Mutagenetix > Incidental Mutation

Incidental Mutation 'R2029:Sema4a'

220916

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

040036-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.913) question?

Stock #

R2029 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

88343266-88368489 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 88358668 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 30 (H30Q)

Ref Sequence

ENSEMBL: ENSMUSP00000138858 (fasta)

Gene Model

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

AlphaFold

Q62178

Predicted Effect

possibly damaging
Transcript: ENSMUST00000029700
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000029700
Gene: ENSMUSG00000028064
AA Change: H184Q

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: ENSMUST00000107531
AA Change: H52Q

PolyPhen 2 Score 0.666 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000103155
Gene: ENSMUSG00000028064
AA Change: H52Q

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

SMART Domains

Protein: ENSMUSP00000119028
Gene: ENSMUSG00000028064

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000127436
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000118706
Gene: ENSMUSG00000028064
AA Change: H184Q

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

possibly damaging
Transcript: ENSMUST00000169222
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000128887
Gene: ENSMUSG00000028064
AA Change: H184Q

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: ENSMUST00000166237
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000125909
Gene: ENSMUSG00000028064
AA Change: H184Q

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: ENSMUST00000147200
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000123061
Gene: ENSMUSG00000028064
AA Change: H184Q

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000165898
AA Change: H184Q

PolyPhen 2 Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000128510
Gene: ENSMUSG00000028064
AA Change: H184Q

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 damaging
Transcript: ENSMUST00000185137
AA Change: H30Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149145

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146921

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184972

Predicted Effect

probably benign
Transcript: ENSMUST00000184487

SMART Domains

Protein: ENSMUSP00000139126
Gene: ENSMUSG00000028064

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: ENSMUST00000184876

SMART Domains

Protein: ENSMUSP00000139159
Gene: ENSMUSG00000028064

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: ENSMUST00000141471

SMART Domains

Protein: ENSMUSP00000114330
Gene: ENSMUSG00000028064

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

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 93.8%

Validation Efficiency

98% (97/99)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam18	C	G	8: 25,140,893 (GRCm39)	G286A	probably damaging	Het
Adcy1	G	A	11: 7,089,142 (GRCm39)	A519T	probably benign	Het
Anxa2	T	A	9: 69,371,762 (GRCm39)	S2T	possibly damaging	Het
Ap3m1	G	A	14: 21,089,217 (GRCm39)	S261L	possibly damaging	Het
Baz2b	A	T	2: 59,743,067 (GRCm39)		probably benign	Het
Brdt	T	A	5: 107,507,090 (GRCm39)	S497T	probably benign	Het
Cdh11	A	G	8: 103,406,404 (GRCm39)	F23S	probably benign	Het
Cdh16	A	C	8: 105,344,434 (GRCm39)	L540R	probably damaging	Het
Ces5a	A	T	8: 94,261,205 (GRCm39)	L74Q	probably damaging	Het
Cfap69	A	G	5: 5,654,306 (GRCm39)	S543P	probably damaging	Het
Cfap74	T	C	4: 155,526,538 (GRCm39)	I763T	possibly damaging	Het
Cma1	T	A	14: 56,181,191 (GRCm39)	R58S	possibly damaging	Het
Csmd3	C	T	15: 47,701,975 (GRCm39)	D1599N	probably damaging	Het
Cyld	A	G	8: 89,471,940 (GRCm39)	K857R	probably benign	Het
Cyp3a16	T	C	5: 145,388,667 (GRCm39)	D270G	probably damaging	Het
D1Pas1	T	C	1: 186,700,286 (GRCm39)	S72P	possibly damaging	Het
Ddx3y	T	C	Y: 1,266,389 (GRCm39)	E331G	probably benign	Het
Degs1l	T	A	1: 180,882,496 (GRCm39)	I86K	probably benign	Het
Dis3l2	T	C	1: 86,782,189 (GRCm39)		probably benign	Het
Dop1a	G	T	9: 86,403,418 (GRCm39)	W1539C	probably damaging	Het
Dop1b	A	G	16: 93,566,323 (GRCm39)	K917E	probably benign	Het
Ecpas	G	A	4: 58,844,165 (GRCm39)	R534*	probably null	Het
Efcab3	T	C	11: 104,990,851 (GRCm39)	I5462T	probably damaging	Het
Eif1ad15	A	T	12: 88,288,191 (GRCm39)	S21T	unknown	Het
Epo	A	G	5: 137,483,447 (GRCm39)		probably benign	Het
Figla	T	A	6: 85,997,624 (GRCm39)		probably benign	Het
Flvcr1	T	C	1: 190,753,353 (GRCm39)	D273G	probably benign	Het
Fryl	T	A	5: 73,179,465 (GRCm39)	R304*	probably null	Het
Gcm1	T	G	9: 77,972,326 (GRCm39)	D422E	possibly damaging	Het
Get3	A	T	8: 85,746,403 (GRCm39)	Y148*	probably null	Het
Ggt6	A	G	11: 72,328,367 (GRCm39)	D251G	possibly damaging	Het
Git2	A	G	5: 114,904,511 (GRCm39)		probably null	Het
Gm18856	A	T	13: 14,139,376 (GRCm39)		probably benign	Het
Gm20939	T	A	17: 95,183,252 (GRCm39)		probably benign	Het
Gpr176	A	G	2: 118,109,913 (GRCm39)	Y449H	probably benign	Het
H2-Eb1	A	G	17: 34,533,366 (GRCm39)	E196G	probably damaging	Het
H2-M10.6	A	G	17: 37,124,799 (GRCm39)	T239A	possibly damaging	Het
Haus5	T	C	7: 30,358,825 (GRCm39)	N237S	possibly damaging	Het
Hectd3	T	C	4: 116,857,882 (GRCm39)	M605T	probably damaging	Het
Hps3	T	C	3: 20,084,691 (GRCm39)	I166V	probably benign	Het
Ighv5-21	A	T	12: 114,286,434 (GRCm39)		probably benign	Het
Kdm6b	C	T	11: 69,294,418 (GRCm39)	G1218D	unknown	Het
Klhl30	A	G	1: 91,285,636 (GRCm39)		probably null	Het
Kmt2a	A	T	9: 44,729,747 (GRCm39)	S3523R	probably benign	Het
Lnpep	A	T	17: 17,788,661 (GRCm39)	N481K	probably damaging	Het
Lrp1b	T	C	2: 41,231,861 (GRCm39)	H1203R	probably benign	Het
Lrrc8a	C	T	2: 30,146,661 (GRCm39)	R492W	probably damaging	Het
Magel2	T	A	7: 62,030,342 (GRCm39)	V1082D	unknown	Het
Memo1	A	C	17: 74,552,049 (GRCm39)	H82Q	probably null	Het
Myh13	A	T	11: 67,252,115 (GRCm39)	T1408S	probably benign	Het
Myh2	A	T	11: 67,085,451 (GRCm39)	N1792Y	possibly damaging	Het
Myo1e	A	T	9: 70,275,969 (GRCm39)	N728I	possibly damaging	Het
Myo1e	T	C	9: 70,285,997 (GRCm39)		probably benign	Het
Myo5c	T	C	9: 75,196,337 (GRCm39)		probably benign	Het
Or11l3	T	A	11: 58,516,319 (GRCm39)	L184F	probably damaging	Het
Or1e19	A	G	11: 73,316,188 (GRCm39)	V207A	probably benign	Het
Or2d2b	T	C	7: 106,705,643 (GRCm39)	I142V	probably benign	Het
Or4c11c	T	A	2: 88,661,749 (GRCm39)	M96K	possibly damaging	Het
Or51g1	T	A	7: 102,633,478 (GRCm39)	T298S	probably damaging	Het
Or52e3	T	C	7: 102,868,967 (GRCm39)	F14S	probably damaging	Het
Parp2	C	T	14: 51,047,543 (GRCm39)	A18V	probably benign	Het
Peli1	T	A	11: 21,098,110 (GRCm39)	C282S	probably damaging	Het
Phf8-ps	G	T	17: 33,286,598 (GRCm39)	S68*	probably null	Het
Piezo2	T	C	18: 63,252,006 (GRCm39)	M404V	possibly damaging	Het
Pkn1	T	A	8: 84,404,592 (GRCm39)	Q496L	possibly damaging	Het
Pla2r1	A	T	2: 60,262,317 (GRCm39)	F1093L	probably damaging	Het
Ppp2r3d	A	G	9: 101,022,680 (GRCm39)	V323A	probably damaging	Het
Pramel16	T	A	4: 143,676,453 (GRCm39)	Y217F	probably benign	Het
Prg2	C	T	2: 84,812,342 (GRCm39)		probably benign	Het
Ptprb	G	A	10: 116,182,958 (GRCm39)	G1545S	probably benign	Het
Rbm19	A	G	5: 120,258,307 (GRCm39)	D174G	possibly damaging	Het
Rhbdf2	T	A	11: 116,491,974 (GRCm39)	T526S	probably damaging	Het
Rpusd4	A	G	9: 35,179,310 (GRCm39)	N42S	probably benign	Het
Ryr3	T	A	2: 112,477,361 (GRCm39)	Q4455L	possibly damaging	Het
Skint1	G	A	4: 111,878,653 (GRCm39)		probably null	Het
Slc1a3	A	G	15: 8,675,153 (GRCm39)	V284A	probably benign	Het
Slc30a9	A	T	5: 67,497,318 (GRCm39)	K288*	probably null	Het
Slc36a1	G	T	11: 55,119,164 (GRCm39)	A380S	probably benign	Het
Slc47a1	G	A	11: 61,268,833 (GRCm39)		probably benign	Het
Snx19	A	T	9: 30,340,296 (GRCm39)	E478V	probably benign	Het
Spag6	T	C	2: 18,738,916 (GRCm39)		probably benign	Het
Stag1	A	T	9: 100,668,740 (GRCm39)	T223S	probably damaging	Het
Terb1	A	T	8: 105,224,732 (GRCm39)		probably benign	Het
Terf1	A	G	1: 15,876,170 (GRCm39)	D90G	possibly damaging	Het
Tex15	A	G	8: 34,061,302 (GRCm39)	D518G	probably damaging	Het
Tmem174	T	A	13: 98,773,546 (GRCm39)	M95L	possibly damaging	Het
Tnnt3	GTCCAGGCATCTC	GTC	7: 142,066,364 (GRCm39)		probably benign	Het
Usp28	A	G	9: 48,896,803 (GRCm39)	D8G	probably benign	Het
Vmn2r105	T	C	17: 20,444,840 (GRCm39)	T551A	probably damaging	Het
Vmn2r107	A	G	17: 20,595,549 (GRCm39)	I701V	probably benign	Het
Vmn2r13	A	C	5: 109,339,943 (GRCm39)	F11V	probably benign	Het
Vmn2r85	G	C	10: 130,261,443 (GRCm39)	S298*	probably null	Het
Wdr6	C	G	9: 108,452,554 (GRCm39)	W443S	probably damaging	Het
Wipi1	A	G	11: 109,474,016 (GRCm39)	V210A	probably damaging	Het
Zfp317	A	G	9: 19,556,532 (GRCm39)	T47A	probably benign	Het
Zfp61	T	C	7: 23,991,714 (GRCm39)	T146A	probably benign	Het
Zfp964	A	G	8: 70,116,567 (GRCm39)	E389G	unknown	Het
Zfyve16	T	C	13: 92,640,985 (GRCm39)	D1253G	probably damaging	Het
Zpld2	T	C	4: 133,929,669 (GRCm39)	K212R	possibly damaging	Het
Zswim7	G	A	11: 62,158,299 (GRCm39)		probably benign	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
R0837:Sema4a	UTSW	3	88,360,405 (GRCm39)	missense	possibly damaging	0.46
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
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'- CAGTTTCAGAAGGGGTAGTGGC -3'
(R):5'- GCTTTGGGAATCTCTGGTCC -3'

Sequencing Primer
(F):5'- GCTAGGCTGTCTGGTTCTCC -3'
(R):5'- AATCTCTGGTCCCTGCGG -3'

Posted On

2014-08-25