TTLL5

tubulin tyrosine ligase like 5, the group of Tubulin tyrosine ligase family

Basic information

Region (hg38): 14:75633624-75955079

Previous symbols: [ "KIAA0998" ]

Links

ENSG00000119685 ∙ NCBI:23093 ∙ OMIM:612268 ∙ HGNC:19963 ∙ Uniprot:Q6EMB2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy 19 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 19 (Moderate), mode of inheritance: AR
• cone-rod dystrophy 19 (Definitive), mode of inheritance: AR
• inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy 19	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	24791901

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTLL5 gene.

• not provided (867 variants)
• Inborn genetic diseases (58 variants)
• Cone-rod dystrophy 19 (11 variants)
• Retinal dystrophy (9 variants)
• not specified (6 variants)
• Cone-rod dystrophy (4 variants)
• TTLL5-related condition (2 variants)
• Central areolar choroidal dystrophy (1 variants)
• Retinitis pigmentosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTLL5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	161	9	175
missense	1		415	12	6	434
nonsense	18	8				26
start loss		1				1
frameshift	25	2	1			28
inframe indel			8			8
splice donor/acceptor (+/-2bp)	2	14	1		1	18
splice region			24	37	10	71
non coding		2	13	86	21	122
Total	46	27	443	259	37

Highest pathogenic variant AF is 0.000112

Variants in TTLL5

This is a list of pathogenic ClinVar variants found in the TTLL5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-75633653-C-T		Fowler syndrome	Pathogenic (Aug 01, 2010)
14-75633674-G-A		Posterior column ataxia-retinitis pigmentosa syndrome	Conflicting classifications of pathogenicity (Apr 06, 2021)
14-75633674-G-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
14-75633685-T-A			Uncertain significance (Aug 10, 2023)
14-75633685-TG-T			Likely pathogenic (Aug 22, 2017)
14-75633695-C-T		Fowler syndrome	Uncertain significance (Jul 14, 2022)
14-75633770-T-C			Likely benign (Jun 17, 2020)
14-75634641-A-C			Benign (Dec 12, 2020)
14-75634779-C-T			Likely benign (Jun 16, 2020)
14-75634905-C-T		FLVCR2-related disorder	Likely benign (Jul 12, 2023)
14-75634942-G-A			Likely benign (Jan 20, 2023)
14-75634948-C-G		Inborn genetic diseases	Uncertain significance (Apr 14, 2022)
14-75634956-C-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
14-75635001-C-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
14-75635007-C-G		Inborn genetic diseases	Uncertain significance (Mar 04, 2022)
14-75635014-G-T			Likely pathogenic (Jan 26, 2024)
14-75635043-T-C			Benign (Sep 04, 2019)
14-75635049-A-G			Benign (Dec 12, 2020)
14-75639155-G-A			Likely benign (Jan 13, 2021)
14-75639167-C-T			Likely benign (Apr 15, 2021)
14-75639383-CTG-C		Posterior column ataxia-retinitis pigmentosa syndrome	Uncertain significance (Aug 25, 2017)
14-75639387-T-C		Inborn genetic diseases	Uncertain significance (Aug 09, 2021)
14-75639388-G-A			Likely benign (Nov 24, 2022)
14-75639398-G-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
14-75639419-C-G		Fowler syndrome	Pathogenic (Mar 12, 2010)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTLL5	protein_coding	protein_coding	ENST00000298832	31	321454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.92e-22	0.999	125511	2	235	125748	0.000943

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0400	725	722	1.00	0.0000404	8371
Missense in Polyphen		140	160.74	0.87099		1870
Synonymous	0.304	252	258	0.976	0.0000138	2478
Loss of Function	3.37	48	80.6	0.595	0.00000495	841

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00223	0.00222
Ashkenazi Jewish	0.00	0.00
East Asian	0.00387	0.00349
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000708	0.000703
Middle Eastern	0.00387	0.00349
South Asian	0.00112	0.00111
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Polyglutamylase which preferentially modifies alpha- tubulin. Involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step (By similarity). Required for CCSAP localization to both spindle and cilia microtubules. Increases the effects of NCOA2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (PubMed:17116691, PubMed:22493317). {ECO:0000250|UniProtKB:Q8CHB8, ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:22493317}.
• Disease: DISEASE: Cone-rod dystrophy 19 (CORD19) [MIM:615860]: A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:24791901}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Intolerance Scores

• loftool: 0.959
• rvis_EVS: -0.92
• rvis_percentile_EVS: 9.83

Haploinsufficiency Scores

• pHI: 0.606
• hipred: N
• hipred_score: 0.426
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ttll5
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: protein polyglutamylation;retina development in camera-type eye
• Cellular component: nucleus;centrosome;cytosol;microtubule;plasma membrane;cilium
• Molecular function: ATP binding;tubulin-glutamic acid ligase activity