Mutagenetix > Incidental Mutation

Incidental Mutation 'G5030:Nmbr'

492

Institutional Source

Beutler Lab

Gene Symbol

Nmbr

Ensembl Gene

ENSMUSG00000019865

Gene Name

neuromedin B receptor

Synonyms

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.067) question?

Stock #

G5030 (G3) of strain 560

Quality Score

Status

Validated

Chromosome

Chromosomal Location

14634894-14647202 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 14642747 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Phenylalanine at position 102 (Y102F)

Ref Sequence

ENSEMBL: ENSMUSP00000140754 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020015] [ENSMUST00000186382] [ENSMUST00000190114] [ENSMUST00000190751] [ENSMUST00000191238]

AlphaFold

O54799

Predicted Effect

probably benign
Transcript: ENSMUST00000020015
AA Change: Y250F

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000020015
Gene: ENSMUSG00000019865
AA Change: Y250F

Domain	Start	End	E-Value	Type
Pfam:7TM_GPCR_Srsx	54	339	5.9e-9	PFAM
Pfam:7tm_1	60	325	2.9e-55	PFAM
Pfam:7TM_GPCR_Srv	92	341	2.6e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000186382
AA Change: Y250F

PolyPhen 2 Score 0.332 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000139612
Gene: ENSMUSG00000019865
AA Change: Y250F

Domain	Start	End	E-Value	Type
Pfam:7tm_1	60	257	1.4e-40	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000190114
AA Change: Y102F

PolyPhen 2 Score 0.950 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000140754
Gene: ENSMUSG00000019865
AA Change: Y102F

Domain	Start	End	E-Value	Type
Pfam:7tm_1	8	119	6.8e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000190751

SMART Domains

Protein: ENSMUSP00000140223
Gene: ENSMUSG00000019865

Domain	Start	End	E-Value	Type
Pfam:7tm_1	60	144	2.7e-21	PFAM
transmembrane domain	152	174	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000191238

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220206

Meta Mutation Damage Score

0.0775

Coding Region Coverage

1x: 81.1%
3x: 60.2%

Het Detection Efficiency

35.6%

Validation Efficiency

87% (206/237)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a 7-transmembrane G protein-coupled receptor that binds neuromedin B, which is a growth factor and mitogen for gastrointestinal epithelial tissue and for normal and neoplastic lung. This receptor may play a role in smooth muscle contraction, neuronal responses, and the regulation of cell growth. Antagonists of this receptor have a potential therapeutic use in inhibiting tumor cell growth. Polymorphisms in this gene may be associated with a susceptibility for schizophrenia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
PHENOTYPE: Mice homozygous for a knock-out allele show a 50% reduction in the thermoregulatory response to neuromedin B as well as impaired maternal behavior in response to restraint-induced stress. [provided by MGI curators]

Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

Other mutations in this stock

Total: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8a	T	A	11: 109,961,165 (GRCm39)	I585F	probably damaging	Het
Adam18	C	G	8: 25,141,872 (GRCm39)	L232F	probably benign	Homo
Atp13a4	A	G	16: 29,274,306 (GRCm39)	I385T	probably damaging	Homo
Ccdc17	T	A	4: 116,455,699 (GRCm39)	S277T	probably benign	Het
Ccng1	A	G	11: 40,644,629 (GRCm39)		probably benign	Het
Ces1f	T	C	8: 94,000,847 (GRCm39)	D99G	probably benign	Het
Clec16a	G	A	16: 10,389,425 (GRCm39)	R187Q	probably damaging	Homo
Cryl1	C	T	14: 57,579,595 (GRCm39)		probably benign	Het
Cryzl2	C	T	1: 157,292,580 (GRCm39)	Q48*	probably null	Het
Dtx4	A	G	19: 12,446,943 (GRCm39)	L583P	probably benign	Het
Ephx4	A	T	5: 107,577,693 (GRCm39)	D339V	probably damaging	Het
Eri2	A	T	7: 119,385,601 (GRCm39)	V300E	possibly damaging	Het
F3	T	A	3: 121,518,648 (GRCm39)	N37K	probably damaging	Homo
Fpr1	A	T	17: 18,097,068 (GRCm39)	L307H	probably damaging	Het
Fv1	T	A	4: 147,953,618 (GRCm39)	N61K	possibly damaging	Het
Gm5548	T	C	3: 112,961,512 (GRCm39)		noncoding transcript	Homo
Il1r1	A	G	1: 40,352,323 (GRCm39)	K498E	possibly damaging	Homo
Myh11	T	C	16: 14,068,443 (GRCm39)	I192M	probably damaging	Homo
Nckap5	T	C	1: 125,953,591 (GRCm39)	K923R	probably damaging	Het
Or6c75	A	G	10: 129,337,406 (GRCm39)	T218A	probably benign	Homo
Pde1a	C	T	2: 79,718,180 (GRCm39)		probably benign	Het
Pex6	T	C	17: 47,026,382 (GRCm39)		probably benign	Het
Rtn2	T	C	7: 19,027,099 (GRCm39)	S305P	probably damaging	Homo
Saal1	G	A	7: 46,342,207 (GRCm39)	T412I	probably damaging	Homo
Slc46a2	A	T	4: 59,913,867 (GRCm39)	I352N	probably damaging	Het
Trim37	A	T	11: 87,033,967 (GRCm39)	H99L	probably damaging	Het
Tubgcp4	C	T	2: 121,014,815 (GRCm39)	R242C	probably damaging	Het
Twf2	C	A	9: 106,084,141 (GRCm39)	L27I	possibly damaging	Het
Usp40	A	T	1: 87,921,941 (GRCm39)	H307Q	probably damaging	Het
Zfhx3	T	G	8: 109,678,091 (GRCm39)	V3047G	possibly damaging	Het

Other mutations in Nmbr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01617:Nmbr	APN	10	14,646,173 (GRCm39)	missense	probably benign	0.19
IGL01874:Nmbr	APN	10	14,642,696 (GRCm39)	missense	probably benign	0.09
IGL02616:Nmbr	APN	10	14,636,431 (GRCm39)	intron	probably benign
IGL02619:Nmbr	APN	10	14,636,331 (GRCm39)	missense	probably damaging	0.99
IGL03015:Nmbr	APN	10	14,636,412 (GRCm39)	missense	probably damaging	1.00
R0057:Nmbr	UTSW	10	14,636,268 (GRCm39)	missense	probably damaging	0.97
R0238:Nmbr	UTSW	10	14,646,139 (GRCm39)	nonsense	probably null
R0238:Nmbr	UTSW	10	14,646,139 (GRCm39)	nonsense	probably null
R0324:Nmbr	UTSW	10	14,636,192 (GRCm39)	missense	possibly damaging	0.50
R1252:Nmbr	UTSW	10	14,636,187 (GRCm39)	missense	probably benign	0.09
R1812:Nmbr	UTSW	10	14,636,283 (GRCm39)	splice site	probably null
R1831:Nmbr	UTSW	10	14,642,609 (GRCm39)	missense	probably benign	0.36
R2140:Nmbr	UTSW	10	14,646,186 (GRCm39)	nonsense	probably null
R2141:Nmbr	UTSW	10	14,646,186 (GRCm39)	nonsense	probably null
R4604:Nmbr	UTSW	10	14,645,908 (GRCm39)	missense	probably damaging	1.00
R4936:Nmbr	UTSW	10	14,642,730 (GRCm39)	missense	probably damaging	1.00
R5965:Nmbr	UTSW	10	14,642,554 (GRCm39)	missense	probably benign	0.01
R6636:Nmbr	UTSW	10	14,645,978 (GRCm39)	missense	probably benign	0.23
R6895:Nmbr	UTSW	10	14,645,704 (GRCm39)	makesense	probably null
R7644:Nmbr	UTSW	10	14,636,433 (GRCm39)	missense	probably damaging	1.00
R8942:Nmbr	UTSW	10	14,646,197 (GRCm39)	missense	probably benign	0.03
Z1177:Nmbr	UTSW	10	14,646,071 (GRCm39)	missense	probably benign	0.01

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at position 749 of the Nmbr transcript in exon 2 of 3 total exons. The mutated nucleotide causes a tyrosine to phenylalanine substitution at amino acid 250 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Nmbr gene encodes the 390 amino acid receptor for neuromedin-B, a potent mitogen and growth factor for normal and neoplastic lung and for gastrointestinal epithelial tissue. NMBR belongs to the G protein coupled receptor (GPCR) family and has seven transmembrane domains (Uniprot O54799).

The Y250F change is located in the cytoplasmic loop between transmembrane domains 5 and 6, and is predicted to be benign by the PolyPhen program (see report).

Posted On

2010-10-26