Mutagenetix > Incidental Mutation

Incidental Mutation 'H8477:Kcnj6'

577

Institutional Source

Beutler Lab

Gene Symbol

Kcnj6

Ensembl Gene

ENSMUSG00000043301

Gene Name

potassium inwardly-rectifying channel, subfamily J, member 6

Synonyms

GIRK2, Kir3.2, KCNJ7

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.081) question?

Stock #

H8477 (G3) of strain 600

Quality Score

Status

Validated

Chromosome

Chromosomal Location

94549495-94798560 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 94633796 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Threonine to Methionine at position 87 (T87M)

Ref Sequence

ENSEMBL: ENSMUSP00000156014 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000095873] [ENSMUST00000099508] [ENSMUST00000165538] [ENSMUST00000232562]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000095873
AA Change: T105M

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

SMART Domains

Protein: ENSMUSP00000093558
Gene: ENSMUSG00000043301
AA Change: T105M

Domain	Start	End	E-Value	Type
Pfam:IRK	59	397	9.3e-166	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000099508
AA Change: T105M

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

SMART Domains

Protein: ENSMUSP00000097108
Gene: ENSMUSG00000043301
AA Change: T105M

Domain	Start	End	E-Value	Type
Pfam:IRK	59	382	8.5e-146	PFAM
low complexity region	396	411	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000165538
AA Change: T87M

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

SMART Domains

Protein: ENSMUSP00000130321
Gene: ENSMUSG00000043301
AA Change: T87M

Domain	Start	End	E-Value	Type
Pfam:IRK	41	302	5.3e-122	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000232128

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000232403

Predicted Effect

probably damaging
Transcript: ENSMUST00000232562
AA Change: T87M

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

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 82.8%
3x: 56.2%

Het Detection Efficiency

41.2%

Validation Efficiency

100% (6/6)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]
PHENOTYPE: A spontaneous mutation exhibits small size, ataxia, hypotonia, high periweaning mortality, Purkinje cell defects, and male sterility. Homozygotes for a targeted null mutation exhibit increased susceptibility to spontaneous and drug-induced seizures. [provided by MGI curators]

Allele List at MGI

All alleles(3) : Targeted, knock-out(1) Gene trapped(1) Spontaneous(1)

Other mutations in this stock

Total: 1 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Dgki	T	A	6: 37,006,786 (GRCm39)		probably benign	Homo

Other mutations in Kcnj6

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01309:Kcnj6	APN	16	94,633,314 (GRCm39)	missense	probably damaging	0.99
IGL01433:Kcnj6	APN	16	94,633,814 (GRCm39)	missense	probably benign	0.21
IGL01603:Kcnj6	APN	16	94,634,058 (GRCm39)	missense	probably benign	0.00
IGL02212:Kcnj6	APN	16	94,633,346 (GRCm39)	missense	probably damaging	1.00
IGL02982:Kcnj6	APN	16	94,633,376 (GRCm39)	missense	possibly damaging	0.89
IGL03351:Kcnj6	APN	16	94,633,442 (GRCm39)	missense	probably damaging	1.00
Seizure	UTSW	16	94,633,518 (GRCm39)	missense	probably damaging	1.00
IGL02796:Kcnj6	UTSW	16	94,633,778 (GRCm39)	missense	probably benign	0.00
R0070:Kcnj6	UTSW	16	94,742,056 (GRCm39)	missense	probably benign
R1558:Kcnj6	UTSW	16	94,563,358 (GRCm39)	missense	possibly damaging	0.57
R1676:Kcnj6	UTSW	16	94,633,443 (GRCm39)	missense	probably damaging	1.00
R2435:Kcnj6	UTSW	16	94,563,538 (GRCm39)	missense	probably damaging	0.99
R3700:Kcnj6	UTSW	16	94,633,865 (GRCm39)	missense	probably damaging	0.96
R3800:Kcnj6	UTSW	16	94,633,886 (GRCm39)	missense	probably damaging	1.00
R4012:Kcnj6	UTSW	16	94,625,877 (GRCm39)	splice site	probably null
R4899:Kcnj6	UTSW	16	94,633,472 (GRCm39)	missense	probably damaging	1.00
R5124:Kcnj6	UTSW	16	94,633,518 (GRCm39)	missense	probably damaging	1.00
R5359:Kcnj6	UTSW	16	94,633,312 (GRCm39)	nonsense	probably null
R5560:Kcnj6	UTSW	16	94,633,824 (GRCm39)	missense	probably benign	0.06
R5583:Kcnj6	UTSW	16	94,634,060 (GRCm39)	missense	probably benign	0.26
R6057:Kcnj6	UTSW	16	94,633,236 (GRCm39)	missense	probably damaging	1.00
R6330:Kcnj6	UTSW	16	94,563,460 (GRCm39)	missense	possibly damaging	0.93
R6582:Kcnj6	UTSW	16	94,633,685 (GRCm39)	missense	possibly damaging	0.93
R6604:Kcnj6	UTSW	16	94,563,504 (GRCm39)	missense	probably damaging	1.00
R6802:Kcnj6	UTSW	16	94,563,436 (GRCm39)	missense	probably benign	0.06
R6866:Kcnj6	UTSW	16	94,563,536 (GRCm39)	missense	probably damaging	1.00
R7304:Kcnj6	UTSW	16	94,742,042 (GRCm39)	missense	probably benign
R7337:Kcnj6	UTSW	16	94,634,073 (GRCm39)	missense	probably benign	0.10
R7396:Kcnj6	UTSW	16	94,563,306 (GRCm39)	missense	probably benign	0.31
R8543:Kcnj6	UTSW	16	94,563,250 (GRCm39)	missense	possibly damaging	0.73
R9614:Kcnj6	UTSW	16	94,633,307 (GRCm39)	missense	probably damaging	1.00

Nature of Mutation

DNA sequencing using the SOLiD technique identified a C to T transition at position 842 of the Kcnj6 transcript in exon 4a of 7 exons using Genbank record NM_001025584.2 Multiple transcripts of the Kcnj6 gene are displayed on Ensembl. The mutated nucleotide causes a threonine to methionine substitution at amino acid 105 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Kcnj6 gene encodes multiple isoforms of an ATP-dependent inwardly rectifying potassium channel. The channel is controlled by G proteins and plays a role in granule cell differentiation, possibly via membrane hyperpolarization. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Isoform A is 425 amino acids long. The protein contains two transmembrane domains at residues 92-116 and 169-190, and a pore forming region at residues 141-159 (Uniprot P48542). A spontaneous mouse mutation (the weaver mutation) exhibits small size, ataxia, hypotonia, high periweaning mortality, Purkinje cell defects, and male sterility. Homozygotes for a targeted null mutation exhibit increased susceptibility to spontaneous and drug-induced seizures.

The T105M alteration occurs in the first transmembrane domain.

Posted On

2011-03-10