TTLL12

protein-coding

tubulin tyrosine ligase like 12, the group of Tubulin tyrosine ligase family

Gene summary

Enables histone H4K20me2 reader activity. Involved in negative regulation of type I interferon-mediated signaling pathway and regulation of mitotic cell cycle. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015140.4

Inheritance

—

ClinVar variants

U:151B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr22:43,166,622-43,187,134

External References & Databases

Ensembl (ENSG00000100304)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 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 TTLL12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 153

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015140.4. 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	7 clinvar	4 clinvar	13
missense			146 clinvar	10 clinvar		156
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	151	17	4	172

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015140.4	RefSeq	NP_055955.1	14	MANE Select
ENST00000216129.7	Ensembl	ENSP00000216129.6	14	MANE Select
ENST00000494035.1	Ensembl	ENSP00000476297.1	2	Standard
ENST00000998714.1	Ensembl	ENSP00000668531.1	14	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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216129
Coding exons: 14
Length: 20512
Individuals with no LoFs: 125674
Homozygous LoFs: 0
Heterozygous LoFs: 74
Defined: 125748
p: 0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.813	440	395	1.12	0.0000265	4179
Missense (PolyPhen)		128	122.72	1.043		1227
Synonymous	-1.15	191	172	1.11	0.0000129	1223
Loss of Function	1.21	27	34.7	0.779	0.00000188	360

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00041	0.00036	rare
South Asian	0.00041	0.00039	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.881
RVIS EVS: -0.46
RVIS percentile EVS: 23.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.677

Gene Damage Prediction

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