Mutagenetix > Incidental Mutation

Incidental Mutation 'G4846:Ttll5'

522

Institutional Source

Beutler Lab

Gene Symbol

Ttll5

Ensembl Gene

ENSMUSG00000012609

Gene Name

tubulin tyrosine ligase-like family, member 5

Synonyms

1700048H13Rik, D630041K24Rik, STAMP, 2310009M18Rik, 4930556H18Rik

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.709) question?

Stock #

G4846 (G3) of strain Worker

Quality Score

Status

Validated

Chromosome

Chromosomal Location

85871417-86100534 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 86071018 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 1297 (I1297N)

Ref Sequence

ENSEMBL: ENSMUSP00000048809 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040179] [ENSMUST00000040273] [ENSMUST00000110224] [ENSMUST00000155448] [ENSMUST00000177114]

AlphaFold

Q8CHB8

Predicted Effect

probably damaging
Transcript: ENSMUST00000040179
AA Change: I1297N

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

SMART Domains

Protein: ENSMUSP00000048809
Gene: ENSMUSG00000012609
AA Change: I1297N

Domain	Start	End	E-Value	Type
Pfam:TTL	110	407	1.9e-94	PFAM
low complexity region	556	575	N/A	INTRINSIC
low complexity region	595	621	N/A	INTRINSIC
low complexity region	747	761	N/A	INTRINSIC
low complexity region	781	793	N/A	INTRINSIC
low complexity region	835	847	N/A	INTRINSIC
low complexity region	1167	1181	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000040273

SMART Domains

Protein: ENSMUSP00000039939
Gene: ENSMUSG00000012609

Domain	Start	End	E-Value	Type
Pfam:TTL	110	407	1e-94	PFAM
low complexity region	556	575	N/A	INTRINSIC
low complexity region	595	621	N/A	INTRINSIC
low complexity region	747	761	N/A	INTRINSIC
low complexity region	781	793	N/A	INTRINSIC
low complexity region	835	847	N/A	INTRINSIC
low complexity region	1167	1181	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000110224

SMART Domains

Protein: ENSMUSP00000105853
Gene: ENSMUSG00000012609

Domain	Start	End	E-Value	Type
Pfam:TTL	110	407	1e-94	PFAM
low complexity region	543	562	N/A	INTRINSIC
low complexity region	582	608	N/A	INTRINSIC
low complexity region	734	748	N/A	INTRINSIC
low complexity region	768	780	N/A	INTRINSIC
low complexity region	822	834	N/A	INTRINSIC
low complexity region	1153	1167	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000155448

SMART Domains

Protein: ENSMUSP00000134971
Gene: ENSMUSG00000012609

Domain	Start	End	E-Value	Type
Pfam:TTL	110	407	6.4e-95	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000175844
AA Change: I265N

SMART Domains

Protein: ENSMUSP00000134934
Gene: ENSMUSG00000012609
AA Change: I265N

Domain	Start	End	E-Value	Type
low complexity region	136	150	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177114

SMART Domains

Protein: ENSMUSP00000135395
Gene: ENSMUSG00000012609

Domain	Start	End	E-Value	Type
Pfam:TTL	110	407	2.1e-95	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000177168
AA Change: I763N

SMART Domains

Protein: ENSMUSP00000134874
Gene: ENSMUSG00000012609
AA Change: I763N

Domain	Start	End	E-Value	Type
low complexity region	3	14	N/A	INTRINSIC
low complexity region	31	57	N/A	INTRINSIC
low complexity region	183	197	N/A	INTRINSIC
low complexity region	217	229	N/A	INTRINSIC
low complexity region	271	283	N/A	INTRINSIC
low complexity region	603	617	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177525

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220906

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 77.7%
3x: 53.3%

Het Detection Efficiency

29.1%

Validation Efficiency

90% (104/115)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]
PHENOTYPE: Mice homozygous for a hypomorphic allele exhibit male infertility associated with abnormal sperm morphology and reduced tubulin polyglutamylation in the spermatozoa. [provided by MGI curators]

Allele List at MGI

All alleles(7) : Targeted, other(3) Gene trapped(4)

Other mutations in this stock

Total: 11 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	A	G	12: 71,184,683 (GRCm39)	I24V	probably benign	Het
Col4a2	T	C	8: 11,458,872 (GRCm39)		probably benign	Homo
Cyp3a13	C	T	5: 137,897,085 (GRCm39)	E410K	possibly damaging	Het
Gm20518	A	T	16: 17,654,509 (GRCm39)		probably benign	Homo
Nbea	T	A	3: 55,994,918 (GRCm39)	D166V	probably damaging	Het
Or5au1	T	A	14: 52,273,434 (GRCm39)	M45L	probably benign	Het
Or6c88	A	T	10: 129,407,039 (GRCm39)	I172F	probably damaging	Het
Plxna4	T	A	6: 32,169,207 (GRCm39)	D1330V	probably damaging	Het
Ppl	A	G	16: 4,905,070 (GRCm39)	S1742P	probably damaging	Homo
Samd4	T	A	14: 47,253,776 (GRCm39)	I80N	probably damaging	Het
Spinkl	T	A	18: 44,302,173 (GRCm39)		probably benign	Het

Other mutations in Ttll5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00844:Ttll5	APN	12	85,890,600 (GRCm39)	missense	probably damaging	1.00
IGL00932:Ttll5	APN	12	85,976,681 (GRCm39)	missense	probably damaging	1.00
IGL00964:Ttll5	APN	12	85,896,057 (GRCm39)	missense	possibly damaging	0.78
IGL00978:Ttll5	APN	12	85,980,256 (GRCm39)	nonsense	probably null
IGL00990:Ttll5	APN	12	85,923,363 (GRCm39)	missense	probably damaging	1.00
IGL01726:Ttll5	APN	12	85,965,708 (GRCm39)	missense	probably benign	0.30
IGL01797:Ttll5	APN	12	86,003,371 (GRCm39)	missense	possibly damaging	0.54
IGL02008:Ttll5	APN	12	85,980,385 (GRCm39)	missense	probably damaging	1.00
IGL02210:Ttll5	APN	12	85,959,319 (GRCm39)	intron	probably benign
IGL02979:Ttll5	APN	12	85,873,356 (GRCm39)	missense	probably damaging	1.00
IGL03079:Ttll5	APN	12	85,923,332 (GRCm39)	missense	probably damaging	1.00
IGL03149:Ttll5	APN	12	85,965,758 (GRCm39)	missense	probably damaging	0.98
PIT4812001:Ttll5	UTSW	12	85,973,635 (GRCm39)	missense	probably benign	0.12
R0045:Ttll5	UTSW	12	85,926,133 (GRCm39)	splice site	probably benign
R0153:Ttll5	UTSW	12	85,878,740 (GRCm39)	missense	probably damaging	1.00
R0282:Ttll5	UTSW	12	86,042,827 (GRCm39)	missense	probably benign	0.12
R0318:Ttll5	UTSW	12	85,923,368 (GRCm39)	critical splice donor site	probably null
R0465:Ttll5	UTSW	12	85,980,100 (GRCm39)	missense	probably benign	0.42
R0540:Ttll5	UTSW	12	85,980,450 (GRCm39)	critical splice donor site	probably null
R1086:Ttll5	UTSW	12	85,937,853 (GRCm39)	missense	possibly damaging	0.66
R1467:Ttll5	UTSW	12	85,965,736 (GRCm39)	splice site	probably null
R1470:Ttll5	UTSW	12	85,926,168 (GRCm39)	missense	possibly damaging	0.59
R1470:Ttll5	UTSW	12	85,926,168 (GRCm39)	missense	possibly damaging	0.59
R1505:Ttll5	UTSW	12	85,926,184 (GRCm39)	missense	probably damaging	1.00
R1524:Ttll5	UTSW	12	85,911,342 (GRCm39)	nonsense	probably null
R1540:Ttll5	UTSW	12	85,938,982 (GRCm39)	nonsense	probably null
R1598:Ttll5	UTSW	12	85,910,372 (GRCm39)	missense	probably damaging	0.98
R1649:Ttll5	UTSW	12	85,969,788 (GRCm39)	missense	probably damaging	1.00
R1774:Ttll5	UTSW	12	85,980,176 (GRCm39)	missense	probably benign	0.09
R2340:Ttll5	UTSW	12	85,938,922 (GRCm39)	missense	probably benign	0.02
R4049:Ttll5	UTSW	12	86,059,573 (GRCm39)	missense	probably benign	0.01
R4094:Ttll5	UTSW	12	86,003,376 (GRCm39)	nonsense	probably null
R4095:Ttll5	UTSW	12	86,003,376 (GRCm39)	nonsense	probably null
R4908:Ttll5	UTSW	12	85,965,948 (GRCm39)	missense	probably benign	0.31
R5012:Ttll5	UTSW	12	85,973,618 (GRCm39)	missense	possibly damaging	0.93
R5137:Ttll5	UTSW	12	85,969,819 (GRCm39)	missense	possibly damaging	0.83
R5416:Ttll5	UTSW	12	86,059,602 (GRCm39)	missense	possibly damaging	0.77
R5773:Ttll5	UTSW	12	85,980,329 (GRCm39)	frame shift	probably null
R5774:Ttll5	UTSW	12	85,980,329 (GRCm39)	frame shift	probably null
R6039:Ttll5	UTSW	12	85,878,729 (GRCm39)	missense	probably damaging	1.00
R6039:Ttll5	UTSW	12	85,878,729 (GRCm39)	missense	probably damaging	1.00
R6173:Ttll5	UTSW	12	85,980,151 (GRCm39)	missense	probably damaging	0.99
R6343:Ttll5	UTSW	12	86,003,473 (GRCm39)	missense	probably benign	0.00
R6449:Ttll5	UTSW	12	86,071,050 (GRCm39)	missense	probably benign	0.00
R6750:Ttll5	UTSW	12	86,003,384 (GRCm39)	missense	probably damaging	0.98
R6802:Ttll5	UTSW	12	85,926,160 (GRCm39)	missense	probably damaging	1.00
R6825:Ttll5	UTSW	12	85,930,102 (GRCm39)	splice site	probably null
R6955:Ttll5	UTSW	12	85,911,353 (GRCm39)	missense	possibly damaging	0.91
R7098:Ttll5	UTSW	12	85,964,447 (GRCm39)	critical splice acceptor site	probably null
R7154:Ttll5	UTSW	12	85,972,538 (GRCm39)	missense	probably damaging	0.98
R7215:Ttll5	UTSW	12	85,980,170 (GRCm39)	missense	probably benign	0.02
R7339:Ttll5	UTSW	12	85,904,238 (GRCm39)	critical splice donor site	probably null
R7520:Ttll5	UTSW	12	85,946,245 (GRCm39)	missense	probably damaging	1.00
R7728:Ttll5	UTSW	12	86,003,406 (GRCm39)	missense	probably benign	0.02
R7894:Ttll5	UTSW	12	85,935,948 (GRCm39)	missense	probably damaging	1.00
R8119:Ttll5	UTSW	12	86,067,322 (GRCm39)	missense	probably damaging	0.98
R8129:Ttll5	UTSW	12	85,937,858 (GRCm39)	critical splice donor site	probably null
R8200:Ttll5	UTSW	12	85,926,184 (GRCm39)	missense	probably damaging	1.00
R8357:Ttll5	UTSW	12	85,923,352 (GRCm39)	missense	probably damaging	1.00
R8413:Ttll5	UTSW	12	85,965,895 (GRCm39)	missense	probably benign	0.00
R8457:Ttll5	UTSW	12	85,923,352 (GRCm39)	missense	probably damaging	1.00
R9086:Ttll5	UTSW	12	86,071,107 (GRCm39)	missense	probably benign
R9086:Ttll5	UTSW	12	85,964,516 (GRCm39)	missense	possibly damaging	0.94
R9265:Ttll5	UTSW	12	85,937,795 (GRCm39)	nonsense	probably null
R9293:Ttll5	UTSW	12	85,937,806 (GRCm39)	missense	probably damaging	1.00
R9302:Ttll5	UTSW	12	85,873,338 (GRCm39)	missense	possibly damaging	0.63
R9621:Ttll5	UTSW	12	85,938,896 (GRCm39)	missense	possibly damaging	0.46

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 4125 of the Ttll5 transcript in exon 33 of 34 total exons. Multiple transcripts of the Ttll5 gene are displayed on Ensembl and Vega. The mutated nucleotide causes an isoleucine to asparagine substitution at amino acid 1297 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Ttll5 gene encodes a 1328 amino acid polyglutamylase, which preferentially modifies alpha-tubulin. The protein is involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step, and increases the effects of the coactivator NCOA2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction. In the presence of steroid, the protein translocates to the nucleus. TTLL5 belongs to the tubulin--tyrosine ligase family, and contains a TTL domain at residues 62-407. Two isoforms are produced by alternative splicing. .(Uniprot Q8CHB8).

The amino acid altered by the Worker mutation in the Ttll5 gene is located only in isoform 1, and is predicted to be benign by the PolyPhen program.

Posted On

2010-11-02