TDRD6

protein-coding

tudor domain containing 6, the group of Tudor domain containing

Gene summary

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]

MANE transcript

NM_001010870.3

Inheritance

AR, AD

ClinVar variants

P:5U:365B:35

Top phenotype

Male infertility

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr6:46,687,875-46,704,319

External References & Databases

Ensembl (ENSG00000180113)

Transcript & Mutation Effects

hg38 • Region Span ~16.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oligospermiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001913

Submitter: Ambry Genetics

schizophreniaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005090

Submitter: Ambry Genetics

male infertility with azoospermia or oligozoospermia due to single gene mutationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate based on, reported in male infertility (PMID: 19345099). Animal model (PMID:17215373). (>1 independent study with several unrelated probands with pathogenic variants, supporting experimental data and no contradictory evidences).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TDRD6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 371

not providedTotal: 18

Male infertilityTotal: 10

TDRD6-related disorderTotal: 7

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010870.3. 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			3 clinvar	7 clinvar		10
missense			361 clinvar	26 clinvar	2 clinvar	389
nonsense	4 clinvar		1 clinvar			5
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	5	0	365	33	2	405

Highest pathogenic variant AF is 0.00036832943

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010870.3	RefSeq	NP_001010870.1	4	MANE Select
ENST00000316081.11	Ensembl	ENSP00000346065.5	4	MANE Select
NM_001168359.2	RefSeq	NP_001161831.1	3	Standard
ENST00000450697.1	Ensembl	ENSP00000397165.1	5	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

multicellular organism development
spermatogenesis
cell differentiation

Cellular Component

cytoplasm
chromatoid body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316081
Coding exons: 4
Length: 16445
Individuals with no LoFs: 125209
Homozygous LoFs: 0
Heterozygous LoFs: 539
Defined: 125748
p: 0.00215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.28	1302	1.09e+3	1.19	0.0000579	13671
Missense (PolyPhen)		346	301.48	1.1477		3797
Synonymous	-1.53	469	429	1.09	0.0000246	4061
Loss of Function	0.0476	68	68.4	0.994	0.00000333	956

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0014	notable
Latino/Admixed American	0.0012	0.0011	notable
Ashkenazi Jewish	0.0010	0.00099	rare
East Asian	0.0011	0.0011	notable
Finnish	0.0073	0.0052	notable
European (Non-Finnish)	0.0025	0.0024	notable
South Asian	0.0016	0.0015	notable
Other	0.0022	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in spermiogenesis, chromatoid body formation and for proper precursor and mature miRNA expression. {ECO:0000250|UniProtKB:P61407}.;

Recessive Scores

pRec: 0.0961

Intolerance Scores

LoFtool: 0.991
RVIS EVS: -0.66
RVIS percentile EVS: 16.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.655

Gene Damage Prediction

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