Incidental Mutation 'C9142:Adnp'
ID 159
Institutional Source Beutler Lab
Gene Symbol Adnp
Ensembl Gene ENSMUSG00000051149
Gene Name activity-dependent neuroprotective protein
Synonyms
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # C9142 (G3) of strain Muskatenwein
Quality Score
Status Validated
Chromosome 2
Chromosomal Location 168022906-168049032 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 168026327 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 323 (S323P)
Ref Sequence ENSEMBL: ENSMUSP00000085316 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000057793] [ENSMUST00000088001] [ENSMUST00000138667]
AlphaFold Q9Z103
Predicted Effect probably damaging
Transcript: ENSMUST00000057793
AA Change: S323P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000056809
Gene: ENSMUSG00000051149
AA Change: S323P

DomainStartEndE-ValueType
ZnF_C2H2 74 97 6.57e0 SMART
ZnF_C2H2 107 129 1.77e1 SMART
low complexity region 130 141 N/A INTRINSIC
ZnF_C2H2 165 188 1.29e1 SMART
ZnF_C2H2 221 244 1.4e1 SMART
low complexity region 423 437 N/A INTRINSIC
ZnF_C2H2 446 468 8.62e1 SMART
ZnF_C2H2 488 509 2.54e1 SMART
ZnF_C2H2 511 534 1.03e-2 SMART
low complexity region 582 596 N/A INTRINSIC
ZnF_C2H2 621 646 1.27e2 SMART
HOX 756 817 2.95e-6 SMART
low complexity region 957 970 N/A INTRINSIC
low complexity region 1012 1023 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000088001
AA Change: S323P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000085316
Gene: ENSMUSG00000051149
AA Change: S323P

DomainStartEndE-ValueType
ZnF_C2H2 74 97 6.57e0 SMART
ZnF_C2H2 107 129 1.77e1 SMART
low complexity region 130 141 N/A INTRINSIC
ZnF_C2H2 165 188 1.29e1 SMART
ZnF_C2H2 221 244 1.4e1 SMART
low complexity region 423 437 N/A INTRINSIC
ZnF_C2H2 446 468 8.62e1 SMART
ZnF_C2H2 488 509 2.54e1 SMART
ZnF_C2H2 511 534 1.03e-2 SMART
low complexity region 582 596 N/A INTRINSIC
ZnF_C2H2 621 646 1.27e2 SMART
HOX 756 817 2.95e-6 SMART
low complexity region 957 970 N/A INTRINSIC
low complexity region 1012 1023 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000138667
SMART Domains Protein: ENSMUSP00000139070
Gene: ENSMUSG00000093752

DomainStartEndE-ValueType
Pfam:Glyco_tranf_2_3 24 240 1.1e-13 PFAM
Pfam:Glyco_tranf_2_2 28 153 8.4e-10 PFAM
Pfam:Glycos_transf_2 28 199 3.8e-40 PFAM
Pfam:Glyco_transf_21 87 200 1.5e-7 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000139984
Meta Mutation Damage Score 0.1278 question?
Coding Region Coverage
  • 1x: 84.8%
  • 3x: 59.3%
Validation Efficiency 82% (72/88)
MGI Phenotype FUNCTION: This gene encodes a member of a protein family characterized by nine zinc finger motifs followed by a homeobox domain. In vitro studies demonstrate that the encoded protein interacts with the brahma-related gene1-associated or hBRM factors (BAF) gene expression regulating complex, components of the protein translation machinery, and microtubule-associated proteins. This gene has been implicated in neuroprotection through various processes that include chromatin remodeling, splicing, cytoskeletal reorganization, and autophagy. Homozygous mutant knockout mice display embryonic lethality with defects in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Developmental defects including the failure of the cranial neural tube to close lead to embryonic death between E8.5 and E9. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

Other mutations in this stock
Total: 7 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Cc2d2a A G 5: 43,892,799 (GRCm39) probably benign Homo
Chrm5 A G 2: 112,310,556 (GRCm39) F187L probably damaging Het
Fmnl3 T C 15: 99,235,508 (GRCm39) probably null Het
Klf7 C T 1: 64,118,316 (GRCm39) A94T possibly damaging Het
Nf1 C T 11: 79,447,557 (GRCm39) R2433C probably damaging Het
Pdlim3 A T 8: 46,349,869 (GRCm39) M60L probably benign Het
Vwde T C 6: 13,168,053 (GRCm39) probably benign Homo
Other mutations in Adnp
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00427:Adnp APN 2 168,024,482 (GRCm39) missense probably benign
IGL00500:Adnp APN 2 168,025,243 (GRCm39) missense possibly damaging 0.85
IGL01604:Adnp APN 2 168,026,258 (GRCm39) missense probably damaging 0.99
IGL01967:Adnp APN 2 168,025,339 (GRCm39) missense possibly damaging 0.85
IGL02470:Adnp APN 2 168,025,114 (GRCm39) missense probably damaging 0.99
R0893:Adnp UTSW 2 168,025,647 (GRCm39) missense possibly damaging 0.85
R1167:Adnp UTSW 2 168,026,420 (GRCm39) missense probably benign 0.11
R1182:Adnp UTSW 2 168,026,716 (GRCm39) missense possibly damaging 0.77
R1480:Adnp UTSW 2 168,025,454 (GRCm39) missense probably damaging 0.99
R1505:Adnp UTSW 2 168,025,661 (GRCm39) missense possibly damaging 0.93
R1906:Adnp UTSW 2 168,024,287 (GRCm39) missense probably benign
R3711:Adnp UTSW 2 168,026,743 (GRCm39) missense probably damaging 0.98
R3943:Adnp UTSW 2 168,026,980 (GRCm39) missense possibly damaging 0.92
R4440:Adnp UTSW 2 168,026,721 (GRCm39) missense possibly damaging 0.92
R4686:Adnp UTSW 2 168,024,309 (GRCm39) missense possibly damaging 0.78
R4916:Adnp UTSW 2 168,029,537 (GRCm39) missense possibly damaging 0.91
R5072:Adnp UTSW 2 168,024,921 (GRCm39) missense probably damaging 0.96
R5312:Adnp UTSW 2 168,026,108 (GRCm39) missense probably benign
R5393:Adnp UTSW 2 168,024,869 (GRCm39) missense possibly damaging 0.95
R5598:Adnp UTSW 2 168,025,645 (GRCm39) missense probably damaging 0.99
R6230:Adnp UTSW 2 168,024,452 (GRCm39) missense probably benign
R7165:Adnp UTSW 2 168,024,287 (GRCm39) missense probably benign 0.07
R7176:Adnp UTSW 2 168,024,578 (GRCm39) missense probably benign
R7238:Adnp UTSW 2 168,025,887 (GRCm39) missense probably damaging 1.00
R7254:Adnp UTSW 2 168,025,918 (GRCm39) missense probably damaging 0.99
R7581:Adnp UTSW 2 168,025,386 (GRCm39) missense probably damaging 0.96
R7676:Adnp UTSW 2 168,025,367 (GRCm39) nonsense probably null
R7863:Adnp UTSW 2 168,031,270 (GRCm39) missense possibly damaging 0.91
R8098:Adnp UTSW 2 168,024,452 (GRCm39) missense probably benign
R8196:Adnp UTSW 2 168,025,092 (GRCm39) missense probably benign
R8970:Adnp UTSW 2 168,031,290 (GRCm39) missense possibly damaging 0.91
R9153:Adnp UTSW 2 168,026,580 (GRCm39) missense possibly damaging 0.96
R9154:Adnp UTSW 2 168,026,580 (GRCm39) missense possibly damaging 0.96
R9228:Adnp UTSW 2 168,026,798 (GRCm39) missense probably damaging 0.98
R9256:Adnp UTSW 2 168,025,945 (GRCm39) missense probably damaging 1.00
R9268:Adnp UTSW 2 168,031,233 (GRCm39) missense possibly damaging 0.86
R9434:Adnp UTSW 2 168,026,377 (GRCm39) missense probably damaging 0.99
R9517:Adnp UTSW 2 168,024,866 (GRCm39) missense possibly damaging 0.93
R9621:Adnp UTSW 2 168,024,663 (GRCm39) missense probably benign 0.22
R9669:Adnp UTSW 2 168,026,918 (GRCm39) missense possibly damaging 0.91
R9737:Adnp UTSW 2 168,026,918 (GRCm39) missense possibly damaging 0.91
Nature of Mutation

 

DNA sequencing using the SOLiD technique identified a T to C transition at position 1461 of the Adnp transcript in exon 4 of 4 total exons. Multiple transcripts of the Adnp gene are displayed on Ensembl. The mutated nucleotide causes a serine to proline substitution at amino acid 323 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction
The Adnp gene encodes an 1108 amino acid transcription factor that contains eight C2H2 zinc finger domains and one homeobox domain at amino acids 756-817 (Uniprot Q5BL11). Homozygotes for a targeted null allele exhibit developmental defects including the failure of the cranial neural tube to close leading to embryonic death between E8.5 and E9.
 
The S323P change does not occur in any predicted domain, and is predicted to be possibly damaging by the PolyPhen program.
Posted On 2010-04-08