TTLL2

protein-coding

tubulin tyrosine ligase like 2, the group of Tubulin tyrosine ligase family

Gene summary

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C6orf104

MANE transcript

NM_031949.5

Inheritance

—

ClinVar variants

U:95B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.05

Max pathogenic AF

—

Genomic locus

chr6:167,325,071-167,359,503

External References & Databases

Ensembl (ENSG00000120440)

Transcript & Mutation Effects

hg38 • Region Span ~34.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTLL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031949.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			95 clinvar	10 clinvar	2 clinvar	107
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	95	10	2	107

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031949.5	RefSeq	NP_114155.4	3	MANE Select
ENST00000239587.10	Ensembl	ENSP00000239587.5	3	MANE Select
NM_001410948.1	RefSeq	NP_001397877.1	1	Standard
ENST00000512917.1	Ensembl	ENSP00000423198.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Carboxyterminal post-translational modifications of tubulin

Biological Process

cellular protein modification process

Molecular Function

ATP binding
ligase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000239587
Coding exons: 3
Length: 34418
Individuals with no LoFs: 125054
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125056
p: 0.00000800

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.189	320	330	0.971	0.0000185	3905
Missense (PolyPhen)		91	89.255	1.0196		1192
Synonymous	-0.331	138	133	1.04	0.00000805	1147
Loss of Function	-0.0845	3	2.85	1.05	1.21e-7	35

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000010	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable tubulin polyglutamylase that forms polyglutamate side chains on tubulin. Probably acts when complexed with other proteins (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.880
RVIS EVS: 1.59
RVIS percentile EVS: 95.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0711

Gene Damage Prediction

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