Incidental Mutation 'B5639:Ercc8'
ID 547
Institutional Source Beutler Lab
Gene Symbol Ercc8
Ensembl Gene ENSMUSG00000021694
Gene Name excision repaiross-complementing rodent repair deficiency, complementation group 8
Synonyms B130065P18Rik, 2810431L23Rik, 4631412O06Rik, 2410022P04Rik, Ckn1, Csa
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.282) question?
Stock # B5639 of strain 3d
Quality Score
Status Validated
Chromosome 13
Chromosomal Location 108295265-108331898 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 108297257 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Glycine to Arginine at position 56 (G56R)
Ref Sequence ENSEMBL: ENSMUSP00000112746 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000054835] [ENSMUST00000120672] [ENSMUST00000123182] [ENSMUST00000123657] [ENSMUST00000129117] [ENSMUST00000142931] [ENSMUST00000133957] [ENSMUST00000152634] [ENSMUST00000225702] [ENSMUST00000223734] [ENSMUST00000163558]
AlphaFold Q8CFD5
Predicted Effect possibly damaging
Transcript: ENSMUST00000054835
AA Change: G56R

PolyPhen 2 Score 0.535 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000059211
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
WD40 35 72 3.21e-1 SMART
WD40 81 128 9.75e-3 SMART
WD40 175 215 2.71e-10 SMART
WD40 234 273 9.24e-4 SMART
WD40 323 362 7.5e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000120672
AA Change: G56R

PolyPhen 2 Score 0.961 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000112746
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
WD40 35 72 3.21e-1 SMART
WD40 81 128 9.75e-3 SMART
Blast:WD40 137 172 6e-6 BLAST
low complexity region 186 198 N/A INTRINSIC
Predicted Effect unknown
Transcript: ENSMUST00000123138
AA Change: G52R
SMART Domains Protein: ENSMUSP00000119212
Gene: ENSMUSG00000021694
AA Change: G52R

DomainStartEndE-ValueType
PDB:4A11|B 2 54 4e-29 PDB
Blast:WD40 28 54 3e-11 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000123182
AA Change: G56R

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
SMART Domains Protein: ENSMUSP00000121777
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
PDB:4A11|B 1 57 9e-32 PDB
Blast:WD40 31 57 2e-11 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000123657
AA Change: G56R

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
SMART Domains Protein: ENSMUSP00000117492
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
PDB:4A11|B 1 57 9e-32 PDB
Blast:WD40 31 57 2e-11 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000129117
AA Change: G56R

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
SMART Domains Protein: ENSMUSP00000116507
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
PDB:4A11|B 1 57 9e-32 PDB
Blast:WD40 31 57 2e-11 BLAST
Predicted Effect possibly damaging
Transcript: ENSMUST00000142931
AA Change: G56R

PolyPhen 2 Score 0.954 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000118154
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
WD40 35 72 3.21e-1 SMART
WD40 81 128 9.75e-3 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000133957
AA Change: G53R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000116226
Gene: ENSMUSG00000021694
AA Change: G53R

DomainStartEndE-ValueType
PDB:4A11|B 1 54 3e-30 PDB
Blast:WD40 28 54 2e-11 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000152634
AA Change: G56R

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
SMART Domains Protein: ENSMUSP00000122802
Gene: ENSMUSG00000021694
AA Change: G56R

DomainStartEndE-ValueType
PDB:4A11|B 1 57 9e-32 PDB
Blast:WD40 31 57 2e-11 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000137425
Predicted Effect probably benign
Transcript: ENSMUST00000225830
Predicted Effect probably benign
Transcript: ENSMUST00000225702
Predicted Effect probably benign
Transcript: ENSMUST00000223734
Predicted Effect probably benign
Transcript: ENSMUST00000163558
SMART Domains Protein: ENSMUSP00000130532
Gene: ENSMUSG00000068184

DomainStartEndE-ValueType
low complexity region 2 13 N/A INTRINSIC
Pfam:NDUFA12 20 135 3.4e-16 PFAM
Meta Mutation Damage Score 0.6696 question?
Coding Region Coverage
  • 1x: 89.7%
  • 3x: 78.3%
Het Detection Efficiency 55.9%
Validation Efficiency 83% (206/248)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
PHENOTYPE: Homozygous mutation of this gene results in skin photosensitivity, increased incidence of skin tumors after UV exposure, and progressive photoreceptor degeneration. [provided by MGI curators]
Allele List at MGI

All alleles(5) : Targeted, knock-out(1) Gene trapped(4)

Other mutations in this stock
Total: 15 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Dnmt1 G A 9: 20,819,264 (GRCm39) probably benign Het
Eno1 A G 4: 150,329,569 (GRCm39) probably benign Het
Fam237b C T 5: 5,624,060 (GRCm39) probably benign Homo
Idh1 A G 1: 65,204,257 (GRCm39) probably null Homo
Incenp G A 19: 9,871,182 (GRCm39) T149I unknown Het
Or5d16 G A 2: 87,773,942 (GRCm39) S10F probably benign Het
Or5k17 A T 16: 58,746,889 (GRCm39) I15K probably benign Homo
Pdk2 T C 11: 94,923,324 (GRCm39) D100G possibly damaging Homo
Prss56 T C 1: 87,114,892 (GRCm39) L465P probably benign Homo
Slc10a3 G A X: 73,413,145 (GRCm39) P416L probably damaging Homo
Syne2 C A 12: 75,976,564 (GRCm39) T1243K probably benign Het
Vwf T C 6: 125,619,947 (GRCm39) Y1542H probably damaging Homo
Zc3h13 G A 14: 75,553,479 (GRCm39) R302Q probably damaging Het
Zfhx4 G T 3: 5,468,235 (GRCm39) G2798W probably damaging Homo
Zfp667 A G 7: 6,293,544 (GRCm39) T15A probably damaging Het
Other mutations in Ercc8
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01832:Ercc8 APN 13 108,305,993 (GRCm39) missense probably damaging 1.00
IGL02074:Ercc8 APN 13 108,295,318 (GRCm39) unclassified probably benign
R0620:Ercc8 UTSW 13 108,310,595 (GRCm39) critical splice donor site probably null
R1909:Ercc8 UTSW 13 108,312,100 (GRCm39) nonsense probably null
R2509:Ercc8 UTSW 13 108,320,251 (GRCm39) splice site probably benign
R2967:Ercc8 UTSW 13 108,297,248 (GRCm39) missense probably damaging 1.00
R3857:Ercc8 UTSW 13 108,330,648 (GRCm39) missense possibly damaging 0.82
R4941:Ercc8 UTSW 13 108,297,301 (GRCm39) unclassified probably benign
R5585:Ercc8 UTSW 13 108,312,123 (GRCm39) missense probably damaging 0.99
R6023:Ercc8 UTSW 13 108,315,111 (GRCm39) missense probably damaging 1.00
R6363:Ercc8 UTSW 13 108,320,404 (GRCm39) missense probably damaging 1.00
R6483:Ercc8 UTSW 13 108,320,344 (GRCm39) missense probably damaging 0.99
R6825:Ercc8 UTSW 13 108,295,343 (GRCm39) missense probably damaging 0.97
R7151:Ercc8 UTSW 13 108,323,816 (GRCm39) critical splice donor site probably null
R7166:Ercc8 UTSW 13 108,305,967 (GRCm39) missense possibly damaging 0.94
R7710:Ercc8 UTSW 13 108,320,397 (GRCm39) missense probably benign
R8395:Ercc8 UTSW 13 108,323,788 (GRCm39) nonsense probably null
R8678:Ercc8 UTSW 13 108,306,027 (GRCm39) critical splice donor site probably null
R8744:Ercc8 UTSW 13 108,320,307 (GRCm39) missense probably benign
R9026:Ercc8 UTSW 13 108,320,389 (GRCm39) missense possibly damaging 0.51
R9191:Ercc8 UTSW 13 108,305,914 (GRCm39) missense probably benign 0.05
R9281:Ercc8 UTSW 13 108,320,364 (GRCm39) missense probably benign 0.14
Nature of Mutation

DNA sequencing using the SOLiD technique identified a G to A transition at position 222 of the Ercc8 transcript, in exon 2 of 12 total exons (NM_028042).  Multiple transcripts are annotated in the Vega and Ensembl databases.  The mutation causes a glycine to arginine change at amino acid 56 of the encoded protein.  The mutation has been confirmed by DNA sequencing using the Sanger method (see trace files for B5639).

Protein Function and Prediction

Ercc8 encodes the 397 amino acid DNA excision repair protein ERCC-8.  The protein functions in transcription-coupled nucleotide excision repair by recruiting XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes (Uniprot Q8CFD5).  ERCC8 contains five WD repeat domains, and is the substrate recognition component of the Cockayne syndrome group A (CSA) complex, a DCX E3 ubiquitin ligase complex that interacts with RNA polymerase II and promotes the ubiquitination and subsequent degradation of ERCC6 in a UV-dependent manner.  ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair.  ERCC8-deficient mice develop normally, but display skin photosensitivity, increased incidence of skin tumors after UV exposure, and progressive retinal photoreceptor degeneration.  Mutations of ERCC8 in humans cause Cockayne syndrome, Type A (CSA, OMIM #216400).

The mutation lies in the most N-terminal WD repeat, and is predicted to be possibly damaging by the PolyPhen-2 program.

Posted On 2010-11-23