TDRD9

tudor domain containing 9, the group of Tudor domain containing

Basic information

Region (hg38): 14:103928456-104052667

Previous symbols: [ "C14orf75" ]

Links

ENSG00000156414 ∙ NCBI:122402 ∙ OMIM:617963 ∙ HGNC:20122 ∙ Uniprot:Q8NDG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 30 (Strong), mode of inheritance: AR
• male infertility with azoospermia or oligozoospermia due to single gene mutation (Supportive), mode of inheritance: AD
• spermatogenic failure 30 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 30	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	28536242

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TDRD9 gene.

• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TDRD9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	2	12
missense			84	4	5	93
nonsense	1					1
start loss						0
frameshift	2	2				4
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region		1		5	2	8
non coding					2	2
Total	3	2	85	14	9

Highest pathogenic variant AF is 0.0000723

Variants in TDRD9

This is a list of pathogenic ClinVar variants found in the TDRD9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-103928555-A-C		Spermatogenic failure 30	Uncertain significance (Feb 14, 2020)
14-103928558-G-T		not specified	Uncertain significance (Feb 24, 2022)
14-103928607-C-T		not specified	Uncertain significance (Oct 25, 2022)
14-103928619-C-T		not specified	Uncertain significance (Feb 03, 2022)
14-103928648-G-T		not specified	Uncertain significance (Nov 10, 2022)
14-103928653-C-T		TDRD9-related disorder	Likely benign (Mar 20, 2019)
14-103928661-G-A		not specified	Uncertain significance (Jan 23, 2024)
14-103928703-G-A		not specified	Uncertain significance (Jul 05, 2023)
14-103928715-C-T		not specified	Uncertain significance (May 15, 2023)
14-103955669-T-G		not specified	Uncertain significance (May 20, 2024)
14-103955740-T-G			Uncertain significance (-)
14-103955743-C-T		not specified	Uncertain significance (Dec 06, 2021)
14-103955744-G-T		not specified	Uncertain significance (Oct 05, 2022)
14-103955765-G-A		not specified	Uncertain significance (Dec 14, 2021)
14-103963069-C-T			Benign (Aug 09, 2018)
14-103963088-C-T		TDRD9-related disorder	Benign (Jul 23, 2018)
14-103963116-A-A			Benign (Nov 09, 2018)
14-103965330-T-C		TDRD9-related disorder	Likely benign (Apr 01, 2019)
14-103965348-G-C		not specified	Uncertain significance (Feb 05, 2024)
14-103965360-G-A		Spermatogenic failure 30 • not specified	Uncertain significance (Dec 07, 2021)
14-103965430-A-C		not specified	Uncertain significance (Jun 13, 2024)
14-103965443-C-T		TDRD9-related disorder	Likely benign (Dec 16, 2019)
14-103965474-C-T		not specified	Uncertain significance (Oct 27, 2022)
14-103965511-G-T		not specified	Uncertain significance (Dec 19, 2023)
14-103965536-A-T		TDRD9-related disorder	Likely benign (Apr 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TDRD9	protein_coding	protein_coding	ENST00000409874	36	124206

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.27e-15	1.00	125472	0	120	125592	0.000478

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	530	706	0.750	0.0000382	9036
Missense in Polyphen		149	227.94	0.65367		2830
Synonymous	0.0220	261	261	0.998	0.0000155	2590
Loss of Function	4.03	36	73.2	0.492	0.00000370	938

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00114	0.00114
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000747	0.000707
Finnish	0.000390	0.000370
European (Non-Finnish)	0.000507	0.000502
Middle Eastern	0.000747	0.000707
South Asian	0.000338	0.000327
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-binding RNA helicase required during spermatogenesis (PubMed:28536242). Required to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Acts downstream of piRNA biogenesis: exclusively required for transposon silencing in the nucleus, suggesting that it acts as a nuclear effector in the nucleus together with PIWIL4. {ECO:0000250|UniProtKB:Q14BI7, ECO:0000269|PubMed:28536242}.
• Disease: DISEASE: Note=Defects in TDRD9 may be a cause of non-obstructive azoospermia, a disorder characterized by the absence of sperm. Female fertility is not affected. {ECO:0000269|PubMed:28536242}.
• Pathway: Gene expression (Transcription);PIWI-interacting RNA (piRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.100

Intolerance Scores

• loftool: 0.988
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.28

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.414
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.155

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tdrd9
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype

Gene ontology

• Biological process: male meiotic nuclear division;male meiosis I;multicellular organism development;spermatogenesis;fertilization;negative regulation of transposition;cell differentiation;gene silencing by RNA;piRNA metabolic process;DNA methylation involved in gamete generation
• Cellular component: nucleus;cytoplasm;piP-body
• Molecular function: RNA binding;ATP binding;ATPase activity;ATP-dependent 3'-5' RNA helicase activity