TTLL8

protein-coding

tubulin tyrosine ligase like 8, the group of Tubulin tyrosine ligase family

Gene summary

Predicted to enable protein-glycine ligase activity, initiating. Predicted to be involved in axoneme assembly; flagellated sperm motility; and spermatogenesis. Predicted to act upstream of or within cilium assembly. Predicted to be located in cilium. Predicted to be active in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001350317.3

Inheritance

—

ClinVar variants

B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr22:50,018,575-50,058,298

External References & Databases

Ensembl (ENSG00000138892)

Transcript & Mutation Effects

hg38 • Region Span ~39.7 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 TTLL8 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001350317.3. 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				2 clinvar		2
missense				1 clinvar		1
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	0	3	0	3

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001350317.3	RefSeq	NP_001337246.1	13	MANE Select
ENST00000433387.2	Ensembl	ENSP00000392252.2	13	MANE Select
XM_024452172.1	RefSeq	XP_024307940.1	13	Standard
XM_024452173.1	RefSeq	XP_024307941.1	13	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

protein polyglycylation

Molecular Function

ATP binding
protein-glycine ligase activity
protein-glycine ligase activity, initiating

Cellular Component

cytosol
microtubule
cilium
axoneme
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000433387
Coding exons: 14
Length: 41813
Individuals with no LoFs: 124123
Homozygous LoFs: 6
Heterozygous LoFs: 651
Defined: 124780
p: 0.00264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.352	451	473	0.954	0.0000294	5453
Missense (PolyPhen)		154	162.7	0.94652		1812
Synonymous	0.280	209	214	0.976	0.0000155	1676
Loss of Function	1.42	27	36.2	0.746	0.00000171	426

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0045	0.0041	notable
Latino/Admixed American	0.00091	0.00090	rare
Ashkenazi Jewish	0.00073	0.00070	rare
East Asian	0.00057	0.00056	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00023	0.00022	rare
South Asian	0.018	0.017	notable
Other	0.0010	0.00099	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Monoglycylase which modifies both tubulin and non- tubulin proteins, generating side chains of glycine on the gamma- carboxyl groups of specific glutamate residues of target proteins. Monoglycylates tubulin, with a preference for alpha-tubulin toward beta-tubulin. Has the ability to modify non-tubulin proteins such as ANP32A, ANP32B, SET and NCL. Involved in the side-chain initiation step of the glycylation reaction by adding a single glycine chain to generate monoglycine side chains. Not involved in elongation step of the polyglycylation reaction (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0958

Essentials

Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.169

Gene Damage Prediction

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