TDRD12

protein-coding

tudor domain containing 12, the group of Tudor domain containing

Gene summary

Predicted to enable several functions, including ATP binding activity; ATP hydrolysis activity; and RNA helicase activity. Predicted to be involved in several processes, including germ-line stem cell division; male meiotic nuclear division; and regulatory ncRNA-mediated gene silencing. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001366102.1

Inheritance

—

ClinVar variants

P:5U:61B:9

Top phenotype

Male infertility

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr19:32,719,753-32,829,580

External References & Databases

Ensembl (ENSG00000173809)

Transcript & Mutation Effects

hg38 • Region Span ~109.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TDRD12 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 65

Male infertilityTotal: 7

not providedTotal: 5

TDRD12-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001366102.1. 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				2 clinvar	1 clinvar	3
missense		2 clinvar	61 clinvar	5 clinvar	1 clinvar	69
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	5	61	7	2	75

Highest pathogenic variant AF is 0.000025393898

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001366102.1	RefSeq	NP_001353031.1	33	MANE Select
ENST00000639142.2	Ensembl	ENSP00000492643.2	33	MANE Select
NM_001110822.2	RefSeq	NP_001104292.1	13	Standard
NM_001437947.1	RefSeq	NP_001424876.1	33	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tdrd12	Danio rerio	Structure: spermatogonium Quality: deformed abnormal

Gene / Model

Organism

Observed Phenotype

tdrd12

Danio rerio

Structure: spermatogonium

Quality: deformed

abnormal

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
multicellular organism development
spermatogenesis
fertilization
cell differentiation

Molecular Function

molecular_function
nucleic acid binding
helicase activity
ATP binding

Cellular Component

cellular_component
PET complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421545
Coding exons: 13
Length: 109825
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.694	142	167	0.849	0.00000799	2597
Missense (PolyPhen)		41	41.47	0.98866		678
Synonymous	2.24	39	61.3	0.636	0.00000332	678
Loss of Function	0.242	20	21.2	0.943	0.00000105	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable ATP-binding RNA helicase required during spermatogenesis to repress transposable elements and preventing 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. Involved in the secondary piRNAs metabolic process. Acts via the PET complex, a multiprotein complex required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs. {ECO:0000250|UniProtKB:Q9CWU0}.;

Intolerance Scores

RVIS EVS: 0.95
RVIS percentile EVS: 89.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0625

Gene Damage Prediction

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