Mutagenetix > Incidental Mutation

Incidental Mutation 'R8189:Nrxn1'

635046

Institutional Source

Beutler Lab

Gene Symbol

Nrxn1

Ensembl Gene

ENSMUSG00000024109

Gene Name

neurexin I

Synonyms

alpha-latrotoxin receptor (calcium-dependent), 1700062G21Rik, neurexin I alpha, neurexin I alpha, 9330127H16Rik, neurexin I beta, neurexin I beta, A230068P09Rik, neurexin I alpha, neurexin I beta

MMRRC Submission

067612-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8189 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

90341059-91400499 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 91011637 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 331 (V331I)

Ref Sequence

ENSEMBL: ENSMUSP00000125407 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000054059] [ENSMUST00000072671] [ENSMUST00000160800] [ENSMUST00000160844] [ENSMUST00000161402] [ENSMUST00000174331]

AlphaFold

Q9CS84

Predicted Effect

probably damaging
Transcript: ENSMUST00000054059
AA Change: V331I

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000057294
Gene: ENSMUSG00000024109
AA Change: V331I

Domain	Start	End	E-Value	Type
low complexity region	9	23	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	304	438	2.3e-36	SMART
LamG	492	644	2.74e-43	SMART
EGF	671	705	1.58e-3	SMART
LamG	730	869	7.27e-25	SMART
LamG	917	1053	8.46e-35	SMART
EGF	1078	1112	1.87e1	SMART
LamG	1140	1297	7.74e-20	SMART
low complexity region	1324	1355	N/A	INTRINSIC
low complexity region	1426	1441	N/A	INTRINSIC
4.1m	1444	1462	1.19e-6	SMART
low complexity region	1481	1493	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000072671
AA Change: V331I

PolyPhen 2 Score 0.296 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000072458
Gene: ENSMUSG00000024109
AA Change: V331I

Domain	Start	End	E-Value	Type
low complexity region	9	23	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	304	438	2.3e-36	SMART
LamG	492	644	2.74e-43	SMART
EGF	671	705	1.58e-3	SMART
LamG	730	869	7.27e-25	SMART
LamG	917	1053	8.46e-35	SMART
EGF	1078	1112	1.87e1	SMART
LamG	1140	1297	7.74e-20	SMART
low complexity region	1324	1355	N/A	INTRINSIC
low complexity region	1423	1438	N/A	INTRINSIC
4.1m	1441	1459	1.19e-6	SMART
low complexity region	1478	1490	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000160800
AA Change: V327I

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000124561
Gene: ENSMUSG00000024109
AA Change: V327I

Domain	Start	End	E-Value	Type
low complexity region	9	23	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	300	434	2.3e-36	SMART
LamG	488	640	2.74e-43	SMART
EGF	667	701	1.58e-3	SMART
LamG	726	865	7.27e-25	SMART
LamG	913	1049	8.46e-35	SMART
EGF	1074	1108	1.87e1	SMART
LamG	1136	1293	7.74e-20	SMART
low complexity region	1320	1351	N/A	INTRINSIC
low complexity region	1422	1437	N/A	INTRINSIC
4.1m	1440	1458	1.19e-6	SMART
low complexity region	1477	1489	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000160844
AA Change: V331I

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000125407
Gene: ENSMUSG00000024109
AA Change: V331I

Domain	Start	End	E-Value	Type
low complexity region	9	23	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	304	446	1.24e-32	SMART
LamG	500	652	2.74e-43	SMART
EGF	679	713	1.58e-3	SMART
LamG	738	877	7.27e-25	SMART
LamG	925	1061	8.46e-35	SMART
EGF	1086	1120	1.87e1	SMART
LamG	1148	1305	7.74e-20	SMART
low complexity region	1332	1363	N/A	INTRINSIC
low complexity region	1434	1449	N/A	INTRINSIC
4.1m	1452	1470	1.19e-6	SMART
low complexity region	1489	1501	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000161402
AA Change: V331I

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000124116
Gene: ENSMUSG00000024109
AA Change: V331I

Domain	Start	End	E-Value	Type
low complexity region	9	23	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	304	453	3.46e-31	SMART
LamG	507	659	2.74e-43	SMART
EGF	686	720	1.58e-3	SMART
LamG	745	884	7.27e-25	SMART
LamG	932	1068	8.46e-35	SMART
EGF	1093	1127	1.87e1	SMART
LamG	1155	1312	7.74e-20	SMART
low complexity region	1339	1370	N/A	INTRINSIC
low complexity region	1441	1456	N/A	INTRINSIC
4.1m	1459	1477	1.19e-6	SMART
low complexity region	1496	1508	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174331
AA Change: V331I

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000133491
Gene: ENSMUSG00000024109
AA Change: V331I

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
LamG	50	192	2.29e-31	SMART
EGF	216	256	4.26e0	SMART
LamG	304	446	1.24e-32	SMART
LamG	500	652	2.74e-43	SMART
EGF	679	713	1.58e-3	SMART
LamG	738	877	7.27e-25	SMART
LamG	925	1061	8.46e-35	SMART
EGF	1086	1120	1.87e1	SMART
LamG	1148	1275	3.29e-23	SMART
low complexity region	1302	1333	N/A	INTRINSIC
low complexity region	1404	1419	N/A	INTRINSIC
4.1m	1422	1440	1.19e-6	SMART
low complexity region	1459	1471	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000197224

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

100% (42/42)

MGI Phenotype

FUNCTION: This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are synaptic transmembrane receptors that bind endogenous ligands that include neuroligins, dystroglycan, and neurexophilins. Neurexin complexes are required for efficient neurotransmission and are involved in synaptogenesis. In vertebrates, alternate promoter usage results in multiple isoform classes, of which the alpha and beta classes are the best characterized. In humans, allelic variants in this gene are associated with Pitt-Hopkins-like syndrome-2, while deletions have been associated with autism and schizophrenia. Mouse knockouts display decreased spontaneous and evoked vesicle release resulting in impaired synaptic transmission. In addition, knockout mice show altered social approach, reduced social investigation, reduced locomotor activity, and in males, increased aggression. Alternative splicing and promoter usage result in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit reduced Ca(2+)-dependent binding of alpha-latrotoxin to brain membranes. Isolated synaptosomes display only a small reduction in alpha-latrotoxin -triggered glutamate release in the absence of Ca(2+) but show a major decrease in the presence of Ca(2+). [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 43 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca12	A	G	1: 71,324,885 (GRCm39)	I1531T	probably damaging	Het
Ankrd13d	G	A	19: 4,320,880 (GRCm39)	P516S	probably benign	Het
Bag6	A	G	17: 35,364,214 (GRCm39)		probably null	Het
Cchcr1	A	G	17: 35,837,563 (GRCm39)	I422V	probably benign	Het
Ceacam1	A	G	7: 25,173,343 (GRCm39)	S282P	probably damaging	Het
Chka	G	T	19: 3,925,759 (GRCm39)	E159*	probably null	Het
Ckmt2	T	C	13: 92,003,894 (GRCm39)	Y368C	probably damaging	Het
Cngb1	TTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGGCTCTGG	TTCTGGCTCTGGCTCTGGCTCTGG	8: 96,030,248 (GRCm39)		probably benign	Het
Ctsq	A	G	13: 61,184,969 (GRCm39)	L239P	probably damaging	Het
D630045J12Rik	A	G	6: 38,135,106 (GRCm39)	L1358P	probably damaging	Het
Dglucy	G	A	12: 100,804,889 (GRCm39)	E127K	probably benign	Het
Dnajb8	C	T	6: 88,199,940 (GRCm39)	R159C	possibly damaging	Het
Fgd6	T	C	10: 93,910,077 (GRCm39)	L794P	probably benign	Het
Fgfr2	G	A	7: 129,774,629 (GRCm39)	T654I	probably damaging	Het
Gmeb2	G	A	2: 180,919,760 (GRCm39)	T38M	probably damaging	Het
Gria1	T	C	11: 57,108,625 (GRCm39)	F243L	probably benign	Het
Gria2	A	T	3: 80,629,489 (GRCm39)	D244E	probably damaging	Het
Ints2	T	A	11: 86,106,396 (GRCm39)	I1005F	probably damaging	Het
Ipo11	T	A	13: 107,061,604 (GRCm39)	S19C	probably damaging	Het
Kmt2b	A	G	7: 30,268,756 (GRCm39)	F2658L	probably damaging	Het
Lrrc38	G	A	4: 143,077,303 (GRCm39)	G189R	probably damaging	Het
Mcf2l	A	G	8: 13,013,164 (GRCm39)	D27G	probably damaging	Het
Mrgprb2	G	T	7: 48,202,502 (GRCm39)	Y74*	probably null	Het
Mtrex	T	A	13: 113,028,515 (GRCm39)	R628S	possibly damaging	Het
Nrcam	C	A	12: 44,617,291 (GRCm39)	P740T	possibly damaging	Het
Or2a57	T	C	6: 43,213,013 (GRCm39)	V157A	probably benign	Het
Or4f17-ps1	T	C	2: 111,358,118 (GRCm39)	V153A		Het
Or5k1b	T	A	16: 58,581,288 (GRCm39)	N84Y	probably damaging	Het
Or5p52	A	G	7: 107,501,939 (GRCm39)	N5S	probably damaging	Het
Or6c66b	T	A	10: 129,377,122 (GRCm39)	C239S	probably damaging	Het
Pla2g4a	A	G	1: 149,733,337 (GRCm39)	F479L	probably benign	Het
Pramel20	T	G	4: 143,298,530 (GRCm39)	Y158D	probably benign	Het
Scaper	A	T	9: 55,819,404 (GRCm39)	F104I	probably damaging	Het
Serpinb3c	A	T	1: 107,204,039 (GRCm39)	C58S	probably benign	Het
Setdb1	A	G	3: 95,254,022 (GRCm39)	V260A	probably damaging	Het
Shank3	A	G	15: 89,433,439 (GRCm39)	T1395A	probably benign	Het
Slc35b4	A	G	6: 34,144,570 (GRCm39)	I95T	probably damaging	Het
Trpm5	A	G	7: 142,635,575 (GRCm39)	V599A	probably benign	Het
Ttk	A	G	9: 83,729,272 (GRCm39)	S352G	probably benign	Het
Ugt2b35	T	A	5: 87,149,302 (GRCm39)	S184R	probably damaging	Het
Usp17le	C	T	7: 104,418,555 (GRCm39)	D196N	probably damaging	Het
Vmn2r15	A	G	5: 109,434,713 (GRCm39)	F664L	probably benign	Het
Vmn2r94	A	T	17: 18,478,618 (GRCm39)	L43Q	probably damaging	Het

Other mutations in Nrxn1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01310:Nrxn1	APN	17	90,366,902 (GRCm39)	critical splice donor site	probably null
IGL01644:Nrxn1	APN	17	90,928,301 (GRCm39)	missense	possibly damaging	0.94
IGL01820:Nrxn1	APN	17	90,950,531 (GRCm39)	missense	probably damaging	0.98
IGL01902:Nrxn1	APN	17	91,395,919 (GRCm39)	splice site	probably null
IGL02079:Nrxn1	APN	17	90,950,511 (GRCm39)	missense	probably damaging	0.99
IGL02089:Nrxn1	APN	17	91,395,829 (GRCm39)	missense	probably benign	0.01
IGL02133:Nrxn1	APN	17	90,950,671 (GRCm39)	missense	probably damaging	1.00
IGL02179:Nrxn1	APN	17	90,937,511 (GRCm39)	missense	probably damaging	0.99
IGL02199:Nrxn1	APN	17	90,344,686 (GRCm39)	missense	probably damaging	1.00
IGL02262:Nrxn1	APN	17	91,011,636 (GRCm39)	missense	probably damaging	1.00
IGL02941:Nrxn1	APN	17	90,515,811 (GRCm39)	missense	probably damaging	1.00
PIT4449001:Nrxn1	UTSW	17	90,905,007 (GRCm39)	missense	probably damaging	1.00
PIT4791001:Nrxn1	UTSW	17	90,762,931 (GRCm39)	intron	probably benign
R0123:Nrxn1	UTSW	17	91,302,915 (GRCm39)	splice site	probably null
R0212:Nrxn1	UTSW	17	90,670,186 (GRCm39)	unclassified	probably benign
R0277:Nrxn1	UTSW	17	91,008,170 (GRCm39)	critical splice donor site	probably null
R0323:Nrxn1	UTSW	17	91,008,170 (GRCm39)	critical splice donor site	probably null
R0384:Nrxn1	UTSW	17	90,515,775 (GRCm39)	missense	probably damaging	1.00
R0395:Nrxn1	UTSW	17	91,395,742 (GRCm39)	missense	possibly damaging	0.90
R0606:Nrxn1	UTSW	17	90,872,801 (GRCm39)	missense	probably damaging	1.00
R0616:Nrxn1	UTSW	17	90,670,285 (GRCm39)	missense	probably damaging	1.00
R0624:Nrxn1	UTSW	17	91,396,117 (GRCm39)	missense	unknown
R0633:Nrxn1	UTSW	17	91,011,609 (GRCm39)	missense	probably damaging	1.00
R0927:Nrxn1	UTSW	17	90,344,758 (GRCm39)	missense	probably damaging	1.00
R1035:Nrxn1	UTSW	17	90,471,302 (GRCm39)	missense	probably damaging	0.96
R1221:Nrxn1	UTSW	17	90,950,722 (GRCm39)	missense	probably damaging	0.97
R1403:Nrxn1	UTSW	17	90,950,481 (GRCm39)	missense	probably benign	0.11
R1403:Nrxn1	UTSW	17	90,950,481 (GRCm39)	missense	probably benign	0.11
R1691:Nrxn1	UTSW	17	90,469,717 (GRCm39)	missense	probably damaging	0.98
R1703:Nrxn1	UTSW	17	90,515,845 (GRCm39)	missense	probably damaging	1.00
R1709:Nrxn1	UTSW	17	90,344,615 (GRCm39)	missense	probably damaging	1.00
R1721:Nrxn1	UTSW	17	90,469,832 (GRCm39)	missense	probably damaging	1.00
R1792:Nrxn1	UTSW	17	90,896,252 (GRCm39)	missense	probably damaging	0.96
R1980:Nrxn1	UTSW	17	91,395,746 (GRCm39)	missense	probably benign	0.01
R2116:Nrxn1	UTSW	17	91,011,705 (GRCm39)	missense	probably damaging	1.00
R2117:Nrxn1	UTSW	17	91,011,705 (GRCm39)	missense	probably damaging	1.00
R2162:Nrxn1	UTSW	17	90,469,859 (GRCm39)	missense	probably damaging	1.00
R3119:Nrxn1	UTSW	17	90,904,947 (GRCm39)	nonsense	probably null
R3409:Nrxn1	UTSW	17	90,515,795 (GRCm39)	missense	probably damaging	1.00
R3683:Nrxn1	UTSW	17	90,930,880 (GRCm39)	missense	probably damaging	1.00
R3885:Nrxn1	UTSW	17	90,930,899 (GRCm39)	missense	probably damaging	1.00
R3939:Nrxn1	UTSW	17	90,515,849 (GRCm39)	missense	probably damaging	1.00
R4475:Nrxn1	UTSW	17	91,009,410 (GRCm39)	missense	probably damaging	0.98
R4640:Nrxn1	UTSW	17	90,868,196 (GRCm39)	missense	probably damaging	1.00
R4678:Nrxn1	UTSW	17	90,930,850 (GRCm39)	missense	probably damaging	1.00
R4690:Nrxn1	UTSW	17	90,344,509 (GRCm39)	missense	probably damaging	1.00
R4790:Nrxn1	UTSW	17	90,762,477 (GRCm39)	missense	possibly damaging	0.86
R4877:Nrxn1	UTSW	17	91,395,605 (GRCm39)	missense	probably benign	0.33
R4989:Nrxn1	UTSW	17	90,928,274 (GRCm39)	intron	probably benign
R5204:Nrxn1	UTSW	17	90,469,792 (GRCm39)	missense	probably damaging	1.00
R5205:Nrxn1	UTSW	17	90,471,302 (GRCm39)	missense	probably damaging	0.96
R5239:Nrxn1	UTSW	17	91,011,537 (GRCm39)	missense	probably damaging	1.00
R5250:Nrxn1	UTSW	17	90,842,869 (GRCm39)	intron	probably benign
R5473:Nrxn1	UTSW	17	90,897,520 (GRCm39)	missense	probably damaging	1.00
R5629:Nrxn1	UTSW	17	90,897,460 (GRCm39)	missense	possibly damaging	0.75
R5743:Nrxn1	UTSW	17	90,950,652 (GRCm39)	missense	probably damaging	1.00
R5910:Nrxn1	UTSW	17	91,011,746 (GRCm39)	nonsense	probably null
R5961:Nrxn1	UTSW	17	90,762,371 (GRCm39)	missense	probably damaging	0.99
R5979:Nrxn1	UTSW	17	91,395,631 (GRCm39)	missense	possibly damaging	0.54
R5992:Nrxn1	UTSW	17	90,930,935 (GRCm39)	missense	probably benign	0.01
R6024:Nrxn1	UTSW	17	90,897,526 (GRCm39)	missense	possibly damaging	0.88
R6031:Nrxn1	UTSW	17	90,896,218 (GRCm39)	missense	probably damaging	1.00
R6031:Nrxn1	UTSW	17	90,896,218 (GRCm39)	missense	probably damaging	1.00
R6185:Nrxn1	UTSW	17	90,344,564 (GRCm39)	missense	probably damaging	1.00
R6220:Nrxn1	UTSW	17	91,395,904 (GRCm39)	missense	probably benign	0.14
R6306:Nrxn1	UTSW	17	90,872,874 (GRCm39)	missense	possibly damaging	0.55
R6621:Nrxn1	UTSW	17	90,469,610 (GRCm39)	missense	probably damaging	1.00
R6669:Nrxn1	UTSW	17	90,366,991 (GRCm39)	missense	probably damaging	0.98
R6770:Nrxn1	UTSW	17	90,344,607 (GRCm39)	missense	probably damaging	1.00
R6798:Nrxn1	UTSW	17	90,937,378 (GRCm39)	missense	probably damaging	1.00
R6923:Nrxn1	UTSW	17	91,395,661 (GRCm39)	missense	probably benign	0.06
R7140:Nrxn1	UTSW	17	91,396,192 (GRCm39)	start gained	probably benign
R7374:Nrxn1	UTSW	17	90,896,097 (GRCm39)	critical splice donor site	probably null
R7564:Nrxn1	UTSW	17	90,670,334 (GRCm39)	missense	possibly damaging	0.64
R7570:Nrxn1	UTSW	17	90,469,807 (GRCm39)	missense	probably benign	0.35
R7800:Nrxn1	UTSW	17	91,396,635 (GRCm39)	unclassified	probably benign
R7828:Nrxn1	UTSW	17	90,366,979 (GRCm39)	missense	probably damaging	0.99
R7974:Nrxn1	UTSW	17	91,008,207 (GRCm39)	missense	probably damaging	1.00
R8001:Nrxn1	UTSW	17	91,395,964 (GRCm39)	missense	possibly damaging	0.49
R8258:Nrxn1	UTSW	17	90,471,249 (GRCm39)	missense	probably damaging	0.99
R8259:Nrxn1	UTSW	17	90,471,249 (GRCm39)	missense	probably damaging	0.99
R8298:Nrxn1	UTSW	17	91,011,597 (GRCm39)	missense	probably damaging	1.00
R8801:Nrxn1	UTSW	17	91,009,393 (GRCm39)	critical splice donor site	probably benign
R8814:Nrxn1	UTSW	17	90,937,529 (GRCm39)	missense	probably damaging	1.00
R8873:Nrxn1	UTSW	17	90,872,821 (GRCm39)	nonsense	probably null
R8954:Nrxn1	UTSW	17	90,897,615 (GRCm39)	missense	probably damaging	1.00
R9086:Nrxn1	UTSW	17	90,469,792 (GRCm39)	missense	probably damaging	1.00
R9110:Nrxn1	UTSW	17	90,869,233 (GRCm39)	nonsense	probably null
R9498:Nrxn1	UTSW	17	90,897,397 (GRCm39)	missense	probably damaging	1.00
R9499:Nrxn1	UTSW	17	90,937,450 (GRCm39)	missense	probably damaging	1.00
R9552:Nrxn1	UTSW	17	90,937,450 (GRCm39)	missense	probably damaging	1.00
R9780:Nrxn1	UTSW	17	90,931,042 (GRCm39)	missense	possibly damaging	0.54
RF005:Nrxn1	UTSW	17	90,670,304 (GRCm39)	missense	probably damaging	1.00
RF024:Nrxn1	UTSW	17	90,670,304 (GRCm39)	missense	probably damaging	1.00
X0021:Nrxn1	UTSW	17	90,897,640 (GRCm39)	missense	probably damaging	1.00
X0063:Nrxn1	UTSW	17	90,670,259 (GRCm39)	missense	possibly damaging	0.54
Z1088:Nrxn1	UTSW	17	90,366,933 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACAGCTGTAGGTACCACAGG -3'
(R):5'- GCTGACTTATGCATGCATATATCTG -3'

Sequencing Primer
(F):5'- CTGTAGGTACCACAGGCACAG -3'
(R):5'- CCCATTCAAAGCAGCAGT -3'

Posted On

2020-07-13