Mutagenetix > Incidental Mutation

Incidental Mutation 'N/A - 535:Cd44'

217

Institutional Source

Beutler Lab

Gene Symbol

Cd44

Ensembl Gene

ENSMUSG00000005087

Gene Name

CD44 antigen

Synonyms

Pgp-1, Ly-24, HERMES

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.238) question?

Stock #

N/A - 535 of strain bumble

Quality Score

Status

Validated

Chromosome

Chromosomal Location

102641486-102732010 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 102644534 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 481 (M481V)

Ref Sequence

ENSEMBL: ENSMUSP00000106822 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005218] [ENSMUST00000060516] [ENSMUST00000099673] [ENSMUST00000111190] [ENSMUST00000111191] [ENSMUST00000111192] [ENSMUST00000111194] [ENSMUST00000111198]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000005218
AA Change: M763V

PolyPhen 2 Score 0.471 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000005218
Gene: ENSMUSG00000005087
AA Change: M763V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	251	276	N/A	INTRINSIC
low complexity region	429	439	N/A	INTRINSIC
low complexity region	640	653	N/A	INTRINSIC
low complexity region	689	703	N/A	INTRINSIC
PDB:2ZPY\|B	710	729	1e-6	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000060516
AA Change: M563V

PolyPhen 2 Score 0.177 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000062330
Gene: ENSMUSG00000005087
AA Change: M563V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	229	239	N/A	INTRINSIC
low complexity region	440	453	N/A	INTRINSIC
low complexity region	489	503	N/A	INTRINSIC
PDB:2ZPY\|B	510	529	1e-6	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000099673
AA Change: M348V

PolyPhen 2 Score 0.263 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000097265
Gene: ENSMUSG00000005087
AA Change: M348V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	225	238	N/A	INTRINSIC
low complexity region	274	288	N/A	INTRINSIC
PDB:2ZPY\|B	295	314	1e-6	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000111190
AA Change: M447V

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000106821
Gene: ENSMUSG00000005087
AA Change: M447V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	324	337	N/A	INTRINSIC
low complexity region	373	387	N/A	INTRINSIC
PDB:2ZPY\|B	394	413	8e-7	PDB

Predicted Effect

possibly damaging
Transcript: ENSMUST00000111191
AA Change: M481V

PolyPhen 2 Score 0.501 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000106822
Gene: ENSMUSG00000005087
AA Change: M481V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	358	371	N/A	INTRINSIC
low complexity region	407	421	N/A	INTRINSIC
PDB:2ZPY\|B	428	447	9e-7	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000111192
AA Change: M417V

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000106823
Gene: ENSMUSG00000005087
AA Change: M417V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	294	307	N/A	INTRINSIC
low complexity region	343	357	N/A	INTRINSIC
PDB:2ZPY\|B	364	383	1e-6	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000111194
AA Change: M560V

PolyPhen 2 Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000106825
Gene: ENSMUSG00000005087
AA Change: M560V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	268	278	N/A	INTRINSIC
low complexity region	302	312	N/A	INTRINSIC
low complexity region	437	450	N/A	INTRINSIC
low complexity region	486	500	N/A	INTRINSIC
PDB:2ZPY\|B	507	526	1e-6	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000111198
AA Change: M640V

PolyPhen 2 Score 0.177 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000106829
Gene: ENSMUSG00000005087
AA Change: M640V

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
LINK	34	125	5.88e-38	SMART
low complexity region	306	316	N/A	INTRINSIC
low complexity region	517	530	N/A	INTRINSIC
low complexity region	566	580	N/A	INTRINSIC
PDB:2ZPY\|B	587	606	1e-6	PDB

Meta Mutation Damage Score

0.0791

Coding Region Coverage

1x: 83.1%
3x: 57.4%

Validation Efficiency

88% (80/91)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations exhibit impaired T lymphocyte trafficking resulting in muted inflammatory responses, altered myeloid progenitor distribution, reduced growth of tumors, and impaired uterine involution and maintenance of lactation. [provided by MGI curators]

Allele List at MGI

All alleles(7) : Targeted, knock-out(4) Targeted, other(3)

Other mutations in this stock

Total: 11 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cacna1e	A	T	1: 154,341,510 (GRCm39)	L1166Q	probably damaging	Het
Eif4g3	T	A	4: 137,847,739 (GRCm39)	V220D	probably damaging	Het
Gm12778	T	A	7: 33,875,347 (GRCm39)		noncoding transcript	Homo
Klhl29	C	T	12: 5,134,019 (GRCm39)	A773T	probably damaging	Homo
Lifr	A	T	15: 7,216,434 (GRCm39)	H803L	possibly damaging	Het
Macf1	T	C	4: 123,367,601 (GRCm39)	T822A	possibly damaging	Het
Obscn	A	T	11: 58,891,134 (GRCm39)	C1653S	possibly damaging	Het
Ogdh	T	C	11: 6,274,911 (GRCm39)	L180P	possibly damaging	Het
Rnf5	T	C	17: 34,822,330 (GRCm39)	S40G	possibly damaging	Het
Sbf2	T	C	7: 109,911,959 (GRCm39)	T1696A	probably benign	Het
Ska2	C	T	11: 87,008,680 (GRCm39)		probably benign	Het

Other mutations in Cd44

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00543:Cd44	APN	2	102,686,292 (GRCm39)	missense	possibly damaging	0.73
IGL01087:Cd44	APN	2	102,652,607 (GRCm39)	missense	probably damaging	1.00
IGL01413:Cd44	APN	2	102,644,632 (GRCm39)	missense	probably damaging	0.99
IGL01830:Cd44	APN	2	102,672,603 (GRCm39)	splice site	probably benign
IGL02221:Cd44	APN	2	102,676,858 (GRCm39)	missense	probably benign	0.01
IGL02271:Cd44	APN	2	102,661,732 (GRCm39)	missense	possibly damaging	0.93
IGL02552:Cd44	APN	2	102,679,076 (GRCm39)	missense	probably benign	0.01
IGL02861:Cd44	APN	2	102,662,826 (GRCm39)	critical splice donor site	probably null
IGL03309:Cd44	APN	2	102,644,522 (GRCm39)	missense	probably damaging	1.00
IGL03352:Cd44	APN	2	102,675,759 (GRCm39)	intron	probably benign
Jialin	UTSW	2	102,695,715 (GRCm39)	missense	probably damaging	0.99
Kale	UTSW	2	102,654,648 (GRCm39)	missense	probably damaging	0.99
R0488:Cd44	UTSW	2	102,664,564 (GRCm39)	splice site	probably benign
R1441:Cd44	UTSW	2	102,676,763 (GRCm39)	missense	probably damaging	0.99
R1482:Cd44	UTSW	2	102,661,728 (GRCm39)	missense	probably damaging	1.00
R1497:Cd44	UTSW	2	102,673,300 (GRCm39)	splice site	probably null
R1803:Cd44	UTSW	2	102,664,597 (GRCm39)	missense	probably damaging	1.00
R1952:Cd44	UTSW	2	102,683,432 (GRCm39)	missense	probably damaging	0.98
R2093:Cd44	UTSW	2	102,644,629 (GRCm39)	missense	probably damaging	1.00
R2180:Cd44	UTSW	2	102,658,955 (GRCm39)	missense	possibly damaging	0.66
R2425:Cd44	UTSW	2	102,691,931 (GRCm39)	missense	probably damaging	1.00
R3687:Cd44	UTSW	2	102,731,695 (GRCm39)	splice site	probably null
R3820:Cd44	UTSW	2	102,731,738 (GRCm39)	splice site	probably null
R3821:Cd44	UTSW	2	102,731,738 (GRCm39)	splice site	probably null
R3822:Cd44	UTSW	2	102,731,738 (GRCm39)	splice site	probably null
R4060:Cd44	UTSW	2	102,731,687 (GRCm39)	missense	probably damaging	1.00
R4633:Cd44	UTSW	2	102,683,392 (GRCm39)	missense	possibly damaging	0.86
R4647:Cd44	UTSW	2	102,668,274 (GRCm39)	missense	possibly damaging	0.68
R4780:Cd44	UTSW	2	102,691,910 (GRCm39)	missense	probably damaging	1.00
R5087:Cd44	UTSW	2	102,661,699 (GRCm39)	missense	possibly damaging	0.83
R5118:Cd44	UTSW	2	102,695,715 (GRCm39)	missense	probably damaging	0.99
R5449:Cd44	UTSW	2	102,662,891 (GRCm39)	missense	probably damaging	1.00
R5642:Cd44	UTSW	2	102,731,687 (GRCm39)	missense	probably damaging	1.00
R5928:Cd44	UTSW	2	102,654,648 (GRCm39)	missense	probably damaging	0.99
R5995:Cd44	UTSW	2	102,692,015 (GRCm39)	missense	probably damaging	1.00
R5999:Cd44	UTSW	2	102,675,742 (GRCm39)	missense	probably benign	0.42
R7050:Cd44	UTSW	2	102,644,482 (GRCm39)	missense	probably damaging	0.99
R7350:Cd44	UTSW	2	102,664,607 (GRCm39)	missense	probably benign	0.19
R7797:Cd44	UTSW	2	102,679,079 (GRCm39)	missense	probably benign	0.34
R7866:Cd44	UTSW	2	102,672,604 (GRCm39)	critical splice donor site	probably null
R8138:Cd44	UTSW	2	102,662,842 (GRCm39)	missense	probably benign	0.00
R8185:Cd44	UTSW	2	102,654,665 (GRCm39)	missense	possibly damaging	0.52
R8732:Cd44	UTSW	2	102,664,645 (GRCm39)	missense	possibly damaging	0.67
R8955:Cd44	UTSW	2	102,683,363 (GRCm39)	missense	probably damaging	0.98
R9249:Cd44	UTSW	2	102,661,747 (GRCm39)	missense	possibly damaging	0.51
R9548:Cd44	UTSW	2	102,661,832 (GRCm39)	missense	possibly damaging	0.58

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 2606 of the Cd44 transcript in exon 19 of 19 total exons. Multiple transcripts of the Cd44 gene are displayed on Ensembl. The mutated nucleotide causes a methionine to valine substitution at amino acid 763 in isoform 1 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Cd44 gene encodes multiple isoforms of a single-pass type I membrane protein. Isoform 1 is 780 amino acids long and contains one hyaluronan (HA)-binding Link domain at residues 34-123. Cd44 is the main cell surface receptor for HA. It is involved in matrix adhesion, lymphocyte activation and lymph node homing (Uniprot P15379). Mice homozygous for targeted null mutations exhibit impaired T lymphocyte trafficking resulting in muted inflammatory responses, altered myeloid progenitor distribution, reduced growth of tumors, and impaired uterine involution and maintenance of lactation.

The M763V change occurs in the cytoplasmic domain, and is predicted to be possibly damaging by the PolyPhen program.

Posted On

2010-05-04