Incidental Mutation 'D4043:Mkks'
ID261
Institutional Source Beutler Lab
Gene Symbol Mkks
Ensembl Gene ENSMUSG00000027274
Gene NameMcKusick-Kaufman syndrome
Synonyms1300013E18Rik, Bbs6
Accession Numbers

Genbank: NM_021527; MGI: 1891836

Is this an essential gene? Possibly essential (E-score: 0.628) question?
Stock #D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome2
Chromosomal Location136873780-136891389 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to T at 136874610 bp
ZygosityHeterozygous
Amino Acid Change Valine to Isoleucine at position 457 (V457I)
Ref Sequence ENSEMBL: ENSMUSP00000105716 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028730] [ENSMUST00000110089]
Predicted Effect probably benign
Transcript: ENSMUST00000028730
AA Change: V457I

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000028730
Gene: ENSMUSG00000027274
AA Change: V457I

DomainStartEndE-ValueType
Pfam:Cpn60_TCP1 29 570 2.5e-109 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110089
AA Change: V457I

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000105716
Gene: ENSMUSG00000027274
AA Change: V457I

DomainStartEndE-ValueType
Pfam:Cpn60_TCP1 29 570 2.3e-90 PFAM
Meta Mutation Damage Score 0.058 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 72.5%
Validation Efficiency 88% (220/249)
MGI Phenotype FUNCTION: This gene encodes a protein which shares sequence similarity with other members of the type II chaperonin family. The encoded protein is a centrosome-shuttling protein and plays an important role in cytokinesis. This protein also interacts with other type II chaperonin members to form a complex known as the BBSome, which involves ciliary membrane biogenesis. This protein is encoded by a downstream open reading frame (dORF). Several upstream open reading frames (uORFs) have been identified, which repress the translation of the dORF, and two of which can encode small mitochondrial membrane proteins. Alternatively spliced transcripts encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
PHENOTYPE: Homozygous null mice display partial embryonic lethality, retinal degeneration, obesity, increased food intake, hypoactivity, increased blood pressure, male infertility with the absence of flagella on spermatozoa, decreased aggression, and impaired olfaction but, do not display limb deformities. [provided by MGI curators]
Allele List at MGI

All alleles(11) : Targeted, knock-out(1) Gene trapped(10)

Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110020G09Rik T A 15: 9,103,385 probably benign Homo
1700029J07Rik A G 8: 45,956,403 V293A probably damaging Het
Adam29 A T 8: 55,872,461 C319* probably null Het
Adgrg1 T C 8: 95,005,229 probably null Homo
Ago3 A T 4: 126,351,003 V630E probably damaging Het
Armc8 G T 9: 99,483,976 N628K probably benign Het
Chd7 A G 4: 8,862,650 D2579G probably damaging Het
Duox1 G A 2: 122,344,795 C1358Y probably benign Het
Fam208a A G 14: 27,471,992 I1050V probably benign Het
Ftsj3 C A 11: 106,254,808 M66I possibly damaging Homo
Iqub C T 6: 24,505,751 E53K possibly damaging Het
Kirrel T A 3: 87,083,203 T771S probably benign Het
Lrrc66 A T 5: 73,607,526 S725T probably benign Het
Mael T C 1: 166,236,886 I104M probably benign Homo
Npas1 T C 7: 16,463,244 probably null Het
Ocrl T C X: 47,936,323 V359A probably benign Homo
Olfr1065 G A 2: 86,445,220 T254M probably damaging Het
Pde6b C T 5: 108,425,356 R531* probably null Het
Polr1a G A 6: 71,941,417 C653Y possibly damaging Het
Rbm26 A G 14: 105,152,540 V216A possibly damaging Het
Rin2 C A 2: 145,822,363 H52Q possibly damaging Het
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Het
Sv2c C T 13: 96,088,481 V107M probably benign Het
Tulp3 G A 6: 128,324,150 S366L probably benign Het
Zfp831 T A 2: 174,645,266 V578E probably benign Homo
Other mutations in Mkks
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL03058:Mkks APN 2 136876170 missense probably damaging 1.00
R0183:Mkks UTSW 2 136880686 missense probably benign 0.01
R0193:Mkks UTSW 2 136877606 unclassified probably null
R1394:Mkks UTSW 2 136880962 missense probably damaging 1.00
R1765:Mkks UTSW 2 136880367 missense probably damaging 1.00
R4484:Mkks UTSW 2 136880574 missense probably benign 0.44
R4678:Mkks UTSW 2 136880281 missense probably benign 0.00
R4791:Mkks UTSW 2 136876162 missense probably benign 0.03
R4825:Mkks UTSW 2 136880655 missense probably benign 0.05
R4902:Mkks UTSW 2 136876174 missense probably benign 0.39
R5709:Mkks UTSW 2 136880736 missense probably benign 0.04
R6449:Mkks UTSW 2 136874286 missense probably damaging 0.98
Nature of Mutation
DNA sequencing using the SOLiD technique identified a G to A transition at position 2365 of the Mkks transcript in exon 6 of 6 total exons. Multiple transcripts of the Mkks gene are displayed on Ensembl and Vega. The mutated nucleotide causes a valine to isoleucine substitution at amino acid 457of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Mkks gene encodes a 570 amino acid molecular chaperone that assists the folding of proteins upon ATP hydrolysis. The protein is a component of the BBS/CCT complex involved in regulating transport vesicles to the cilia, and also plays a role in cytokinesis. ATP binding occurs at amino acids 192-199 (Uniprot Q9JI70). Homozygous null mice display partial embryonic lethality, retinal degeneration, obesity, increased food intake, hypoactivity, increased blood pressure, male infertility with the absence of flagella on spermatozoa, decreased aggression and impaired olfaction, but do not display limb deformities. In humans, homozygous or compound heterozygous mutations in MKKS result in McKusick-Kaufman syndrome (MKKS; OMIM 236700) and Bardet-Biedl syndrome (BBS6; OMIM 209900). MKKS is characterized by urogenital and cardiovascular defects. Bardet-Biedl syndrome is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism, and renal malformations, with secondary features that include diabetes mellitus, endocrinologic dysfunction, and behavioral abnormalities.
 
The V457I change is predicted to be benign by the PolyPhen program.
Posted On2010-08-09