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6 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TENT5D
terminal nucleotidyltransferase 5D
Chromosome X · Xq21.1
NCBI Gene: 169966Ensembl: ENSG00000174016.12HGNC: HGNC:28399UniProt: Q8NEK8
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpoly(A) RNA polymerase activitymRNA stabilizationazoospermiaspermatogenic failure 54spermatogenic failure 41partial chromosome Y deletion
✦AI Summary

TENT5D (terminal nucleotidyltransferase 5D) is a noncanonical poly(A) polymerase that catalyzes adenosine transfer to mRNA poly(A) tails, functioning as a key regulator of mRNA stability 1. Structurally belonging to the nucleotidyltransferase fold superfamily 2, TENT5D localizes to endoplasmic reticulum membranes where it selectively stabilizes mRNAs encoding secretory and ER-imported proteins, thereby promoting expression of secretory cargoes and proteins involved in protein folding and trafficking 1. TENT5D is predominantly expressed in spermatid heads and flagella during gametogenesis 3. Pathogenic mutations in X-linked TENT5D cause male infertility through teratozoospermia and oligoasthenoteratozoospermia (OAT) 43. Loss-of-function variants result in severely decreased sperm count with multiple morphologic abnormalities including abnormal flagellar structures with disrupted 9+2 microtubular organization and poor motility 43. TENT5D deficiency impairs post-transcriptional gene expression regulation critical for proper spermatogenesis 5. Clinically, intracytoplasmic sperm injection (ICSI) successfully rescues male infertility caused by TENT5D mutations, achieving viable pregnancies 4. This represents an important therapeutic option for affected patients, as TENT5D mutations are rare but highly deleterious causes of unexplained male infertility.

Sources cited
1
TENT5D loss-of-function mutations cause oligoasthenoteratozoospermia and male infertility with severe sperm count reduction and morphologic abnormalities; ICSI rescues infertility
PMID: 36746179
2
TENT5D is a noncanonical poly(A) polymerase that stabilizes mRNAs encoding ER-imported secretory proteins; TENT5D alterations result in male infertility
PMID: 40407157
3
Novel TENT5D variations cause teratozoospermia with spermatozoa morphology abnormalities including missing or irregularly arranged 9+2 flagellar structures; TENT5D localization in spermatid heads and flagella
PMID: 38228861
4
TENT5D deficiency during gametogenesis impairs post-transcriptional gene expression regulation and poly(A) tail metabolism; TENT5D defect causes human infertility
PMID: 39794363
5
FAM46 proteins (including TENT5D/FAM46D) are noncanonical poly(A) polymerases belonging to the nucleotidyltransferase fold superfamily
PMID: 27060136
Disease Associationsⓘ20
azoospermiaOpen Targets
0.10Weak
spermatogenic failure 54Open Targets
0.08Suggestive
spermatogenic failure 41Open Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
spermatogenic failure, X-linked, 8Open Targets
0.08Suggestive
spermatogenic failure 39Open Targets
0.08Suggestive
spermatogenic failure 64Open Targets
0.08Suggestive
spermatogenic failure 91Open Targets
0.08Suggestive
spermatogenic failure 65Open Targets
0.08Suggestive
spermatogenic failure 84Open Targets
0.08Suggestive
spermatogenic failure 93Open Targets
0.08Suggestive
spermatogenic failure 56Open Targets
0.08Suggestive
spermatogenic failure 92Open Targets
0.08Suggestive
spermatogenic failure 94Open Targets
0.08Suggestive
spermatogenic failure 58Open Targets
0.08Suggestive
spermatogenic failure 42Open Targets
0.08Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.08Suggestive
spermatogenic failure 40Open Targets
0.08Suggestive
spermatogenic failure 76Open Targets
0.08Suggestive
spermatogenic failure 80Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TAF15Shared pathway100%TENT5CShared pathway50%LARP1BShared pathway50%ZC3H14Shared pathway33%TENT5AShared pathway33%FAM76BShared pathway25%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
100%
Heart
0%
Liver
0%
Brain
0%
Lung
0%
Gene Interaction Network
Click a node to explore
TENT5DTAF15TENT5CLARP1BZC3H14TENT5AFAM76B
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8NEK8
View on AlphaFold ↗
RankingsWhere TENT5D stands among ~20K protein-coding genes
  • #15,712of 20,598
    Most Researched15
Genes detectedTENT5D
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
TENT5D disruption causes oligoasthenoteratozoospermia and male infertility.
PMID: 36746179
Andrology · 2023
1.00
2
TENT5/FAM46: An Enigmatic Family of Secretory Tuners.
PMID: 40407157
Traffic · 2025
0.83
3
Novel variations in TENT5D lead to teratozoospermia in infertile patients.
PMID: 38228861
Andrology · 2024
0.67
4
Comprehensive analysis of poly(A) tails in mouse testes and ovaries using Nanopore Direct RNA Sequencing.
PMID: 39794363
Sci Data · 2025
0.50
5
FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases.
PMID: 27060136
Nucleic Acids Res · 2016
0.33