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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TTC12
tetratricopeptide repeat domain 12
Chromosome 11 Β· 11q23.2
NCBI Gene: 54970Ensembl: ENSG00000149292.17HGNC: HGNC:23700UniProt: A8K8G6
34PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sperm axoneme assemblyaxonemal dynein complex assemblycytoplasmcentrosomeciliary dyskinesia, primary, 45Abnormal sperm morphologyprimary ciliary dyskinesiaReduced sperm motility
✦AI Summary

TTC12 is a cytoplasmic protein essential for assembling dynein arm complexes in motile cilia and sperm flagella. Loss-of-function mutations in TTC12 cause primary ciliary dyskinesia (PCD), characterized by selective defects in inner dynein arms (IDAs) in respiratory cilia and both outer and inner dynein arm defects in sperm flagella, revealing distinct assembly mechanisms between these organelles 1. Ultrastructural analyses confirm that TTC12 deficiency results in inner dynein arm ultrastructural abnormalities 2. Beyond ciliary function, TTC12 is part of the NTAD gene cluster (NCAM1-TTC12-ANKK1-DRD2) on chromosome 11, which influences dopaminergic neurotransmission 3. Genetic variants in TTC12 associate with nicotine dependence in African-American and European-American populations 4, and with smoking behavior in adolescents through effects on striatal dopamine signaling 5. TTC12 variants also show shared genetic architecture with problematic alcohol use and psychiatric disorders including major depression and schizophrenia 6. These findings indicate TTC12 has dual roles: a primary ciliary function in dynein assembly and a secondary role in addiction vulnerability through dopaminergic pathways, though the mechanistic connection between these functions remains unclear.

Sources cited
1
TTC12 loss-of-function mutations cause primary ciliary dyskinesia with selective IDA defects in respiratory cilia and combined ODA-IDA defects in sperm flagella
PMID: 31978331
2
TTC12 mutations cause inner dynein arm ultrastructural defects and are associated with multisystem ciliopathy syndromes
PMID: 36273201
3
TTC12 is part of the NTAD cluster related to neurogenesis and dopaminergic neurotransmission with ancient evolutionary conservation
PMID: 23412349
4
TTC12 variants show strong association with nicotine dependence in both African-American and European-American populations
PMID: 17085484
5
TTC12 rs2236709 variant associates with adolescent smoking and increased striatal dopamine D2 receptor signaling during reward processing
PMID: 30104163
6
TTC12 and ANKK1 are identified as potential causal genes for shared genetic architecture between problematic alcohol use and psychiatric disorders
PMID: 40329641
Disease Associationsβ“˜21
ciliary dyskinesia, primary, 45Open Targets
0.68Moderate
Abnormal sperm morphologyOpen Targets
0.46Moderate
primary ciliary dyskinesiaOpen Targets
0.46Moderate
Reduced sperm motilityOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.41Moderate
depressive disorderOpen Targets
0.33Weak
mental or behavioural disorderOpen Targets
0.33Weak
mood disorderOpen Targets
0.33Weak
major depressive disorderOpen Targets
0.29Weak
neurotic disorderOpen Targets
0.29Weak
Phenotypic abnormalityOpen Targets
0.16Weak
PainOpen Targets
0.12Weak
response to xenobiotic stimulusOpen Targets
0.12Weak
glomerulonephritisOpen Targets
0.11Weak
continuous positive airway pressureOpen Targets
0.10Weak
type 2 diabetes mellitusOpen Targets
0.07Suggestive
Autosomal dominant striatal neurodegenerationOpen Targets
0.04Suggestive
metabolic syndromeOpen Targets
0.04Suggestive
left ventricular hypertrophyOpen Targets
0.04Suggestive
nervous system diseaseOpen Targets
0.03Suggestive
Ciliary dyskinesia, primary, 45UniProt
Pathogenic Variants8
NM_017868.4(TTC12):c.283C>T (p.Arg95Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 95
NM_017868.4(TTC12):c.1468del (p.Asp490fs)Pathogenic
Reduced sperm motility;Abnormal sperm morphology
β˜…β˜†β˜†β˜†β†’ Residue 490
NM_017868.4(TTC12):c.1139del (p.His380fs)Pathogenic
Reduced sperm motility;Abnormal sperm morphology
β˜…β˜†β˜†β˜†β†’ Residue 380
NM_017868.4(TTC12):c.1117G>A (p.Gly373Arg)Pathogenic
Reduced sperm motility;Abnormal sperm morphology
β˜…β˜†β˜†β˜†β†’ Residue 373
NM_017868.4(TTC12):c.1678C>T (p.Arg560Ter)Pathogenic
Ciliary dyskinesia, primary, 45|Ovarian serous cystadenocarcinoma
β˜†β˜†β˜†β˜†2020β†’ Residue 560
NM_017868.4(TTC12):c.1614+3A>TPathogenic
Ciliary dyskinesia, primary, 45
β˜†β˜†β˜†β˜†2020
NM_017868.4(TTC12):c.607del (p.Glu202_Ile203insTer)Pathogenic
Ciliary dyskinesia, primary, 45
β˜†β˜†β˜†β˜†2020β†’ Residue 202
NM_017868.4(TTC12):c.1700T>G (p.Met567Arg)Pathogenic
Ciliary dyskinesia, primary, 45
β˜†β˜†β˜†β˜†2020β†’ Residue 567
View on ClinVar β†—
Related Genes
ANKK1Protein interaction95%CFAP157Shared pathway50%CFAP97D1Shared pathway50%DNAAF3Shared pathway33%CFAP47Shared pathway33%DNAAF10Shared pathway33%
Tissue Expression6 tissues
Ovary
100%
Heart
76%
Liver
58%
Lung
47%
Bone Marrow
32%
Brain
20%
Gene Interaction Network
Click a node to explore
TTC12ANKK1CFAP157CFAP97D1DNAAF3CFAP47DNAAF10
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q53G14
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.93LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.59–0.93]
RankingsWhere TTC12 stands among ~20K protein-coding genes
  • #11,265of 20,598
    Most Researched34
  • #3,114of 5,498
    Most Pathogenic Variants8
  • #8,654of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedTTC12
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response.
PMID: 30104163
Eur Neuropsychopharmacol Β· 2018
1.00
2
Relationship Between Problematic Alcohol Use and Various Psychiatric Disorders: A Genetically Informed Study.
PMID: 40329641
Am J Psychiatry Β· 2025
0.90
3
Linking dopamine neurotransmission and neurogenesis: The evolutionary history of the NTAD (NCAM1-TTC12-ANKK1-DRD2) gene cluster.
PMID: 23412349
Genet Mol Biol Β· 2012
0.80
4
Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.
PMID: 36273201
Hum Genomics Β· 2022
0.70
5
Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations.
PMID: 17085484
Hum Mol Genet Β· 2006
0.60