TDRKH

protein-coding

tudor and KH domain containing, the group of Tudor domain containing

Gene summary

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]

MANE transcript

NM_001083965.2

Inheritance

—

ClinVar variants

P:2U:50B:2

Top phenotype

Distal spinal muscular atrophy

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr1:151,770,107-151,791,416

External References & Databases

Ensembl (ENSG00000182134)

Transcript & Mutation Effects

hg38 • Region Span ~21.3 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 TDRKH variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 1

Distal spinal muscular atrophyTotal: 1

AzoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001083965.2. 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			2
missense		1 clinvar	45 clinvar	2 clinvar		48
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	1	50	2	0	54

Highest pathogenic variant AF is 0.0000030978933

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 85 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001083965.2	RefSeq	NP_001077434.1	12	MANE Select
ENST00000368824.8	Ensembl	ENSP00000357815.3	12	MANE Select
NM_001083963.1	RefSeq	NP_001077432.1	12	Standard
NM_001083964.1	RefSeq	NP_001077433.1	12	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
spermatogenesis
fertilization
cell differentiation
gene silencing by RNA

Molecular Function

RNA binding

Cellular Component

mitochondrion
pi-body
piP-body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368822
Coding exons: 12
Length: 21310
Individuals with no LoFs: 125085
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125155
p: 0.000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.80	224	314	0.713	0.0000165	3658
Missense (PolyPhen)		67	101.1	0.66271		1185
Synonymous	1.37	94	113	0.835	0.00000572	1108
Loss of Function	3.47	8	27.7	0.288	0.00000132	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.0017	0.0017	notable
East Asian	0.00067	0.00065	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00026	0.00026	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. The piRNA metabolic process 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 the final steps of primary piRNA biogenesis by participating in the processing of 31-37 nt intermediates into mature piRNAs. May act in pi-bodies and piP-bodies by transferring piRNA precursors or intermediates to or between these granules. {ECO:0000250|UniProtKB:Q80VL1}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.912
RVIS EVS: 0.69
RVIS percentile EVS: 85.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.337

Gene Damage Prediction

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