Mutagenetix > Incidental Mutation

Incidental Mutation 'R0837:Sema4a'

77979

Institutional Source

Beutler Lab

Gene Symbol

Sema4a

Ensembl Gene

ENSMUSG00000028064

Gene Name

sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4A

Synonyms

SemB, SemB, Semab

MMRRC Submission

039016-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.902) question?

Stock #

R0837 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

88343266-88368489 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 88360405 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 58 (Q58L)

Ref Sequence

ENSEMBL: ENSMUSP00000114330 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029700] [ENSMUST00000107531] [ENSMUST00000123753] [ENSMUST00000125526] [ENSMUST00000127436] [ENSMUST00000169222] [ENSMUST00000141471] [ENSMUST00000184876] [ENSMUST00000165898] [ENSMUST00000184487] [ENSMUST00000147200] [ENSMUST00000166237] [ENSMUST00000185137]

AlphaFold

Q62178

Predicted Effect

probably benign
Transcript: ENSMUST00000029700
AA Change: Q58L

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000029700
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Sema	64	478	1.96e-166	SMART
PSI	496	547	9.33e-13	SMART
transmembrane domain	680	702	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000107531

SMART Domains

Protein: ENSMUSP00000103155
Gene: ENSMUSG00000028064

Domain	Start	End	E-Value	Type
Sema	2	346	2.06e-101	SMART
PSI	364	415	9.33e-13	SMART
transmembrane domain	548	570	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000123753

Predicted Effect

probably benign
Transcript: ENSMUST00000125526
AA Change: Q58L

PolyPhen 2 Score 0.041 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000119028
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Sema	64	113	8.2e-9	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000127436
AA Change: Q58L

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

SMART Domains

Protein: ENSMUSP00000118706
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Sema	64	234	5.5e-53	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135539

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135732

Predicted Effect

probably benign
Transcript: ENSMUST00000169222
AA Change: Q58L

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000128887
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Sema	64	478	1.96e-166	SMART
PSI	496	547	9.33e-13	SMART
transmembrane domain	680	702	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000141471
AA Change: Q58L

PolyPhen 2 Score 0.462 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000114330
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000184876
AA Change: Q58L

PolyPhen 2 Score 0.016 (Sensitivity: 0.95; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000139159
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Sema	64	179	7.7e-31	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000165898
AA Change: Q58L

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000128510
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Sema	64	478	1.96e-166	SMART
PSI	496	547	9.33e-13	SMART
transmembrane domain	680	702	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000184487
AA Change: Q58L

PolyPhen 2 Score 0.027 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000139126
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Sema	64	168	1.5e-30	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000147200
AA Change: Q58L

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000123061
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Sema	64	203	3.5e-45	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000166237
AA Change: Q58L

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000125909
Gene: ENSMUSG00000028064
AA Change: Q58L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Sema	64	478	1.96e-166	SMART
PSI	496	547	9.33e-13	SMART
transmembrane domain	680	702	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146921

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149145

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184972

Predicted Effect

probably benign
Transcript: ENSMUST00000185137

Meta Mutation Damage Score

0.0625

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.4%
20x: 94.8%

Validation Efficiency

96% (44/46)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]
PHENOTYPE: Homozygotes for a knock-out allele show no obvious brain defects but exhibit impaired T cell priming and defective Th1 responses. Homozygotes for a gene trap allele show severe retinal degeneration with reduced retinal vessels, depigmentation and dysfunction of both rod and cone photoreceptors. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 44 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930563I02Rik	T	C	14: 60,333,375 (GRCm39)		probably benign	Het
4930579C12Rik	A	G	9: 89,050,260 (GRCm39)		noncoding transcript	Het
Adam34	T	A	8: 44,104,537 (GRCm39)	K369N	probably benign	Het
Ap1g1	T	C	8: 110,577,697 (GRCm39)	W481R	probably damaging	Het
Bicdl1	G	A	5: 115,869,351 (GRCm39)	P26S	probably benign	Het
Cacna1c	A	T	6: 118,607,231 (GRCm39)	C1224*	probably null	Het
Cpsf2	C	T	12: 101,963,501 (GRCm39)		probably benign	Het
Cyp11b2	G	A	15: 74,725,490 (GRCm39)	R210W	probably damaging	Het
Dock7	C	T	4: 98,877,495 (GRCm39)	V1048I	probably benign	Het
Dync2h1	C	A	9: 7,077,979 (GRCm39)	A2908S	probably benign	Het
Elane	A	G	10: 79,722,942 (GRCm39)	D116G	probably damaging	Het
Epb41l2	C	T	10: 25,383,714 (GRCm39)	R153C	probably damaging	Het
Gucy2c	G	A	6: 136,699,418 (GRCm39)	P617L	probably damaging	Het
H2ac21	G	A	3: 96,127,439 (GRCm39)	A70T	probably damaging	Het
Kcnq4	T	A	4: 120,604,058 (GRCm39)	I106L	probably benign	Het
Man2b1	A	G	8: 85,823,458 (GRCm39)	N931D	possibly damaging	Het
Mthfs	A	G	9: 89,097,443 (GRCm39)	E100G	probably damaging	Het
Mto1	A	T	9: 78,381,072 (GRCm39)	I639F	probably damaging	Het
Myo15a	A	G	11: 60,378,077 (GRCm39)	E177G	probably damaging	Het
Naip5	T	A	13: 100,367,251 (GRCm39)	M282L	probably benign	Het
Or10aa1	A	G	1: 173,870,053 (GRCm39)	D179G	probably damaging	Het
Pik3c2g	G	A	6: 139,903,425 (GRCm39)		probably benign	Het
Prl7d1	T	A	13: 27,898,321 (GRCm39)	M64L	probably benign	Het
Prnp	A	T	2: 131,778,444 (GRCm39)	N32I	probably damaging	Het
Ptpn11	C	T	5: 121,287,174 (GRCm39)	V406I	probably benign	Het
Rab40c	G	A	17: 26,103,667 (GRCm39)	T151I	probably damaging	Het
Rb1cc1	T	A	1: 6,304,495 (GRCm39)		probably null	Het
Rnf145	T	C	11: 44,415,815 (GRCm39)	V10A	probably benign	Het
Rtn4rl2	T	C	2: 84,711,036 (GRCm39)	N70S	probably damaging	Het
Scaper	A	T	9: 55,766,326 (GRCm39)	C483*	probably null	Het
Slf1	T	C	13: 77,249,067 (GRCm39)		probably null	Het
Sycp1	G	T	3: 102,822,561 (GRCm39)	N364K	probably benign	Het
Tenm4	T	C	7: 96,545,482 (GRCm39)		probably benign	Het
Tnfaip2	A	G	12: 111,417,141 (GRCm39)	T537A	probably damaging	Het
Trappc12	A	G	12: 28,753,596 (GRCm39)	I573T	possibly damaging	Het
Ugt2b38	G	A	5: 87,559,632 (GRCm39)	T420I	probably damaging	Het
Ulk1	A	T	5: 110,937,411 (GRCm39)		probably benign	Het
Unc80	G	A	1: 66,688,103 (GRCm39)	C2367Y	possibly damaging	Het
Usp7	C	A	16: 8,521,366 (GRCm39)	G135C	probably damaging	Het
Vmn2r103	A	G	17: 20,014,189 (GRCm39)	Y327C	probably damaging	Het
Vmn2r28	T	A	7: 5,491,026 (GRCm39)	H407L	probably damaging	Het
Zfp804a	A	C	2: 82,089,506 (GRCm39)	T1112P	probably damaging	Het
Zfr2	A	G	10: 81,081,242 (GRCm39)	K431E	probably damaging	Het
Zfy1	A	T	Y: 725,850 (GRCm39)	Y638*	probably null	Het

Other mutations in Sema4a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00913:Sema4a	APN	3	88,357,117 (GRCm39)	missense	probably damaging	1.00
IGL01722:Sema4a	APN	3	88,345,491 (GRCm39)	missense	probably benign	0.14
IGL01769:Sema4a	APN	3	88,357,063 (GRCm39)	missense	possibly damaging	0.86
IGL02076:Sema4a	APN	3	88,357,829 (GRCm39)	missense	probably damaging	0.99
IGL02202:Sema4a	APN	3	88,357,050 (GRCm39)	missense	probably damaging	1.00
R0145:Sema4a	UTSW	3	88,358,729 (GRCm39)	missense	probably damaging	1.00
R0386:Sema4a	UTSW	3	88,344,107 (GRCm39)	missense	possibly damaging	0.75
R0863:Sema4a	UTSW	3	88,355,456 (GRCm39)	unclassified	probably benign
R1567:Sema4a	UTSW	3	88,359,353 (GRCm39)	missense	probably damaging	1.00
R1675:Sema4a	UTSW	3	88,362,073 (GRCm39)	missense	possibly damaging	0.66
R1739:Sema4a	UTSW	3	88,344,145 (GRCm39)	missense	possibly damaging	0.94
R1801:Sema4a	UTSW	3	88,344,056 (GRCm39)	missense	probably benign	0.04
R1961:Sema4a	UTSW	3	88,345,483 (GRCm39)	splice site	probably benign
R2029:Sema4a	UTSW	3	88,358,668 (GRCm39)	missense	probably damaging	1.00
R4934:Sema4a	UTSW	3	88,345,568 (GRCm39)	missense	probably damaging	1.00
R5006:Sema4a	UTSW	3	88,344,091 (GRCm39)	missense	probably benign
R5309:Sema4a	UTSW	3	88,344,343 (GRCm39)	missense	probably damaging	1.00
R5312:Sema4a	UTSW	3	88,344,343 (GRCm39)	missense	probably damaging	1.00
R5338:Sema4a	UTSW	3	88,358,804 (GRCm39)	missense	probably benign	0.01
R5481:Sema4a	UTSW	3	88,360,347 (GRCm39)	nonsense	probably null
R5510:Sema4a	UTSW	3	88,357,293 (GRCm39)	critical splice donor site	probably null
R6046:Sema4a	UTSW	3	88,348,008 (GRCm39)	missense	probably damaging	1.00
R7242:Sema4a	UTSW	3	88,357,416 (GRCm39)	missense	probably damaging	1.00
R8403:Sema4a	UTSW	3	88,359,341 (GRCm39)	missense	probably damaging	0.98
R8798:Sema4a	UTSW	3	88,344,004 (GRCm39)	missense	possibly damaging	0.76
R9328:Sema4a	UTSW	3	88,345,613 (GRCm39)	nonsense	probably null
R9638:Sema4a	UTSW	3	88,357,066 (GRCm39)	missense	probably damaging	1.00
R9728:Sema4a	UTSW	3	88,348,187 (GRCm39)	critical splice acceptor site	probably null
Z1176:Sema4a	UTSW	3	88,344,500 (GRCm39)	missense	probably damaging	0.97

Predicted Primers

PCR Primer
(F):5'- TGGCTGGGGTTACTGTAAGACCAC -3'
(R):5'- TGCCCTGCTGTTGAAGGATGAAG -3'

Sequencing Primer
(F):5'- CTGTCACTGCTGACTCAGAG -3'
(R):5'- CTGCTGTTGAAGGATGAAGGAAATG -3'

Posted On

2013-10-16