Mutagenetix > Incidental Mutation

Incidental Mutation 'R8845:Ldb3'

674675

Institutional Source

Beutler Lab

Gene Symbol

Ldb3

Ensembl Gene

ENSMUSG00000021798

Gene Name

LIM domain binding 3

Synonyms

ZASP, cypher

MMRRC Submission

068734-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8845 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

34248560-34310639 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 34258634 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 657 (Y657C)

Ref Sequence

ENSEMBL: ENSMUSP00000022327 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022327] [ENSMUST00000022328] [ENSMUST00000064098] [ENSMUST00000090040] [ENSMUST00000228044]

AlphaFold

Q9JKS4

PDB Structure

Solution structure of PDZ domain of mouse Cypher protein [SOLUTION NMR]

Predicted Effect

probably damaging
Transcript: ENSMUST00000022327
AA Change: Y657C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000022327
Gene: ENSMUSG00000021798
AA Change: Y657C

Domain	Start	End	E-Value	Type
PDZ	11	84	1.68e-16	SMART
low complexity region	138	147	N/A	INTRINSIC
ZM	186	211	1.33e-8	SMART
low complexity region	214	229	N/A	INTRINSIC
low complexity region	309	353	N/A	INTRINSIC
low complexity region	359	376	N/A	INTRINSIC
low complexity region	418	473	N/A	INTRINSIC
LIM	546	597	2.72e-16	SMART
LIM	605	656	2.65e-19	SMART
LIM	664	717	1.04e-17	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000022328
AA Change: Y595C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000022328
Gene: ENSMUSG00000021798
AA Change: Y595C

Domain	Start	End	E-Value	Type
PDZ	11	84	1.68e-16	SMART
low complexity region	138	147	N/A	INTRINSIC
ZM	186	211	1.33e-8	SMART
low complexity region	214	229	N/A	INTRINSIC
low complexity region	297	314	N/A	INTRINSIC
low complexity region	356	411	N/A	INTRINSIC
LIM	484	535	2.72e-16	SMART
LIM	543	594	2.65e-19	SMART
LIM	602	655	1.04e-17	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000064098
AA Change: Y613C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000066784
Gene: ENSMUSG00000021798
AA Change: Y613C

Domain	Start	End	E-Value	Type
PDZ	11	84	1.68e-16	SMART
ZM	148	173	5.18e-11	SMART
low complexity region	265	309	N/A	INTRINSIC
low complexity region	315	332	N/A	INTRINSIC
low complexity region	374	429	N/A	INTRINSIC
LIM	502	553	2.72e-16	SMART
LIM	561	612	2.65e-19	SMART
LIM	620	673	1.04e-17	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000090040
AA Change: Y618C

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000087494
Gene: ENSMUSG00000021798
AA Change: Y618C

Domain	Start	End	E-Value	Type
PDZ	11	84	1.68e-16	SMART
ZM	148	173	5.18e-11	SMART
low complexity region	270	314	N/A	INTRINSIC
low complexity region	320	337	N/A	INTRINSIC
low complexity region	379	434	N/A	INTRINSIC
LIM	507	558	2.72e-16	SMART
LIM	566	617	2.65e-19	SMART
LIM	625	678	1.04e-17	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000228044
AA Change: Y556C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]
PHENOTYPE: Homozygous mutation of this gene results in lethality within a few days after birth from muscle abnormalities. Mutant mice exhibit myopathy, dysphagia, heart vascular congestion, dilated heart ventricles, cyanosis, and respiratory distress. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	C	T	7: 119,846,428 (GRCm39)	P627S	probably benign	Het
Abca4	G	A	3: 121,930,651 (GRCm39)	V1383M	probably damaging	Het
Acer3	A	G	7: 97,910,832 (GRCm39)	S77P	probably damaging	Het
Adgrv1	G	T	13: 81,629,478 (GRCm39)	T3640N	possibly damaging	Het
Agmo	T	C	12: 37,294,364 (GRCm39)	L104P	probably benign	Het
Alox12	C	A	11: 70,137,877 (GRCm39)	G421V	probably damaging	Het
Atad2	A	G	15: 57,989,532 (GRCm39)	V182A	probably damaging	Het
Bnc2	C	T	4: 84,194,338 (GRCm39)	A929T	possibly damaging	Het
Bola3	T	C	6: 83,335,154 (GRCm39)	M83T	probably damaging	Het
Brca2	T	C	5: 150,466,847 (GRCm39)	F2204L	possibly damaging	Het
Cachd1	T	C	4: 100,810,343 (GRCm39)	V315A	probably benign	Het
Ccdc154	C	A	17: 25,390,138 (GRCm39)	N547K	probably damaging	Het
Ccdc62	C	A	5: 124,092,470 (GRCm39)	T485K	probably benign	Het
Cdc40	G	A	10: 40,717,790 (GRCm39)	T371I	possibly damaging	Het
Cep112	T	C	11: 108,461,193 (GRCm39)	F657L	probably damaging	Het
Cirbp	A	G	10: 80,005,931 (GRCm39)	D62G	probably damaging	Het
Cntf	A	C	19: 12,741,664 (GRCm39)	S65R	probably benign	Het
Cxxc4	CGGC	CGGCGGGGGC	3: 133,945,912 (GRCm39)		probably benign	Het
Cyfip1	G	T	7: 55,579,834 (GRCm39)	G1229V	probably benign	Het
Cyp4a30b	A	C	4: 115,315,493 (GRCm39)	N238T	probably benign	Het
Dbx2	G	A	15: 95,552,517 (GRCm39)	R43C	probably benign	Het
Efcab3	A	T	11: 104,899,787 (GRCm39)	I4350F	possibly damaging	Het
Fbxw13	G	T	9: 109,023,833 (GRCm39)	F70L	possibly damaging	Het
Fhod3	A	G	18: 25,265,976 (GRCm39)	T1555A	probably damaging	Het
Fnbp4	A	G	2: 90,606,368 (GRCm39)	M763V	probably benign	Het
Gdf7	A	G	12: 8,348,905 (GRCm39)	S131P	unknown	Het
Gm9938	A	T	19: 23,701,941 (GRCm39)	E93V	unknown	Het
Golim4	A	T	3: 75,802,272 (GRCm39)	M340K	probably damaging	Het
Gphn	A	G	12: 78,538,953 (GRCm39)	S200G	probably benign	Het
Hpse	T	C	5: 100,859,248 (GRCm39)	D99G	probably benign	Het
Iqgap2	A	T	13: 95,794,392 (GRCm39)	N1193K	possibly damaging	Het
Jag2	A	T	12: 112,883,714 (GRCm39)	C256S	probably damaging	Het
Lmtk2	T	A	5: 144,110,704 (GRCm39)	Y475N	probably damaging	Het
Mep1b	A	T	18: 21,230,379 (GRCm39)	K644*	probably null	Het
Muc4	A	C	16: 32,576,889 (GRCm39)	T60P	possibly damaging	Het
Nckap5	G	T	1: 125,909,423 (GRCm39)	Q1603K	possibly damaging	Het
Npy6r	C	T	18: 44,408,606 (GRCm39)	T9I	probably benign	Het
Nsd2	T	C	5: 34,039,885 (GRCm39)	C846R	probably damaging	Het
Oard1	A	C	17: 48,721,259 (GRCm39)	K64Q	probably benign	Het
Or4c103	T	A	2: 88,513,735 (GRCm39)	I114F	possibly damaging	Het
Or52e19b	A	T	7: 103,032,357 (GRCm39)	V284D	probably damaging	Het
Or5w8	G	T	2: 87,687,545 (GRCm39)	V9L	probably benign	Het
Or6c208	A	G	10: 129,224,065 (GRCm39)	T188A	probably damaging	Het
Pkhd1l1	T	G	15: 44,368,650 (GRCm39)	S823A	probably benign	Het
Pla2r1	A	G	2: 60,259,053 (GRCm39)	S1112P	possibly damaging	Het
Plekho2	T	C	9: 65,465,963 (GRCm39)	T142A	probably damaging	Het
Prr35	A	T	17: 26,165,823 (GRCm39)	V488E	probably benign	Het
Prrc2b	T	A	2: 32,102,105 (GRCm39)	M726K	possibly damaging	Het
Prrc2b	A	T	2: 32,106,162 (GRCm39)	K1514I	possibly damaging	Het
Rin1	A	T	19: 5,104,947 (GRCm39)	D669V	probably damaging	Het
Setd1b	C	T	5: 123,282,310 (GRCm39)	A146V	unknown	Het
Sigmar1	G	A	4: 41,741,234 (GRCm39)	R7W	probably damaging	Het
Slain1	C	T	14: 103,925,747 (GRCm39)	T365I	possibly damaging	Het
Slc38a2	G	A	15: 96,592,900 (GRCm39)	T186I	probably benign	Het
Tas2r130	A	T	6: 131,607,642 (GRCm39)	V51E	probably benign	Het
Tgfb1i1	A	T	7: 127,851,690 (GRCm39)	H332L	possibly damaging	Het
Trav7n-4	T	C	14: 53,328,846 (GRCm39)	L15S	probably damaging	Het
Ttc28	T	C	5: 111,372,041 (GRCm39)	V861A	probably benign	Het
Ttn	A	G	2: 76,632,658 (GRCm39)	I14132T	probably damaging	Het
Ttn	T	C	2: 76,606,380 (GRCm39)	E18143G	probably damaging	Het
Vmn1r203	C	T	13: 22,708,720 (GRCm39)	S167L	possibly damaging	Het
Vmn2r108	A	T	17: 20,691,361 (GRCm39)	H387Q	probably benign	Het
Vps33a	A	T	5: 123,709,538 (GRCm39)		probably null	Het
Vps50	G	A	6: 3,504,926 (GRCm39)	V31I	probably benign	Het
Wdcp	A	G	12: 4,901,439 (GRCm39)	T432A	probably benign	Het
Wdr36	T	A	18: 32,994,098 (GRCm39)	Y645*	probably null	Het

Other mutations in Ldb3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01124:Ldb3	APN	14	34,266,157 (GRCm39)	missense	probably damaging	0.99
IGL01485:Ldb3	APN	14	34,264,519 (GRCm39)	missense	probably damaging	1.00
IGL01983:Ldb3	APN	14	34,299,156 (GRCm39)	missense	probably benign	0.00
R0323:Ldb3	UTSW	14	34,266,002 (GRCm39)	missense	probably damaging	1.00
R0335:Ldb3	UTSW	14	34,300,608 (GRCm39)	missense	possibly damaging	0.77
R0483:Ldb3	UTSW	14	34,258,541 (GRCm39)	missense	probably damaging	1.00
R0920:Ldb3	UTSW	14	34,289,460 (GRCm39)	missense	probably benign	0.05
R1524:Ldb3	UTSW	14	34,277,313 (GRCm39)	missense	probably benign	0.01
R2161:Ldb3	UTSW	14	34,289,353 (GRCm39)	critical splice donor site	probably null
R2246:Ldb3	UTSW	14	34,251,432 (GRCm39)	missense	probably damaging	0.99
R2865:Ldb3	UTSW	14	34,251,460 (GRCm39)	missense	probably damaging	1.00
R3113:Ldb3	UTSW	14	34,251,418 (GRCm39)	makesense	probably null
R3765:Ldb3	UTSW	14	34,300,639 (GRCm39)	splice site	probably null
R3870:Ldb3	UTSW	14	34,289,440 (GRCm39)	missense	probably damaging	1.00
R4018:Ldb3	UTSW	14	34,274,128 (GRCm39)	splice site	probably benign
R4797:Ldb3	UTSW	14	34,277,470 (GRCm39)	missense	possibly damaging	0.95
R4963:Ldb3	UTSW	14	34,288,815 (GRCm39)	missense	probably damaging	0.98
R5705:Ldb3	UTSW	14	34,298,986 (GRCm39)	missense	probably null	0.01
R6401:Ldb3	UTSW	14	34,299,291 (GRCm39)	missense	probably benign	0.33
R6549:Ldb3	UTSW	14	34,263,854 (GRCm39)	missense	probably damaging	0.99
R6682:Ldb3	UTSW	14	34,274,221 (GRCm39)	missense	possibly damaging	0.77
R6917:Ldb3	UTSW	14	34,277,321 (GRCm39)	missense	probably null	0.03
R7132:Ldb3	UTSW	14	34,298,992 (GRCm39)	missense	probably benign	0.25
R7327:Ldb3	UTSW	14	34,293,759 (GRCm39)	missense	probably damaging	1.00
R7488:Ldb3	UTSW	14	34,289,402 (GRCm39)	missense	probably damaging	1.00
R7760:Ldb3	UTSW	14	34,264,460 (GRCm39)	missense	probably damaging	1.00
R8755:Ldb3	UTSW	14	34,299,256 (GRCm39)	missense	probably damaging	1.00
R8954:Ldb3	UTSW	14	34,277,301 (GRCm39)	missense	probably null	0.17
R9179:Ldb3	UTSW	14	34,277,312 (GRCm39)	missense	probably benign
R9321:Ldb3	UTSW	14	34,266,099 (GRCm39)	nonsense	probably null
R9702:Ldb3	UTSW	14	34,299,090 (GRCm39)	missense	probably benign	0.03
Z1176:Ldb3	UTSW	14	34,277,322 (GRCm39)	missense	probably benign	0.21
Z1177:Ldb3	UTSW	14	34,266,060 (GRCm39)	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- GATCATTCCGGCACCAGAATG -3'
(R):5'- CTGAGTCAACACACCATTGGTAC -3'

Sequencing Primer
(F):5'- AGAATGCCACAGTCGCGTC -3'
(R):5'- GGTACAAATTATCAAAAGAGCGAAAC -3'

Posted On

2021-07-15