Incidental Mutation 'R3822:Hlcs'
ID 275242
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 040884-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3822 (G1)
Quality Score 225
Status Validated
Chromosome 16
Chromosomal Location 93929741-94114430 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 94068840 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Aspartic acid at position 274 (N274D)
Ref Sequence ENSEMBL: ENSMUSP00000153773 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000099512] [ENSMUST00000163193] [ENSMUST00000227141]
AlphaFold Q920N2
Predicted Effect probably benign
Transcript: ENSMUST00000099512
AA Change: N127D

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000097112
Gene: ENSMUSG00000040820
AA Change: N127D

DomainStartEndE-ValueType
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: N127D

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000130981
Gene: ENSMUSG00000040820
AA Change: N127D

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000227141
AA Change: N274D

PolyPhen 2 Score 0.042 (Sensitivity: 0.94; Specificity: 0.83)
Meta Mutation Damage Score 0.0654 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.6%
  • 20x: 95.9%
Validation Efficiency 100% (34/34)
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: 36 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aarsd1 T A 11: 101,301,971 (GRCm39) I332F probably damaging Het
Acp3 G T 9: 104,201,916 (GRCm39) Q76K probably damaging Het
Anp32e A T 3: 95,842,181 (GRCm39) I100L probably benign Het
Ccdc13 C A 9: 121,660,085 (GRCm39) L76F probably damaging Het
Cd44 T C 2: 102,731,738 (GRCm39) probably null Het
Chka A G 19: 3,932,038 (GRCm39) probably benign Het
Cnot6 A T 11: 49,579,999 (GRCm39) S98T probably benign Het
Cth A G 3: 157,624,136 (GRCm39) F127S probably benign Het
Dnah9 C A 11: 65,741,829 (GRCm39) probably null Het
Dysf T C 6: 84,184,070 (GRCm39) probably benign Het
Flad1 T A 3: 89,318,494 (GRCm39) I20F probably damaging Het
Gm20730 C T 6: 43,058,656 (GRCm39) S52N probably benign Het
Gpr89 A G 3: 96,800,260 (GRCm39) S113P probably benign Het
Herpud2 G A 9: 25,036,220 (GRCm39) Q147* probably null Het
Hivep1 A T 13: 42,337,787 (GRCm39) H2622L possibly damaging Het
Ido2 T C 8: 25,023,771 (GRCm39) I356V probably benign Het
Insyn2b T C 11: 34,353,007 (GRCm39) S350P probably benign Het
Itgam A G 7: 127,711,458 (GRCm39) probably null Het
Lama1 C A 17: 68,086,041 (GRCm39) probably null Het
Lrrc4b T A 7: 44,111,982 (GRCm39) V618E probably damaging Het
Man1a2 A G 3: 100,539,913 (GRCm39) I176T possibly damaging Het
Mns1 A G 9: 72,346,730 (GRCm39) E71G probably damaging Het
Ncoa6 T A 2: 155,248,858 (GRCm39) N1482I probably damaging Het
Neto2 C A 8: 86,389,924 (GRCm39) E180* probably null Het
Psmb7 A T 2: 38,503,440 (GRCm39) probably benign Het
Rin2 C T 2: 145,664,550 (GRCm39) T60M probably benign Het
Slc28a3 A G 13: 58,706,092 (GRCm39) V639A probably benign Het
Tenm2 A T 11: 35,915,147 (GRCm39) I2129N probably damaging Het
Topaz1 A G 9: 122,626,848 (GRCm39) D1492G possibly damaging Het
Trank1 G A 9: 111,207,887 (GRCm39) G1711R probably damaging Het
Trpm1 A G 7: 63,867,451 (GRCm39) probably benign Het
Ugt1a6a T A 1: 88,066,251 (GRCm39) V19E probably benign Het
Vmn2r60 A T 7: 41,785,125 (GRCm39) E112D probably damaging Het
Wdr4 T G 17: 31,731,195 (GRCm39) Q55P probably damaging Het
Xpnpep1 G A 19: 52,992,250 (GRCm39) probably benign Het
Zfyve16 A T 13: 92,657,769 (GRCm39) L714Q probably damaging Het
Other mutations in Hlcs
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- CAGTCAGTCAGGACAGATCG -3'
(R):5'- AAGGTGTCATGGAGCATGC -3'

Sequencing Primer
(F):5'- AGTCAGGACAGATCGCACCTG -3'
(R):5'- CATGCTGGCCAAGGTGATTGC -3'
Posted On 2015-04-02