TDRD9

protein-coding

tudor domain containing 9, the group of Tudor domain containing

Gene summary

Predicted to enable ATP hydrolysis activity; RNA binding activity; and helicase activity. Involved in spermatogenesis. Located in cytoplasm and nucleus. Implicated in spermatogenic failure 30. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C14orf75

MANE transcript

NM_153046.3

Inheritance

AR, AD

ClinVar variants

P:11U:216B:28

Top phenotype

Spermatogenic failure 30

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr14:103,928,456-104,052,667

External References & Databases

Ensembl (ENSG00000156414)

Transcript & Mutation Effects

hg38 • Region Span ~124.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 30STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020851

Submitter: Labcorp Genetics (formerly Invitae)

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

spermatogenic failure 30LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020851

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spermatogenic failure 30AR

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 28536242

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TDRD9 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 210

not providedTotal: 18

TDRD9-related disorderTotal: 18

Spermatogenic failure 30Total: 10

Male infertilityTotal: 4

AzoospermiaTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153046.3. 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			4 clinvar	13 clinvar	2 clinvar	19
missense			205 clinvar	9 clinvar	4 clinvar	218
nonsense	1 clinvar	2 clinvar	4 clinvar			7
start loss						0
frameshift	4 clinvar	4 clinvar				8
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	5	6	216	22	6	255

Highest pathogenic variant AF is 0.0003444117

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153046.3	RefSeq	NP_694591.2	36	MANE Select
ENST00000409874.9	Ensembl	ENSP00000387303.4	36	MANE Select
ENST00000557332.5	Ensembl	ENSP00000451637.1	26	Standard
ENST00000967811.1	Ensembl	ENSP00000637870.1	35	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
PIWI-interacting RNA (piRNA) biogenesis
Gene Silencing by RNA

Biological Process

male meiotic nuclear division
male meiosis I
multicellular organism development
spermatogenesis
fertilization

Molecular Function

RNA binding
ATP binding
ATPase activity
ATP-dependent 3'-5' RNA helicase activity

Cellular Component

nucleus
cytoplasm
piP-body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409874
Coding exons: 36
Length: 124206
Individuals with no LoFs: 125472
Homozygous LoFs: 0
Heterozygous LoFs: 120
Defined: 125592
p: 0.000478

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	530	706	0.750	0.0000382	9036
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00075	0.00071	rare
Finnish	0.00039	0.00037	rare
European (Non-Finnish)	0.00051	0.00050	rare
South Asian	0.00034	0.00033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.988
RVIS EVS: -0.19
RVIS percentile EVS: 39.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.155

Gene Damage Prediction

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