TDRD6

Chr 6

tudor domain containing 6

Also known as: CT41.2, NY-CO-45, SPATA36, TDR2, bA446F17.4

NCBI Gene: 221400ENSG00000180113UniProt: O60522

This gene encodes a tudor domain-containing protein and component of the chromatoid body, a type of ribonucleoprotein granule present in male germ cells. Studies in rodents have demonstrated a role for the encoded protein in spermiogenesis and the nonsense mediated decay (NMD) pathway. This protein is a major autoantigen in human patients with autoimmune polyendocrine syndrome type 1 (APS1). [provided by RefSeq, Oct 2016]

397
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TDRD6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 353 VUS of 397 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.22LOEUF
pLI 0.000
Z-score 0.05
OE 0.99 (0.82–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-2.28Z-score
OE missense 1.19 (1.14–1.25)
1302 obs / 1089.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.99 (0.82–1.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.19 (1.14–1.25)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 68 / 68.4Missense obs/exp: 1302 / 1089.8Syn Z: -1.53

ClinVar Variant Classifications

397 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS353
Likely Benign33
Benign2
Conflicting1
6
Pathogenic
2
Likely Pathogenic
353
VUS
33
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
352
1
0
353
Likely Benign
0
25
1
7
33
Benign
0
2
0
0
2
Conflicting
—1
Total0379107397

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TDRD6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss-of-function variant in TDRD6 cause male infertility with severe oligo-astheno-teratozoospermia in human and mice.
Bi X et al.·J Cell Mol Med
2024
Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans.
Guo R et al.·J Med Genet
2024
TDRD6 is associated with oligoasthenoteratozoospermia by sequencing the patient from a consanguineous family.
Sha YW et al.·Gene
2018Case report
Comprehensive transcriptome analysis and lncRNA-miRNA-mRNA establishment of schizophrenia based on induced pluripotent stem cells.
Jia N et al.·Schizophr Res
2025
Integrated analysis of RNA-binding proteins in thyroid cancer.
Zhen J et al.·PLoS One
2021
Integrative predictive model of coronary artery calcification in atherosclerosis.
McGeachie M et al.·Circulation
2009Functional
Network-based analysis of prostate cancer cell lines reveals novel marker gene candidates associated with radioresistance and patient relapse.
Seifert M et al.·PLoS Comput Biol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools