Mutagenetix > Incidental Mutation

Incidental Mutation 'R0731:Hlcs'

67592

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

038912-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0731 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

94128882-94313571 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 94131852 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 851 (H851L)

Ref Sequence

ENSEMBL: ENSMUSP00000153773 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000072182] [ENSMUST00000099512] [ENSMUST00000163193] [ENSMUST00000227141] [ENSMUST00000227698] [ENSMUST00000228910] [ENSMUST00000231688]

AlphaFold

Q920N2

Predicted Effect

probably benign
Transcript: ENSMUST00000072182

SMART Domains

Protein: ENSMUSP00000072043
Gene: ENSMUSG00000062713

Domain	Start	End	E-Value	Type
HLH	6	58	6.99e-5	SMART
PAS	79	145	7.8e-13	SMART
PAS	220	286	1.31e-5	SMART
PAC	292	335	2.44e-5	SMART
Pfam:SIM_C	358	650	4.5e-89	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000099512
AA Change: H704L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000097112
Gene: ENSMUSG00000040820
AA Change: H704L

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 damaging
Transcript: ENSMUST00000163193
AA Change: H704L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000130981
Gene: ENSMUSG00000040820
AA Change: H704L

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

probably damaging
Transcript: ENSMUST00000227141
AA Change: H851L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227447

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227618

Predicted Effect

probably benign
Transcript: ENSMUST00000227698

Predicted Effect

possibly damaging
Transcript: ENSMUST00000228910
AA Change: H309L

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)

Predicted Effect

probably benign
Transcript: ENSMUST00000231688

Meta Mutation Damage Score

0.1419

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.6%
20x: 95.5%

Validation Efficiency

97% (73/75)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930430F08Rik	T	C	10: 100,586,203	T66A	probably damaging	Het
4933406M09Rik	A	C	1: 134,389,975	M162L	probably benign	Het
Acsm3	A	T	7: 119,768,024	R27*	probably null	Het
Actg1	A	G	11: 120,346,949	F255S	probably damaging	Het
Ahdc1	T	A	4: 133,062,951	V501E	possibly damaging	Het
Alpk2	A	T	18: 65,305,390	D1444E	probably damaging	Het
Btaf1	T	G	19: 36,997,495		probably null	Het
Cacnb2	A	G	2: 14,985,706	H489R	possibly damaging	Het
Ccdc162	C	A	10: 41,579,143	K398N	probably damaging	Het
Cd79b	G	T	11: 106,312,433	S145R	probably damaging	Het
Cdh11	T	A	8: 102,668,019	N264Y	probably damaging	Het
Celsr1	T	C	15: 85,901,597	D2892G	probably benign	Het
Chuk	A	G	19: 44,103,766		probably benign	Het
Clk3	T	C	9: 57,751,126		probably benign	Het
Dcaf8	A	T	1: 172,172,509	D78V	possibly damaging	Het
Dctn1	A	G	6: 83,183,089	T87A	probably damaging	Het
Ddx50	T	C	10: 62,616,249	N732D	unknown	Het
Dnah5	A	T	15: 28,311,143	Y1756F	possibly damaging	Het
Dock3	A	T	9: 106,969,856	V858E	probably damaging	Het
Fer1l4	A	G	2: 156,024,070	F1566S	probably benign	Het
Fpr-rs7	T	C	17: 20,113,854	I125V	probably benign	Het
Fuca2	C	T	10: 13,506,027	P228L	probably benign	Het
Galntl6	A	G	8: 58,535,984	F57L	probably benign	Het
Gigyf2	T	A	1: 87,407,727		probably benign	Het
Gm16505	A	T	13: 3,361,329		noncoding transcript	Het
Gm4781	T	C	10: 100,396,777		noncoding transcript	Het
Gm9956	T	A	10: 56,745,543	Y100*	probably null	Het
Gpr137c	T	A	14: 45,246,349	C178S	probably damaging	Het
Gpr83	A	G	9: 14,868,644	R331G	probably benign	Het
Kbtbd6	C	A	14: 79,451,884	Y6*	probably null	Het
Kif23	T	C	9: 61,925,032	R610G	possibly damaging	Het
Kifc3	G	A	8: 95,105,733	T487I	probably damaging	Het
Klra5	A	C	6: 129,908,796	D133E	possibly damaging	Het
Klra6	T	C	6: 130,022,705	E100G	probably damaging	Het
Klre1	T	A	6: 129,585,568		probably benign	Het
Lancl1	C	T	1: 67,009,910		probably null	Het
Lgr6	C	T	1: 134,994,010	A199T	probably damaging	Het
Man1b1	A	G	2: 25,338,155	I146V	possibly damaging	Het
Map4k5	T	A	12: 69,874,264		probably benign	Het
Mast3	A	G	8: 70,781,321	S178P	probably damaging	Het
Mau2	A	G	8: 70,023,612		probably null	Het
Mkrn2	A	T	6: 115,614,651	N312Y	probably damaging	Het
Mrvi1	T	C	7: 110,876,900	S615G	probably benign	Het
Myh1	A	G	11: 67,202,533	E150G	probably damaging	Het
Myo7b	T	A	18: 31,961,825		probably null	Het
Nyap1	A	G	5: 137,735,298	V491A	probably damaging	Het
Olfr1284	A	G	2: 111,379,293	M98V	probably damaging	Het
Olfr484	T	C	7: 108,124,734	I176M	probably benign	Het
Olfr518	A	T	7: 108,881,533	N24K	probably damaging	Het
Olfr954	T	C	9: 39,461,532	F34L	probably damaging	Het
Oxsm	A	T	14: 16,240,893	H385Q	probably damaging	Het
Pbld2	T	C	10: 63,056,811	S242P	probably damaging	Het
Pdzd7	T	C	19: 45,029,305	Y675C	probably damaging	Het
Pnkd	T	A	1: 74,351,541	H266Q	probably damaging	Het
Rbfox2	A	G	15: 77,099,279	S141P	probably benign	Het
Rdx	A	G	9: 52,068,218	T214A	probably benign	Het
Ripor2	A	T	13: 24,680,644	E219V	probably damaging	Het
Rufy2	G	A	10: 63,011,844		probably benign	Het
Slf2	T	A	19: 44,975,726		probably benign	Het
Snrnp200	G	T	2: 127,226,145		probably benign	Het
Snx7	T	A	3: 117,829,671		probably benign	Het
Stt3a	T	C	9: 36,735,512	I602V	probably damaging	Het
Tacr3	G	A	3: 134,855,000		probably null	Het
Tcerg1	C	T	18: 42,571,840	T978M	probably damaging	Het
Tcf7l1	G	T	6: 72,788,269	P126Q	possibly damaging	Het
Trank1	A	G	9: 111,365,488	D860G	probably damaging	Het
Try4	T	C	6: 41,304,367	L81P	probably benign	Het
Ucp1	T	C	8: 83,297,847		probably benign	Het
Ugt2b38	G	A	5: 87,420,452	A328V	probably damaging	Het
Wfikkn1	T	A	17: 25,878,017	R444S	probably damaging	Het
Zfc3h1	A	G	10: 115,410,632	T875A	probably benign	Het
Zfp11	A	G	5: 129,657,264	S378P	probably damaging	Het
Zfp984	T	A	4: 147,756,232	N54I	probably damaging	Het

Other mutations in Hlcs

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01078:Hlcs	APN	16	94133160	missense	probably damaging	0.99
IGL02026:Hlcs	APN	16	94134705	missense	probably damaging	0.99
IGL02341:Hlcs	APN	16	94231110	missense	probably damaging	0.99
IGL03075:Hlcs	APN	16	94138847	missense	probably damaging	1.00
PIT4515001:Hlcs	UTSW	16	94267416	missense	probably benign	0.45
R0372:Hlcs	UTSW	16	94138907	missense	possibly damaging	0.69
R0664:Hlcs	UTSW	16	94231311	missense	probably damaging	1.00
R1465:Hlcs	UTSW	16	94268292	missense	probably damaging	0.99
R1465:Hlcs	UTSW	16	94268292	missense	probably damaging	0.99
R1761:Hlcs	UTSW	16	94268007	missense	probably benign	0.05
R2013:Hlcs	UTSW	16	94262740	missense	probably benign	0.17
R2014:Hlcs	UTSW	16	94262740	missense	probably benign	0.17
R2015:Hlcs	UTSW	16	94262740	missense	probably benign	0.17
R2204:Hlcs	UTSW	16	94231152	missense	probably benign	0.30
R2371:Hlcs	UTSW	16	94268067	missense	probably damaging	0.98
R3816:Hlcs	UTSW	16	94133088	missense	probably benign	0.11
R3822:Hlcs	UTSW	16	94267981	missense	probably benign	0.04
R4422:Hlcs	UTSW	16	94138960	missense	possibly damaging	0.56
R4657:Hlcs	UTSW	16	94262698	missense	probably benign	0.00
R4783:Hlcs	UTSW	16	94268539	missense	possibly damaging	0.82
R5347:Hlcs	UTSW	16	94267524	missense	possibly damaging	0.93
R5808:Hlcs	UTSW	16	94262632	missense	probably benign	0.00
R5940:Hlcs	UTSW	16	94134712	missense	probably damaging	0.99
R6341:Hlcs	UTSW	16	94231163	missense	probably damaging	1.00
R6943:Hlcs	UTSW	16	94141402	missense	possibly damaging	0.75
R7053:Hlcs	UTSW	16	94268015	missense	possibly damaging	0.91
R7157:Hlcs	UTSW	16	94268164	nonsense	probably null
R7166:Hlcs	UTSW	16	94262726	missense	possibly damaging	0.92
R7313:Hlcs	UTSW	16	94267503	missense	probably damaging	1.00
R7427:Hlcs	UTSW	16	94267899	missense	probably benign	0.00
R7428:Hlcs	UTSW	16	94267899	missense	probably benign	0.00
R7547:Hlcs	UTSW	16	94231172	nonsense	probably null
R7548:Hlcs	UTSW	16	94133017	nonsense	probably null
R8172:Hlcs	UTSW	16	94267626	missense	probably damaging	1.00
R8241:Hlcs	UTSW	16	94267818	missense	probably damaging	1.00
R8500:Hlcs	UTSW	16	94262758	missense	possibly damaging	0.89
R8940:Hlcs	UTSW	16	94231226	missense	probably benign
R9274:Hlcs	UTSW	16	94287926	missense	possibly damaging	0.85
R9360:Hlcs	UTSW	16	94131813	missense	probably damaging	1.00
R9361:Hlcs	UTSW	16	94138940	missense	probably benign	0.10
R9564:Hlcs	UTSW	16	94134721	missense	probably benign	0.01
X0065:Hlcs	UTSW	16	94133173	missense	probably damaging	1.00
Z1176:Hlcs	UTSW	16	94262659	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GTCAATCCTCACCAGATGCACCTTC -3'
(R):5'- ATTGTAAGCCTTAGCCTGTCGCC -3'

Sequencing Primer
(F):5'- GAATTAACAACTGGCCTCTAACTCTG -3'
(R):5'- GTCCCCTTGTAATGGGAAGTCAC -3'

Posted On

2013-09-03