Incidental Mutation 'N/A:Ankrd26'
ID 32
Institutional Source Beutler Lab
Gene Symbol Ankrd26
Ensembl Gene ENSMUSG00000007827
Gene Name ankyrin repeat domain 26
Synonyms 5730521P14Rik
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # N/A of strain 294
Quality Score
Status Validated
Chromosome 6
Chromosomal Location 118478269-118539187 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 118506535 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Aspartic acid to Glycine at position 646 (D646G)
Ref Sequence ENSEMBL: ENSMUSP00000108449 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000112830]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000112830
AA Change: D646G

PolyPhen 2 Score 0.038 (Sensitivity: 0.94; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000108449
Gene: ENSMUSG00000007827
AA Change: D646G

DomainStartEndE-ValueType
ANK 80 109 1.5e-7 SMART
ANK 113 142 3.5e-4 SMART
ANK 146 175 1.9e-6 SMART
ANK 179 208 2.2e-4 SMART
low complexity region 306 316 N/A INTRINSIC
low complexity region 568 580 N/A INTRINSIC
Blast:BRLZ 692 754 4e-10 BLAST
Pfam:CCDC144C 886 1190 2e-142 PFAM
low complexity region 1298 1315 N/A INTRINSIC
low complexity region 1345 1357 N/A INTRINSIC
coiled coil region 1407 1444 N/A INTRINSIC
low complexity region 1473 1486 N/A INTRINSIC
Pfam:DUF3496 1495 1602 1.3e-47 PFAM
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 76.0%
Validation Efficiency 91% (106/116)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein containing N-terminal ankyrin repeats which function in protein-protein interactions. Mutations in this gene are associated with autosomal dominant thrombocytopenia-2. Pseudogenes of this gene are found on chromosome 7, 10, 13 and 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
PHENOTYPE: Mice homozygous for a gene trapped allele have enlarged kidneys and hearts, exhibit increased lean body mass and adiposity, develop extreme obesity associated with hyperphagia rather than reduced energy expenditure, and show insulin resistance and gigantism. [provided by MGI curators]
Allele List at MGI

All alleles(3) : Gene trapped(3)
Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700016P04Rik T A 6: 13,415,772 (GRCm39) noncoding transcript Homo
Aif1 A G 17: 35,391,496 (GRCm39) L7S possibly damaging Homo
Cacna1s A G 1: 136,001,247 (GRCm39) I233V probably benign Homo
Cfap92 A T 6: 87,667,773 (GRCm39) noncoding transcript Homo
Chchd4 T C 6: 91,442,187 (GRCm39) Y77C probably damaging Homo
Crocc G A 4: 140,749,057 (GRCm39) R1419C probably damaging Homo
Cyp4f39 A C 17: 32,687,655 (GRCm39) M74L probably benign Homo
Fgf9 C A 14: 58,327,421 (GRCm39) probably benign Homo
Gimap6 T C 6: 48,679,349 (GRCm39) D229G probably damaging Homo
Glp1r T C 17: 31,150,257 (GRCm39) F393S probably damaging Homo
Lrrc7 T G 3: 157,865,977 (GRCm39) I1255L probably benign Homo
Mtrr C A 13: 68,723,516 (GRCm39) probably benign Homo
Pde6b A T 5: 108,576,969 (GRCm39) probably benign Homo
Rbm19 A T 5: 120,282,162 (GRCm39) I840F probably damaging Homo
Serpina3c A C 12: 104,115,864 (GRCm39) S227A probably benign Homo
Spag17 G A 3: 99,889,570 (GRCm39) probably benign Homo
Spmip3 G A 1: 177,561,100 (GRCm39) R13H probably damaging Homo
Zbtb8b T C 4: 129,326,361 (GRCm39) D268G probably benign Homo
Other mutations in Ankrd26
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00965:Ankrd26 APN 6 118,536,319 (GRCm39) nonsense probably null
IGL01286:Ankrd26 APN 6 118,536,068 (GRCm39) missense probably damaging 1.00
IGL01574:Ankrd26 APN 6 118,516,659 (GRCm39) missense probably damaging 1.00
IGL01727:Ankrd26 APN 6 118,488,597 (GRCm39) missense probably damaging 1.00
IGL01954:Ankrd26 APN 6 118,535,966 (GRCm39) missense possibly damaging 0.62
IGL02200:Ankrd26 APN 6 118,536,302 (GRCm39) missense probably damaging 1.00
IGL02708:Ankrd26 APN 6 118,495,379 (GRCm39) splice site probably benign
IGL02973:Ankrd26 APN 6 118,500,511 (GRCm39) missense probably damaging 0.98
IGL03233:Ankrd26 APN 6 118,512,107 (GRCm39) splice site probably null
guillemot UTSW 6 118,484,598 (GRCm39) critical splice donor site probably null
Iceland UTSW 6 118,526,389 (GRCm39) missense probably benign 0.30
murre UTSW 6 118,526,598 (GRCm39) critical splice donor site probably null
ANU74:Ankrd26 UTSW 6 118,529,736 (GRCm39) missense probably benign 0.02
R0078:Ankrd26 UTSW 6 118,512,030 (GRCm39) splice site probably benign
R0083:Ankrd26 UTSW 6 118,500,215 (GRCm39) missense probably benign 0.36
R0165:Ankrd26 UTSW 6 118,517,445 (GRCm39) missense probably benign 0.01
R0344:Ankrd26 UTSW 6 118,484,598 (GRCm39) critical splice donor site probably null
R0828:Ankrd26 UTSW 6 118,510,434 (GRCm39) splice site probably benign
R1532:Ankrd26 UTSW 6 118,499,919 (GRCm39) missense probably damaging 1.00
R1809:Ankrd26 UTSW 6 118,502,883 (GRCm39) splice site probably benign
R1875:Ankrd26 UTSW 6 118,517,410 (GRCm39) critical splice donor site probably null
R1940:Ankrd26 UTSW 6 118,488,654 (GRCm39) missense probably damaging 1.00
R2164:Ankrd26 UTSW 6 118,502,752 (GRCm39) missense probably damaging 1.00
R2202:Ankrd26 UTSW 6 118,500,843 (GRCm39) missense possibly damaging 0.79
R2204:Ankrd26 UTSW 6 118,500,843 (GRCm39) missense possibly damaging 0.79
R2205:Ankrd26 UTSW 6 118,500,843 (GRCm39) missense possibly damaging 0.79
R3107:Ankrd26 UTSW 6 118,533,204 (GRCm39) missense probably benign 0.01
R3419:Ankrd26 UTSW 6 118,512,068 (GRCm39) missense probably damaging 1.00
R3552:Ankrd26 UTSW 6 118,484,737 (GRCm39) missense probably damaging 1.00
R3899:Ankrd26 UTSW 6 118,526,389 (GRCm39) missense probably benign 0.30
R4157:Ankrd26 UTSW 6 118,484,782 (GRCm39) missense probably damaging 1.00
R4194:Ankrd26 UTSW 6 118,500,639 (GRCm39) missense probably benign 0.21
R4230:Ankrd26 UTSW 6 118,536,349 (GRCm39) splice site probably null
R4651:Ankrd26 UTSW 6 118,492,787 (GRCm39) missense probably benign 0.03
R4701:Ankrd26 UTSW 6 118,483,446 (GRCm39) missense possibly damaging 0.65
R4747:Ankrd26 UTSW 6 118,504,718 (GRCm39) missense probably benign 0.01
R4752:Ankrd26 UTSW 6 118,517,426 (GRCm39) missense probably null 1.00
R4834:Ankrd26 UTSW 6 118,500,679 (GRCm39) missense probably benign 0.08
R4835:Ankrd26 UTSW 6 118,525,811 (GRCm39) nonsense probably null
R4849:Ankrd26 UTSW 6 118,509,257 (GRCm39) missense probably benign 0.00
R5149:Ankrd26 UTSW 6 118,535,957 (GRCm39) missense probably benign 0.05
R5389:Ankrd26 UTSW 6 118,485,536 (GRCm39) missense possibly damaging 0.82
R5473:Ankrd26 UTSW 6 118,492,797 (GRCm39) missense probably benign 0.04
R5518:Ankrd26 UTSW 6 118,525,869 (GRCm39) missense probably benign 0.00
R5525:Ankrd26 UTSW 6 118,504,692 (GRCm39) missense probably benign 0.00
R5608:Ankrd26 UTSW 6 118,488,583 (GRCm39) missense probably damaging 1.00
R5639:Ankrd26 UTSW 6 118,516,685 (GRCm39) missense possibly damaging 0.72
R5704:Ankrd26 UTSW 6 118,500,843 (GRCm39) missense probably damaging 0.96
R5927:Ankrd26 UTSW 6 118,484,597 (GRCm39) critical splice donor site probably null
R5943:Ankrd26 UTSW 6 118,482,707 (GRCm39) missense probably damaging 1.00
R5976:Ankrd26 UTSW 6 118,494,855 (GRCm39) critical splice donor site probably null
R6181:Ankrd26 UTSW 6 118,525,838 (GRCm39) missense probably benign 0.15
R6478:Ankrd26 UTSW 6 118,488,599 (GRCm39) missense probably benign 0.28
R6667:Ankrd26 UTSW 6 118,484,749 (GRCm39) missense probably benign 0.02
R6865:Ankrd26 UTSW 6 118,500,442 (GRCm39) missense possibly damaging 0.90
R7224:Ankrd26 UTSW 6 118,516,688 (GRCm39) missense probably benign 0.07
R7287:Ankrd26 UTSW 6 118,526,598 (GRCm39) critical splice donor site probably null
R7301:Ankrd26 UTSW 6 118,488,624 (GRCm39) missense possibly damaging 0.62
R7348:Ankrd26 UTSW 6 118,485,525 (GRCm39) missense probably damaging 1.00
R7414:Ankrd26 UTSW 6 118,485,741 (GRCm39) missense possibly damaging 0.60
R7789:Ankrd26 UTSW 6 118,504,760 (GRCm39) missense possibly damaging 0.82
R7789:Ankrd26 UTSW 6 118,504,759 (GRCm39) missense probably damaging 0.98
R7964:Ankrd26 UTSW 6 118,500,160 (GRCm39) missense probably benign 0.03
R8078:Ankrd26 UTSW 6 118,494,854 (GRCm39) splice site probably null
R8224:Ankrd26 UTSW 6 118,502,716 (GRCm39) missense probably damaging 1.00
R8917:Ankrd26 UTSW 6 118,535,902 (GRCm39) missense probably damaging 1.00
R8962:Ankrd26 UTSW 6 118,512,104 (GRCm39) missense probably benign 0.02
R9072:Ankrd26 UTSW 6 118,500,350 (GRCm39) missense probably damaging 1.00
R9073:Ankrd26 UTSW 6 118,500,350 (GRCm39) missense probably damaging 1.00
R9087:Ankrd26 UTSW 6 118,536,230 (GRCm39) critical splice donor site probably null
R9334:Ankrd26 UTSW 6 118,509,262 (GRCm39) missense probably benign
R9417:Ankrd26 UTSW 6 118,504,725 (GRCm39) missense possibly damaging 0.46
R9521:Ankrd26 UTSW 6 118,517,420 (GRCm39) missense possibly damaging 0.94
R9720:Ankrd26 UTSW 6 118,498,902 (GRCm39) missense probably damaging 1.00
R9766:Ankrd26 UTSW 6 118,500,067 (GRCm39) missense possibly damaging 0.86
X0028:Ankrd26 UTSW 6 118,484,722 (GRCm39) missense probably damaging 1.00
Z1177:Ankrd26 UTSW 6 118,500,493 (GRCm39) missense possibly damaging 0.77
Z1177:Ankrd26 UTSW 6 118,500,556 (GRCm39) missense probably damaging 0.99
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 2136 of the Ankrd26 transcript, in exon 20 of 34 total exons. Multiple transcripts of Ankrd26 exist on Ensembl. The mutated nucleotide causes an aspartic acid to glycine substitution at amino acid 646. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
 
 
Protein Function and Prediction
The Ankrd26 gene encodes a 1581 amino acid protein that contains five ankyrin (ANK) repeats located between amino acids 46 and 208.  The ankyrin repeat is a common protein-protein interaction motif with tandemly repeated modules of about 33 amino acids. ANKRD26 also contains several coiled-coil domains located in the C-terminal region of the protein between amino acids 715 and 1550. The protein is also phosphorylated at amino acid 239 (Uniprot Q811D2).  Mice homozygous for partial inactivation of the Ankrd26 gene develop extreme obesity, insulin resistance, and a dramatic increase in body size. The obesity was associated with hyperphagia with no reduction in energy expenditure or activity, and is likely due to loss of function in the arcuate and ventromedial nuclei within the hypothalamus. ANKRD26 is also expressed in the circumventricular organs that act as an interface between the peripheral circulation and the brain.
 
The D646G mutation is predicted to be possibly damaging by the PolyPhen program.
Posted On 2009-11-09