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

93929741-94114430 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 93932711 bp (GRCm39)

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
Acsm3	A	T	7: 119,367,247 (GRCm39)	R27*	probably null	Het
Actg1	A	G	11: 120,237,775 (GRCm39)	F255S	probably damaging	Het
Ahdc1	T	A	4: 132,790,262 (GRCm39)	V501E	possibly damaging	Het
Alpk2	A	T	18: 65,438,461 (GRCm39)	D1444E	probably damaging	Het
Btaf1	T	G	19: 36,974,895 (GRCm39)		probably null	Het
Cacnb2	A	G	2: 14,990,517 (GRCm39)	H489R	possibly damaging	Het
Ccdc162	C	A	10: 41,455,139 (GRCm39)	K398N	probably damaging	Het
Cd79b	G	T	11: 106,203,259 (GRCm39)	S145R	probably damaging	Het
Cdh11	T	A	8: 103,394,651 (GRCm39)	N264Y	probably damaging	Het
Celsr1	T	C	15: 85,785,798 (GRCm39)	D2892G	probably benign	Het
Chuk	A	G	19: 44,092,205 (GRCm39)		probably benign	Het
Clk3	T	C	9: 57,658,409 (GRCm39)		probably benign	Het
Dcaf8	A	T	1: 172,000,076 (GRCm39)	D78V	possibly damaging	Het
Dctn1	A	G	6: 83,160,071 (GRCm39)	T87A	probably damaging	Het
Ddx50	T	C	10: 62,452,028 (GRCm39)	N732D	unknown	Het
Dnah5	A	T	15: 28,311,289 (GRCm39)	Y1756F	possibly damaging	Het
Dock3	A	T	9: 106,847,055 (GRCm39)	V858E	probably damaging	Het
Fer1l4	A	G	2: 155,865,990 (GRCm39)	F1566S	probably benign	Het
Fpr-rs7	T	C	17: 20,334,116 (GRCm39)	I125V	probably benign	Het
Fuca2	C	T	10: 13,381,771 (GRCm39)	P228L	probably benign	Het
Galntl6	A	G	8: 58,989,018 (GRCm39)	F57L	probably benign	Het
Gigyf2	T	A	1: 87,335,449 (GRCm39)		probably benign	Het
Gm16505	A	T	13: 3,411,329 (GRCm39)		noncoding transcript	Het
Gm4781	T	C	10: 100,232,639 (GRCm39)		noncoding transcript	Het
Gm9956	T	A	10: 56,621,639 (GRCm39)	Y100*	probably null	Het
Gpr137c	T	A	14: 45,483,806 (GRCm39)	C178S	probably damaging	Het
Gpr83	A	G	9: 14,779,940 (GRCm39)	R331G	probably benign	Het
Irag1	T	C	7: 110,476,107 (GRCm39)	S615G	probably benign	Het
Kbtbd6	C	A	14: 79,689,324 (GRCm39)	Y6*	probably null	Het
Kif23	T	C	9: 61,832,314 (GRCm39)	R610G	possibly damaging	Het
Kifc3	G	A	8: 95,832,361 (GRCm39)	T487I	probably damaging	Het
Klra5	A	C	6: 129,885,759 (GRCm39)	D133E	possibly damaging	Het
Klra6	T	C	6: 129,999,668 (GRCm39)	E100G	probably damaging	Het
Klre1	T	A	6: 129,562,531 (GRCm39)		probably benign	Het
Lancl1	C	T	1: 67,049,069 (GRCm39)		probably null	Het
Lgr6	C	T	1: 134,921,748 (GRCm39)	A199T	probably damaging	Het
Man1b1	A	G	2: 25,228,167 (GRCm39)	I146V	possibly damaging	Het
Map4k5	T	A	12: 69,921,038 (GRCm39)		probably benign	Het
Mast3	A	G	8: 71,233,965 (GRCm39)	S178P	probably damaging	Het
Mau2	A	G	8: 70,476,262 (GRCm39)		probably null	Het
Mgat4f	A	C	1: 134,317,713 (GRCm39)	M162L	probably benign	Het
Mkrn2	A	T	6: 115,591,612 (GRCm39)	N312Y	probably damaging	Het
Myh1	A	G	11: 67,093,359 (GRCm39)	E150G	probably damaging	Het
Myo7b	T	A	18: 32,094,878 (GRCm39)		probably null	Het
Nyap1	A	G	5: 137,733,560 (GRCm39)	V491A	probably damaging	Het
Or10a3	A	T	7: 108,480,740 (GRCm39)	N24K	probably damaging	Het
Or4g17	A	G	2: 111,209,638 (GRCm39)	M98V	probably damaging	Het
Or5p60	T	C	7: 107,723,941 (GRCm39)	I176M	probably benign	Het
Or8g34	T	C	9: 39,372,828 (GRCm39)	F34L	probably damaging	Het
Oxsm	A	T	14: 16,240,893 (GRCm38)	H385Q	probably damaging	Het
Pbld2	T	C	10: 62,892,590 (GRCm39)	S242P	probably damaging	Het
Pdzd7	T	C	19: 45,017,744 (GRCm39)	Y675C	probably damaging	Het
Pnkd	T	A	1: 74,390,700 (GRCm39)	H266Q	probably damaging	Het
Rbfox2	A	G	15: 76,983,479 (GRCm39)	S141P	probably benign	Het
Rdx	A	G	9: 51,979,518 (GRCm39)	T214A	probably benign	Het
Ripor2	A	T	13: 24,864,627 (GRCm39)	E219V	probably damaging	Het
Rlig1	T	C	10: 100,422,065 (GRCm39)	T66A	probably damaging	Het
Rufy2	G	A	10: 62,847,623 (GRCm39)		probably benign	Het
Slf2	T	A	19: 44,964,165 (GRCm39)		probably benign	Het
Snrnp200	G	T	2: 127,068,065 (GRCm39)		probably benign	Het
Snx7	T	A	3: 117,623,320 (GRCm39)		probably benign	Het
Stt3a	T	C	9: 36,646,808 (GRCm39)	I602V	probably damaging	Het
Tacr3	G	A	3: 134,560,761 (GRCm39)		probably null	Het
Tcerg1	C	T	18: 42,704,905 (GRCm39)	T978M	probably damaging	Het
Tcf7l1	G	T	6: 72,765,252 (GRCm39)	P126Q	possibly damaging	Het
Trank1	A	G	9: 111,194,556 (GRCm39)	D860G	probably damaging	Het
Try4	T	C	6: 41,281,301 (GRCm39)	L81P	probably benign	Het
Ucp1	T	C	8: 84,024,476 (GRCm39)		probably benign	Het
Ugt2b38	G	A	5: 87,568,311 (GRCm39)	A328V	probably damaging	Het
Wfikkn1	T	A	17: 26,096,991 (GRCm39)	R444S	probably damaging	Het
Zfc3h1	A	G	10: 115,246,537 (GRCm39)	T875A	probably benign	Het
Zfp11	A	G	5: 129,734,328 (GRCm39)	S378P	probably damaging	Het
Zfp984	T	A	4: 147,840,689 (GRCm39)	N54I	probably damaging	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
R0372:Hlcs	UTSW	16	93,939,766 (GRCm39)	missense	possibly damaging	0.69
R0664:Hlcs	UTSW	16	94,032,170 (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'- GTCAATCCTCACCAGATGCACCTTC -3'
(R):5'- ATTGTAAGCCTTAGCCTGTCGCC -3'

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

Posted On

2013-09-03