Mutagenetix > Incidental Mutation

Incidental Mutation 'R4689:Hexb'

354786

Institutional Source

Beutler Lab

Gene Symbol

Hexb

Ensembl Gene

ENSMUSG00000021665

Gene Name

hexosaminidase B

Synonyms

MMRRC Submission

041940-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4689 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

97312839-97334865 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 97317600 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 366 (Y366H)

Ref Sequence

ENSEMBL: ENSMUSP00000022169 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022169] [ENSMUST00000022170] [ENSMUST00000042084] [ENSMUST00000161639] [ENSMUST00000161825]

AlphaFold

P20060

Predicted Effect

probably damaging
Transcript: ENSMUST00000022169
AA Change: Y366H

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000022169
Gene: ENSMUSG00000021665
AA Change: Y366H

Domain	Start	End	E-Value	Type
signal peptide	1	31	N/A	INTRINSIC
Pfam:Glycohydro_20b2	35	157	7.1e-24	PFAM
Pfam:Glyco_hydro_20	179	496	1.2e-94	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000022170

SMART Domains

Protein: ENSMUSP00000022170
Gene: ENSMUSG00000021666

Domain	Start	End	E-Value	Type
Pfam:GTP_EFTU	66	349	9.9e-64	PFAM
Pfam:GTP_EFTU_D2	379	446	4.3e-8	PFAM
low complexity region	447	473	N/A	INTRINSIC
Pfam:EFG_II	482	556	3.9e-29	PFAM
EFG_IV	558	677	2.94e-17	SMART
EFG_C	679	766	1.9e-20	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000042084

SMART Domains

Protein: ENSMUSP00000048373
Gene: ENSMUSG00000021666

Domain	Start	End	E-Value	Type
Pfam:GTP_EFTU	68	324	4.6e-64	PFAM
Pfam:GTP_EFTU_D2	354	421	4.2e-8	PFAM
low complexity region	422	448	N/A	INTRINSIC
Pfam:EFG_II	457	531	3.7e-29	PFAM
EFG_IV	533	652	2.94e-17	SMART
EFG_C	654	741	1.9e-20	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159321

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000160989

Predicted Effect

probably benign
Transcript: ENSMUST00000161639

SMART Domains

Protein: ENSMUSP00000125656
Gene: ENSMUSG00000021666

Domain	Start	End	E-Value	Type
Pfam:GTP_EFTU	68	351	1.2e-68	PFAM
low complexity region	449	475	N/A	INTRINSIC
Pfam:EFG_II	484	558	4.5e-30	PFAM
EFG_IV	560	679	2.94e-17	SMART
EFG_C	681	768	1.9e-20	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000161825

SMART Domains

Protein: ENSMUSP00000125088
Gene: ENSMUSG00000021666

Domain	Start	End	E-Value	Type
Pfam:GTP_EFTU	68	351	2.3e-64	PFAM
Pfam:GTP_EFTU_D2	381	448	1.1e-8	PFAM
low complexity region	449	475	N/A	INTRINSIC
Pfam:EFG_II	484	558	7.1e-30	PFAM
EFG_IV	560	679	2.94e-17	SMART
EFG_C	681	738	3.46e-2	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000222700

Meta Mutation Damage Score

0.7021

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.3%

Validation Efficiency

97% (72/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous mutants exhibit spasticity, muscle weakness, rigidity, tremors, and ataxia beginning around 4 months of age and resulting in death about 6 weeks later. Mutants accumulate GM2 ganglioside and glycolipid GA2 in brain. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc10	C	A	17: 46,634,996 (GRCm39)	V336L	probably benign	Het
Acbd4	T	C	11: 102,996,194 (GRCm39)	L165P	possibly damaging	Het
Adam10	T	C	9: 70,673,236 (GRCm39)	S456P	possibly damaging	Het
Adgre4	T	C	17: 56,109,096 (GRCm39)	F368L	probably damaging	Het
Ahcyl1	G	T	3: 107,572,834 (GRCm39)	Y528*	probably null	Het
Aldh3b3	G	A	19: 4,014,516 (GRCm39)	V84M	probably damaging	Het
Cdca8	C	T	4: 124,824,896 (GRCm39)	G78E	probably damaging	Het
Cry2	T	C	2: 92,254,899 (GRCm39)	D152G	probably benign	Het
Cyp2c67	T	C	19: 39,627,032 (GRCm39)	Y266C	probably benign	Het
Dkk4	T	C	8: 23,115,336 (GRCm39)	F62S	probably benign	Het
Dnah12	G	A	14: 26,427,994 (GRCm39)	V207I	probably benign	Het
Dthd1	T	C	5: 63,000,255 (GRCm39)	C526R	probably damaging	Het
Dubr	A	T	16: 50,552,866 (GRCm39)		noncoding transcript	Het
F5	T	C	1: 163,979,542 (GRCm39)		probably benign	Het
Flcn	A	C	11: 59,691,870 (GRCm39)	W260G	possibly damaging	Het
Fmnl1	G	A	11: 103,084,562 (GRCm39)		probably null	Het
Frem2	A	T	3: 53,455,056 (GRCm39)	D2173E	probably benign	Het
Fstl4	C	T	11: 52,959,477 (GRCm39)	Q173*	probably null	Het
Gfra3	G	A	18: 34,823,640 (GRCm39)	P381S	unknown	Het
Gm28308	C	A	6: 52,190,291 (GRCm39)		probably benign	Het
Gm8730	T	A	8: 103,592,379 (GRCm39)		noncoding transcript	Het
Gzmd	T	C	14: 56,368,683 (GRCm39)		probably null	Het
Hydin	A	T	8: 111,322,046 (GRCm39)	H4566L	probably benign	Het
Ifi213	G	A	1: 173,417,986 (GRCm39)	T142I	possibly damaging	Het
Kif13b	T	A	14: 65,010,513 (GRCm39)	C1271S	probably damaging	Het
Krtap9-5	G	T	11: 99,840,286 (GRCm39)	C329F	unknown	Het
Larp1	G	T	11: 57,932,439 (GRCm39)	G207W	probably damaging	Het
Lfng	A	G	5: 140,600,194 (GRCm39)	D368G	probably damaging	Het
Mbd5	G	A	2: 49,148,291 (GRCm39)	V834I	possibly damaging	Het
Mterf1b	T	A	5: 4,247,263 (GRCm39)	Y301*	probably null	Het
Myh7b	T	C	2: 155,472,434 (GRCm39)	I1305T	possibly damaging	Het
Myo16	T	C	8: 10,488,890 (GRCm39)	V687A	probably damaging	Het
Naip2	A	T	13: 100,285,320 (GRCm39)	I1292N	probably damaging	Het
Nmral1	A	G	16: 4,532,422 (GRCm39)	F130L	probably damaging	Het
Nos1	A	G	5: 118,017,450 (GRCm39)	N271S	probably benign	Het
Nrap	A	G	19: 56,374,458 (GRCm39)	S23P	probably damaging	Het
Or12d16-ps1	A	T	17: 37,705,662 (GRCm39)	N77I	probably damaging	Het
Or2aj4	A	T	16: 19,385,263 (GRCm39)	Y123*	probably null	Het
Or4e2	T	C	14: 52,688,671 (GRCm39)	I267T	probably benign	Het
Or6c210	T	C	10: 129,496,185 (GRCm39)	V170A	probably benign	Het
Pkdcc	C	G	17: 83,523,290 (GRCm39)	C132W	probably damaging	Het
Plekhg6	G	A	6: 125,350,144 (GRCm39)	L265F	probably benign	Het
Prkaa1	A	G	15: 5,208,177 (GRCm39)	T473A	probably benign	Het
Prpf3	G	A	3: 95,743,801 (GRCm39)	Q451*	probably null	Het
Psma5-ps	T	A	10: 85,150,065 (GRCm39)		noncoding transcript	Het
Ptprh	T	A	7: 4,600,996 (GRCm39)	D127V	possibly damaging	Het
Rab36	T	C	10: 74,877,765 (GRCm39)		probably null	Het
Rasa1	A	T	13: 85,386,282 (GRCm39)	Y427*	probably null	Het
Rgs11	T	C	17: 26,423,521 (GRCm39)		probably null	Het
Serpinb13	C	T	1: 106,910,574 (GRCm39)	S66L	probably damaging	Het
Shank2	G	A	7: 143,974,342 (GRCm39)	V1087I	probably benign	Het
Slc39a10	A	C	1: 46,875,173 (GRCm39)	M43R	probably benign	Het
Slc40a1	T	A	1: 45,951,473 (GRCm39)	Q228L	probably benign	Het
Slc45a1	A	T	4: 150,722,996 (GRCm39)	L296Q	probably benign	Het
Stambpl1	A	G	19: 34,213,691 (GRCm39)	T307A	probably benign	Het
Stt3a	T	C	9: 36,644,225 (GRCm39)	T705A	possibly damaging	Het
Tec	G	A	5: 72,980,980 (GRCm39)		probably benign	Het
Trp63	A	T	16: 25,684,012 (GRCm39)	T300S	possibly damaging	Het
Vmn1r235	A	G	17: 21,482,623 (GRCm39)	H316R	probably benign	Het
Vmn2r1	A	G	3: 64,012,074 (GRCm39)	H645R	possibly damaging	Het
Wdfy4	A	G	14: 32,831,505 (GRCm39)	I907T	possibly damaging	Het
Zcchc10	A	G	11: 53,218,151 (GRCm39)	T33A	probably benign	Het
Zfp318	T	A	17: 46,710,560 (GRCm39)	V761D	probably damaging	Het
Zfp358	T	C	8: 3,546,146 (GRCm39)		probably null	Het
Zfp661	G	A	2: 127,419,468 (GRCm39)	P224L	probably damaging	Het
Zfp937	T	C	2: 150,078,706 (GRCm39)	M33T	probably damaging	Het
Zfp955a	T	C	17: 33,461,040 (GRCm39)	H364R	probably damaging	Het

Other mutations in Hexb

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00509:Hexb	APN	13	97,318,437 (GRCm39)	missense	probably damaging	1.00
IGL02010:Hexb	APN	13	97,313,353 (GRCm39)	missense	probably benign	0.01
IGL02126:Hexb	APN	13	97,314,532 (GRCm39)	missense	possibly damaging	0.93
IGL02303:Hexb	APN	13	97,313,401 (GRCm39)	missense	probably damaging	1.00
IGL02955:Hexb	APN	13	97,317,584 (GRCm39)	utr 3 prime	probably benign
IGL02988:Hexb	UTSW	13	97,334,729 (GRCm39)	missense	unknown
R0311:Hexb	UTSW	13	97,320,327 (GRCm39)	unclassified	probably benign
R0470:Hexb	UTSW	13	97,314,507 (GRCm39)	missense	probably damaging	0.97
R0520:Hexb	UTSW	13	97,317,618 (GRCm39)	missense	probably benign	0.00
R0893:Hexb	UTSW	13	97,322,135 (GRCm39)	missense	probably benign	0.02
R1869:Hexb	UTSW	13	97,327,767 (GRCm39)	missense	probably benign
R2295:Hexb	UTSW	13	97,322,120 (GRCm39)	missense	probably damaging	1.00
R2884:Hexb	UTSW	13	97,320,208 (GRCm39)	missense	probably damaging	1.00
R4237:Hexb	UTSW	13	97,313,259 (GRCm39)	intron	probably benign
R4238:Hexb	UTSW	13	97,313,259 (GRCm39)	intron	probably benign
R4239:Hexb	UTSW	13	97,313,259 (GRCm39)	intron	probably benign
R5166:Hexb	UTSW	13	97,318,512 (GRCm39)	missense	probably benign	0.13
R6665:Hexb	UTSW	13	97,315,893 (GRCm39)	missense	probably benign	0.01
R7379:Hexb	UTSW	13	97,317,672 (GRCm39)	missense	probably damaging	1.00
R7553:Hexb	UTSW	13	97,334,681 (GRCm39)	missense	probably benign	0.01
R8307:Hexb	UTSW	13	97,330,707 (GRCm39)	missense	probably benign	0.02
R8830:Hexb	UTSW	13	97,330,762 (GRCm39)	missense	probably benign
R8980:Hexb	UTSW	13	97,330,689 (GRCm39)	missense	probably damaging	0.99
R9144:Hexb	UTSW	13	97,317,599 (GRCm39)	missense	probably damaging	1.00
R9155:Hexb	UTSW	13	97,314,414 (GRCm39)	missense	probably damaging	1.00
R9186:Hexb	UTSW	13	97,325,836 (GRCm39)	missense	probably damaging	1.00
R9393:Hexb	UTSW	13	97,313,336 (GRCm39)	nonsense	probably null
R9546:Hexb	UTSW	13	97,322,176 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCAGCTTCTAAATGCAAAATGCTC -3'
(R):5'- TCAGCTTTGTAAGGGCCTGG -3'

Sequencing Primer
(F):5'- TGCTCAGCATTATAAAGAGAACAG -3'
(R):5'- AGCAGATTCAGACTCCCTGTG -3'

Posted On

2015-10-21