Incidental Mutation 'D6062:Ncoa7'
ID 240
Institutional Source Beutler Lab
Gene Symbol Ncoa7
Ensembl Gene ENSMUSG00000039697
Gene Name nuclear receptor coactivator 7
Synonyms 9030406N13Rik
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # D6062 of strain 376
Quality Score
Status Validated
Chromosome 10
Chromosomal Location 30521578-30683401 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 30598651 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Tyrosine to Histidine at position 91 (Y91H)
Ref Sequence ENSEMBL: ENSMUSP00000150021 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000068567] [ENSMUST00000213836] [ENSMUST00000215725] [ENSMUST00000215740] [ENSMUST00000215926]
AlphaFold Q6DFV7
Predicted Effect possibly damaging
Transcript: ENSMUST00000068567
AA Change: Y91H

PolyPhen 2 Score 0.904 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000066741
Gene: ENSMUSG00000039697
AA Change: Y91H

DomainStartEndE-ValueType
coiled coil region 1 32 N/A INTRINSIC
LysM 118 161 2.24e-7 SMART
low complexity region 165 176 N/A INTRINSIC
TLDc 781 943 2.86e-64 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000213836
AA Change: Y91H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
Predicted Effect possibly damaging
Transcript: ENSMUST00000215725
AA Change: Y91H

PolyPhen 2 Score 0.904 (Sensitivity: 0.82; Specificity: 0.94)
Predicted Effect possibly damaging
Transcript: ENSMUST00000215740
AA Change: Y91H

PolyPhen 2 Score 0.904 (Sensitivity: 0.82; Specificity: 0.94)
Predicted Effect probably damaging
Transcript: ENSMUST00000215926
AA Change: Y91H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect probably benign
Transcript: ENSMUST00000217398
AA Change: Y17H

PolyPhen 2 Score 0.144 (Sensitivity: 0.92; Specificity: 0.86)
Meta Mutation Damage Score 0.1055 question?
Coding Region Coverage
  • 1x: 71.6%
  • 3x: 37.9%
Validation Efficiency 85% (121/143)
Allele List at MGI

All alleles(108) : Gene trapped(108)
Other mutations in this stock
Total: 4 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ccdc117 T A 11: 5,475,039 (GRCm39) probably benign Homo
Nell1 A G 7: 49,907,939 (GRCm39) E366G probably benign Het
Rpl29 T C 9: 106,307,186 (GRCm39) S4P probably damaging Het
Zbtb7a C T 10: 80,980,192 (GRCm39) R129C probably damaging Het
Other mutations in Ncoa7
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01406:Ncoa7 APN 10 30,566,836 (GRCm39) missense probably damaging 1.00
IGL01716:Ncoa7 APN 10 30,538,330 (GRCm39) missense probably damaging 0.96
IGL02114:Ncoa7 APN 10 30,538,360 (GRCm39) missense probably damaging 1.00
IGL02170:Ncoa7 APN 10 30,565,849 (GRCm39) missense possibly damaging 0.94
IGL02436:Ncoa7 APN 10 30,570,143 (GRCm39) missense probably damaging 1.00
IGL02499:Ncoa7 APN 10 30,566,885 (GRCm39) missense probably benign 0.04
IGL02533:Ncoa7 APN 10 30,598,781 (GRCm39) missense probably damaging 1.00
IGL02533:Ncoa7 APN 10 30,566,895 (GRCm39) missense possibly damaging 0.87
IGL02590:Ncoa7 APN 10 30,570,159 (GRCm39) missense probably damaging 1.00
IGL02657:Ncoa7 APN 10 30,528,972 (GRCm39) missense probably damaging 1.00
IGL03065:Ncoa7 APN 10 30,523,993 (GRCm39) missense probably damaging 1.00
IGL03088:Ncoa7 APN 10 30,574,121 (GRCm39) splice site probably null
IGL03090:Ncoa7 APN 10 30,538,396 (GRCm39) missense probably damaging 0.96
IGL03196:Ncoa7 APN 10 30,523,510 (GRCm39) utr 3 prime probably benign
R0058:Ncoa7 UTSW 10 30,523,537 (GRCm39) missense probably damaging 1.00
R0058:Ncoa7 UTSW 10 30,523,537 (GRCm39) missense probably damaging 1.00
R0578:Ncoa7 UTSW 10 30,577,913 (GRCm39) critical splice donor site probably null
R0729:Ncoa7 UTSW 10 30,567,575 (GRCm39) missense probably benign 0.00
R1538:Ncoa7 UTSW 10 30,570,207 (GRCm39) missense probably damaging 0.99
R1539:Ncoa7 UTSW 10 30,647,725 (GRCm39) missense probably damaging 1.00
R1574:Ncoa7 UTSW 10 30,570,097 (GRCm39) missense probably damaging 1.00
R1574:Ncoa7 UTSW 10 30,570,097 (GRCm39) missense probably damaging 1.00
R1624:Ncoa7 UTSW 10 30,580,655 (GRCm39) missense possibly damaging 0.87
R1639:Ncoa7 UTSW 10 30,577,988 (GRCm39) missense probably damaging 1.00
R1655:Ncoa7 UTSW 10 30,574,241 (GRCm39) critical splice acceptor site probably null
R1876:Ncoa7 UTSW 10 30,574,122 (GRCm39) intron probably benign
R1885:Ncoa7 UTSW 10 30,524,448 (GRCm39) missense possibly damaging 0.81
R1886:Ncoa7 UTSW 10 30,524,448 (GRCm39) missense possibly damaging 0.81
R1887:Ncoa7 UTSW 10 30,524,448 (GRCm39) missense possibly damaging 0.81
R1909:Ncoa7 UTSW 10 30,565,796 (GRCm39) missense probably damaging 1.00
R1938:Ncoa7 UTSW 10 30,574,166 (GRCm39) missense probably benign 0.02
R1965:Ncoa7 UTSW 10 30,530,426 (GRCm39) nonsense probably null
R1978:Ncoa7 UTSW 10 30,567,295 (GRCm39) missense probably benign
R2303:Ncoa7 UTSW 10 30,530,431 (GRCm39) missense probably damaging 1.00
R3777:Ncoa7 UTSW 10 30,565,752 (GRCm39) missense probably damaging 1.00
R3778:Ncoa7 UTSW 10 30,565,752 (GRCm39) missense probably damaging 1.00
R4026:Ncoa7 UTSW 10 30,598,720 (GRCm39) missense probably benign 0.02
R4230:Ncoa7 UTSW 10 30,574,253 (GRCm39) splice site probably null
R4667:Ncoa7 UTSW 10 30,566,786 (GRCm39) missense probably damaging 1.00
R4786:Ncoa7 UTSW 10 30,531,638 (GRCm39) missense probably benign 0.28
R4809:Ncoa7 UTSW 10 30,647,758 (GRCm39) missense possibly damaging 0.92
R4820:Ncoa7 UTSW 10 30,524,472 (GRCm39) missense probably damaging 1.00
R4839:Ncoa7 UTSW 10 30,598,655 (GRCm39) missense possibly damaging 0.93
R4861:Ncoa7 UTSW 10 30,580,608 (GRCm39) missense probably benign
R4861:Ncoa7 UTSW 10 30,580,608 (GRCm39) missense probably benign
R5271:Ncoa7 UTSW 10 30,598,725 (GRCm39) missense probably benign 0.02
R5384:Ncoa7 UTSW 10 30,598,813 (GRCm39) missense probably benign 0.00
R5418:Ncoa7 UTSW 10 30,524,035 (GRCm39) missense probably damaging 1.00
R5964:Ncoa7 UTSW 10 30,580,632 (GRCm39) missense probably damaging 1.00
R6257:Ncoa7 UTSW 10 30,570,173 (GRCm39) missense probably damaging 1.00
R6683:Ncoa7 UTSW 10 30,647,717 (GRCm39) missense probably damaging 0.99
R6813:Ncoa7 UTSW 10 30,572,188 (GRCm39) missense probably damaging 1.00
R6910:Ncoa7 UTSW 10 30,570,117 (GRCm39) missense possibly damaging 0.89
R7123:Ncoa7 UTSW 10 30,530,435 (GRCm39) missense probably benign 0.28
R7327:Ncoa7 UTSW 10 30,565,796 (GRCm39) missense probably damaging 1.00
R7412:Ncoa7 UTSW 10 30,598,847 (GRCm39) missense possibly damaging 0.94
R7638:Ncoa7 UTSW 10 30,598,794 (GRCm39) missense probably benign 0.35
R7653:Ncoa7 UTSW 10 30,570,239 (GRCm39) missense probably damaging 1.00
R7848:Ncoa7 UTSW 10 30,524,414 (GRCm39) missense possibly damaging 0.82
R7861:Ncoa7 UTSW 10 30,567,056 (GRCm39) missense probably benign 0.38
R8125:Ncoa7 UTSW 10 30,570,087 (GRCm39) missense possibly damaging 0.80
R8198:Ncoa7 UTSW 10 30,580,664 (GRCm39) missense probably benign 0.00
R8240:Ncoa7 UTSW 10 30,567,725 (GRCm39) missense probably benign 0.45
R8353:Ncoa7 UTSW 10 30,570,155 (GRCm39) missense probably damaging 1.00
R8509:Ncoa7 UTSW 10 30,572,048 (GRCm39) missense probably benign 0.00
R8861:Ncoa7 UTSW 10 30,567,364 (GRCm39) missense probably benign 0.02
R9040:Ncoa7 UTSW 10 30,530,389 (GRCm39) missense probably benign 0.00
R9136:Ncoa7 UTSW 10 30,567,628 (GRCm39) missense probably benign 0.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 612 of the Ncoa7 transcript in exon 3 of 17 total exons. Four transcripts of the Ncoa7 gene are displayed on Ensembl. The mutated nucleotide causes a tyrosine to histidine substitution at amino acid 91 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Ncoa7 gene encodes a 943 amino acid protein enhances the transcriptional activities of several nuclear receptors including ESR1 (estrogen receptor), THRB (thyroid hormone receptor), PPARG (peroxisome-proliferator activated receptor) and RARA (retinoic acid receptor). The protein is highly expressed in brain and kidney and weakly expressed in mammary gland, lung and testis. In the brain, expression is found in neurons of cerebral cortex, thalamus, hypothalamus, hippocampus, cerebellum, striatum and choroid plexus.  NCOA7 contains one LysM repeat at residues 119-161 and one TLD domain at residues 807-943. The LysM domain is found in a variety of enzymes involved in bacterial cell wall degradation and may be involved in peptidoglycan binding. The TLD domain is of unknown function. Up to six isoforms have been reported, but with no experimental evidence (Uniprot Q6DFV7). According to SMART analysis, the protein also contains a GRAM domain at residues 288-357, found in glucosyltransferases, myotubularins and other putative membrane-associated proteins.  SMART analysis places the LysM domain at residues 190-233 and the TLD domain at residues 853-1033.
 
The Y91H change is predicted to be possibly damaging by the PolyPhen program.
Posted On 2010-06-24