TTLL1

protein-coding

TTL family tubulin polyglutamylase complex subunit L1, the group of Tubulin polyglutamylase complex subunits|Tubulin tyrosine ligase family

Gene summary

Enables tubulin-glutamic acid ligase activity. Involved in microtubule cytoskeleton organization. Is active in microtubule. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C22orf7

MANE transcript

NM_012263.5

Inheritance

—

ClinVar variants

U:52B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr22:43,039,516-43,089,419

External References & Databases

Ensembl (ENSG00000100271)

Transcript & Mutation Effects

hg38 • Region Span ~49.9 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 TTLL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012263.5. 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			1 clinvar	1 clinvar		2
missense			46 clinvar	1 clinvar	1 clinvar	48
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	52	2	1	55

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012263.5	RefSeq	NP_036395.1	9	MANE Select
ENST00000266254.12	Ensembl	ENSP00000266254.7	9	MANE Select
ENST00000331018.8	Ensembl	ENSP00000333734.7	8	Standard
ENST00000439248.5	Ensembl	ENSP00000401518.1	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

epithelial cilium movement
sperm axoneme assembly
protein polyglutamylation
sperm flagellum movement involved in flagellated sperm motility

Molecular Function

ATP binding
tubulin-glutamic acid ligase activity

Cellular Component

cytoplasm
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266254
Coding exons: 9
Length: 49913
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125747
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	194	260	0.745	0.0000166	2778
Missense (PolyPhen)		56	90.334	0.61992		1004
Synonymous	-0.658	118	109	1.08	0.00000767	785
Loss of Function	2.03	12	22.3	0.537	0.00000120	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000098	0.000098	rare
Other	0.00039	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of the neuronal tubulin polyglutamylase complex. Modifies alpha- and beta-tubulin, generating side chains of glutamate on the gamma-carboxyl groups of specific glutamate residues within the C-terminal tail of alpha- and beta-tubulin (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.804
RVIS EVS: -0.84
RVIS percentile EVS: 11.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.529

Gene Damage Prediction

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