Mutagenetix > Incidental Mutation

Incidental Mutation 'R0372:Hlcs'

30564

Institutional Source

Beutler Lab

Gene Symbol

Hlcs

Ensembl Gene

ENSMUSG00000040820

Gene Name

holocarboxylase synthetase (biotin- [propriony-Coenzyme A-carboxylase (ATP-hydrolysing)] ligase)

Synonyms

D16Jhu34, 410I21.SP6

MMRRC Submission

038578-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0372 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

93929741-94114430 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 93939766 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Valine at position 671 (I671V)

Ref Sequence

ENSEMBL: ENSMUSP00000153773 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000099512] [ENSMUST00000163193] [ENSMUST00000227141] [ENSMUST00000227698] [ENSMUST00000228910]

AlphaFold

Q920N2

Predicted Effect

probably benign
Transcript: ENSMUST00000099512
AA Change: I524V

PolyPhen 2 Score 0.183 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000097112
Gene: ENSMUSG00000040820
AA Change: I524V

Domain	Start	End	E-Value	Type
low complexity region	38	55	N/A	INTRINSIC
low complexity region	377	391	N/A	INTRINSIC
Pfam:BPL_LplA_LipB	467	599	1.9e-21	PFAM
Pfam:BPL_C	665	714	3.7e-12	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000163193
AA Change: I524V

PolyPhen 2 Score 0.183 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000130981
Gene: ENSMUSG00000040820
AA Change: I524V

Domain	Start	End	E-Value	Type
low complexity region	38	55	N/A	INTRINSIC
low complexity region	377	391	N/A	INTRINSIC
Pfam:BPL_LplA_LipB	467	599	3.6e-30	PFAM
Pfam:BPL_C	665	714	4.9e-13	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000227141
AA Change: I671V

PolyPhen 2 Score 0.687 (Sensitivity: 0.86; Specificity: 0.92)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227447

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227618

Predicted Effect

probably benign
Transcript: ENSMUST00000227698
AA Change: I43V

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

Predicted Effect

probably benign
Transcript: ENSMUST00000228910
AA Change: I129V

PolyPhen 2 Score 0.062 (Sensitivity: 0.94; Specificity: 0.84)

Meta Mutation Damage Score

0.0935

Coding Region Coverage

1x: 99.0%
3x: 97.9%
10x: 95.2%
20x: 88.6%

Validation Efficiency

97% (70/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]

Allele List at MGI

Other mutations in this stock

Total: 70 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930578I06Rik	T	A	14: 64,210,931 (GRCm39)	Q99L	probably damaging	Het
Abca2	A	G	2: 25,327,365 (GRCm39)	Y641C	probably damaging	Het
Abhd10	A	G	16: 45,557,254 (GRCm39)		probably null	Het
Acan	G	T	7: 78,750,349 (GRCm39)	A1707S	probably benign	Het
Ankrd61	T	A	5: 143,827,993 (GRCm39)	R284S	probably benign	Het
Ap3d1	T	C	10: 80,559,401 (GRCm39)	K258E	probably damaging	Het
Arl6ip6	T	G	2: 53,092,933 (GRCm39)	F153V	probably damaging	Het
Atp2c2	C	A	8: 120,484,180 (GRCm39)	F930L	probably benign	Het
Avl9	T	C	6: 56,703,309 (GRCm39)		probably null	Het
Axin2	A	G	11: 108,814,159 (GRCm39)	S16G	probably damaging	Het
Axin2	T	A	11: 108,814,936 (GRCm39)		probably benign	Het
Bbs7	A	T	3: 36,656,981 (GRCm39)	D282E	probably benign	Het
Ccny	A	T	18: 9,345,201 (GRCm39)	V191D	probably damaging	Het
Cdk11b	A	G	4: 155,725,957 (GRCm39)		probably benign	Het
Chd1	T	A	17: 17,607,552 (GRCm39)	C367S	probably benign	Het
Cnnm4	G	A	1: 36,537,091 (GRCm39)	V472M	probably damaging	Het
Cpb2	T	A	14: 75,479,817 (GRCm39)	I8N	probably benign	Het
Dusp11	A	G	6: 85,935,712 (GRCm39)		probably benign	Het
Elmo1	T	C	13: 20,756,629 (GRCm39)		probably null	Het
Gbf1	C	T	19: 46,274,143 (GRCm39)	P1726S	probably benign	Het
Hal	A	G	10: 93,343,415 (GRCm39)		probably benign	Het
Ifnab	A	G	4: 88,609,071 (GRCm39)	S132P	probably benign	Het
Ing5	T	C	1: 93,740,142 (GRCm39)	I70T	probably damaging	Het
Ints1	T	C	5: 139,758,193 (GRCm39)	N228S	probably damaging	Het
Itgb6	T	A	2: 60,458,185 (GRCm39)	I523F	probably benign	Het
Kat2b	T	C	17: 53,945,565 (GRCm39)	F328S	possibly damaging	Het
Kbtbd3	A	T	9: 4,316,950 (GRCm39)	I34F	possibly damaging	Het
Klhl11	A	T	11: 100,354,348 (GRCm39)	I491N	probably damaging	Het
Lmo7	A	T	14: 102,155,489 (GRCm39)		probably benign	Het
Lrp1	G	T	10: 127,428,005 (GRCm39)	P523T	probably damaging	Het
Lrp1b	T	A	2: 40,620,810 (GRCm39)	D3556V	probably benign	Het
Lrp2	T	A	2: 69,365,387 (GRCm39)	H262L	probably benign	Het
Lrrc27	T	A	7: 138,806,103 (GRCm39)	I256K	probably benign	Het
Lrrc47	G	A	4: 154,104,089 (GRCm39)	R523K	probably benign	Het
Lrrc71	A	T	3: 87,653,084 (GRCm39)	S111T	probably benign	Het
Map3k7cl	T	C	16: 87,378,100 (GRCm39)	V72A	probably damaging	Het
Mphosph10	G	T	7: 64,038,603 (GRCm39)		probably benign	Het
Nlrp4a	T	C	7: 26,148,657 (GRCm39)		probably benign	Het
Nsd2	A	T	5: 34,048,895 (GRCm39)	M1140L	probably damaging	Het
Nt5dc3	T	C	10: 86,661,155 (GRCm39)	M440T	possibly damaging	Het
Oog4	A	T	4: 143,164,259 (GRCm39)	L424Q	probably damaging	Het
Or5h17	T	C	16: 58,820,450 (GRCm39)	V134A	probably benign	Het
Orc5	A	T	5: 22,738,782 (GRCm39)	Y160N	possibly damaging	Het
Papola	T	C	12: 105,785,097 (GRCm39)	F410L	probably benign	Het
Pcdh10	A	G	3: 45,333,932 (GRCm39)	E82G	probably damaging	Het
Pcdh20	T	C	14: 88,706,439 (GRCm39)	Y287C	probably damaging	Het
Pld1	T	A	3: 28,142,787 (GRCm39)		probably null	Het
Plekha8	G	A	6: 54,593,743 (GRCm39)		probably null	Het
Ppbp	C	T	5: 90,917,202 (GRCm39)	T93M	possibly damaging	Het
Prpsap2	A	G	11: 61,631,826 (GRCm39)	I177T	possibly damaging	Het
Rab3gap2	C	T	1: 184,994,891 (GRCm39)	T810M	possibly damaging	Het
Rassf9	A	G	10: 102,381,872 (GRCm39)	N418S	possibly damaging	Het
Rnf20	C	G	4: 49,650,176 (GRCm39)	R582G	possibly damaging	Het
Serpine2	T	C	1: 79,799,147 (GRCm39)	I36V	probably damaging	Het
Sf3b2	C	T	19: 5,324,852 (GRCm39)	D845N	probably damaging	Het
Slc24a2	A	T	4: 87,145,529 (GRCm39)	V175E	probably damaging	Het
Sned1	T	C	1: 93,213,673 (GRCm39)		probably benign	Het
Snrnp40	C	G	4: 130,271,836 (GRCm39)		probably null	Het
Spg11	GCC	G	2: 121,889,928 (GRCm39)		probably null	Het
Tecrl	C	T	5: 83,442,506 (GRCm39)	C189Y	probably damaging	Het
Tert	A	G	13: 73,797,110 (GRCm39)	D1116G	probably damaging	Het
Thnsl2	T	C	6: 71,116,774 (GRCm39)	Y126C	probably damaging	Het
Tll2	T	C	19: 41,171,752 (GRCm39)		probably null	Het
Ubqln4	C	T	3: 88,463,276 (GRCm39)	S147L	probably benign	Het
Ugt2b5	A	T	5: 87,288,117 (GRCm39)	C17S	probably benign	Het
Vps41	A	T	13: 19,026,417 (GRCm39)	Q505L	probably benign	Het
Zfp386	T	C	12: 116,018,436 (GRCm39)	M35T	possibly damaging	Het
Zfp777	T	C	6: 48,021,410 (GRCm39)	M71V	possibly damaging	Het
Zfp938	A	T	10: 82,063,662 (GRCm39)	L34Q	probably damaging	Het
Zfp974	A	T	7: 27,620,120 (GRCm39)		probably null	Het

Other mutations in Hlcs

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01078:Hlcs	APN	16	93,934,019 (GRCm39)	missense	probably damaging	0.99
IGL02026:Hlcs	APN	16	93,935,564 (GRCm39)	missense	probably damaging	0.99
IGL02341:Hlcs	APN	16	94,031,969 (GRCm39)	missense	probably damaging	0.99
IGL03075:Hlcs	APN	16	93,939,706 (GRCm39)	missense	probably damaging	1.00
PIT4515001:Hlcs	UTSW	16	94,068,275 (GRCm39)	missense	probably benign	0.45
R0664:Hlcs	UTSW	16	94,032,170 (GRCm39)	missense	probably damaging	1.00
R0731:Hlcs	UTSW	16	93,932,711 (GRCm39)	missense	probably damaging	1.00
R1465:Hlcs	UTSW	16	94,069,151 (GRCm39)	missense	probably damaging	0.99
R1465:Hlcs	UTSW	16	94,069,151 (GRCm39)	missense	probably damaging	0.99
R1761:Hlcs	UTSW	16	94,068,866 (GRCm39)	missense	probably benign	0.05
R2013:Hlcs	UTSW	16	94,063,599 (GRCm39)	missense	probably benign	0.17
R2014:Hlcs	UTSW	16	94,063,599 (GRCm39)	missense	probably benign	0.17
R2015:Hlcs	UTSW	16	94,063,599 (GRCm39)	missense	probably benign	0.17
R2204:Hlcs	UTSW	16	94,032,011 (GRCm39)	missense	probably benign	0.30
R2371:Hlcs	UTSW	16	94,068,926 (GRCm39)	missense	probably damaging	0.98
R3816:Hlcs	UTSW	16	93,933,947 (GRCm39)	missense	probably benign	0.11
R3822:Hlcs	UTSW	16	94,068,840 (GRCm39)	missense	probably benign	0.04
R4422:Hlcs	UTSW	16	93,939,819 (GRCm39)	missense	possibly damaging	0.56
R4657:Hlcs	UTSW	16	94,063,557 (GRCm39)	missense	probably benign	0.00
R4783:Hlcs	UTSW	16	94,069,398 (GRCm39)	missense	possibly damaging	0.82
R5347:Hlcs	UTSW	16	94,068,383 (GRCm39)	missense	possibly damaging	0.93
R5808:Hlcs	UTSW	16	94,063,491 (GRCm39)	missense	probably benign	0.00
R5940:Hlcs	UTSW	16	93,935,571 (GRCm39)	missense	probably damaging	0.99
R6341:Hlcs	UTSW	16	94,032,022 (GRCm39)	missense	probably damaging	1.00
R6943:Hlcs	UTSW	16	93,942,261 (GRCm39)	missense	possibly damaging	0.75
R7053:Hlcs	UTSW	16	94,068,874 (GRCm39)	missense	possibly damaging	0.91
R7157:Hlcs	UTSW	16	94,069,023 (GRCm39)	nonsense	probably null
R7166:Hlcs	UTSW	16	94,063,585 (GRCm39)	missense	possibly damaging	0.92
R7313:Hlcs	UTSW	16	94,068,362 (GRCm39)	missense	probably damaging	1.00
R7427:Hlcs	UTSW	16	94,068,758 (GRCm39)	missense	probably benign	0.00
R7428:Hlcs	UTSW	16	94,068,758 (GRCm39)	missense	probably benign	0.00
R7547:Hlcs	UTSW	16	94,032,031 (GRCm39)	nonsense	probably null
R7548:Hlcs	UTSW	16	93,933,876 (GRCm39)	nonsense	probably null
R8172:Hlcs	UTSW	16	94,068,485 (GRCm39)	missense	probably damaging	1.00
R8241:Hlcs	UTSW	16	94,068,677 (GRCm39)	missense	probably damaging	1.00
R8500:Hlcs	UTSW	16	94,063,617 (GRCm39)	missense	possibly damaging	0.89
R8940:Hlcs	UTSW	16	94,032,085 (GRCm39)	missense	probably benign
R9274:Hlcs	UTSW	16	94,088,785 (GRCm39)	missense	possibly damaging	0.85
R9360:Hlcs	UTSW	16	93,932,672 (GRCm39)	missense	probably damaging	1.00
R9361:Hlcs	UTSW	16	93,939,799 (GRCm39)	missense	probably benign	0.10
R9564:Hlcs	UTSW	16	93,935,580 (GRCm39)	missense	probably benign	0.01
X0065:Hlcs	UTSW	16	93,934,032 (GRCm39)	missense	probably damaging	1.00
Z1176:Hlcs	UTSW	16	94,063,518 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGGAAGCAATTACCCACAGTAGCAC -3'
(R):5'- TGTCGCATGAATCCCTAGAACATCAAG -3'

Sequencing Primer
(F):5'- gccaggcgagcactttac -3'
(R):5'- TCCCTAGAACATCAAGGTGTG -3'

Posted On

2013-04-24