Mutagenetix > Incidental Mutation

Incidental Mutation 'R0010:Sgk1'

8055

Institutional Source

Beutler Lab

Gene Symbol

Sgk1

Ensembl Gene

ENSMUSG00000019970

Gene Name

serum/glucocorticoid regulated kinase 1

Synonyms

Sgk, Sgk1

MMRRC Submission

038305-MU

Accession Numbers

Ncbi RefSeq: NM_001161845.2, NM_001161847.2, NM_001161848.2, NM_001161849.2, NM_001161850.2, NM_011361.3; MGI:1340062

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0010 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

21882184-21999903 bp(+) (GRCm38)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

G to A at 21997438 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000128873 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020145] [ENSMUST00000092673] [ENSMUST00000100036] [ENSMUST00000120509] [ENSMUST00000124350] [ENSMUST00000142174] [ENSMUST00000150089] [ENSMUST00000164659]

AlphaFold

Q9WVC6

Predicted Effect

probably null
Transcript: ENSMUST00000020145

SMART Domains

Protein: ENSMUSP00000020145
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	36	72	4e-10	BLAST
low complexity region	73	80	N/A	INTRINSIC
S_TKc	98	355	6.15e-106	SMART
S_TK_X	356	425	2.51e-19	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000092673

SMART Domains

Protein: ENSMUSP00000090343
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
low complexity region	7	20	N/A	INTRINSIC
Blast:S_TKc	50	86	5e-10	BLAST
low complexity region	87	94	N/A	INTRINSIC
S_TKc	112	369	6.15e-106	SMART
S_TK_X	370	439	2.51e-19	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000100036

SMART Domains

Protein: ENSMUSP00000097614
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	22	58	5e-10	BLAST
low complexity region	59	66	N/A	INTRINSIC
S_TKc	84	341	6.15e-106	SMART
S_TK_X	342	411	2.51e-19	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000120509

SMART Domains

Protein: ENSMUSP00000114074
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	129	165	1e-9	BLAST
low complexity region	166	173	N/A	INTRINSIC
S_TKc	191	448	6.15e-106	SMART
S_TK_X	449	518	2.51e-19	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000124350

SMART Domains

Protein: ENSMUSP00000114691
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	9	45	2e-12	BLAST
low complexity region	46	53	N/A	INTRINSIC
Pfam:Pkinase	71	266	3.2e-62	PFAM
Pfam:Pkinase_Tyr	71	266	4.4e-34	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126560

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135195

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141218

Predicted Effect

probably benign
Transcript: ENSMUST00000142174

SMART Domains

Protein: ENSMUSP00000120882
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	9	45	3e-14	BLAST
PDB:3HDN\|A	33	82	7e-18	PDB
SCOP:d1koba_	43	82	4e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000150089

SMART Domains

Protein: ENSMUSP00000115073
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	22	58	4e-14	BLAST
PDB:3HDN\|A	46	89	3e-13	PDB

Predicted Effect

probably null
Transcript: ENSMUST00000164659

SMART Domains

Protein: ENSMUSP00000128873
Gene: ENSMUSG00000019970

Domain	Start	End	E-Value	Type
Blast:S_TKc	9	45	5e-10	BLAST
low complexity region	46	53	N/A	INTRINSIC
S_TKc	71	328	6.15e-106	SMART
S_TK_X	329	398	2.51e-19	SMART

Meta Mutation Damage Score

0.9486

Coding Region Coverage

1x: 79.6%
3x: 70.9%
10x: 47.0%
20x: 26.4%

Validation Efficiency

91% (78/86)

MGI Phenotype

Strain: 3846797; 2445418
FUNCTION: This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. This enzyme is activated by protein phosphorylation and degraded via the ubiquitination and proteasome pathway. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene was identified on chromosome 12. [provided by RefSeq, Sep 2009]
PHENOTYPE: Mice homozygous for a disruption in this gene display an essentially normal phenotype. Sodium retention is compromised on a low salt diet. [provided by MGI curators]

Allele List at MGI

All alleles(143) : Targeted(6) Gene trapped(137)

Other mutations in this stock

Total: 32 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrl3	C	T	5: 81,792,403	A1320V	possibly damaging	Het
Ahrr	G	A	13: 74,283,024		probably benign	Het
BC037034	T	C	5: 138,260,293		probably null	Het
Cd74	A	T	18: 60,809,071	H124L	probably benign	Het
Cdk5rap2	T	C	4: 70,243,459	E270G	probably benign	Het
Cldnd1	T	A	16: 58,731,259		probably benign	Het
Dennd4a	T	C	9: 64,896,715	L1112P	probably benign	Het
Evc2	T	A	5: 37,417,449	L1016Q	probably damaging	Het
Fam135b	T	C	15: 71,622,032	K16R	probably damaging	Het
Frem1	T	C	4: 83,000,098	I536V	probably benign	Het
Ginm1	T	C	10: 7,775,374		probably benign	Het
Glrb	A	T	3: 80,860,315		probably benign	Het
Glt6d1	C	A	2: 25,794,727		probably null	Het
Gm10320	T	C	13: 98,489,546	Y110C	probably damaging	Het
Intu	T	C	3: 40,654,272		probably benign	Het
Ltbp1	A	G	17: 75,363,391	T1476A	probably damaging	Het
Mcoln2	C	T	3: 146,183,561	T374M	probably damaging	Het
Mitf	A	G	6: 97,807,281	K33R	probably benign	Het
Nlgn1	G	T	3: 25,435,842		probably benign	Het
Nup133	A	T	8: 123,904,579	I1072N	probably damaging	Het
Rock1	T	A	18: 10,084,380	D951V	probably damaging	Het
Scgb2b26	T	A	7: 33,944,349	E55D	probably damaging	Het
Scn8a	T	C	15: 101,013,573	V958A	probably damaging	Het
Shprh	C	T	10: 11,151,931	T94I	probably benign	Het
Smg1	A	T	7: 118,171,859		probably benign	Het
Spta1	G	A	1: 174,217,943	V1556I	probably benign	Het
Trappc4	G	A	9: 44,405,231		probably benign	Het
Txlna	T	G	4: 129,629,086	D487A	probably benign	Het
Ube2d2b	T	C	5: 107,830,636	F51S	possibly damaging	Het
Wdfy3	T	C	5: 101,848,349	T3234A	probably damaging	Het
Zbtb41	T	G	1: 139,423,530	V127G	probably damaging	Het
Zfp608	A	T	18: 54,895,214		probably benign	Het

Other mutations in Sgk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02318:Sgk1	APN	10	21995541	missense	probably damaging	1.00
IGL02670:Sgk1	APN	10	21928546	missense	probably benign
IGL03220:Sgk1	APN	10	21997391	missense	probably null	1.00
R0010:Sgk1	UTSW	10	21997438	critical splice donor site	probably null
R0467:Sgk1	UTSW	10	21996358	splice site	probably benign
R0479:Sgk1	UTSW	10	21996310	missense	probably benign	0.00
R0650:Sgk1	UTSW	10	21882657	missense	probably damaging	0.98
R0652:Sgk1	UTSW	10	21882657	missense	probably damaging	0.98
R0688:Sgk1	UTSW	10	21998160	missense	probably benign
R0990:Sgk1	UTSW	10	21997086	missense	probably damaging	1.00
R1769:Sgk1	UTSW	10	21997108	splice site	probably benign
R2009:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R2218:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R2314:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R2909:Sgk1	UTSW	10	21994816	missense	probably benign
R2915:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R3176:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R3177:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R3276:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R3277:Sgk1	UTSW	10	21996601	missense	probably damaging	1.00
R3802:Sgk1	UTSW	10	21997412	missense	probably damaging	1.00
R5974:Sgk1	UTSW	10	21996249	missense	probably damaging	1.00
R6943:Sgk1	UTSW	10	21882694	missense	probably damaging	0.99
R7360:Sgk1	UTSW	10	21994073	missense	probably benign	0.01
R7425:Sgk1	UTSW	10	21994110	missense	probably damaging	0.97
R7665:Sgk1	UTSW	10	21996662	missense	probably damaging	1.00
R7973:Sgk1	UTSW	10	21994155	missense	probably benign	0.01
R8252:Sgk1	UTSW	10	21997399	missense	probably damaging	1.00
R8855:Sgk1	UTSW	10	21995827	missense	probably benign	0.12
R9199:Sgk1	UTSW	10	21882659	missense	probably damaging	0.99
R9492:Sgk1	UTSW	10	21998197	missense	probably damaging	0.97
R9670:Sgk1	UTSW	10	21992391	frame shift	probably null
R9683:Sgk1	UTSW	10	21992391	frame shift	probably null
R9723:Sgk1	UTSW	10	21996340	missense	probably damaging	1.00

Protein Function and Prediction

Serum- and glucocorticoid-inducible kinase 1 (SGK1) functions in the regulation of several physiological processes including: renal electrolyte transport, potassium transport (renal and extrarenal), hormone release, neuroexcitability, inflammation, coagulation, cell proliferation, apoptosis, and blood pressure control [reviewed in (1-4)].

Expression/Localization

Human SGK1 is expressed all tissues tested by Northern blot, with highest expression observed in pancreas, liver, and cardiac muscle (5). In mouse, RT-PCR detected two splice variants; Sgk1.1 was expressed exclusively in the brain, while Sgk1.2 was expressed in all examined tissues (6).

Background

Sgk1^{tm1.2Palm/tm1.2Palm}; MGI:3846797

129/Sv-Sgk1^tm1.2Palm

Mice homozygous for a disruption in this gene display an essentially normal phenotype. Sodium retention is compromised on a low salt diet (7).

Sgk1^{tm1Kuhl/tm1Kuhl}; MGI:2445418

either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * 129X1/SvJ)

Mice homozygous for a disruption in this gene display an essentially normal phenotype. Sodium retention is compromised on a low salt diet (8).

References

1. Lang, F., Artunc, F., and Vallon, V. (2009) The Physiological Impact of the Serum and Glucocorticoid-Inducible Kinase SGK1. Curr Opin Nephrol Hypertens. 18, 439-448.

2. Lang, F., Huang, D. Y., and Vallon, V. (2010) SGK, Renal Function and Hypertension. J Nephrol. 23 Suppl 16, S124-9.

3. Lang, F., and Vallon, V. (2012) Serum- and Glucocorticoid-Inducible Kinase 1 in the Regulation of Renal and Extrarenal Potassium Transport. Clin Exp Nephrol. 16, 73-80.

4. Lang, F., Strutz-Seebohm, N., Seebohm, G., and Lang, U. E. (2010) Significance of SGK1 in the Regulation of Neuronal Function. J Physiol. 588, 3349-3354.