Mutagenetix > Incidental Mutation

Incidental Mutation 'R1465:Hlcs'

201104

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

039519-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1465 (G1)

Quality Score

201

Status

Not validated

Chromosome

Chromosomal Location

93929741-94114430 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 94069151 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 170 (D170G)

Ref Sequence

ENSEMBL: ENSMUSP00000153773 (fasta)

Gene Model

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

AlphaFold

Q920N2

Predicted Effect

probably damaging
Transcript: ENSMUST00000099512
AA Change: D23G

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000097112
Gene: ENSMUSG00000040820
AA Change: D23G

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: D23G

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000130981
Gene: ENSMUSG00000040820
AA Change: D23G

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

noncoding transcript
Transcript: ENSMUST00000226776

Predicted Effect

probably damaging
Transcript: ENSMUST00000227141
AA Change: D170G

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

Coding Region Coverage

1x: 97.3%
3x: 96.5%
10x: 93.6%
20x: 86.6%

Validation Efficiency

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: 105 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310030G06Rik	A	G	9: 50,651,866 (GRCm39)	Y121H	probably damaging	Het
Abca13	G	T	11: 9,349,303 (GRCm39)	G3626W	probably damaging	Het
Acvr1c	A	G	2: 58,174,973 (GRCm39)	Y192H	probably damaging	Het
Afm	A	T	5: 90,698,200 (GRCm39)	D534V	probably damaging	Het
Agl	T	C	3: 116,565,021 (GRCm39)	E1076G	probably benign	Het
Ahcyl	T	C	16: 45,974,211 (GRCm39)	K389E	probably benign	Het
Angptl3	A	T	4: 98,925,757 (GRCm39)	H361L	probably benign	Het
Apob	T	C	12: 8,061,421 (GRCm39)	F3301S	possibly damaging	Het
Arhgef33	T	A	17: 80,674,730 (GRCm39)	C376S	possibly damaging	Het
Ass1	A	G	2: 31,410,428 (GRCm39)	*413W	probably null	Het
Atp6v1h	T	A	1: 5,165,911 (GRCm39)	L127Q	probably damaging	Het
Bcl2l1	G	A	2: 152,671,870 (GRCm39)	S14F	probably damaging	Het
Bhmt1b	T	G	18: 87,775,382 (GRCm39)	F302V	probably damaging	Het
Birc6	G	A	17: 74,930,853 (GRCm39)	A2477T	probably benign	Het
Bpifb9a	G	A	2: 154,112,941 (GRCm39)	A589T	possibly damaging	Het
Casp9	C	A	4: 141,533,151 (GRCm39)	T252K	probably benign	Het
Cct4	G	A	11: 22,952,922 (GRCm39)	D533N	probably damaging	Het
Clcn6	A	C	4: 148,098,358 (GRCm39)	I555S	probably damaging	Het
Col4a4	A	T	1: 82,475,543 (GRCm39)		probably null	Het
Cyp2d10	A	T	15: 82,288,129 (GRCm39)		probably null	Het
D930048N14Rik	A	G	11: 51,545,740 (GRCm39)		probably benign	Het
Dhfr	A	G	13: 92,504,815 (GRCm39)		probably benign	Het
Dlg5	T	C	14: 24,204,764 (GRCm39)		probably null	Het
Dnah11	T	C	12: 118,002,430 (GRCm39)	E2240G	probably damaging	Het
Dnmt3a	A	G	12: 3,916,088 (GRCm39)	E17G	probably damaging	Het
Dock1	A	G	7: 134,384,138 (GRCm39)	T670A	probably benign	Het
Dpy19l2	A	G	9: 24,580,618 (GRCm39)	M241T	probably benign	Het
Dpy19l4	A	G	4: 11,296,034 (GRCm39)	S212P	probably damaging	Het
Ephb6	T	C	6: 41,593,040 (GRCm39)	F426S	probably damaging	Het
F5	A	T	1: 164,026,402 (GRCm39)	D1658V	probably benign	Het
Faah	A	T	4: 115,856,755 (GRCm39)	V469E	probably damaging	Het
Fas	T	C	19: 34,294,013 (GRCm39)	C123R	probably damaging	Het
Fhod1	T	C	8: 106,065,546 (GRCm39)		probably benign	Het
Filip1	A	G	9: 79,805,589 (GRCm39)	V55A	probably benign	Het
Frmpd1	G	A	4: 45,273,197 (GRCm39)	R372Q	probably damaging	Het
Glyctk	C	T	9: 106,034,806 (GRCm39)	G87S	probably damaging	Het
Golga3	T	C	5: 110,357,744 (GRCm39)	L1080P	probably damaging	Het
Gpr137	T	C	19: 6,915,812 (GRCm39)	T281A	probably benign	Het
Grap2	T	A	15: 80,532,612 (GRCm39)		probably null	Het
Hook1	A	G	4: 95,901,493 (GRCm39)	T484A	probably benign	Het
Hoxa5	T	A	6: 52,180,771 (GRCm39)	H187L	probably benign	Het
Inpp1	G	T	1: 52,829,253 (GRCm39)	S255R	probably benign	Het
Inpp4b	T	A	8: 82,494,786 (GRCm39)	V67E	probably damaging	Het
Iqgap3	A	G	3: 87,994,616 (GRCm39)	N105S	probably damaging	Het
Kcnq5	A	G	1: 21,539,692 (GRCm39)		probably null	Het
Klhl1	T	C	14: 96,477,649 (GRCm39)	N473S	probably benign	Het
Klk1b24	C	A	7: 43,840,785 (GRCm39)	T71N	probably benign	Het
Loxhd1	A	G	18: 77,468,269 (GRCm39)		probably null	Het
Lrp1b	C	T	2: 41,001,071 (GRCm39)	R2165Q	probably benign	Het
Lrp2bp	A	T	8: 46,478,272 (GRCm39)	Q328L	possibly damaging	Het
Lrrc63	T	A	14: 75,344,829 (GRCm39)	K419N	possibly damaging	Het
Lrrc9	A	G	12: 72,547,533 (GRCm39)	N150S	probably benign	Het
Lrrn4	C	A	2: 132,713,995 (GRCm39)	C317F	probably damaging	Het
Ltbp2	T	C	12: 84,860,074 (GRCm39)	S627G	probably damaging	Het
Macf1	A	T	4: 123,386,947 (GRCm39)	S1224T	probably damaging	Het
Meis2	A	C	2: 115,889,151 (GRCm39)	H200Q	probably benign	Het
Mesd	C	A	7: 83,544,790 (GRCm39)	A80E	probably benign	Het
Mtor	G	T	4: 148,610,450 (GRCm39)		probably benign	Het
Myo3a	T	C	2: 22,467,939 (GRCm39)	F398L	probably benign	Het
Nagpa	G	T	16: 5,019,392 (GRCm39)		probably benign	Het
Nanp	A	G	2: 150,872,749 (GRCm39)	C60R	probably benign	Het
Nectin2	T	G	7: 19,464,041 (GRCm39)	M313L	probably benign	Het
Nek4	C	T	14: 30,678,844 (GRCm39)	H123Y	probably damaging	Het
Nploc4	A	G	11: 120,299,607 (GRCm39)	V371A	probably damaging	Het
Ntrk3	T	C	7: 78,005,762 (GRCm39)		probably benign	Het
Or11g7	A	G	14: 50,690,634 (GRCm39)	T42A	possibly damaging	Het
Or13c7b	A	G	4: 43,820,723 (GRCm39)	F213L	probably benign	Het
Or52n4	T	C	7: 104,294,153 (GRCm39)	N140S	probably benign	Het
Or5b109	T	A	19: 13,212,265 (GRCm39)	V217E	possibly damaging	Het
Pcdh20	T	A	14: 88,706,673 (GRCm39)	Q209L	probably benign	Het
Pcdhb20	G	A	18: 37,637,750 (GRCm39)	R92H	probably damaging	Het
Pgap1	T	C	1: 54,567,714 (GRCm39)	H377R	probably benign	Het
Phyhipl	G	T	10: 70,406,798 (GRCm39)	P52Q	probably damaging	Het
Plekhg4	T	C	8: 106,107,672 (GRCm39)		probably benign	Het
Pwwp2a	T	A	11: 43,596,383 (GRCm39)	V516E	possibly damaging	Het
Rack1	T	C	11: 48,692,586 (GRCm39)	V69A	probably damaging	Het
Rexo5	T	A	7: 119,400,581 (GRCm39)		probably null	Het
Rnf123	T	C	9: 107,948,665 (GRCm39)		probably benign	Het
Rock1	G	T	18: 10,072,863 (GRCm39)	Q1161K	possibly damaging	Het
Rps6ka2	T	C	17: 7,560,266 (GRCm39)	L568P	probably damaging	Het
Seh1l	T	C	18: 67,917,054 (GRCm39)	S78P	probably damaging	Het
Serpinb3b	A	T	1: 107,083,573 (GRCm39)		probably null	Het
Setd1a	T	C	7: 127,387,512 (GRCm39)		probably benign	Het
Setx	G	T	2: 29,030,401 (GRCm39)		probably null	Het
Sh3bp1	T	C	15: 78,791,545 (GRCm39)		probably benign	Het
Shc2	G	T	10: 79,467,136 (GRCm39)	R146S	probably damaging	Het
Skap2	T	C	6: 51,886,348 (GRCm39)	T5A	probably benign	Het
Skor2	A	T	18: 76,964,340 (GRCm39)		probably benign	Het
Slc35a3	T	C	3: 116,480,983 (GRCm39)	I93M	probably benign	Het
Sohlh1	C	T	2: 25,733,359 (GRCm39)	G295D	probably damaging	Het
Speg	A	G	1: 75,405,128 (GRCm39)		probably benign	Het
Sult2a8	A	C	7: 14,150,208 (GRCm39)	C168G	probably benign	Het
Tax1bp1	T	C	6: 52,704,179 (GRCm39)		probably benign	Het
Tbc1d4	T	C	14: 101,685,124 (GRCm39)	I1176V	possibly damaging	Het
Tcof1	A	G	18: 60,952,026 (GRCm39)		probably benign	Het
Thada	A	T	17: 84,744,104 (GRCm39)	F735I	possibly damaging	Het
Tle1	A	C	4: 72,058,068 (GRCm39)	H52Q	probably damaging	Het
Tmem101	A	T	11: 102,044,155 (GRCm39)	V244E	probably damaging	Het
Tnfrsf26	C	A	7: 143,171,668 (GRCm39)	C95F	probably damaging	Het
Uspl1	T	C	5: 149,150,842 (GRCm39)	S482P	probably benign	Het
Vmn2r118	G	T	17: 55,917,935 (GRCm39)	N192K	probably benign	Het
Vmn2r14	C	T	5: 109,368,195 (GRCm39)	V266I	possibly damaging	Het
Vmn2r51	A	G	7: 9,834,249 (GRCm39)	I263T	probably damaging	Het
Zfp937	T	A	2: 150,080,967 (GRCm39)	C332*	probably null	Het
Zscan21	T	A	5: 138,123,470 (GRCm39)	S50T	probably benign	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
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
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'- TCCAGACACTCGTGACAGATGGAC -3'
(R):5'- TCCCAAAGCCATGACTTAGGGGAC -3'

Sequencing Primer
(F):5'- TCACTTTCAGGGGCACAG -3'
(R):5'- GCCATGACTTAGGGGACTATTTAC -3'

Posted On

2014-05-23