TDRKH

Chr 1

tudor and KH domain containing

Also known as: TDRD2

NCBI Gene: 11022 ENSG00000182134 UniProt: Q9Y2W6 OMIM: 609501

Predicted to enable RNA binding activity. Predicted to be involved in several processes, including P granule organization; male meiotic nuclear division; and piRNA processing. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.52

Clinical Summary— TDRKH

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 43 VUS of 75 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.032

Z-score 3.47

OE 0.29 (0.17–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.80Z-score

OE missense 0.71 (0.64–0.80)

224 obs / 314.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.17–0.52)

0≤0.351.4

Missense OE?0.71 (0.64–0.80)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 8 / 27.7Missense obs/exp: 224 / 314.0Syn Z: 1.37

This gene — mechanism propensity

0.6357th %ile

GOF

0.6346th %ile

LOF

0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS43

Likely Benign2

Conflicting1

Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	43	0	0	43
Likely Benign	0	2	0	0	2
Benign	0	0	0	0	0
Conflicting	—				1
Total	1	45	0	0	47

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap TDRKH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →