Mutagenetix > Incidental Mutation

Incidental Mutation 'R5940:Hlcs'

462529

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

044132-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5940 (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 93935571 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 574 (M574V)

Ref Sequence

ENSEMBL: ENSMUSP00000130981 (fasta)

Gene Model

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

AlphaFold

Q920N2

Predicted Effect

probably damaging
Transcript: ENSMUST00000099512
AA Change: M574V

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000097112
Gene: ENSMUSG00000040820
AA Change: M574V

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: M574V

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000130981
Gene: ENSMUSG00000040820
AA Change: M574V

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: M721V

PolyPhen 2 Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227447

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227618

Predicted Effect

probably benign
Transcript: ENSMUST00000227698
AA Change: M93V

PolyPhen 2 Score 0.016 (Sensitivity: 0.95; Specificity: 0.79)

Predicted Effect

probably benign
Transcript: ENSMUST00000228910
AA Change: M179V

PolyPhen 2 Score 0.204 (Sensitivity: 0.92; Specificity: 0.88)

Meta Mutation Damage Score

0.1075

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 95.0%

Validation Efficiency

96% (88/92)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3425401B19Rik	T	C	14: 32,384,645 (GRCm39)	Y440C	possibly damaging	Het
Aasdh	G	T	5: 77,030,745 (GRCm39)	S618R	probably benign	Het
Alpk1	T	G	3: 127,464,595 (GRCm39)	T1228P	probably benign	Het
Ank3	T	C	10: 69,756,316 (GRCm39)	V850A	probably benign	Het
Apeh	A	T	9: 107,969,098 (GRCm39)		probably null	Het
Ash1l	C	T	3: 88,891,343 (GRCm39)	T1074I	probably damaging	Het
C3	G	A	17: 57,517,244 (GRCm39)	S1297F	possibly damaging	Het
Cchcr1	G	A	17: 35,835,890 (GRCm39)	R284Q	probably damaging	Het
Cd93	A	T	2: 148,284,152 (GRCm39)	I398N	probably benign	Het
Cdcp3	A	T	7: 130,839,992 (GRCm39)	D638V	probably damaging	Het
Chrd	G	T	16: 20,553,336 (GRCm39)	R226L	probably null	Het
Clvs1	A	T	4: 9,449,443 (GRCm39)	N344I	possibly damaging	Het
Cyp4v3	A	T	8: 45,774,821 (GRCm39)	I111N	probably damaging	Het
Cysltr2	T	A	14: 73,267,389 (GRCm39)	Y107F	probably damaging	Het
Cysltr2	T	C	14: 73,266,931 (GRCm39)	K260E	probably benign	Het
Czib	A	G	4: 107,750,485 (GRCm39)		probably benign	Het
Defb47	A	T	14: 63,238,359 (GRCm39)	E28D	probably benign	Het
Dnajc30	T	A	5: 135,093,413 (GRCm39)	Y103*	probably null	Het
Drap1	T	C	19: 5,473,028 (GRCm39)	T160A	probably benign	Het
Dsp	A	G	13: 38,380,002 (GRCm39)	E2249G	possibly damaging	Het
E2f8	T	A	7: 48,520,825 (GRCm39)	I499F	probably benign	Het
Ebf1	T	A	11: 44,512,048 (GRCm39)	Y116N	probably damaging	Het
Ecrg4	C	T	1: 43,776,401 (GRCm39)	R41*	probably null	Het
Ect2	C	A	3: 27,169,614 (GRCm39)	E746D	probably benign	Het
Enpep	T	A	3: 129,106,227 (GRCm39)	Y333F	probably damaging	Het
Fat4	T	C	3: 38,943,798 (GRCm39)	V897A	probably benign	Het
Gja3	T	A	14: 57,273,317 (GRCm39)	S352C	probably damaging	Het
Gpr153	C	A	4: 152,367,832 (GRCm39)	P561Q	probably benign	Het
Hmcn1	A	G	1: 150,532,973 (GRCm39)	V3070A	probably benign	Het
Hsd3b2	G	T	3: 98,619,287 (GRCm39)	N219K	probably benign	Het
Htra3	T	C	5: 35,810,324 (GRCm39)	I453V	possibly damaging	Het
Klrc1	A	T	6: 129,651,898 (GRCm39)	M220K	possibly damaging	Het
Kntc1	T	G	5: 123,924,258 (GRCm39)	I1048S	probably benign	Het
Lrrc37	T	C	11: 103,504,712 (GRCm39)	S243G	probably benign	Het
Macf1	T	A	4: 123,326,674 (GRCm39)	D2822V	probably damaging	Het
Mcu	T	A	10: 59,292,554 (GRCm39)	I42F	possibly damaging	Het
Mkln1	T	A	6: 31,466,307 (GRCm39)	D521E	probably damaging	Het
Ms4a13	T	C	19: 11,170,330 (GRCm39)	N5D	possibly damaging	Het
Msh3	T	G	13: 92,386,351 (GRCm39)	N838T	probably damaging	Het
Msl2	T	A	9: 100,978,290 (GRCm39)	C221*	probably null	Het
Ncapd2	A	G	6: 125,145,832 (GRCm39)	S1310P	probably benign	Het
Ncoa6	A	T	2: 155,257,785 (GRCm39)	M586K	probably damaging	Het
Ndel1	C	T	11: 68,713,397 (GRCm39)		probably benign	Het
Ndst4	T	C	3: 125,355,068 (GRCm39)		probably benign	Het
Nes	T	G	3: 87,883,259 (GRCm39)	V506G	probably damaging	Het
Nrg1	T	C	8: 32,339,372 (GRCm39)	K200E	probably damaging	Het
Nt5c1b	A	G	12: 10,425,515 (GRCm39)	K295E	probably damaging	Het
Or4f54	G	A	2: 111,122,729 (GRCm39)	V39M	possibly damaging	Het
Or5b123	T	A	19: 13,596,517 (GRCm39)		probably null	Het
Or6s1	T	A	14: 51,308,179 (GRCm39)	I224L	probably damaging	Het
Or8b4	C	T	9: 37,830,733 (GRCm39)	T260I	probably damaging	Het
Or8g51	G	T	9: 38,609,007 (GRCm39)	Y218*	probably null	Het
Or8k38	A	T	2: 86,488,394 (GRCm39)	M136K	probably damaging	Het
Otx1	C	A	11: 21,947,037 (GRCm39)	A91S	probably damaging	Het
Pde1a	A	G	2: 79,718,183 (GRCm39)		probably null	Het
Pds5a	A	G	5: 65,801,328 (GRCm39)		probably benign	Het
Plbd1	A	T	6: 136,590,719 (GRCm39)		probably benign	Het
Plod2	T	A	9: 92,473,450 (GRCm39)	V292E	probably benign	Het
Polg	A	G	7: 79,103,819 (GRCm39)	V879A	possibly damaging	Het
Ppargc1a	C	T	5: 51,631,253 (GRCm39)	A459T	probably damaging	Het
Prorp	T	A	12: 55,351,659 (GRCm39)	W323R	probably damaging	Het
Psip1	T	C	4: 83,394,559 (GRCm39)	E83G	probably damaging	Het
Rhbdf1	T	C	11: 32,159,847 (GRCm39)	D843G	probably benign	Het
Rnpepl1	G	T	1: 92,845,434 (GRCm39)	C451F	probably damaging	Het
Rrp1	T	C	10: 78,241,249 (GRCm39)	D206G	probably damaging	Het
Setbp1	A	T	18: 78,798,703 (GRCm39)	D1492E	probably damaging	Het
Sh3bp5	C	A	14: 31,099,452 (GRCm39)	R265L	probably benign	Het
Slc16a6	C	T	11: 109,364,022 (GRCm39)		probably benign	Homo
Slc7a6os	A	G	8: 106,937,437 (GRCm39)	S37P	probably damaging	Het
Tenm4	T	A	7: 96,495,102 (GRCm39)	S1140T	probably damaging	Het
Thoc6	C	A	17: 23,889,315 (GRCm39)	R115L	probably benign	Het
Tmem63c	C	T	12: 87,121,946 (GRCm39)	H385Y	probably benign	Het
Trpm8	G	T	1: 88,279,137 (GRCm39)	E649*	probably null	Het
Usf1	A	G	1: 171,245,347 (GRCm39)	E253G	possibly damaging	Het
Vps13d	T	C	4: 144,801,545 (GRCm39)	T443A	probably benign	Het
Wdr86	T	C	5: 24,927,660 (GRCm39)	Y93C	probably damaging	Het
Zfp597	A	T	16: 3,683,685 (GRCm39)	I357N	probably damaging	Het
Zfp709	A	G	8: 72,644,064 (GRCm39)	I497V	possibly damaging	Het
Zxdc	T	C	6: 90,347,307 (GRCm39)	S223P	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
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
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'- CCTCACACTCTATAGCTGCAAG -3'
(R):5'- TGCCACACATATCAGTTGAGAGG -3'

Sequencing Primer
(F):5'- TCACACTCTATAGCTGCAAGACTAG -3'
(R):5'- GAGGTCAACTGTCTGAGGC -3'

Posted On

2017-02-28