TENT5B

Summary

TENT5B (terminal nucleotidyltransferase 5B, HGNC:28273) is a protein-coding gene on chromosome 1p36.11, encoding Terminal nucleotidyltransferase 5B (Q96A09). Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group in an ATP hydrolysis-dependent manner.

Enables poly(A) RNA polymerase activity. Involved in several processes, including negative regulation of apoptotic process; negative regulation of cell population proliferation; and positive regulation of translation. Located in cytoplasm and nucleus.

Source: NCBI Gene 115572 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_052943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28273
Approved symbol	TENT5B
Name	terminal nucleotidyltransferase 5B
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC16491
Ensembl gene	ENSG00000158246
Ensembl biotype	protein_coding
OMIM	619069
Entrez	115572

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000289166

RefSeq mRNA: 1 — MANE Select: NM_052943 NM_052943

CCDS: CCDS294

Canonical transcript exons

ENST00000289166 — 2 exons

Exon	Start	End
ENSE00001821832	27012407	27012850
ENSE00001949494	27005020	27006957

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3292 / max 457.7647, expressed in 1000 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11212	8.3292	1000

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	96.05	gold quality
lower esophagus mucosa	UBERON:0035834	95.75	gold quality
esophagus mucosa	UBERON:0002469	95.51	gold quality
secondary oocyte	CL:0000655	95.35	gold quality
esophagus	UBERON:0001043	95.31	gold quality
lower esophagus	UBERON:0013473	95.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.28	gold quality
skin of abdomen	UBERON:0001416	95.09	gold quality
zone of skin	UBERON:0000014	94.82	gold quality
gingiva	UBERON:0001828	94.76	gold quality
popliteal artery	UBERON:0002250	94.74	gold quality
tibial artery	UBERON:0007610	94.71	gold quality
esophagus squamous epithelium	UBERON:0006920	94.27	gold quality
gingival epithelium	UBERON:0001949	94.09	gold quality
right coronary artery	UBERON:0001625	93.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.01	gold quality
aorta	UBERON:0000947	92.55	gold quality
parotid gland	UBERON:0001831	92.31	gold quality
descending thoracic aorta	UBERON:0002345	92.30	gold quality
oral cavity	UBERON:0000167	90.89	gold quality
oocyte	CL:0000023	90.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.28	gold quality
left coronary artery	UBERON:0001626	90.22	gold quality
thoracic aorta	UBERON:0001515	89.85	gold quality
upper leg skin	UBERON:0004262	89.76	gold quality
ascending aorta	UBERON:0001496	89.42	gold quality
apex of heart	UBERON:0002098	89.04	gold quality
coronary artery	UBERON:0001621	88.99	gold quality
pharyngeal mucosa	UBERON:0000355	88.24	gold quality
nipple	UBERON:0002030	88.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting TENT5B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013

Literature-anchored findings (GeneRIF, showing 2)

• these data show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of beta-catenin (PMID:30532005)
• FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. (PMID:32009146)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	tent5bb	ENSDARG00000011797
danio_rerio	tent5ba	ENSDARG00000039943
mus_musculus	Tent5b	ENSMUSG00000046694
rattus_norvegicus	AABR07033236.1	ENSRNOG00000029763
rattus_norvegicus	Tent5b	ENSRNOG00000074445
drosophila_melanogaster	CG46385	FBGN0286778
caenorhabditis_elegans	tent-5	WBGENE00004131
caenorhabditis_elegans		WBGENE00011957
caenorhabditis_elegans		WBGENE00016596
caenorhabditis_elegans		WBGENE00017841
caenorhabditis_elegans		WBGENE00044662
caenorhabditis_elegans		WBGENE00219325

Paralogs (3): TENT5A (ENSG00000112773), TENT5D (ENSG00000174016), TENT5C (ENSG00000183508)

Protein

Protein identifiers

Terminal nucleotidyltransferase 5B — Q96A09 (reviewed: Q96A09)

Alternative names: Non-canonical poly(A) polymerase FAM46B

All UniProt accessions (1): Q96A09

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group in an ATP hydrolysis-dependent manner. May be involved in maintaining the translation efficiency of at least some genes through preventing degradation of their mRNAs. Prefers RNA molecules that are adenosine-rich close to 3’-end. In addition, may inhibit cell proliferation and cell cycle progression through ubiquitination of beta-catenin/CTNNB1.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the TENT family.

RefSeq proteins (1): NP_443175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012937	TET5	Family

Pfam: PF07984

Enzyme classification (BRENDA):

• EC 2.7.7.19 — polynucleotide adenylyltransferase (BRENDA: 35 organisms, 181 substrates, 125 inhibitors, 114 Km, 53 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.028–2.191	54
RNA (A)15	0.51–24.99	23
CTP	0.1036–4.7	7
(A)N	0.0468–0.711	5
OLIGO(A)14	0.0005–0.037	5
(A)15	0.0009–0.0053	3
GTP	0.055–0.062	2
OLIGO(A)18	0.0468–0.0642	2
OLIGO(A)N	0.01–0.3	2
2-AMINOPURINE RIBOSIDE TRIPHOSPHATE	0.0197	1
DATP	0.06	1
OLIGO(A)12	0.0004	1
OLIGO(A)17C	0.0263	1
OLIGOADENYLATE	0.2	1
POLY(A)N	0.0036	1

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + ATP = RNA(n)-3’-adenine ribonucleotide + diphosphate (RHEA:11332)

UniProt features (24 total): mutagenesis site 21, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A09-F1	83.10	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (21):

Position	Phenotype
181	reduces polyadenylation activity.
201	loss of polyadenylation activity.
203	loss of polyadenylation activity.
210	loss of polyadenylation activity.
213	substantially reduces polyadenylation activity.
216	substantially reduces polyadenylation activity.
269	substantially reduces polyadenylation activity.
272	substantially reduces polyadenylation activity.
275	loss of polyadenylation activity.
281	loss of polyadenylation activity.
303	does not affect polyadenylation activity.
321	loss of polyadenylation activity.
330	loss of polyadenylation activity.
331	does not affect polyadenylation activity.
108	loss of polyadenylation activity.
109	loss of polyadenylation activity.
124	does not affect polyadenylation activity.
125	loss of polyadenylation activity.
127	loss of polyadenylation activity.
176	loss of polyadenylation activity.
179	loss of polyadenylation activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, AP1_01, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP2_Q3, GOBP_TRANSLATION, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, AP1_Q4_01, E2F_Q3, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, BACH2_01, TGANTCA_AP1_C

GO Biological Process (5): negative regulation of cell population proliferation (GO:0008285), negative regulation of apoptotic process (GO:0043066), positive regulation of translation (GO:0045727), negative regulation of cell cycle (GO:0045786), mRNA stabilization (GO:0048255)

GO Molecular Function (4): poly(A) RNA polymerase activity (GO:1990817), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	2
cell population proliferation	1
regulation of cell population proliferation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
cell cycle	1
regulation of cell cycle	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
adenylyltransferase activity	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENT5B	TENT2	Q6PIY7	428
TENT5B	TUT7	Q5VYS8	402
TENT5B	MTPAP	Q9NVV4	393
TENT5B	FAM43B	Q6ZT52	373
TENT5B	EFCAB11	Q9BUY7	369
TENT5B	TENT4B	Q8NDF8	360
TENT5B	ITPRIPL2	Q3MIP1	358
TENT5B	PAPOLA	P51003	355
TENT5B	TENT4A	Q5XG87	350
TENT5B	MAB21L4	Q08AI8	348
TENT5B	MAB21L3	Q8N8X9	344
TENT5B	TUT4	Q5TAX3	332
TENT5B	RBM43	Q6ZSC3	330
TENT5B	C6orf136	Q5SQH8	329
TENT5B	TMEM102	Q8N9M5	325

IntAct

264 interactions, top by confidence:

A	B	Type	Score
ATXN1	TENT5B	psi-mi:“MI:0915”(physical association)	0.830
TENT5B	DAZAP2	psi-mi:“MI:0915”(physical association)	0.700
DAZAP2	TENT5B	psi-mi:“MI:0915”(physical association)	0.700
TENT5B	RHOXF2	psi-mi:“MI:0915”(physical association)	0.670
TENT5B	SH2D2A	psi-mi:“MI:0915”(physical association)	0.570
TENT5B	SOX5	psi-mi:“MI:0915”(physical association)	0.560
SOX5	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	ZNF620	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	CIMIP2B	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
USP54	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
PLK4	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
KRT34	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TNS2	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TRIP13	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	RIMBP3	psi-mi:“MI:0915”(physical association)	0.560
FOSB	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB2	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
RBPMS2	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
TLE5	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
RFX6	TENT5B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (74): FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), SH2D2A (Affinity Capture-Luminescence), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid), FAM46B (Two-hybrid)

ESM2 similar proteins: A3KN95, A4IFG4, A7E2I7, E2RDP2, J3QMI4, O94810, O95382, P0C5W1, P23677, P82350, Q15628, Q16586, Q1RMX3, Q24JP5, Q28686, Q29RH2, Q3T904, Q3U0S6, Q45T69, Q49LS1, Q5FWU3, Q5RCS0, Q5U651, Q64255, Q674R7, Q684M2, Q68FE2, Q68FE7, Q6EBV9, Q6GQT5, Q6NY19, Q6P9Q4, Q6PEY1, Q7Z3C6, Q80WF4, Q80XF7, Q86TL0, Q86XJ0, Q8C052, Q8C152

Diamond homologs: B0BNK8, D3Z5S8, F7E7M3, Q29RH2, Q4R8X4, Q5SSF7, Q5VWP2, Q5XIV0, Q5ZL95, Q7ZUP1, Q8C152, Q8NEK8, Q96A09, Q96IP4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

89 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

156 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27006954:CCAC:C	acceptor_gain	1.0000
1:27006955:CACC:C	acceptor_gain	1.0000
1:27006956:AC:A	acceptor_gain	1.0000
1:27006957:CC:C	acceptor_gain	1.0000
1:27012401:TCTCA:T	donor_loss	1.0000
1:27012402:CTCA:C	donor_loss	1.0000
1:27012403:TCA:T	donor_loss	1.0000
1:27012404:CAC:C	donor_loss	1.0000
1:27012405:A:T	donor_loss	1.0000
1:27012406:C:A	donor_loss	1.0000
1:27006953:ACCAC:A	acceptor_gain	0.9900
1:27006954:CCACC:C	acceptor_gain	0.9900
1:27006955:CAC:C	acceptor_gain	0.9900
1:27006958:C:CC	acceptor_gain	0.9900
1:27006956:ACCTG:A	acceptor_gain	0.9800
1:27006957:CCTGC:C	acceptor_gain	0.9800
1:27006958:C:A	acceptor_gain	0.9800
1:27006961:C:CT	acceptor_gain	0.9800
1:27006962:A:T	acceptor_gain	0.9800
1:27010445:T:TA	donor_gain	0.9800
1:27012405:A:AC	donor_gain	0.9800
1:27012406:C:CC	donor_gain	0.9800
1:27012406:CCTG:C	donor_gain	0.9800
1:27006959:T:G	acceptor_gain	0.9700
1:27006971:C:CT	acceptor_gain	0.9700
1:27010446:C:A	donor_gain	0.9700
1:27006955:CACCT:C	acceptor_gain	0.9600
1:27006958:C:T	acceptor_gain	0.9500
1:27006972:A:T	acceptor_gain	0.9400
1:27012398:T:TA	donor_gain	0.9200

AlphaMissense

2715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27006580:G:C	F214L	0.999
1:27006580:G:T	F214L	0.999
1:27006582:A:G	F214L	0.999
1:27006577:G:C	S215R	0.998
1:27006577:G:T	S215R	0.998
1:27006579:T:G	S215R	0.998
1:27006656:A:G	L189P	0.998
1:27006283:A:C	F313L	0.997
1:27006283:A:T	F313L	0.997
1:27006285:A:G	F313L	0.997
1:27006295:G:C	F309L	0.997
1:27006295:G:T	F309L	0.997
1:27006296:A:G	F309S	0.997
1:27006297:A:G	F309L	0.997
1:27006425:A:T	I266N	0.997
1:27006663:A:G	W187R	0.997
1:27006663:A:T	W187R	0.997
1:27006148:C:A	M358I	0.996
1:27006148:C:G	M358I	0.996
1:27006148:C:T	M358I	0.996
1:27006290:A:T	I311N	0.996
1:27006581:A:G	F214S	0.996
1:27006586:A:C	F212L	0.996
1:27006586:A:T	F212L	0.996
1:27006588:A:G	F212L	0.996
1:27006610:A:C	F204L	0.996
1:27006610:A:T	F204L	0.996
1:27006612:A:G	F204L	0.996
1:27006658:G:C	S188R	0.996
1:27006658:G:T	S188R	0.996

dbSNP variants (sampled 300 via entrez): RS1000029318 (1:27005050 T>G), RS1000072607 (1:27009632 C>G), RS1001668955 (1:27005703 A>G), RS1001747447 (1:27008189 G>A), RS1001763769 (1:27005467 G>A), RS1001940959 (1:27011431 C>T), RS1002070951 (1:27012866 G>A,T), RS1002505257 (1:27013050 A>C,T), RS1003426854 (1:27013999 G>A), RS1004082243 (1:27010426 G>A,C), RS1004507533 (1:27012746 C>A,G,T), RS1005664803 (1:27005778 G>A), RS1005759662 (1:27008851 C>T), RS1005790794 (1:27009192 C>T), RS1006096882 (1:27007552 C>T)

Disease associations

OMIM: gene MIM:619069 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002398_46	Neutrophil count	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
mivebresib	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
3,4-dichloroaniline	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
cupric chloride	decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	increases methylation	1
Leflunomide	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.