TTLL4

tubulin tyrosine ligase like 4, the group of Tubulin tyrosine ligase family

Basic information

Region (hg38): 2:218710835-218755416

Links

ENSG00000135912 ∙ NCBI:9654 ∙ OMIM:618738 ∙ HGNC:28976 ∙ Uniprot:Q14679 ∙ 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 TTLL4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTLL4 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					3	3
missense			59	2	1	62
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	59	2	4

Variants in TTLL4

This is a list of pathogenic ClinVar variants found in the TTLL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-218737717-G-T		not specified	Uncertain significance (Jan 07, 2022)
2-218737787-G-A			Benign (May 21, 2018)
2-218737788-G-A		not specified	Uncertain significance (Oct 03, 2024)
2-218737817-G-T			Benign (Dec 31, 2019)
2-218737996-C-T		not specified	Uncertain significance (Apr 17, 2024)
2-218738004-G-C		not specified	Uncertain significance (Aug 05, 2024)
2-218738013-A-G		not specified	Uncertain significance (Oct 27, 2023)
2-218738034-C-T		not specified	Uncertain significance (Sep 26, 2023)
2-218738056-C-T		not specified	Uncertain significance (Jun 27, 2022)
2-218738085-C-T		not specified	Uncertain significance (Feb 17, 2023)
2-218738089-C-T			Likely benign (May 24, 2018)
2-218738211-A-G		not specified	Uncertain significance (Nov 18, 2024)
2-218738236-C-T		not specified	Uncertain significance (Feb 02, 2022)
2-218738261-G-T		not specified	Uncertain significance (Dec 13, 2023)
2-218738271-T-C		not specified	Uncertain significance (Dec 03, 2024)
2-218738338-C-G		not specified	Uncertain significance (May 28, 2024)
2-218738404-C-T		not specified	Uncertain significance (Jul 11, 2023)
2-218738418-C-A		not specified	Uncertain significance (Oct 27, 2023)
2-218738484-G-T		not specified	Uncertain significance (Mar 03, 2022)
2-218738533-C-A		not specified	Uncertain significance (Nov 08, 2022)
2-218738544-G-A		not specified	Uncertain significance (Aug 15, 2023)
2-218738623-C-T		not specified	Uncertain significance (Nov 28, 2024)
2-218738668-C-G		not specified	Uncertain significance (Feb 21, 2024)
2-218738679-C-T		not specified	Uncertain significance (Jun 18, 2021)
2-218738680-G-A		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTLL4	protein_coding	protein_coding	ENST00000392102	18	44572

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.68e-13	1.00	125482	3	263	125748	0.00106

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.754	612	667	0.918	0.0000381	7846
Missense in Polyphen		108	142.62	0.75725		1715
Synonymous	-0.958	280	260	1.08	0.0000150	2386
Loss of Function	3.45	30	58.4	0.513	0.00000345	626

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00313	0.00313
Ashkenazi Jewish	0.00119	0.00119
East Asian	0.000326	0.000326
Finnish	0.00102	0.00102
European (Non-Finnish)	0.00107	0.00106
Middle Eastern	0.000326	0.000326
South Asian	0.000196	0.000163
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glutamylase which preferentially modifies beta-tubulin and non-tubulin proteins, such as NAP1L1, NAP1L4 and CGAS. Involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step. Involved in formation of short side-chains. Mediates initiation of polyglutamylation of nucleosome assembly proteins NAP1L1 and NAP1L4. Also acts as a monoglutamylase: generates monoglutamylation of CGAS, leading to impair the nucleotidyltransferase activity of CGAS. {ECO:0000250|UniProtKB:Q80UG8}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Recessive Scores

• pRec: 0.0937

Intolerance Scores

• loftool: 0.775
• rvis_EVS: 1.68
• rvis_percentile_EVS: 96.34

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.372
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.108

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttll4
• Phenotype: growth/size/body region phenotype

Gene ontology

• Biological process: protein polyglutamylation;peptidyl-glutamic acid modification
• Cellular component: cytosol;microtubule;cilium
• Molecular function: ATP binding;tubulin binding;protein-glutamic acid ligase activity;tubulin-glutamic acid ligase activity