Incidental Mutation 'C9142:Pdlim3'
ID 161
Institutional Source Beutler Lab
Gene Symbol Pdlim3
Ensembl Gene ENSMUSG00000031636
Gene Name PDZ and LIM domain 3
Synonyms ALP
Accession Numbers 
Genbank: NM_016798; MGI: 1859274
Essential gene? Possibly essential (E-score: 0.703) question?
Stock # C9142 (G3) of strain Muskatenwein
Quality Score
Status Validated
Chromosome 8
Chromosomal Location 45885461-45919548 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) A to T at 45896832 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Methionine to Leucine at position 60 (M60L)
Ref Sequence ENSEMBL: ENSMUSP00000148113 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034053] [ENSMUST00000210422]
AlphaFold O70209
Predicted Effect probably benign
Transcript: ENSMUST00000034053
AA Change: M60L

PolyPhen 2 Score 0.248 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000034053
Gene: ENSMUSG00000031636
AA Change: M60L

DomainStartEndE-ValueType
PDZ 11 84 3.86e-16 SMART
ZM 137 162 5.55e-11 SMART
LIM 245 296 3.73e-14 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000210422
AA Change: M60L

PolyPhen 2 Score 0.372 (Sensitivity: 0.90; Specificity: 0.89)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211190
Meta Mutation Damage Score 0.1657 question?
Coding Region Coverage
  • 1x: 84.8%
  • 3x: 59.3%
Validation Efficiency 82% (72/88)
MGI Phenotype PHENOTYPE: Homozygotes for a knock-out allele show no major defects in skeletal muscle. However, homozygotes for another knock-out allele show partial background-sensitive prenatal lethality, embryonic right ventricular (RV) dilation and dysplasia, hypotrabeculation, and RV cardiomyopathy in surviving adults. [provided by MGI curators]
Allele List at MGI

All alleles(2) : Targeted, knock-out(1) Targeted, other(1)
Other mutations in this stock
Total: 7 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adnp A G 2: 168,184,407 S323P probably damaging Het
Cc2d2a A G 5: 43,735,457 probably benign Homo
Chrm5 A G 2: 112,480,211 F187L probably damaging Het
Fmnl3 T C 15: 99,337,627 probably null Het
Klf7 C T 1: 64,079,157 A94T possibly damaging Het
Nf1 C T 11: 79,556,731 R2433C probably damaging Het
Vwde T C 6: 13,168,054 probably benign Homo
Other mutations in Pdlim3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00767:Pdlim3 APN 8 45896790 missense probably damaging 1.00
IGL01341:Pdlim3 APN 8 45915240 missense probably benign
IGL02189:Pdlim3 APN 8 45885593 missense probably damaging 1.00
IGL02834:Pdlim3 APN 8 45917532 missense probably benign 0.02
IGL03165:Pdlim3 APN 8 45918998 missense possibly damaging 0.82
R0244:Pdlim3 UTSW 8 45908460 intron probably benign
R0369:Pdlim3 UTSW 8 45917506 missense probably benign
R1052:Pdlim3 UTSW 8 45896800 missense probably damaging 1.00
R1142:Pdlim3 UTSW 8 45918961 missense probably damaging 1.00
R1531:Pdlim3 UTSW 8 45896763 missense probably damaging 1.00
R1607:Pdlim3 UTSW 8 45896859 missense probably damaging 1.00
R1645:Pdlim3 UTSW 8 45896748 missense probably benign 0.37
R5641:Pdlim3 UTSW 8 45915263 splice site probably null
R5731:Pdlim3 UTSW 8 45915247 missense probably benign
R6501:Pdlim3 UTSW 8 45908602 missense possibly damaging 0.95
R7111:Pdlim3 UTSW 8 45917502 missense probably damaging 0.99
R7637:Pdlim3 UTSW 8 45909065 missense probably damaging 1.00
R7701:Pdlim3 UTSW 8 45908539 missense probably benign 0.17
R8223:Pdlim3 UTSW 8 45900525 missense possibly damaging 0.80
R8380:Pdlim3 UTSW 8 45917535 missense probably benign
R9163:Pdlim3 UTSW 8 45885674 critical splice donor site probably null
R9673:Pdlim3 UTSW 8 45915158 missense possibly damaging 0.52
Z1177:Pdlim3 UTSW 8 45909079 missense possibly damaging 0.63
Z1177:Pdlim3 UTSW 8 45909080 missense possibly damaging 0.77
Z1177:Pdlim3 UTSW 8 45918984 nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to T transversion at position 273 of the Pdlim3 transcript. The mutated nucleotide causes a methionine to leucine substitution at amino acid 60 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Pdlim3 gene encodes a 316 amino acid protein known as the actinin-associated LIM protein (ALP). ALP localizes to myofiber Z-lines, and may play a role in the organization of actin filament arrays within muscle cells. ALP contains a PDZ domain at amino acids 1-84, and a LIM zinc binding domain at amino acids 244-303 (Uniprot O70209). ALP-deficient mice maintain normal development and structure of skeletal muscle.
 
The M60L change occurs in the PDZ domain, and is predicted to be possibly damaging by the PolyPhen program.
Posted On 2010-04-08