TTC21A (tetratricopeptide repeat domain 21A)

Gene

• Entrez ID: 199223
• Gene name: Tetratricopeptide repeat domain 21A
• Gene symbol: TTC21A
• Synonyms (NCBI Gene): IFT139A, SPGF37, STI2, Thm2
• Chromosome: 3
• Chromosome location: 3p22.2

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs750057655	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, genic upstream transcript variant, upstream transcript variant, missense variant
rs780431020	C>A,T	Pathogenic	Intron variant, stop gained, non coding transcript variant, missense variant, coding sequence variant
rs1559674534	G>A	Pathogenic	Splice donor variant
rs1559708295	G>-	Pathogenic	3 prime UTR variant, intron variant, non coding transcript variant, stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019173	hsa-miR-335-5p	Microarray	18185580
MIRT1461036	hsa-miR-1470	CLIP-seq
MIRT1461037	hsa-miR-4667-3p	CLIP-seq
MIRT1461038	hsa-miR-587	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005929	Component	Cilium	IEA
GO:0007283	Process	Spermatogenesis	IEA
GO:0007286	Process	Spermatid development	IMP	30929735
GO:0030154	Process	Cell differentiation	IEA
GO:0030317	Process	Flagellated sperm motility	IMP	30929735
GO:0030991	Component	Intraciliary transport particle A	IBA
GO:0035721	Process	Intraciliary retrograde transport	IBA
GO:0061512	Process	Protein localization to cilium	IBA

Other IDs

• MIM: 611430
• HGNC: 30761
• e!Ensembl: ENSG00000168026

Protein

• UniProt ID: Q8NDW8
• Protein name: Tetratricopeptide repeat protein 21A (TPR repeat protein 21A) (Stress-inducible protein 2)
• Protein function: Intraflagellar transport (IFT)-associated protein required for spermatogenesis (PubMed:30929735). Required for sperm flagellar formation and intraflagellar transport (PubMed:30929735).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13432	TPR_16	732 → 795		Family
  PF13181	TPR_8	797 → 825	Tetratricopeptide repeat	Repeat
  PF14559	TPR_19	899 → 966		Domain

• Tissue specificity: TISSUE SPECIFICITY: Strongly expressed in testis. {ECO:0000269|PubMed:12543795}.
• Sequence:

  MSSNDSSLMAGIIYYSQEKYFHHVQQAAAVGLEKFSNDPVLKFFKAYGVLKEEHIQDAIS
  DLESIRHHPDVSLCSTMALIYAHKRCEIIDREAIQELEYSLKEIRKTVSGTALYYAGLFL
  WLIGRHDKAKEYIDRMLKISRGFREAYVLRGWVDLTSDKPHTAKKAIEYLEQGIQDTKDV
  LGLMGKAMYFMMQQNYSEALEVVNQITVTSGSFLPALVLKMQLFLARQDWEQTVEMGHRI
  LEKDESNIDACQILTVHELAREGNMTTVSSLKTQKATNHVRNLIKALETREPENPSLHLK
  KIIVVSRLCGSHQVILGLVCSFIERTFMATPSYVHVATELGYLFILKNQVKEALLWYSEA
  MKLDKDGMAGLTGIILCHILEGHLEEAEYRLEFLKEVQKSLGKSEVLIFLQALLMSRKHK
  GEEETTALLKEAVELHFSSMQGIPLGSEYFEKLDPYFLVCIAKEYLLFCPKQPRLPGQIV
  SPLLKQVAVILNPVVKAAPALIDPLYLMAQVRYYSELENAQSILQRCLELDPASVDAHLL
  MCQIYLAQGNFGMCFHCLELGVSHNFQVRDHPLYHLIKARALNKAGDYPEAIKTLKMVIK
  LPALKKEEGRKFLRPSVQPSQRASILLELVEALRLNGELHEATKVMQDTINEFGGTPEEN
  RITIANVDLVLSKGNVDVALNMLRNILPKQSCYMEAREKMANIYLQTLRDRRLYIRCYRE
  LCEHLPGPHTSLLLGDALMSILEPEKALEVYDEAYRQNPHDASLASRIGHAYVKAHQYTE
  AIEYYEAAQKINGQDFLCCDLGKLLLKLKKVNKAEKVLKQALEHDIVQDIPSMMNDVKCL
  LLLAKVYKSHKKEAVIETLNKALDLQSRILKRVPLEQPEMIPSQKQLAASICIQFAEHYL
  AEKEYDKAVQSYKDVFSYLPTDNKVMLELAQLYLLQGHLDLCEQHCAILLQTEQNHETAS
  VLMADLMFRKQKHEAAINLYHQVLEKAPDNFLVLHKLIDLLRRSGKLEDIPAFFELAKKV
  SSRVPLEPGFNYCRGIYCWHIGQPNEALKFLNKARKDSTWGQSAIYHMVQICLNPDNEVV
  GGEAFENQGAESNYMEKKELEQQGVSTAEKLLREFYPHSDSSQTQLRLLQGLCRLATREK
  ANMEAALGSFIQIAQAEKDSVPALLALAQAYVFLKQIPKARMQLKRLAKTPWVLSEAEDL
  EKSWLLLADIYCQGSKFDLALELLRRCVQYNKSCYKAYEYMGFIMEKEQSYKDAVTNYKL
  AWKYSHHANPAIGFKLAFNYLKDKKFVEAIEICNDVLREHPDYPKIREEILEKARRSLRP
  

• Sequence length: 1320

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Acute myeloid leukemia	Pathogenic	rs148431487	RCV005897364	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lung cancer	Pathogenic	rs148431487	RCV005897366	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lymphoma	Pathogenic	rs148431487	RCV005897365	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spermatogenic failure 37	Pathogenic	rs1559674534, rs780431020, rs750057655, rs1559708295, rs148431487	RCV000770961 RCV000770962 RCV000770963 RCV000770964 RCV000770965	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TTC21A-related disorder	Likely pathogenic	rs2039119649	RCV003410845	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL IMPAIRMENT OF SPERMATOZOA MOTILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TERATOZOOSPERMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	31812070		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	38151293	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	24977159	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	GWASCAT_DG	26252872		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31812070		★☆☆☆☆ Found in Text Mining only
Non-syndromic male infertility due to sperm motility disorder	Non-Syndromic Male Infertility Due To Sperm Motility Disorder	Orphanet			★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Sjogren syndrome	Pubtator	37383223	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	38151293	Associate	★☆☆☆☆ Found in Text Mining only