA Change: D51E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000135447
Gene: ENSMUSG00000039130
AA Change: D51E

DomainStartEndE-ValueType
Pfam:zf-C3HC 72 201 9e-38 PFAM
low complexity region 216 231 N/A INTRINSIC
low complexity region 364 378 N/A INTRINSIC
Meta Mutation Damage Score 0.172 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 74.0%
Validation Efficiency 88% (165/188)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an F-box-containing protein that is a component of an SCF-type E3 ubiquitin ligase complex that regulates the onset of cell division. The G2/M transition in the cell cycle requires the interaction of the proteins cyclin B1 and cyclin-dependent kinase 1. The activated ubiquitin ligase complex targets the protein cyclin B1 for degradation, preventing this transition to mitosis. [provided by RefSeq, Aug 2013]
PHENOTYPE: Mice homozygous for a null mutation display partial lethality with male infertility, reduced female fertility, arrest of meiosis, impaired synaptonemal complex formation and delayed double strand DNA break repair. [provided by MGI curators]
Allele List at MGI

All alleles(12) : Targeted, other(2) Gene trapped(10)

Other mutations in this stock
Total: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca14 G A 7: 120,325,038 V1638M probably damaging Het
Agrn C T 4: 156,174,179 R972Q probably benign Het
Anxa3 T C 5: 96,824,994 probably benign Het
Bpifa6 G T 2: 153,987,158 D202Y probably damaging Het
Ccdc15 G A 9: 37,315,640 T346I probably damaging Homo
Celsr3 G A 9: 108,835,067 R1731H probably benign Het
Ces4a A G 8: 105,147,227 R443G possibly damaging Het
Chd2 T C 7: 73,507,872 Q175R possibly damaging Het
Dpyd T A 3: 118,804,134 probably null Het
Dscam G T 16: 97,056,460 H117N possibly damaging Het
F13a1 A G 13: 36,972,025 Y205H probably damaging Het
Fat3 A C 9: 16,006,789 L1446R probably damaging Homo
Golga4 T C 9: 118,553,457 L515S probably damaging Het
Hoxb1 A T 11: 96,365,902 T26S probably benign Het
Igsf10 T G 3: 59,331,060 T567P probably damaging Het
Lamb2 T C 9: 108,482,556 V365A probably benign Het
Mepe A G 5: 104,337,376 I127M possibly damaging Het
Mpi A T 9: 57,546,549 M230K probably benign Homo
Myh4 A G 11: 67,255,457 D1447G probably null Homo
Olfr161 A G 16: 3,593,163 I256V possibly damaging Het
Olfr350 A G 2: 36,850,807 T254A probably benign Het
Panx2 T C 15: 89,068,010 Y227H probably damaging Homo
Pdzd7 A G 19: 45,036,734 W441R probably damaging Het
Poldip2 A G 11: 78,519,194 I267M probably damaging Homo
Pros1 T A 16: 62,924,639 V539E probably damaging Het
Sacs T C 14: 61,212,976 M4157T probably benign Het
Slc45a3 A G 1: 131,981,337 E424G probably benign Homo
Slc9a1 A G 4: 133,422,146 E761G probably benign Homo
Stab2 G A 10: 86,855,171 P2178L probably damaging Het
Syt4 C T 18: 31,444,221 V27I possibly damaging Homo
Thumpd1 T A 7: 119,720,576 K56* probably null Het
Tpr A G 1: 150,393,562 K19E possibly damaging Homo
Ttll10 A G 4: 156,048,318 I74T probably benign Het
Txnrd1 C T 10: 82,866,989 Q95* probably null Homo
Zc3h7b A G 15: 81,778,671 E421G possibly damaging Homo
Other mutations in Zc3hc1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01571:Zc3hc1 APN 6 30390863 missense probably benign 0.43
IGL01843:Zc3hc1 APN 6 30372730 splice site probably benign
IGL02358:Zc3hc1 APN 6 30376058 missense probably benign 0.04
IGL02379:Zc3hc1 APN 6 30390975 missense probably benign 0.38
IGL02567:Zc3hc1 APN 6 30374849 missense probably benign
R0376:Zc3hc1 UTSW 6 30372790 missense probably damaging 1.00
R0532:Zc3hc1 UTSW 6 30374930 splice site probably benign
R1521:Zc3hc1 UTSW 6 30376025 missense probably benign 0.00
R1690:Zc3hc1 UTSW 6 30390941 missense probably damaging 0.96
R1861:Zc3hc1 UTSW 6 30374838 missense probably benign
R3085:Zc3hc1 UTSW 6 30374764 critical splice donor site probably null
R4619:Zc3hc1 UTSW 6 30387524 missense probably benign 0.27
R4721:Zc3hc1 UTSW 6 30374900 missense probably benign 0.03
R4847:Zc3hc1 UTSW 6 30375982 missense probably benign 0.18
R5000:Zc3hc1 UTSW 6 30375988 missense possibly damaging 0.67
R5870:Zc3hc1 UTSW 6 30382683 nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to A transversion at position 161 of the Zc3hc1 transcript in exon 2 of 11 total exons.  Multiple transcripts of the Zc3hc1 gene are displayed at Ensembl. The mutated nucleotide causes an aspartic acid to glutamic acid substitution at amino acid 51 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
 
 
Protein Function and Prediction
The Zc3hc1 gene encodes a 501amino acid component of the SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1). The cell-cycle-dependent phosphorylation of Zc3hc1 regulates the assembly of the SCF(NIPA) complex, restricting CCNB1 ubiquitination activity to interphase. Zc3hc1 may negatively regulate apoptosis. The protein contains a C3HC-type zinc finger at amino acids 102-156, an F-box-like domain at residues 170-210, and a nuclear localization signal at residues 395-401 (Uniprot Q80YV2).    
 
The D51E change is predicted to be benign by the PolyPhen program.
Posted On2010-05-06