TTL

tubulin tyrosine ligase, the group of Tubulin tyrosine ligase family

Basic information

Region (hg38): 2:112482156-112541739

Links

ENSG00000114999 ∙ NCBI:150465 ∙ OMIM:608291 ∙ HGNC:21586 ∙ Uniprot:Q8NG68 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTL 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					1	1
missense			12	1	1	14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	12	1	3

Variants in TTL

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

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

Position	Type	Phenotype	Significance	ClinVar
2-112482480-C-T		not specified	Uncertain significance (Apr 12, 2023)
2-112485935-T-G		not specified	Uncertain significance (Feb 01, 2025)
2-112494134-A-T			Benign (Dec 31, 2019)
2-112494189-C-G		not specified	Uncertain significance (May 15, 2024)
2-112494213-A-G		not specified	Uncertain significance (Jan 24, 2025)
2-112494246-A-G		not specified	Uncertain significance (Sep 08, 2024)
2-112494247-A-G		not specified	Uncertain significance (Oct 21, 2021)
2-112494264-A-G		not specified	Likely benign (Feb 27, 2023)
2-112494303-G-A			Benign (Dec 31, 2019)
2-112494334-A-G		not specified	Uncertain significance (Jan 23, 2023)
2-112494341-C-T			Benign (Apr 13, 2018)
2-112501232-G-C		not specified	Uncertain significance (Jan 30, 2024)
2-112501320-G-C		not specified	Uncertain significance (Mar 20, 2023)
2-112501326-G-A		not specified	Uncertain significance (Nov 17, 2023)
2-112501339-C-T			Benign (Sep 08, 2017)
2-112503120-A-T		not specified	Uncertain significance (Mar 23, 2022)
2-112503124-G-A		not specified	Uncertain significance (Nov 24, 2024)
2-112528749-A-G		not specified	Uncertain significance (Jan 31, 2025)
2-112528754-G-A		not specified	Uncertain significance (Mar 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTL	protein_coding	protein_coding	ENST00000233336	7	59586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.357	0.643	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	135	204	0.663	0.0000100	2466
Missense in Polyphen		31	79.208	0.39137		912
Synonymous	-0.222	84	81.4	1.03	0.00000447	710
Loss of Function	3.01	4	17.6	0.227	7.92e-7	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000898	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin. {ECO:0000269|PubMed:25908662}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.0843
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.221
• hipred: Y
• hipred_score: 0.700
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.234

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ttl
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;C-terminal protein-tyrosinylation;regulation of axon extension;positive regulation of mitotic cell cycle;regulation of metaphase plate congression
• Cellular component: cell
• Molecular function: tubulin-tyrosine ligase activity;ATP binding