Incidental Mutation '3370:Mnx1'
ID69
Institutional Source Beutler Lab
Gene Symbol Mnx1
Ensembl Gene ENSMUSG00000001566
Gene Namemotor neuron and pancreas homeobox 1
SynonymsHlxb9, HB9, MNR2
Accession Numbers

Genbank: NM_019944; MGI: 109160

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #3370 of strain dazzle
Quality Score
Status Validated
Chromosome5
Chromosomal Location29473034-29478470 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 29474887 bp
ZygosityHomozygous
Amino Acid Change Cysteine to Arginine at position 241 (C241R)
Ref Sequence ENSEMBL: ENSMUSP00000129503 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001608] [ENSMUST00000165512]
Predicted Effect unknown
Transcript: ENSMUST00000001608
AA Change: C241R
SMART Domains Protein: ENSMUSP00000001608
Gene: ENSMUSG00000001566
AA Change: C241R

DomainStartEndE-ValueType
low complexity region 39 64 N/A INTRINSIC
low complexity region 90 158 N/A INTRINSIC
low complexity region 168 176 N/A INTRINSIC
HOX 241 303 1.39e-25 SMART
low complexity region 346 366 N/A INTRINSIC
low complexity region 380 392 N/A INTRINSIC
Predicted Effect unknown
Transcript: ENSMUST00000165512
AA Change: C241R
SMART Domains Protein: ENSMUSP00000129503
Gene: ENSMUSG00000001566
AA Change: C241R

DomainStartEndE-ValueType
low complexity region 39 64 N/A INTRINSIC
low complexity region 90 158 N/A INTRINSIC
low complexity region 168 176 N/A INTRINSIC
HOX 241 303 1.39e-25 SMART
low complexity region 346 366 N/A INTRINSIC
low complexity region 380 392 N/A INTRINSIC
Meta Mutation Damage Score 0.3682 question?
Coding Region Coverage
  • 1x: 78.5%
  • 3x: 41.6%
Validation Efficiency 55% (17/31)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
PHENOTYPE: Homozygous null mice die at birth exhibiting pancreas dorsal lobe agenesis, small pancreatic islets, and aberrant beta-cell function and motor axon guidance. Mice homozygous for other reporter/null alleles show neonatal death, atelectasis, and impaired motor neuron and pancreas differentiation. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Targeted, knock-out(1) Targeted, other(5)

Other mutations in this stock
Total: 5 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Clca2 C T 3: 145,077,977 A626T probably damaging Homo
Dido1 A G 2: 180,671,542 M979T probably benign Homo
Rab38 A G 7: 88,490,651 H176R probably benign Homo
Tap2 A G 17: 34,209,279 probably null Homo
Tmem167 A C 13: 90,098,466 K36N probably damaging Homo
Other mutations in Mnx1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01602:Mnx1 APN 5 29477593 missense unknown
IGL01605:Mnx1 APN 5 29477593 missense unknown
PIT4472001:Mnx1 UTSW 5 29474107 missense unknown
R1752:Mnx1 UTSW 5 29477729 missense unknown
R1785:Mnx1 UTSW 5 29474189 missense unknown
R1786:Mnx1 UTSW 5 29474189 missense unknown
R1854:Mnx1 UTSW 5 29477782 missense unknown
R1866:Mnx1 UTSW 5 29474045 missense unknown
R1893:Mnx1 UTSW 5 29477830 missense unknown
R1899:Mnx1 UTSW 5 29473957 missense unknown
R2131:Mnx1 UTSW 5 29474189 missense unknown
R4698:Mnx1 UTSW 5 29474059 missense unknown
R4713:Mnx1 UTSW 5 29478131 missense probably damaging 1.00
R5171:Mnx1 UTSW 5 29474853 missense unknown
R6126:Mnx1 UTSW 5 29478112 missense possibly damaging 0.94
R7427:Mnx1 UTSW 5 29474213 missense unknown
Z1176:Mnx1 UTSW 5 29474088 missense unknown
Z1176:Mnx1 UTSW 5 29474174 nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to G transversion at position 916 of the Mnx1 transcript in exon 2 of 2 total exons. The mutated nucleotide causes a cysteine to arginine substitution at amino acid 241 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Mnx1 gene encodes a 404 amino acid transcription factor known as HB9.  HB9 contains a DNA-binding homeobox domain at amino acids 241-300 (Uniprot Q9QZW9). Mice that are homozygous for a targeted null mutation of Mnx1 die at birth, and exhibit motor neuron defects, pancreas dorsal lobe agenesis, and islets containing reduced numbers of insulin-producing beta-cells.
 
The C241R change occurs at the beginning of the homeobox domain, and is predicted to be probably damaging by the PolyPhen program.
Posted On2009-12-08