Incidental Mutation 'N/A:Crocc'
ID 38
Institutional Source Beutler Lab
Gene Symbol Crocc
Ensembl Gene ENSMUSG00000040860
Gene Name ciliary rootlet coiled-coil, rootletin
Synonyms
Accession Numbers
Essential gene? Probably non essential (E-score: 0.174) question?
Stock # N/A of strain 294
Quality Score
Status Validated
Chromosome 4
Chromosomal Location 140743948-140787861 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 140749057 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Arginine to Cysteine at position 1419 (R1419C)
Ref Sequence ENSEMBL: ENSMUSP00000126543 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000040222] [ENSMUST00000097816] [ENSMUST00000102491] [ENSMUST00000168157]
AlphaFold Q8CJ40
Predicted Effect probably damaging
Transcript: ENSMUST00000040222
AA Change: R1419C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000037679
Gene: ENSMUSG00000040860
AA Change: R1419C

DomainStartEndE-ValueType
Pfam:Rootletin 1 173 6.1e-48 PFAM
low complexity region 190 217 N/A INTRINSIC
internal_repeat_2 298 315 1.08e-6 PROSPERO
low complexity region 329 350 N/A INTRINSIC
internal_repeat_3 363 393 5.38e-6 PROSPERO
internal_repeat_6 369 392 2.67e-5 PROSPERO
low complexity region 397 411 N/A INTRINSIC
low complexity region 412 430 N/A INTRINSIC
low complexity region 453 474 N/A INTRINSIC
low complexity region 624 643 N/A INTRINSIC
low complexity region 699 716 N/A INTRINSIC
low complexity region 845 875 N/A INTRINSIC
internal_repeat_4 886 904 2.67e-5 PROSPERO
internal_repeat_7 893 906 5.96e-5 PROSPERO
internal_repeat_2 893 910 1.08e-6 PROSPERO
internal_repeat_4 897 914 2.67e-5 PROSPERO
internal_repeat_1 912 937 1.97e-8 PROSPERO
internal_repeat_7 1028 1041 5.96e-5 PROSPERO
low complexity region 1107 1124 N/A INTRINSIC
internal_repeat_5 1138 1164 2.67e-5 PROSPERO
low complexity region 1190 1201 N/A INTRINSIC
low complexity region 1253 1269 N/A INTRINSIC
low complexity region 1270 1289 N/A INTRINSIC
low complexity region 1297 1309 N/A INTRINSIC
internal_repeat_6 1533 1556 2.67e-5 PROSPERO
low complexity region 1559 1576 N/A INTRINSIC
coiled coil region 1580 1707 N/A INTRINSIC
coiled coil region 1728 1832 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000097816
AA Change: R1419C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000095425
Gene: ENSMUSG00000040860
AA Change: R1419C

DomainStartEndE-ValueType
Pfam:Rootletin 1 173 6.1e-48 PFAM
low complexity region 190 217 N/A INTRINSIC
internal_repeat_2 298 315 1.08e-6 PROSPERO
low complexity region 329 350 N/A INTRINSIC
internal_repeat_3 363 393 5.38e-6 PROSPERO
internal_repeat_6 369 392 2.67e-5 PROSPERO
low complexity region 397 411 N/A INTRINSIC
low complexity region 412 430 N/A INTRINSIC
low complexity region 453 474 N/A INTRINSIC
low complexity region 624 643 N/A INTRINSIC
low complexity region 699 716 N/A INTRINSIC
low complexity region 845 875 N/A INTRINSIC
internal_repeat_4 886 904 2.67e-5 PROSPERO
internal_repeat_7 893 906 5.96e-5 PROSPERO
internal_repeat_2 893 910 1.08e-6 PROSPERO
internal_repeat_4 897 914 2.67e-5 PROSPERO
internal_repeat_1 912 937 1.97e-8 PROSPERO
internal_repeat_7 1028 1041 5.96e-5 PROSPERO
low complexity region 1107 1124 N/A INTRINSIC
internal_repeat_5 1138 1164 2.67e-5 PROSPERO
low complexity region 1190 1201 N/A INTRINSIC
low complexity region 1253 1269 N/A INTRINSIC
low complexity region 1270 1289 N/A INTRINSIC
low complexity region 1297 1309 N/A INTRINSIC
internal_repeat_6 1533 1556 2.67e-5 PROSPERO
low complexity region 1559 1576 N/A INTRINSIC
coiled coil region 1580 1707 N/A INTRINSIC
coiled coil region 1728 1832 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000102491
AA Change: R1583C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000099549
Gene: ENSMUSG00000040860
AA Change: R1583C

DomainStartEndE-ValueType
low complexity region 2 15 N/A INTRINSIC
low complexity region 77 93 N/A INTRINSIC
Pfam:Rootletin 158 336 9.7e-65 PFAM
low complexity region 354 381 N/A INTRINSIC
internal_repeat_2 462 479 1.77e-6 PROSPERO
low complexity region 493 514 N/A INTRINSIC
internal_repeat_3 527 557 8.63e-6 PROSPERO
internal_repeat_6 533 556 4.21e-5 PROSPERO
low complexity region 561 575 N/A INTRINSIC
low complexity region 576 594 N/A INTRINSIC
low complexity region 617 638 N/A INTRINSIC
low complexity region 788 807 N/A INTRINSIC
low complexity region 863 880 N/A INTRINSIC
low complexity region 1009 1039 N/A INTRINSIC
internal_repeat_4 1050 1068 4.21e-5 PROSPERO
internal_repeat_7 1057 1070 9.31e-5 PROSPERO
internal_repeat_2 1057 1074 1.77e-6 PROSPERO
internal_repeat_4 1061 1078 4.21e-5 PROSPERO
internal_repeat_1 1076 1101 3.36e-8 PROSPERO
internal_repeat_7 1192 1205 9.31e-5 PROSPERO
low complexity region 1271 1288 N/A INTRINSIC
internal_repeat_5 1302 1328 4.21e-5 PROSPERO
low complexity region 1354 1365 N/A INTRINSIC
low complexity region 1417 1433 N/A INTRINSIC
low complexity region 1434 1453 N/A INTRINSIC
low complexity region 1461 1473 N/A INTRINSIC
internal_repeat_6 1697 1720 4.21e-5 PROSPERO
low complexity region 1723 1740 N/A INTRINSIC
coiled coil region 1744 1871 N/A INTRINSIC
coiled coil region 1892 1996 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000122846
Predicted Effect noncoding transcript
Transcript: ENSMUST00000124286
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126973
Predicted Effect probably damaging
Transcript: ENSMUST00000168157
AA Change: R1419C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000126543
Gene: ENSMUSG00000040860
AA Change: R1419C

DomainStartEndE-ValueType
Pfam:Rootletin 1 173 6.1e-48 PFAM
low complexity region 190 217 N/A INTRINSIC
internal_repeat_2 298 315 1.08e-6 PROSPERO
low complexity region 329 350 N/A INTRINSIC
internal_repeat_3 363 393 5.38e-6 PROSPERO
internal_repeat_6 369 392 2.67e-5 PROSPERO
low complexity region 397 411 N/A INTRINSIC
low complexity region 412 430 N/A INTRINSIC
low complexity region 453 474 N/A INTRINSIC
low complexity region 624 643 N/A INTRINSIC
low complexity region 699 716 N/A INTRINSIC
low complexity region 845 875 N/A INTRINSIC
internal_repeat_4 886 904 2.67e-5 PROSPERO
internal_repeat_7 893 906 5.96e-5 PROSPERO
internal_repeat_2 893 910 1.08e-6 PROSPERO
internal_repeat_4 897 914 2.67e-5 PROSPERO
internal_repeat_1 912 937 1.97e-8 PROSPERO
internal_repeat_7 1028 1041 5.96e-5 PROSPERO
low complexity region 1107 1124 N/A INTRINSIC
internal_repeat_5 1138 1164 2.67e-5 PROSPERO
low complexity region 1190 1201 N/A INTRINSIC
low complexity region 1253 1269 N/A INTRINSIC
low complexity region 1270 1289 N/A INTRINSIC
low complexity region 1297 1309 N/A INTRINSIC
internal_repeat_6 1533 1556 2.67e-5 PROSPERO
low complexity region 1559 1576 N/A INTRINSIC
coiled coil region 1580 1707 N/A INTRINSIC
coiled coil region 1728 1832 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151455
Predicted Effect noncoding transcript
Transcript: ENSMUST00000137721
Meta Mutation Damage Score 0.1397 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 76.0%
Validation Efficiency 91% (106/116)
MGI Phenotype PHENOTYPE: Mice homozygous for a null mutation show no apparent functional deficits in phototransduction and ciliary beating in sensory and motile cilia. However, photoreceptors degenerate over time, and lungs appear prone to pathological changes. [provided by MGI curators]
Allele List at MGI

All alleles(4) : Targeted, knock-out(1) Gene trapped(3)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700016P04Rik T A 6: 13,415,772 (GRCm39) noncoding transcript Homo
Aif1 A G 17: 35,391,496 (GRCm39) L7S possibly damaging Homo
Ankrd26 T C 6: 118,506,535 (GRCm39) D646G probably benign Homo
Cacna1s A G 1: 136,001,247 (GRCm39) I233V probably benign Homo
Cfap92 A T 6: 87,667,773 (GRCm39) noncoding transcript Homo
Chchd4 T C 6: 91,442,187 (GRCm39) Y77C probably damaging Homo
Cyp4f39 A C 17: 32,687,655 (GRCm39) M74L probably benign Homo
Fgf9 C A 14: 58,327,421 (GRCm39) probably benign Homo
Gimap6 T C 6: 48,679,349 (GRCm39) D229G probably damaging Homo
Glp1r T C 17: 31,150,257 (GRCm39) F393S probably damaging Homo
Lrrc7 T G 3: 157,865,977 (GRCm39) I1255L probably benign Homo
Mtrr C A 13: 68,723,516 (GRCm39) probably benign Homo
Pde6b A T 5: 108,576,969 (GRCm39) probably benign Homo
Rbm19 A T 5: 120,282,162 (GRCm39) I840F probably damaging Homo
Serpina3c A C 12: 104,115,864 (GRCm39) S227A probably benign Homo
Spag17 G A 3: 99,889,570 (GRCm39) probably benign Homo
Spmip3 G A 1: 177,561,100 (GRCm39) R13H probably damaging Homo
Zbtb8b T C 4: 129,326,361 (GRCm39) D268G probably benign Homo
Other mutations in Crocc
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01389:Crocc APN 4 140,749,423 (GRCm39) missense probably damaging 1.00
IGL01474:Crocc APN 4 140,762,703 (GRCm39) splice site probably benign
IGL01859:Crocc APN 4 140,756,601 (GRCm39) missense probably benign 0.07
IGL02161:Crocc APN 4 140,761,302 (GRCm39) missense probably benign 0.01
IGL02244:Crocc APN 4 140,765,231 (GRCm39) missense probably benign 0.00
IGL02970:Crocc APN 4 140,757,557 (GRCm39) missense possibly damaging 0.49
R0158:Crocc UTSW 4 140,769,553 (GRCm39) splice site probably benign
R0280:Crocc UTSW 4 140,755,737 (GRCm39) missense probably damaging 1.00
R0448:Crocc UTSW 4 140,769,502 (GRCm39) missense probably damaging 1.00
R0532:Crocc UTSW 4 140,757,558 (GRCm39) missense possibly damaging 0.95
R0597:Crocc UTSW 4 140,744,382 (GRCm39) missense probably benign
R0597:Crocc UTSW 4 140,747,224 (GRCm39) missense probably benign 0.06
R0761:Crocc UTSW 4 140,774,387 (GRCm39) missense probably benign 0.01
R0761:Crocc UTSW 4 140,757,087 (GRCm39) missense probably benign 0.00
R1238:Crocc UTSW 4 140,762,675 (GRCm39) missense probably benign 0.00
R1460:Crocc UTSW 4 140,756,551 (GRCm39) nonsense probably null
R1515:Crocc UTSW 4 140,747,048 (GRCm39) missense probably benign 0.00
R1557:Crocc UTSW 4 140,752,776 (GRCm39) missense probably damaging 0.96
R1561:Crocc UTSW 4 140,757,579 (GRCm39) missense probably damaging 1.00
R1641:Crocc UTSW 4 140,744,388 (GRCm39) missense probably benign 0.00
R1709:Crocc UTSW 4 140,753,410 (GRCm39) critical splice donor site probably null
R1785:Crocc UTSW 4 140,749,113 (GRCm39) missense probably damaging 0.99
R1786:Crocc UTSW 4 140,749,113 (GRCm39) missense probably damaging 0.99
R1793:Crocc UTSW 4 140,746,620 (GRCm39) missense probably damaging 1.00
R1897:Crocc UTSW 4 140,746,047 (GRCm39) missense probably damaging 1.00
R1935:Crocc UTSW 4 140,761,369 (GRCm39) missense possibly damaging 0.78
R2037:Crocc UTSW 4 140,774,253 (GRCm39) critical splice donor site probably null
R2127:Crocc UTSW 4 140,744,407 (GRCm39) missense probably damaging 1.00
R2129:Crocc UTSW 4 140,744,407 (GRCm39) missense probably damaging 1.00
R2130:Crocc UTSW 4 140,756,413 (GRCm39) missense probably benign 0.04
R2136:Crocc UTSW 4 140,760,265 (GRCm39) missense probably damaging 1.00
R2298:Crocc UTSW 4 140,752,770 (GRCm39) missense probably benign 0.30
R2847:Crocc UTSW 4 140,746,067 (GRCm39) missense probably damaging 0.97
R2848:Crocc UTSW 4 140,746,067 (GRCm39) missense probably damaging 0.97
R2913:Crocc UTSW 4 140,747,661 (GRCm39) missense probably damaging 1.00
R3415:Crocc UTSW 4 140,773,758 (GRCm39) missense possibly damaging 0.75
R3416:Crocc UTSW 4 140,773,758 (GRCm39) missense possibly damaging 0.75
R3417:Crocc UTSW 4 140,773,758 (GRCm39) missense possibly damaging 0.75
R4082:Crocc UTSW 4 140,761,282 (GRCm39) splice site probably null
R4454:Crocc UTSW 4 140,747,716 (GRCm39) missense possibly damaging 0.52
R4591:Crocc UTSW 4 140,745,983 (GRCm39) missense probably damaging 1.00
R4597:Crocc UTSW 4 140,747,088 (GRCm39) missense probably damaging 1.00
R4984:Crocc UTSW 4 140,761,763 (GRCm39) missense probably damaging 1.00
R4992:Crocc UTSW 4 140,773,977 (GRCm39) missense probably damaging 0.98
R5109:Crocc UTSW 4 140,755,722 (GRCm39) missense probably damaging 1.00
R5143:Crocc UTSW 4 140,768,350 (GRCm39) missense probably benign 0.01
R5381:Crocc UTSW 4 140,756,622 (GRCm39) missense possibly damaging 0.95
R5684:Crocc UTSW 4 140,778,455 (GRCm39) missense probably damaging 0.99
R5757:Crocc UTSW 4 140,770,875 (GRCm39) missense probably damaging 1.00
R5795:Crocc UTSW 4 140,769,118 (GRCm39) frame shift probably null
R5796:Crocc UTSW 4 140,769,118 (GRCm39) frame shift probably null
R5798:Crocc UTSW 4 140,769,118 (GRCm39) frame shift probably null
R5815:Crocc UTSW 4 140,762,507 (GRCm39) missense probably damaging 0.99
R5955:Crocc UTSW 4 140,745,229 (GRCm39) missense possibly damaging 0.75
R6031:Crocc UTSW 4 140,761,668 (GRCm39) critical splice donor site probably null
R6063:Crocc UTSW 4 140,773,851 (GRCm39) missense probably damaging 1.00
R6063:Crocc UTSW 4 140,769,032 (GRCm39) missense probably benign 0.08
R7086:Crocc UTSW 4 140,774,368 (GRCm39) missense possibly damaging 0.47
R7282:Crocc UTSW 4 140,749,652 (GRCm39) missense probably damaging 1.00
R7293:Crocc UTSW 4 140,770,867 (GRCm39) missense probably benign 0.17
R7404:Crocc UTSW 4 140,753,497 (GRCm39) missense possibly damaging 0.46
R7571:Crocc UTSW 4 140,773,360 (GRCm39) critical splice acceptor site probably null
R7646:Crocc UTSW 4 140,748,966 (GRCm39) missense probably null 0.94
R7782:Crocc UTSW 4 140,752,597 (GRCm39) missense probably benign 0.05
R8053:Crocc UTSW 4 140,770,230 (GRCm39) critical splice donor site probably null
R8762:Crocc UTSW 4 140,761,369 (GRCm39) missense possibly damaging 0.78
R9021:Crocc UTSW 4 140,749,674 (GRCm39) missense probably benign 0.00
R9188:Crocc UTSW 4 140,747,151 (GRCm39) missense probably benign 0.04
R9272:Crocc UTSW 4 140,747,132 (GRCm39) missense probably benign 0.00
R9411:Crocc UTSW 4 140,749,577 (GRCm39) critical splice donor site probably null
R9647:Crocc UTSW 4 140,774,335 (GRCm39) missense probably benign 0.00
R9667:Crocc UTSW 4 140,748,988 (GRCm39) missense probably damaging 1.00
R9706:Crocc UTSW 4 140,746,046 (GRCm39) missense possibly damaging 0.76
R9780:Crocc UTSW 4 140,756,556 (GRCm39) missense probably benign 0.01
X0065:Crocc UTSW 4 140,769,103 (GRCm39) missense possibly damaging 0.57
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to T transition at position 4829 of the Crocc transcript, in exon 32 of 39 total exons. Multiple isoforms of Crocc are displayed on Ensembl. The mutated nucleotide causes an arginine to threonine substitution at amino acid 1583. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Crocc gene encodes a 2009 amino acid protein, known as rootletin, that is a major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells that originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus. Rootletin also contributes to centrosome cohesion before mitosis. Rootletin forms homopolymers and is detected in all major ciliated epithelia with highest expression in photoreceptor cells. The protein consists of multiple internal repeats that have a coiled coil structure (Uniprot  Q8CJ40). Mice homozygous for a null mutation in the Crocc gene show no apparent functional deficits in phototransduction and ciliary beating in sensory and motile cilia. However, photoreceptors degenerate over time, and lungs appear prone to pathological changes. 
 
The R1583T mutation is located in one of the coiled coil regions of rootletin, but is predicted to be benign by the PolyPhen program.
Posted On 2009-11-09