Mutagenetix > Incidental Mutation

Incidental Mutation 'C9142:Chrm5'

158

Institutional Source

Beutler Lab

Gene Symbol

Chrm5

Ensembl Gene

ENSMUSG00000074939

Gene Name

cholinergic receptor, muscarinic 5

Synonyms

muscarinic acetylcholine receptor 5, M5R

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.082) question?

Stock #

C9142 (G3) of strain Muskatenwein

Quality Score

Status

Validated

Chromosome

Chromosomal Location

112309516-112311114 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 112310556 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 187 (F187L)

Ref Sequence

ENSEMBL: ENSMUSP00000097185 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000099589]

AlphaFold

Q920H4

Predicted Effect

probably damaging
Transcript: ENSMUST00000099589
AA Change: F187L

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

SMART Domains

Protein: ENSMUSP00000097185
Gene: ENSMUSG00000074939
AA Change: F187L

Domain	Start	End	E-Value	Type
Pfam:7TM_GPCR_Srx	38	242	2.3e-8	PFAM
Pfam:7TM_GPCR_Srsx	41	253	7.5e-8	PFAM
Pfam:7tm_1	47	495	1.5e-79	PFAM
low complexity region	507	518	N/A	INTRINSIC

Meta Mutation Damage Score

0.4360

Coding Region Coverage

1x: 84.8%
3x: 59.3%

Validation Efficiency

82% (72/88)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for a targeted null allele exhibit loss of acetylcholine-induced dilation of cerebral arteries, decreased pilocarpine-induced salivation, increased water-deprivation induced drinking, and attenuated morphine reinforcement and withdrawal. [provided by MGI curators]

Allele List at MGI

All alleles(3) : Targeted, knock-out(3)

Other mutations in this stock

Total: 7 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adnp	A	G	2: 168,026,327 (GRCm39)	S323P	probably damaging	Het
Cc2d2a	A	G	5: 43,892,799 (GRCm39)		probably benign	Homo
Fmnl3	T	C	15: 99,235,508 (GRCm39)		probably null	Het
Klf7	C	T	1: 64,118,316 (GRCm39)	A94T	possibly damaging	Het
Nf1	C	T	11: 79,447,557 (GRCm39)	R2433C	probably damaging	Het
Pdlim3	A	T	8: 46,349,869 (GRCm39)	M60L	probably benign	Het
Vwde	T	C	6: 13,168,053 (GRCm39)		probably benign	Homo

Other mutations in Chrm5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01532:Chrm5	APN	2	112,309,577 (GRCm39)	missense	probably benign
IGL01611:Chrm5	APN	2	112,310,651 (GRCm39)	nonsense	probably null
IGL02152:Chrm5	APN	2	112,310,913 (GRCm39)	missense	probably damaging	1.00
IGL03002:Chrm5	APN	2	112,310,706 (GRCm39)	missense	probably damaging	1.00
R0200:Chrm5	UTSW	2	112,311,065 (GRCm39)	missense	probably benign
R0432:Chrm5	UTSW	2	112,310,000 (GRCm39)	missense	possibly damaging	0.76
R1158:Chrm5	UTSW	2	112,310,214 (GRCm39)	missense	probably benign	0.00
R1611:Chrm5	UTSW	2	112,309,532 (GRCm39)	missense	possibly damaging	0.74
R1621:Chrm5	UTSW	2	112,310,182 (GRCm39)	missense	probably benign	0.00
R1693:Chrm5	UTSW	2	112,309,625 (GRCm39)	missense	probably damaging	1.00
R1988:Chrm5	UTSW	2	112,310,597 (GRCm39)	missense	probably damaging	0.99
R1989:Chrm5	UTSW	2	112,310,597 (GRCm39)	missense	probably damaging	0.99
R2071:Chrm5	UTSW	2	112,309,572 (GRCm39)	missense	probably null	0.93
R2890:Chrm5	UTSW	2	112,310,048 (GRCm39)	missense	probably benign	0.00
R4659:Chrm5	UTSW	2	112,310,102 (GRCm39)	missense	probably benign
R4785:Chrm5	UTSW	2	112,309,930 (GRCm39)	missense	probably benign	0.25
R5196:Chrm5	UTSW	2	112,310,729 (GRCm39)	missense	probably damaging	1.00
R5734:Chrm5	UTSW	2	112,310,445 (GRCm39)	missense	probably benign	0.28
R6343:Chrm5	UTSW	2	112,309,793 (GRCm39)	missense	probably damaging	1.00
R6499:Chrm5	UTSW	2	112,310,825 (GRCm39)	missense	probably benign
R6672:Chrm5	UTSW	2	112,310,141 (GRCm39)	missense	probably benign
R6905:Chrm5	UTSW	2	112,309,901 (GRCm39)	missense	probably benign	0.00
R7192:Chrm5	UTSW	2	112,310,672 (GRCm39)	missense	probably damaging	0.97
R7775:Chrm5	UTSW	2	112,310,301 (GRCm39)	missense	probably benign	0.07
R7778:Chrm5	UTSW	2	112,310,301 (GRCm39)	missense	probably benign	0.07
R8780:Chrm5	UTSW	2	112,310,453 (GRCm39)	missense	possibly damaging	0.64
R9287:Chrm5	UTSW	2	112,309,610 (GRCm39)	missense	probably damaging	1.00
R9436:Chrm5	UTSW	2	112,309,824 (GRCm39)	missense	possibly damaging	0.69
R9502:Chrm5	UTSW	2	112,311,040 (GRCm39)	missense	probably damaging	1.00
X0023:Chrm5	UTSW	2	112,310,826 (GRCm39)	missense	probably benign

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 559 of the Chrm5 transcript. The mutated nucleotide causes a phenylalanine to leucine substitution at amino acid 187 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Chrm5 gene encodes the 532 amino acid seven-transmembrane muscarinic acetylcholine receptor that is a member of the G-protein-coupled receptor 1 family. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins (Uniprot Q920H4). Homozygotes for a targeted null allele exhibit loss of acetylcholine-induced dilation of cerebral arteries, decreased pilocarpine-induced salivation, increased water-deprivation induced drinking, and attenuated morphine reinforcement and withdrawal.

The F187L change occurs in the extracellular region between transmembrane domains 4 and 5, and is predicted to be possibly damaging by the PolyPhen program.

Posted On

2010-04-08