TENT5D

Summary

TENT5D (terminal nucleotidyltransferase 5D, HGNC:28399) is a protein-coding gene on chromosome Xq21.1, encoding Terminal nucleotidyltransferase 5D (Q8NEK8). Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group.

Antibodies against the protein encoded by this gene were found only in plasma from cancer patients. While it may be a target for immunotherapy, the function of this gene is unknown.

Source: NCBI Gene 169966 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_152630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28399
Approved symbol	TENT5D
Name	terminal nucleotidyltransferase 5D
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC26999, CT1.26, CT112
Ensembl gene	ENSG00000174016
Ensembl biotype	protein_coding
OMIM	300976
Entrez	169966

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000308293, ENST00000538312, ENST00000927364

RefSeq mRNA: 2 — MANE Select: NM_152630 NM_001170574, NM_152630

CCDS: CCDS14446

Canonical transcript exons

ENST00000308293 — 3 exons

Exon	Start	End
ENSE00001190867	80438610	80438732
ENSE00003978175	80442522	80445309
ENSE00003978176	80420447	80420563

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 81.08.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	81.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.98	gold quality
secondary oocyte	CL:0000655	73.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.88	gold quality
testis	UBERON:0000473	54.13	gold quality
oocyte	CL:0000023	53.91	gold quality
right testis	UBERON:0004534	52.43	gold quality
left testis	UBERON:0004533	52.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
lower lobe of lung	UBERON:0008949	41.27	silver quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
oviduct epithelium	UBERON:0004804	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
cortical plate	UBERON:0005343	40.02	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting TENT5D, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of FAM46D is associated with neoplasms. (PMID:19540335)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tent5d	ENSDARG00000062830
mus_musculus	Tent5d	ENSMUSG00000073007
rattus_norvegicus	Tent5d	ENSRNOG00000023637
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), TENT5B (ENSG00000158246), TENT5C (ENSG00000183508)

Protein

Protein identifiers

Terminal nucleotidyltransferase 5D — Q8NEK8 (reviewed: Q8NEK8)

Alternative names: Non-canonical poly(A) polymerase FAM46D

All UniProt accessions (1): Q8NEK8

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.

Tissue specificity. restricted to testis.

Similarity. Belongs to the TENT family.

RefSeq proteins (2): NP_001164045, NP_689843* (*=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 (8 total): mutagenesis site 4, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEK8-F1	87.45	0.71

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 (4):

Position	Phenotype
136	decrease about 50% the poly(a) elongation activity; when associated with e-312 and e-313.
158	loss of poly(a) elongation activity.
312	does not affect poly (a) elongation activity; when associated with e-313. decrease about 50% the poly(a) elongation acti
313	does not affect poly (a) elongation activity; when associated with e-312. decrease about 50% the poly(a) elongation acti

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CEBP_Q2, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BRN2_01, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, RFX1_01, GOMF_ADENYLYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, chrXq21, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_RNA_CATABOLIC_PROCESS, GOMF_POLY_A_RNA_POLYMERASE_ACTIVITY

GO Biological Process (1): 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 (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENT5D	SPANXN4	Q5MJ08	545
TENT5D	FAM133A	Q8N9E0	492
TENT5D	GPRASP1	Q5JY77	487
TENT5D	PTGR2	Q8N8N7	487
TENT5D	SATL1	Q86VE3	455
TENT5D	SLC25A14	O95258	447
TENT5D	ATG16L2	Q8NAA4	443
TENT5D	BEX1	Q9HBH7	425
TENT5D	TUT7	Q5VYS8	416
TENT5D	TENT2	Q6PIY7	414
TENT5D	CHD3	Q12873	403
TENT5D	MTPAP	Q9NVV4	397
TENT5D	TUT4	Q5TAX3	396
TENT5D	TENT4A	Q5XG87	394
TENT5D	SPANXN3	Q5MJ09	390

IntAct

47 interactions, top by confidence:

A	B	Type	Score
TENT5D	C1orf94	psi-mi:“MI:0915”(physical association)	0.560
C1orf94	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
TENT5D	KRTAP19-2	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG4	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
TENT5D	HEY1	psi-mi:“MI:0915”(physical association)	0.560
TENT5D	PABPC3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP11-1	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
C10orf55	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
MSX2	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-2	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
TENT5D	DYDC2	psi-mi:“MI:0915”(physical association)	0.560
PTPN3	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
RHOXF2	TENT5D	psi-mi:“MI:0915”(physical association)	0.370
CAPRIN1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
EIF2S3	EIF3CL	psi-mi:“MI:0914”(association)	0.350
RPL4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
EPHA3	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
TENT5D	PTPN3	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	C10orf55	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	HEY1	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	PABPC3	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
TENT5D	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): FAM46D (Two-hybrid), FAM46D (Two-hybrid), FAM46D (Biochemical Activity), FAM46D (Two-hybrid), FAM46D (Two-hybrid), FAM46D (Two-hybrid), FAM46D (Two-hybrid), FAM46D (Two-hybrid), FAM46D (Two-hybrid), KRTAP11-1 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP19-2 (Two-hybrid), PLEKHG4 (Two-hybrid), ARID5A (Two-hybrid), C10orf55 (Two-hybrid)

ESM2 similar proteins: A0AVI4, A0JMH2, A2ARP1, B0BNK8, F7E7M3, O00562, O08674, O35954, P0C644, P10588, P17105, P23677, Q08DJ7, Q08DK0, Q15173, Q28647, Q29RH2, Q4R7D0, Q4R8X4, Q5R5N9, Q5SSF7, Q5U2N3, Q5VWP2, Q5XIL6, Q5XIV0, Q5ZL95, Q6PD28, Q6PFW1, Q7ZUP1, Q80W83, Q80YU0, Q86TL0, Q8C152, Q8K304, Q8N159, Q8NEK8, Q8R071, Q8R307, Q8R4H7, Q8VDR9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

829 predictions. Top by Δscore:

Variant	Effect	Δscore
X:80438733:G:GG	donor_gain	1.0000
X:80442520:A:AG	acceptor_gain	1.0000
X:80442521:G:GG	acceptor_gain	1.0000
X:80442521:GT:G	acceptor_gain	1.0000
X:80427011:T:A	acceptor_gain	0.9900
X:80438608:A:AG	acceptor_gain	0.9900
X:80438609:G:GG	acceptor_gain	0.9900
X:80438731:AT:A	donor_gain	0.9900
X:80440474:T:G	donor_gain	0.9900
X:80442512:T:TA	acceptor_gain	0.9900
X:80442515:T:A	acceptor_gain	0.9900
X:80442518:CTA:C	acceptor_loss	0.9900
X:80442519:TAG:T	acceptor_loss	0.9900
X:80442520:AGT:A	acceptor_gain	0.9900
X:80442521:GTG:G	acceptor_gain	0.9900
X:80442521:GTGA:G	acceptor_gain	0.9900
X:80442521:GTGAT:G	acceptor_gain	0.9900
X:80438731:ATGTA:A	donor_loss	0.9800
X:80438732:TG:T	donor_loss	0.9800
X:80438733:GTA:G	donor_loss	0.9800
X:80438734:TA:T	donor_loss	0.9800
X:80438735:A:AC	donor_loss	0.9800
X:80438736:AG:A	donor_loss	0.9800
X:80438737:G:C	donor_loss	0.9800
X:80438609:GT:G	acceptor_gain	0.9700
X:80438609:GTT:G	acceptor_gain	0.9700
X:80442508:T:TA	acceptor_gain	0.9700
X:80336434:AAACT:A	donor_gain	0.9600
X:80342499:GATT:G	acceptor_gain	0.9600
X:80438729:CAAT:C	donor_gain	0.9600

AlphaMissense

2611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:80442976:T:C	L146P	0.997
X:80443050:T:C	F171L	0.997
X:80443052:T:A	F171L	0.997
X:80443052:T:G	F171L	0.997
X:80443053:A:C	S172R	0.995
X:80443055:T:A	S172R	0.995
X:80443055:T:G	S172R	0.995
X:80443020:T:C	F161L	0.994
X:80443022:T:A	F161L	0.994
X:80443022:T:G	F161L	0.994
X:80442969:T:A	W144R	0.993
X:80442969:T:C	W144R	0.993
X:80443044:T:C	F169L	0.993
X:80443046:T:A	F169L	0.993
X:80443046:T:G	F169L	0.993
X:80442972:A:C	S145R	0.992
X:80442974:T:A	S145R	0.992
X:80442974:T:G	S145R	0.992
X:80443051:T:C	F171S	0.992
X:80443347:T:C	F270L	0.992
X:80443349:T:A	F270L	0.992
X:80443349:T:G	F270L	0.992
X:80443435:T:C	L299P	0.991
X:80443335:T:C	F266L	0.990
X:80443337:C:A	F266L	0.990
X:80443337:C:G	F266L	0.990
X:80443015:T:C	L159P	0.989
X:80442971:G:C	W144C	0.988
X:80442971:G:T	W144C	0.988
X:80443155:A:C	S206R	0.988

dbSNP variants (sampled 300 via entrez): RS1000074159 (X:80404872 G>T), RS1000086672 (X:80395774 G>A,T), RS1000109106 (X:80345542 C>T), RS1000150752 (X:80369150 T>C), RS1000228614 (X:80340529 C>G), RS1000287293 (X:80435967 G>A), RS1000354293 (X:80346648 G>A,T), RS1000355417 (X:80420545 TCTA>T), RS1000378736 (X:80377387 A>G), RS1000429180 (X:80386626 G>A,T), RS1000458228 (X:80395125 C>T), RS1000474453 (X:80385278 A>G), RS1000489580 (X:80420125 AT>A), RS1000552389 (X:80441828 T>C), RS1000590756 (X:80379446 G>A)

Disease associations

OMIM: gene MIM:300976 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
2-palmitoylglycerol	increases expression	1

Clinical trials (associated diseases)

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