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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TTC21A
tetratricopeptide repeat domain 21A
Chromosome 3 Β· 3p22.2
NCBI Gene: 199223Ensembl: ENSG00000168026.19HGNC: HGNC:30761UniProt: A0A140VJY5
22PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
flagellated sperm motilityspermatid developmentprotein localization to ciliumintraciliary retrograde transportazoospermianon-syndromic male infertility due to sperm motility disorderReduced sperm motilityoligospermia
✦AI Summary

TTC21A (tetratricopeptide repeat domain 21A) is an intraflagellar transport (IFT)-associated protein essential for male reproductive function. Functionally, TTC21A is required for spermatogenesis and sperm flagellar formation through its role in intraflagellar transport 1. The protein localizes to cilia and participates in intraciliary retrograde transport as part of IFT particle A complexes, containing multiple tetratricopeptide repeat domains crucial for ciliary function 1. Clinically, bi-allelic mutations in TTC21A cause asthenoteratospermia and multiple morphological abnormalities of sperm flagella (MMAF), accounting for approximately 5% of MMAF cases in Han Chinese populations 1. Affected individuals present with reduced sperm motility, abnormal flagellar morphology, and defective head-tail conjunction 1. TTC21A interacts with other ciliary proteins, including CEP78, which regulates its stability and localization at centrioles 2. Male infertility caused by TTC21A mutations is designated Spermatogenic failure 37 3. Beyond reproductive function, emerging evidence suggests TTC21A participates in immune regulation, with increased expression correlating with favorable prognosis in lung adenocarcinoma and head and neck squamous cell carcinoma, associated with enhanced immune cell infiltration 45.

Sources cited
1
TTC21A is an IFT-associated protein required for spermatogenesis, sperm flagellar formation, and intraflagellar transport; bi-allelic mutations cause asthenoteratospermia and MMAF
PMID: 30929735
2
TTC21A interacts with CEP78 and regulates centriolar localization and ciliary function
PMID: 36756949
3
TTC21A variants identified in patients with primary male infertility; associated with Spermatogenic failure 37
PMID: 39267058
4
Increased TTC21A expression correlates with favorable prognosis and immune cell infiltration in lung adenocarcinoma
PMID: 31812070
5
TTC21A expression is decreased in head and neck squamous cell carcinoma and associated with favorable outcomes and immune cell infiltration
PMID: 38151293
Disease Associationsβ“˜21
azoospermiaOpen Targets
0.66Moderate
non-syndromic male infertility due to sperm motility disorderOpen Targets
0.37Weak
Abnormal sperm morphologyOpen Targets
0.34Weak
oligospermiaOpen Targets
0.34Weak
Reduced sperm motilityOpen Targets
0.34Weak
hypotensionOpen Targets
0.29Weak
skin diseaseOpen Targets
0.21Weak
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 78Open Targets
0.07Suggestive
spermatogenic failure 72Open Targets
0.07Suggestive
spermatogenic failure, X-linked, 5Open Targets
0.07Suggestive
spermatogenic failure 18Open Targets
0.07Suggestive
spermatogenic failure 27Open Targets
0.07Suggestive
spermatogenic failure 46Open Targets
0.07Suggestive
spermatogenic failure 65Open Targets
0.07Suggestive
spermatogenic failure 19Open Targets
0.07Suggestive
spermatogenic failure 43Open Targets
0.07Suggestive
spermatogenic failure 45Open Targets
0.07Suggestive
spermatogenic failure 82Open Targets
0.07Suggestive
Spermatogenic failure 37UniProt
Pathogenic Variants8
NM_001366900.1(TTC21A):c.3025_3043del (p.Leu1009fs)Likely pathogenic
TTC21A-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 1009
NM_001366900.1(TTC21A):c.1192-1G>TLikely pathogenic
Spermatogenic failure 37
β˜…β˜†β˜†β˜†2023
NM_001366900.1(TTC21A):c.3450+2delPathogenic
Oligospermia;Reduced sperm motility;Abnormal sperm morphology
β˜…β˜†β˜†β˜†
NM_001366900.1(TTC21A):c.2542del (p.Ala847_Val848insTer)Pathogenic
Spermatogenic failure 37
β˜†β˜†β˜†β˜†2019β†’ Residue 847
NM_001366900.1(TTC21A):c.716+1G>APathogenic
Spermatogenic failure 37
β˜†β˜†β˜†β˜†2019
NM_001366900.1(TTC21A):c.2308C>T (p.Gln770Ter)Pathogenic
Spermatogenic failure 37
β˜†β˜†β˜†β˜†2019β†’ Residue 770
NM_001366900.1(TTC21A):c.341A>G (p.Tyr114Cys)Pathogenic
Spermatogenic failure 37
β˜†β˜†β˜†β˜†2019β†’ Residue 114
NM_001366900.1(TTC21A):c.3095+5G>TPathogenic
Spermatogenic failure 37|Acute myeloid leukemia|Lung cancer|Lymphoma
β˜†β˜†β˜†β˜†2019
View on ClinVar β†—
Related Genes
CFAP43Protein interaction74%TTC29Protein interaction74%IFT140Protein interaction72%IFT81Protein interaction72%IFT52Protein interaction72%IFT122Protein interaction72%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
97%
Lung
65%
Liver
40%
Heart
29%
Brain
18%
Gene Interaction Network
Click a node to explore
TTC21ACFAP43TTC29IFT140IFT81IFT52IFT122
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8NDW8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.91LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.67–0.91]
RankingsWhere TTC21A stands among ~20K protein-coding genes
  • #13,789of 20,598
    Most Researched22
  • #3,135of 5,498
    Most Pathogenic Variants8
  • #8,209of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedTTC21A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Whole exome sequencing analysis of 167 men with primary infertility.
PMID: 39267058
BMC Med Genomics Β· 2024
1.00
2
Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual.
PMID: 36756949
Elife Β· 2023
0.90
3
Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice.
PMID: 30929735
Am J Hum Genet Β· 2019
0.80
4
Identification of
PMID: 38151293
Cancer Genomics Proteomics Β· 2024
0.70
5
Increased expression of TTC21A in lung adenocarcinoma infers favorable prognosis and high immune infiltrating level.
PMID: 31812070
Int Immunopharmacol Β· 2020
0.60