TDRD5

Summary

TDRD5 (tudor domain containing 5, HGNC:20614) is a protein-coding gene on chromosome 1q25.2, encoding Tudor domain-containing protein 5 (Q8NAT2). Required during spermiogenesis to participate in the repression transposable elements and prevent their mobilization, which is essential for the germline integrity.

Predicted to be involved in P granule organization; spermatid development; and transposable element silencing by piRNA-mediated DNA methylation. Predicted to be located in chromatoid body and pi-body. Predicted to be active in synapse.

Source: NCBI Gene 163589 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 131 total
• MANE Select transcript: NM_001199085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20614
Approved symbol	TDRD5
Name	tudor domain containing 5
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34823, TUDOR3
Ensembl gene	ENSG00000162782
Ensembl biotype	protein_coding
OMIM	617748
Entrez	163589

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000294848, ENST00000367614, ENST00000417329, ENST00000444136, ENST00000897478, ENST00000897479, ENST00000897480, ENST00000897481, ENST00000918852

RefSeq mRNA: 6 — MANE Select: NM_001199085 NM_001199085, NM_001199089, NM_001199091, NM_001199092, NM_001349923, NM_173533

CCDS: CCDS1332, CCDS55663

Canonical transcript exons

ENST00000444136 — 18 exons

Exon	Start	End
ENSE00003713070	179591832	179592125
ENSE00003888695	179621035	179621091
ENSE00003890263	179595628	179595818
ENSE00003890613	179634457	179634629
ENSE00003891152	179690696	179691272
ENSE00003891400	179662104	179662286
ENSE00003892523	179639839	179640051
ENSE00003892830	179652039	179652197
ENSE00003893350	179630767	179630920
ENSE00003893936	179635667	179635887
ENSE00003894054	179654201	179654362
ENSE00003894285	179593460	179593867
ENSE00003894304	179618599	179618682
ENSE00003894445	179650867	179651067
ENSE00003894527	179663348	179663491
ENSE00003895438	179640379	179640445
ENSE00003895756	179592602	179592847
ENSE00003895793	179669194	179669404

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 84.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2534 / max 57.2878, expressed in 127 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6914	0.1401	82
6913	0.0671	37
6915	0.0462	21

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	84.44	gold quality
left testis	UBERON:0004533	83.63	gold quality
testis	UBERON:0000473	81.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.68	gold quality
mucosa of transverse colon	UBERON:0004991	67.23	gold quality
lower esophagus mucosa	UBERON:0035834	63.97	gold quality
islet of Langerhans	UBERON:0000006	63.31	gold quality
nucleus accumbens	UBERON:0001882	62.94	gold quality
pituitary gland	UBERON:0000007	62.69	gold quality
cortical plate	UBERON:0005343	62.63	gold quality
adenohypophysis	UBERON:0002196	61.43	gold quality
putamen	UBERON:0001874	60.30	gold quality
caudate nucleus	UBERON:0001873	60.03	gold quality
prefrontal cortex	UBERON:0000451	57.52	gold quality
rectum	UBERON:0001052	57.16	gold quality
right lobe of thyroid gland	UBERON:0001119	56.46	gold quality
left lobe of thyroid gland	UBERON:0001120	56.43	gold quality
pancreatic ductal cell	CL:0002079	55.93	silver quality
Brodmann (1909) area 9	UBERON:0013540	55.75	gold quality
thyroid gland	UBERON:0002046	55.52	gold quality
hypothalamus	UBERON:0001898	54.97	gold quality
adult organism	UBERON:0007023	54.76	gold quality
metanephros cortex	UBERON:0010533	54.70	gold quality
adult mammalian kidney	UBERON:0000082	54.63	gold quality
cortex of kidney	UBERON:0001225	54.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.16	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05
E-MTAB-8060	no	37.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting TDRD5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-5094	98.63	67.11	1062

Literature-anchored findings (GeneRIF, showing 1)

• Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. (PMID:32059713)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tdrd5	ENSMUSG00000060985
rattus_norvegicus	Tdrd5	ENSRNOG00000004018
drosophila_melanogaster	qin	FBGN0263974

Paralogs (6): TDRD1 (ENSG00000095627), TDRD10 (ENSG00000163239), TDRD6 (ENSG00000180113), TDRKH (ENSG00000182134), TDRD7 (ENSG00000196116), TDRD15 (ENSG00000218819)

Protein

Protein identifiers

Tudor domain-containing protein 5 — Q8NAT2 (reviewed: Q8NAT2)

All UniProt accessions (3): A0A024R910, A0A0C4DG74, Q8NAT2

UniProt curated annotations — full annotation on UniProt →

Function. Required during spermiogenesis to participate in the repression transposable elements and prevent their mobilization, which is essential for the germline integrity. Probably 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 govern the methylation and subsequent repression of transposons. Required for chromatoid body (CB) assembly.

Subcellular location. Cytoplasm.

Similarity. Belongs to the TDRD5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NAT2-3	3	yes
Q8NAT2-1	1

RefSeq proteins (6): NP_001186014, NP_001186018, NP_001186020, NP_001186021, NP_001336852, NP_775804 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002999	Tudor	Domain
IPR025605	OST-HTH/LOTUS_dom	Domain
IPR035437	SNase_OB-fold_sf	Homologous_superfamily
IPR037982	TDRD5_LOTUS_2	Domain
IPR041966	LOTUS-like	Homologous_superfamily
IPR050621	Tudor_domain_containing	Family

Pfam: PF00567, PF12872

UniProt features (26 total): helix 5, domain 4, sequence variant 4, strand 3, compositionally biased region 3, region of interest 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3S93	X-RAY DIFFRACTION	2.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAT2-F1	60.07	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 892

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GOBP_AXIS_SPECIFICATION, TGCGCANK_UNKNOWN, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GCANCTGNY_MYOD_Q6, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, FOXO1_01, EVI1_05, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_CELL_MATURATION, GOBP_EMBRYONIC_PATTERN_SPECIFICATION, RYTAAWNNNTGAY_UNKNOWN

GO Biological Process (6): spermatid development (GO:0007286), P granule organization (GO:0030719), transposable element silencing by piRNA-mediated DNA methylation (GO:0141196), germ cell development (GO:0007281), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (4): chromatoid body (GO:0033391), synapse (GO:0045202), pi-body (GO:0071546), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
germ cell development	1
spermatid differentiation	1
organelle organization	1
pole plasm assembly	1
transposable element silencing by heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
cellular developmental process	1
cytoplasmic ribonucleoprotein granule	1
cell junction	1
P granule	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

909 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TDRD5	PIWIL1	Q96J94	859
TDRD5	TDRD9	Q8NDG6	847
TDRD5	PIWIL2	Q8TC59	779
TDRD5	MARF1	Q9Y4F3	755
TDRD5	PIWIL4	Q7Z3Z4	741
TDRD5	MOV10L1	Q9BXT6	703
TDRD5	TDRD12	Q587J7	698
TDRD5	PLD6	Q8N2A8	635
TDRD5	STK31	Q9BXU1	624
TDRD5	MAEL	Q96JY0	608
TDRD5	NANOS3	P60323	595
TDRD5	PNLDC1	Q8NA58	593
TDRD5	PIWIL3	Q7Z3Z3	560
TDRD5	FKBP6	O75344	559
TDRD5	EXD1	Q8NHP7	541

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TDRD5	UBB	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): TDRD5 (Affinity Capture-MS), FABP5 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), TDRD5 (Affinity Capture-MS), UBB (Affinity Capture-MS), SRSF9 (Affinity Capture-MS), EIF4B (Affinity Capture-MS), TDRD5 (Affinity Capture-MS), MRPL27 (Cross-Linking-MS (XL-MS)), TDRD5 (Protein-RNA)

ESM2 similar proteins: A0JM98, A1L1H3, B7ZS37, D2H3M0, D3ZF42, E1BPH3, E2QTD3, F6YVB9, O75113, O88866, P62287, P62288, Q01804, Q13129, Q1L981, Q2T9I9, Q5H9M0, Q5HZN1, Q5QJC4, Q5SW75, Q5T5J6, Q5VCS6, Q5XIS7, Q5ZIX8, Q5ZKI7, Q5ZLE9, Q61194, Q63679, Q6A037, Q6DJS0, Q6GQJ2, Q6IE81, Q6IE82, Q6IFT4, Q6IVY4, Q6NRK3, Q6PCM1, Q6PJP8, Q6PUR7, Q6YI93

Diamond homologs: A0JM98, A1L1H3, A6NAF9, A6QLE1, B4F7C4, D2H0H6, D2H3M0, E1BPH3, E1C3S7, E2QTD3, E2RDV1, E7FDW8, Q1L981, Q5M7P8, Q5RAH6, Q5VCS6, Q6NU04, Q8K1H1, Q8NAT2, Q8NHU6, Q9R1R4, A9CPT4, H9JD76, Q1XG89, Q24180, Q3TPE9, Q58EK5, Q7M6Z3, Q80VL1, Q8R5A0, Q8VZG7, Q99MV1, Q9BXT4, Q9FLT0, Q9Y2W6, B5MCY1, Q4R3G4, Q99MV7, Q9BXT8, A4SG26

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

131 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3053 predictions. Top by Δscore:

Variant	Effect	Δscore
1:179593637:G:GG	donor_gain	1.0000
1:179618594:CATA:C	acceptor_loss	1.0000
1:179618595:ATAG:A	acceptor_loss	1.0000
1:179618596:T:G	acceptor_gain	1.0000
1:179618596:TAGC:T	acceptor_loss	1.0000
1:179618597:A:AG	acceptor_gain	1.0000
1:179618597:AGCT:A	acceptor_gain	1.0000
1:179618598:G:A	acceptor_loss	1.0000
1:179618598:G:GG	acceptor_gain	1.0000
1:179618598:GCT:G	acceptor_gain	1.0000
1:179618598:GCTG:G	acceptor_gain	1.0000
1:179618674:A:G	donor_gain	1.0000
1:179618678:AATTT:A	donor_gain	1.0000
1:179618679:ATTT:A	donor_gain	1.0000
1:179618680:TTT:T	donor_gain	1.0000
1:179618681:TT:T	donor_gain	1.0000
1:179618683:G:GG	donor_gain	1.0000
1:179635666:GCAA:G	acceptor_gain	1.0000
1:179639808:AT:A	acceptor_gain	1.0000
1:179639822:ATTAT:A	acceptor_gain	1.0000
1:179639826:T:TA	acceptor_gain	1.0000
1:179640052:G:GG	donor_gain	1.0000
1:179651081:G:GT	donor_gain	1.0000
1:179652034:CTTA:C	acceptor_loss	1.0000
1:179652035:TTAG:T	acceptor_loss	1.0000
1:179652036:TA:T	acceptor_loss	1.0000
1:179652037:A:AC	acceptor_loss	1.0000
1:179652037:A:AG	acceptor_gain	1.0000
1:179652037:AG:A	acceptor_gain	1.0000
1:179652038:G:GT	acceptor_gain	1.0000

AlphaMissense

6765 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:179635815:C:A	P483H	0.999
1:179635823:T:C	F486L	0.999
1:179635824:T:C	F486S	0.999
1:179635825:C:A	F486L	0.999
1:179635825:C:G	F486L	0.999
1:179639939:T:A	W541R	0.999
1:179639939:T:C	W541R	0.999
1:179639942:T:A	W542R	0.999
1:179639942:T:C	W542R	0.999
1:179639948:C:G	R544G	0.999
1:179640005:T:C	F563L	0.999
1:179640007:T:A	F563L	0.999
1:179640007:T:G	F563L	0.999
1:179640009:G:A	G564E	0.999
1:179640009:G:T	G564V	0.999
1:179640418:T:G	C591W	0.999
1:179650873:T:A	W603R	0.999
1:179650873:T:C	W603R	0.999
1:179650875:G:C	W603C	0.999
1:179650875:G:T	W603C	0.999
1:179650898:T:C	F611S	0.999
1:179650973:T:C	L636S	0.999
1:179592671:T:C	L19P	0.998
1:179592782:T:C	L56P	0.998
1:179593643:T:C	L139S	0.998
1:179593708:T:C	F161L	0.998
1:179593710:T:A	F161L	0.998
1:179593710:T:G	F161L	0.998
1:179593741:T:C	F172L	0.998
1:179593743:T:A	F172L	0.998

dbSNP variants (sampled 300 via entrez): RS1000007668 (1:179630552 C>T), RS1000016898 (1:179603303 A>G), RS1000065994 (1:179670602 C>A,T), RS1000084488 (1:179596389 G>A), RS1000090083 (1:179603587 C>T), RS1000130424 (1:179604998 G>T), RS1000176041 (1:179609725 C>G), RS1000181047 (1:179650139 G>A), RS1000184549 (1:179622125 T>C), RS1000306055 (1:179602862 T>C), RS1000351788 (1:179616489 A>G), RS1000426023 (1:179656206 G>T), RS1000451830 (1:179652348 A>G,T), RS1000486532 (1:179615725 A>G), RS1000486927 (1:179661334 T>C)

Disease associations

OMIM: gene MIM:617748 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006627_10	Diastolic blood pressure	1.000000e-10
GCST009441_11	Age-related cognitive decline (memory) (slope of z-scores)	3.000000e-06
GCST009441_14	Age-related cognitive decline (memory) (slope of z-scores)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
bisphenol A	decreases expression, decreases methylation	2
terbufos	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cisplatin	affects expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Parathion	increases methylation	1
Phthalic Acids	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.