Mutagenetix > Incidental Mutation

Incidental Mutation 'P0005:Tns2'

7578

Institutional Source

Beutler Lab

Gene Symbol

Tns2

Ensembl Gene

ENSMUSG00000037003

Gene Name

tensin 2

Synonyms

nep, Tenc1, nph

MMRRC Submission

038262-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

P0005 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

102008848-102024836 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 102022491 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 1188 (Q1188R)

Ref Sequence

ENSEMBL: ENSMUSP00000155830 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000046144] [ENSMUST00000154032] [ENSMUST00000169627] [ENSMUST00000228958] [ENSMUST00000230474]

AlphaFold

Q8CGB6

Predicted Effect

probably damaging
Transcript: ENSMUST00000046144
AA Change: Q1195R

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000041087
Gene: ENSMUSG00000037003
AA Change: Q1195R

Domain	Start	End	E-Value	Type
C1	32	79	2.78e-9	SMART
SCOP:d1d5ra2	128	295	8e-24	SMART
PTEN_C2	297	424	6.63e-40	SMART
low complexity region	494	513	N/A	INTRINSIC
SH2	1136	1236	1.69e-16	SMART
PTB	1269	1407	6.66e-28	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000128884

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139279

Predicted Effect

probably benign
Transcript: ENSMUST00000154032

SMART Domains

Protein: ENSMUSP00000121493
Gene: ENSMUSG00000036966

Domain	Start	End	E-Value	Type
low complexity region	28	38	N/A	INTRINSIC
SPRY	76	201	1.66e-11	SMART
SPRY	256	441	3.28e-15	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000169627
AA Change: Q1188R

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000129146
Gene: ENSMUSG00000037003
AA Change: Q1188R

Domain	Start	End	E-Value	Type
C1	32	79	2.78e-9	SMART
SCOP:d1d5ra2	128	295	8e-24	SMART
PTEN_C2	297	424	6.63e-40	SMART
low complexity region	494	513	N/A	INTRINSIC
SH2	1129	1229	1.69e-16	SMART
PTB	1262	1400	6.66e-28	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000228958
AA Change: Q1188R

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000229035

Predicted Effect

probably damaging
Transcript: ENSMUST00000230474
AA Change: Q1180R

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000229097

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000229800

Meta Mutation Damage Score

0.1507

Coding Region Coverage

1x: 85.5%
3x: 80.5%
10x: 66.1%
20x: 49.6%

Validation Efficiency

95% (104/109)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the tensin family. Tensin is a focal adhesion molecule that binds to actin filaments and participates in signaling pathways. This protein plays a role in regulating cell migration. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Affected mice homozygous for a spontaneous deletion show reduced female fertility, increased blood urea nitrogen, low hematocrit, proteinuria, hypoproteinemia, hypercholesterolemia, small kidneys with a yellowish granular surface, glomerular lesions and premature death; some develop systemic edema. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 20 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Atp13a1	T	C	8: 70,256,397 (GRCm39)	V845A	possibly damaging	Het
Casp6	T	C	3: 129,705,792 (GRCm39)	V153A	probably benign	Het
Col6a1	A	G	10: 76,553,163 (GRCm39)		probably benign	Het
Dars2	A	G	1: 160,881,509 (GRCm39)		probably null	Het
Hmgcll1	T	A	9: 75,982,041 (GRCm39)	M162K	possibly damaging	Het
Hydin	A	T	8: 111,220,921 (GRCm39)		probably null	Het
Ift74	A	G	4: 94,550,813 (GRCm39)		probably benign	Het
Itpr1	A	T	6: 108,358,218 (GRCm39)	I595F	probably damaging	Het
Mgat4f	T	A	1: 134,315,646 (GRCm39)	M15K	probably benign	Het
Mmp17	T	C	5: 129,673,695 (GRCm39)	V258A	probably benign	Het
Nek6	T	C	2: 38,459,749 (GRCm39)		probably null	Het
Nomo1	A	T	7: 45,686,981 (GRCm39)		probably null	Het
Nudt3	A	G	17: 27,815,689 (GRCm39)		probably benign	Het
Pramel32	A	G	4: 88,546,187 (GRCm39)	L385P	probably damaging	Het
Prkg2	A	C	5: 99,117,806 (GRCm39)	F512V	probably damaging	Het
Ptp4a3	T	A	15: 73,627,160 (GRCm39)	D72E	possibly damaging	Het
Rpgrip1l	A	T	8: 92,025,853 (GRCm39)		probably benign	Het
Rrp9	G	A	9: 106,358,376 (GRCm39)	R101H	probably benign	Het
Slc7a6os	T	C	8: 106,931,154 (GRCm39)	I161V	probably benign	Het
Tex15	T	C	8: 34,060,896 (GRCm39)	F109L	probably benign	Het

Other mutations in Tns2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01575:Tns2	APN	15	102,021,626 (GRCm39)	missense	probably damaging	1.00
IGL01935:Tns2	APN	15	102,020,069 (GRCm39)	splice site	probably null
IGL01994:Tns2	APN	15	102,019,814 (GRCm39)	missense	possibly damaging	0.81
IGL02025:Tns2	APN	15	102,020,484 (GRCm39)	nonsense	probably null
IGL02135:Tns2	APN	15	102,021,461 (GRCm39)	missense	probably damaging	1.00
IGL02355:Tns2	APN	15	102,020,725 (GRCm39)	missense	probably benign
IGL02362:Tns2	APN	15	102,020,725 (GRCm39)	missense	probably benign
IGL02439:Tns2	APN	15	102,022,978 (GRCm39)	missense	probably damaging	1.00
IGL02488:Tns2	APN	15	102,021,178 (GRCm39)	missense	probably benign
IGL02546:Tns2	APN	15	102,019,375 (GRCm39)	missense	probably damaging	1.00
IGL02616:Tns2	APN	15	102,019,850 (GRCm39)	missense	probably benign
IGL02628:Tns2	APN	15	102,020,263 (GRCm39)	missense	probably benign	0.04
IGL02658:Tns2	APN	15	102,016,231 (GRCm39)	splice site	probably benign
IGL03267:Tns2	APN	15	102,013,813 (GRCm39)	critical splice donor site	probably null
R0586:Tns2	UTSW	15	102,018,020 (GRCm39)	splice site	probably benign
R0791:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R0817:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R0818:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R0819:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R0820:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1451:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1452:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1453:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1454:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1455:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1487:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1510:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1579:Tns2	UTSW	15	102,019,645 (GRCm39)	missense	probably damaging	1.00
R1698:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1772:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1779:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1843:Tns2	UTSW	15	102,021,568 (GRCm39)	splice site	probably null
R1923:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1924:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1927:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R1980:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2051:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2087:Tns2	UTSW	15	102,015,554 (GRCm39)	missense	possibly damaging	0.70
R2100:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2103:Tns2	UTSW	15	102,021,100 (GRCm39)	critical splice acceptor site	probably null
R2105:Tns2	UTSW	15	102,015,941 (GRCm39)	missense	probably benign	0.27
R2224:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2225:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2227:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2252:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2253:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2290:Tns2	UTSW	15	102,020,458 (GRCm39)	missense	probably damaging	0.99
R2304:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2318:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2446:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2447:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2448:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2566:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2567:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2897:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R2898:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3159:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3160:Tns2	UTSW	15	102,021,771 (GRCm39)	missense	possibly damaging	0.88
R3162:Tns2	UTSW	15	102,021,771 (GRCm39)	missense	possibly damaging	0.88
R3162:Tns2	UTSW	15	102,021,771 (GRCm39)	missense	possibly damaging	0.88
R3196:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3237:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3426:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3427:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3428:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3695:Tns2	UTSW	15	102,021,184 (GRCm39)	missense	probably null
R3767:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R3911:Tns2	UTSW	15	102,022,272 (GRCm39)	critical splice donor site	probably null
R4113:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4157:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4394:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4395:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4396:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4439:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4441:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4537:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4538:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4541:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4599:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4600:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4602:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4773:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4774:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4775:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4776:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R4880:Tns2	UTSW	15	102,020,474 (GRCm39)	missense	probably damaging	0.98
R4989:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5014:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5058:Tns2	UTSW	15	102,016,295 (GRCm39)	missense	possibly damaging	0.68
R5253:Tns2	UTSW	15	102,019,888 (GRCm39)	missense	probably damaging	1.00
R5336:Tns2	UTSW	15	102,019,664 (GRCm39)	missense	probably damaging	1.00
R5351:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5452:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5453:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5629:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5630:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5631:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R5685:Tns2	UTSW	15	102,015,538 (GRCm39)	missense	probably benign	0.02
R5844:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6048:Tns2	UTSW	15	102,019,846 (GRCm39)	missense	probably damaging	1.00
R6067:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6079:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6130:Tns2	UTSW	15	102,019,676 (GRCm39)	missense	probably damaging	1.00
R6136:Tns2	UTSW	15	102,015,465 (GRCm39)	missense	probably damaging	1.00
R6138:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6199:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6210:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
R6426:Tns2	UTSW	15	102,015,472 (GRCm39)	missense	possibly damaging	0.65
R6544:Tns2	UTSW	15	102,022,269 (GRCm39)	missense	possibly damaging	0.93
R6594:Tns2	UTSW	15	102,018,994 (GRCm39)	missense	probably benign	0.00
R6596:Tns2	UTSW	15	102,018,994 (GRCm39)	missense	probably benign	0.00
R6734:Tns2	UTSW	15	102,011,551 (GRCm39)	missense	probably damaging	0.96
R7061:Tns2	UTSW	15	102,012,914 (GRCm39)	start codon destroyed	probably null
R7070:Tns2	UTSW	15	102,012,968 (GRCm39)	missense	possibly damaging	0.58
R7110:Tns2	UTSW	15	102,013,801 (GRCm39)	missense	probably damaging	0.99
R7410:Tns2	UTSW	15	102,018,961 (GRCm39)	missense	probably damaging	1.00
R7447:Tns2	UTSW	15	102,019,351 (GRCm39)	missense	probably damaging	1.00
R7751:Tns2	UTSW	15	102,018,163 (GRCm39)	missense	probably benign	0.02
R8052:Tns2	UTSW	15	102,021,280 (GRCm39)	missense	probably damaging	1.00
R8114:Tns2	UTSW	15	102,019,825 (GRCm39)	missense	probably benign	0.01
R8906:Tns2	UTSW	15	102,020,039 (GRCm39)	missense	probably damaging	1.00
R8964:Tns2	UTSW	15	102,011,553 (GRCm39)	missense	possibly damaging	0.73
R9192:Tns2	UTSW	15	102,021,416 (GRCm39)	missense	probably damaging	1.00
R9273:Tns2	UTSW	15	102,021,478 (GRCm39)	missense	probably damaging	1.00
R9307:Tns2	UTSW	15	102,018,996 (GRCm39)	missense	probably damaging	0.97
R9402:Tns2	UTSW	15	102,021,623 (GRCm39)	missense	probably damaging	0.99
R9612:Tns2	UTSW	15	102,015,577 (GRCm39)	missense	probably damaging	1.00
R9655:Tns2	UTSW	15	102,012,933 (GRCm39)	missense	probably benign	0.03
U15987:Tns2	UTSW	15	102,017,369 (GRCm39)	missense	probably damaging	1.00
X0009:Tns2	UTSW	15	102,020,900 (GRCm39)	missense	possibly damaging	0.94
X0026:Tns2	UTSW	15	102,018,937 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

The tensins are intracellular proteins that are postulated to act as signaling bridges between the extracellular space and the cytoskeleton (1). Tensin 2 has been shown to regulate cell motility (2) as well as it inhibits Akt signaling and cell survival (1).

Expression/Localization

Tensin 2 is highly expressed in the heart, kidney, skeletal muscle, and liver (2). Tensin 2 is localized to focal adhesions (2).

Background

The ICGN mouse is often used to study kidney disease and presents with proteinuria, hyperlipidemia, and edema (3). Studies have identified a spontaneous mutation in Tensin 2 (Tns2^nep) (3). Further studies found that the severity of glomerulsclerosis (i.e., a condition that results in proteinuria, podocyte morphological abnormalities, and increased extracellular matrix accumulation in the glomeruli with eventual renal failure) observed in these mice is dependent on the genetic background of the mice. For example, C57BL/6J mice are resistant to GS caused by this mutation (4), and mice in the 129/Sv (129T) background did not exhibit severe pathological changes until ~16 weeks of age (5). Examination of Tns2^nepmice in the (ICGN/Oa genetic background) determined that tensin 2 is necessary for nephrin expression in the glomerulus and severe albuminuria was exhibited by the mice (6). Furthermore, these mice (in this genetic background) developed proteinuria, resulting in nephrotic syndrome as early as 5 weeks and chronic kidney disesase by 15 weeks (7).

Tenc1^nph or Tns2^nep; MGI:2447990

involves: ICR

Mice develop kidney disease around 40 to 150 days after birth and death occurs within two months of onset (8). The urine protein levels as well as blood urea nitrogen and circulaing cholesterol levels are increased and the glomerulus is thickened (9).

References

1. Hafizi, S., Gustafsson, A., Oslakovic, C., Idevall-Hagren, O., Tengholm, A., Sperandio, O., Villoutreix, B. O., and Dahlback, B. (2010) Tensin2 Reduces Intracellular Phosphatidylinositol 3,4,5-Trisphosphate Levels at the Plasma Membrane. Biochem Biophys Res Commun. 399, 396-401.

2. Chen, H., Duncan, I. C., Bozorgchami, H., and Lo, S. H. (2002) Tensin1 and a Previously Undocumented Family Member, tensin2, Positively Regulate Cell Migration. Proc Natl Acad Sci U S A. 99, 733-738.

3. Cho, A. R., Uchio-Yamada, K., Torigai, T., Miyamoto, T., Miyoshi, I., Matsuda, J., Kurosawa, T., Kon, Y., Asano, A., Sasaki, N., and Agui, T. (2006) Deficiency of the tensin2 Gene in the ICGN Mouse: An Animal Model for Congenital Nephrotic Syndrome. Mamm Genome. 17, 407-416.

4. Nishino, T., Sasaki, N., Nagasaki, K., Ahmad, Z., and Agui, T. (2010) Genetic Background Strongly Influences the Severity of Glomerulosclerosis in Mice. J Vet Med Sci. 72, 1313-1318.

5. Nishino, T., Sasaki, N., Nagasaki, K., Ichii, O., Kon, Y., and Agui, T. (2012) The 129 Genetic Background Affects Susceptibility to Glomerulosclerosis in tensin2-Deficient Mice. Biomed Res. 33, 53-56.

6. Kato, T., Mizuno, S., Taketo, M. M., and Kurosawa, T. M. (2008) The Possible Involvement of tensin2 in the Expression and Extension of Nephrin by Glomerular Podocytes in Mice. Biomed Res. 29, 279-287.

7. Kato, T., Kurosawa, T. M., and Taketo, M. M. (2009) Proteinuria-Induced Chronic Kidney Disease in the ICGN/Oa Mice with a Mutation of Tensin2 Gene. Ren Fail. 31, 229-238.

8. Ogura, A., Asano, T., Matsuda, J., Noguchi, Y., Yamamoto, Y., Takano, K., and Nakagawa, M. (1989) Development of Nephrotic ICGN Mice--the Origin, Reproductive Ability, and Incidence of Glomerulonephritis. Jikken Dobutsu. 38, 349-352.

9. Ogura, A., Asano, T., Matsuda, J., Takano, K., Nakagawa, M., and Fukui, M. (1989) Characteristics of Mutant Mice (ICGN) with Spontaneous Renal Lesions: A New Model for Human Nephrotic Syndrome. Lab Anim. 23, 169-174.

Posted On

2012-10-05

Science Writer

Anne Murray