Mutagenetix > Incidental Mutation

Incidental Mutation 'A4554:Kel'

Institutional Source

Beutler Lab

Gene Symbol

Kel

Ensembl Gene

ENSMUSG00000029866

Gene Name

Kell blood group

Synonyms

CD238

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.088) question?

Stock #

A4554 of strain gemini

Quality Score

Status

Validated

Chromosome

Chromosomal Location

41663263-41681268 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 41674353 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Aspartic acid to Valine at position 359 (D359V)

Ref Sequence

ENSEMBL: ENSMUSP00000031899 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031899]

AlphaFold

Q9EQF2

Predicted Effect

possibly damaging
Transcript: ENSMUST00000031899
AA Change: D359V

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000031899
Gene: ENSMUSG00000029866
AA Change: D359V

Domain	Start	End	E-Value	Type
transmembrane domain	28	50	N/A	INTRINSIC
Pfam:Peptidase_M13_N	81	463	1.5e-68	PFAM
Pfam:Peptidase_M13	521	712	2.1e-58	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000192118

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000192406

Meta Mutation Damage Score

0.2232

Coding Region Coverage

1x: 85.5%
3x: 63.0%

Validation Efficiency

84% (92/109)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit decreased heart rate, altered hematological parameters and ECG waveform features, decreased erythrocyte Mg2+ and K+ ion content, mild motor deficits, and giant axon changes with varying degrees of paranodal demyelination in the spinal cord and sciatic nerve. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 18 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Asap1	T	C	15: 63,996,560 (GRCm39)		probably benign	Het
Bpifb5	A	T	2: 154,069,100 (GRCm39)	Y139F	possibly damaging	Homo
Chd2	A	C	7: 73,130,716 (GRCm39)	V782G	probably benign	Homo
Chst4	G	T	8: 110,756,520 (GRCm39)	Q448K	probably benign	Homo
Dido1	T	C	2: 180,317,164 (GRCm39)	K8E	probably damaging	Homo
Evpl	A	G	11: 116,111,660 (GRCm39)	L2010P	probably damaging	Homo
Fgl2	A	G	5: 21,577,776 (GRCm39)	E21G	probably benign	Homo
Greb1l	A	T	18: 10,532,862 (GRCm39)	M919L	possibly damaging	Homo
Lmtk2	A	G	5: 144,103,135 (GRCm39)	D298G	possibly damaging	Homo
Masp1	A	T	16: 23,273,690 (GRCm39)		probably null	Homo
Mrgprb8	A	T	7: 48,039,156 (GRCm39)	I276F	probably damaging	Homo
Nde1	T	C	16: 14,006,274 (GRCm39)		probably benign	Homo
Rbck1	G	T	2: 152,161,092 (GRCm39)	N385K	probably damaging	Homo
Senp6	G	T	9: 80,055,740 (GRCm39)		probably benign	Het
Tm4sf4	T	A	3: 57,345,188 (GRCm39)		probably null	Homo
Ubn2	A	T	6: 38,461,045 (GRCm39)	H488L	probably damaging	Homo
Vmn2r120	A	G	17: 57,832,715 (GRCm39)	F155L	probably benign	Homo
Vmn2r65	T	A	7: 84,595,791 (GRCm39)	T298S	probably damaging	Homo

Other mutations in Kel

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00743:Kel	APN	6	41,665,509 (GRCm39)	missense	probably damaging	1.00
IGL00792:Kel	APN	6	41,678,946 (GRCm39)	missense	probably damaging	1.00
IGL00972:Kel	APN	6	41,665,000 (GRCm39)	missense	possibly damaging	0.62
IGL01121:Kel	APN	6	41,679,343 (GRCm39)	missense	probably benign	0.00
IGL01286:Kel	APN	6	41,665,051 (GRCm39)	splice site	probably null
IGL01461:Kel	APN	6	41,678,845 (GRCm39)	critical splice donor site	probably null
IGL01836:Kel	APN	6	41,674,372 (GRCm39)	missense	possibly damaging	0.50
IGL02037:Kel	APN	6	41,674,408 (GRCm39)	missense	probably benign	0.01
IGL02103:Kel	APN	6	41,679,323 (GRCm39)	missense	probably benign	0.18
IGL02604:Kel	APN	6	41,664,516 (GRCm39)	missense	probably damaging	0.98
IGL03102:Kel	APN	6	41,679,917 (GRCm39)	missense	probably benign	0.00
IGL03274:Kel	APN	6	41,664,929 (GRCm39)	splice site	probably null
IGL03355:Kel	APN	6	41,675,821 (GRCm39)	critical splice donor site	probably null
R0121:Kel	UTSW	6	41,678,998 (GRCm39)	unclassified	probably benign
R0153:Kel	UTSW	6	41,678,877 (GRCm39)	missense	probably benign	0.08
R0535:Kel	UTSW	6	41,667,772 (GRCm39)	missense	probably null	0.21
R0658:Kel	UTSW	6	41,679,965 (GRCm39)	missense	probably damaging	1.00
R1005:Kel	UTSW	6	41,665,551 (GRCm39)	missense	probably damaging	1.00
R1199:Kel	UTSW	6	41,665,525 (GRCm39)	missense	possibly damaging	0.95
R1272:Kel	UTSW	6	41,680,404 (GRCm39)	missense	probably benign	0.00
R1531:Kel	UTSW	6	41,665,560 (GRCm39)	missense	probably damaging	0.99
R1880:Kel	UTSW	6	41,664,479 (GRCm39)	missense	possibly damaging	0.95
R2102:Kel	UTSW	6	41,663,418 (GRCm39)	missense	possibly damaging	0.86
R2118:Kel	UTSW	6	41,666,234 (GRCm39)	missense	probably benign
R2571:Kel	UTSW	6	41,665,001 (GRCm39)	missense	possibly damaging	0.62
R4209:Kel	UTSW	6	41,675,359 (GRCm39)	nonsense	probably null
R4210:Kel	UTSW	6	41,675,359 (GRCm39)	nonsense	probably null
R4260:Kel	UTSW	6	41,663,357 (GRCm39)	utr 3 prime	probably benign
R4382:Kel	UTSW	6	41,675,334 (GRCm39)	missense	probably benign	0.13
R5023:Kel	UTSW	6	41,665,045 (GRCm39)	missense	probably damaging	1.00
R5033:Kel	UTSW	6	41,675,989 (GRCm39)	missense	probably damaging	1.00
R5239:Kel	UTSW	6	41,665,048 (GRCm39)	nonsense	probably null
R5431:Kel	UTSW	6	41,675,354 (GRCm39)	missense	probably benign	0.23
R5742:Kel	UTSW	6	41,675,961 (GRCm39)	missense	probably damaging	1.00
R5745:Kel	UTSW	6	41,675,961 (GRCm39)	missense	probably damaging	1.00
R5746:Kel	UTSW	6	41,675,961 (GRCm39)	missense	probably damaging	1.00
R5978:Kel	UTSW	6	41,664,979 (GRCm39)	missense	probably benign	0.00
R6023:Kel	UTSW	6	41,674,409 (GRCm39)	missense	probably benign
R6109:Kel	UTSW	6	41,665,796 (GRCm39)	missense	probably benign	0.06
R6125:Kel	UTSW	6	41,667,720 (GRCm39)	missense	probably damaging	1.00
R6319:Kel	UTSW	6	41,679,381 (GRCm39)	missense	probably benign	0.05
R6368:Kel	UTSW	6	41,665,785 (GRCm39)	nonsense	probably null
R6864:Kel	UTSW	6	41,680,694 (GRCm39)	critical splice donor site	probably null
R6956:Kel	UTSW	6	41,664,907 (GRCm39)	missense	probably damaging	1.00
R7644:Kel	UTSW	6	41,667,742 (GRCm39)	missense	probably benign	0.03
R7938:Kel	UTSW	6	41,675,310 (GRCm39)	missense	probably benign	0.06
R8028:Kel	UTSW	6	41,675,958 (GRCm39)	missense	probably benign	0.21
R8082:Kel	UTSW	6	41,680,424 (GRCm39)	missense	possibly damaging	0.94
R8465:Kel	UTSW	6	41,666,472 (GRCm39)	critical splice donor site	probably null
R9158:Kel	UTSW	6	41,664,905 (GRCm39)	missense	probably benign	0.10
R9518:Kel	UTSW	6	41,679,334 (GRCm39)	missense	probably damaging	1.00
R9726:Kel	UTSW	6	41,678,971 (GRCm39)	missense	probably damaging	1.00
R9769:Kel	UTSW	6	41,678,990 (GRCm39)	missense	probably damaging	1.00
X0028:Kel	UTSW	6	41,675,285 (GRCm39)	missense	probably damaging	0.99
Z1176:Kel	UTSW	6	41,664,506 (GRCm39)	missense	probably damaging	1.00
Z1177:Kel	UTSW	6	41,666,493 (GRCm39)	missense	probably benign

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at position 1333 of the Kel transcript in exon 10of 19 total exons. Three transcripts of the Kel gene are displayed on Ensembl. The mutated nucleotide causes an aspartic acid to valine substitution at amino acid 359 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Kel gene encodes a 713 amino acid single-pass type II membrane protein known as CD238 that belongs to the peptidase M13 family. CD238 is a zinc endopeptidase with endothelin-3-converting enzyme activity. It is highly expressed in the spleen with weaker expression in the testis and heart, spans the erythrocyte membrane, and is attached to the underlying cytoskeleton (Uniprot Q9EQF2).

The D359V change occurs in the extracellular domain and is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-03-16