TENT4B

Summary

TENT4B (terminal nucleotidyltransferase 4B, HGNC:30758) is a protein-coding gene on chromosome 16q12.1, encoding Terminal nucleotidyltransferase 4B (Q8NDF8). Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3’ poly(A) tail creating a heterogeneous 3’ poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation.

Enables guanylyltransferase activity; poly(A) RNA polymerase activity; and telomerase RNA binding activity. Involved in RNA metabolic process; carbohydrate homeostasis; and regulation of nucleobase-containing compound metabolic process. Located in cytosol; nucleolus; and plasma membrane. Part of TRAMP complex.

Source: NCBI Gene 64282 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• MANE Select transcript: NM_001365324

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30758
Approved symbol	TENT4B
Name	terminal nucleotidyltransferase 4B
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	TRF4-2, TUT3
Ensembl gene	ENSG00000121274
Ensembl biotype	protein_coding
OMIM	605540
Entrez	64282

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000357464, ENST00000436909, ENST00000561678, ENST00000562717

RefSeq mRNA: 4 — MANE Select: NM_001365324 NM_001040284, NM_001040285, NM_001365323, NM_001365324

CCDS: CCDS54006, CCDS92158

Canonical transcript exons

ENST00000561678 — 12 exons

Exon	Start	End
ENSE00002612576	50153306	50154259
ENSE00003485417	50214221	50214267
ENSE00003544799	50211323	50211446
ENSE00003577122	50224891	50224994
ENSE00003586810	50216075	50216195
ENSE00003612971	50217556	50217663
ENSE00003613625	50223174	50223387
ENSE00003624655	50222306	50222434
ENSE00003642873	50224657	50224783
ENSE00003673302	50229152	50235310
ENSE00003691440	50225098	50225285
ENSE00003728149	50227839	50228003

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0428 / max 65.8086, expressed in 1665 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153978	3.0508	1425
153979	1.0430	614
153981	0.6575	370
153980	0.5767	320
153982	0.5230	208
153983	0.1918	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.26	gold quality
secondary oocyte	CL:0000655	94.85	gold quality
jejunal mucosa	UBERON:0000399	94.51	gold quality
oocyte	CL:0000023	93.98	gold quality
kidney epithelium	UBERON:0004819	93.39	gold quality
oviduct epithelium	UBERON:0004804	91.50	gold quality
epithelial cell of pancreas	CL:0000083	90.84	gold quality
sperm	CL:0000019	90.18	gold quality
nipple	UBERON:0002030	89.08	gold quality
pancreatic ductal cell	CL:0002079	89.01	gold quality
superficial temporal artery	UBERON:0001614	88.87	gold quality
jejunum	UBERON:0002115	88.76	gold quality
urethra	UBERON:0000057	88.59	gold quality
cauda epididymis	UBERON:0004360	88.47	gold quality
saphenous vein	UBERON:0007318	88.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.28	gold quality
caput epididymis	UBERON:0004358	87.72	gold quality
cortical plate	UBERON:0005343	86.98	gold quality
tibialis anterior	UBERON:0001385	86.87	gold quality
adrenal tissue	UBERON:0018303	86.51	gold quality
tibia	UBERON:0000979	86.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.19	gold quality
renal medulla	UBERON:0000362	86.05	gold quality
testis	UBERON:0000473	85.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.52	gold quality
left testis	UBERON:0004533	85.41	gold quality
duodenum	UBERON:0002114	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.34	gold quality
calcaneal tendon	UBERON:0003701	85.29	gold quality
lower lobe of lung	UBERON:0008949	85.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.87

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• PAPD5 catalyzes the polyadenylation of different types of RNA substrates in vitro. (PMID:21788334)
• PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21. (PMID:25049417)
• We analyzed the interactions of the human TRAMP-like proteins, PAPD5, ZCCHC7, and MTR4, with the nuclear exosome. PAPD5 and ZCCHC7 exhibited mutual interactions in presence of the exosome catalytic subunit RRP6, whereas MTR4 was dispensable for their assembly (PMID:27434818)
• A novel post-transcriptional regulatory network involving carbohydrate metabolism and glucose homeostasis mediated by GLD4. (PMID:28383716)
• TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. (PMID:30026317)
• We find that mature hTR derives from extended precursors but that in PARN-mutant cells hTR maturation kinetically stalls and unprocessed precursors are degraded. Loss of poly(A)polymerase PAPD5 in PARN-mutant cells accelerates hTR maturation and restores hTR processing, indicating that oligoadenylation and deadenylation set rates of hTR maturation (PMID:30930056)
• Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing. (PMID:32451488)
• Chemical inhibition of PAPD5/7 rescues telomerase function and hematopoiesis in dyskeratosis congenita. (PMID:32559291)
• The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis. (PMID:35867748)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tent4b	ENSDARG00000060071
mus_musculus	Tent4b	ENSMUSG00000036779
rattus_norvegicus	Tent4b	ENSRNOG00000024212
drosophila_melanogaster	Trf4-1	FBGN0030049
drosophila_melanogaster	Trf4-2	FBGN0039251
caenorhabditis_elegans	gld-4	WBGENE00014115

Paralogs (1): TENT4A (ENSG00000112941)

Protein

Protein identifiers

Terminal nucleotidyltransferase 4B — Q8NDF8 (reviewed: Q8NDF8)

Alternative names: Non-canonical poly(A) RNA polymerase PAPD5, PAP-associated domain-containing protein 5, Terminal guanylyltransferase, Terminal uridylyltransferase 3, Topoisomerase-related function protein 4-2

All UniProt accessions (3): A0A7N4YH79, E9PC61, Q8NDF8

UniProt curated annotations — full annotation on UniProt →

Function. Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3’ poly(A) tail creating a heterogeneous 3’ poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation. Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Doesn’t need a cofactor for polyadenylation activity (in vitro). Required for cytoplasmic polyadenylation of mRNAs involved in carbohydrate metabolism, including the glucose transporter SLC2A1/GLUT1. Plays a role in replication-dependent histone mRNA degradation, probably through terminal uridylation of mature histone mRNAs. May play a role in sister chromatid cohesion. Mediates 3’ adenylation of the microRNA MIR21 followed by its 3’-to-5’ trimming by the exoribonuclease PARN leading to degradation. Mediates 3’ adenylation of H/ACA box snoRNAs (small nucleolar RNAs) followed by its 3’-to-5’ trimming by the exoribonuclease PARN which enhances snoRNA stability and maturation.

Subunit / interactions. Component of a nucleolar TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes. Interacts with CPEB1; the interaction is required for TENT4B-mediated translational control.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Similarity. Belongs to the DNA polymerase type-B-like family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NDF8-1	1	yes
Q8NDF8-2	2
Q8NDF8-3	3
Q8NDF8-4	4
Q8NDF8-5	5

RefSeq proteins (4): NP_001035374, NP_001035375, NP_001352252, NP_001352253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002058	PAP_assoc	Domain
IPR043519	NT_sf	Homologous_superfamily
IPR045862	Trf4-like	Family
IPR054708	MTPAP-like_central	Domain

Pfam: PF03828, PF22600

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 (34 total): binding site 8, splice variant 8, compositionally biased region 7, cross-link 5, region of interest 2, chain 1, domain 1, modified residue 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDF8-F1	71.51	0.52

Functional residue map

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

Ligand- & substrate-binding residues (8): 177; 179; 240; 265; 283; 284; 368; 372

Post-translational modifications (6): 484, 470, 497, 512, 526, 151

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 274 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_SNO_S_RNA_METABOLIC_PROCESS, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, AAAYRNCTG_UNKNOWN

GO Biological Process (14): rRNA processing (GO:0006364), RNA catabolic process (GO:0006401), miRNA catabolic process (GO:0010587), RNA 3’-end processing (GO:0031123), mRNA 3’-end processing (GO:0031124), negative regulation of telomere maintenance via telomerase (GO:0032211), carbohydrate homeostasis (GO:0033500), polyadenylation-dependent ncRNA catabolic process (GO:0043634), cell division (GO:0051301), negative regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060212), histone mRNA catabolic process (GO:0071044), poly(A)-dependent snoRNA 3’-end processing (GO:0071051), positive regulation of 3’-UTR-mediated mRNA stabilization (GO:1905870), mRNA processing (GO:0006397)

GO Molecular Function (11): RNA binding (GO:0003723), ATP binding (GO:0005524), metal ion binding (GO:0046872), telomerase RNA binding (GO:0070034), adenylyltransferase activity (GO:0070566), guanylyltransferase activity (GO:0070568), poly(A) RNA polymerase activity (GO:1990817), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (6): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), TRAMP complex (GO:0031499), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	3
nucleotidyltransferase activity	2
cellular anatomical structure	2
rRNA metabolic process	1
ribosome biogenesis	1
RNA metabolic process	1
nucleic acid catabolic process	1
RNA catabolic process	1
miRNA metabolic process	1
mRNA processing	1
RNA 3’-end processing	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
chemical homeostasis	1
polyadenylation-dependent RNA catabolic process	1
cellular process	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
histone mRNA metabolic process	1
sno(s)RNA 3’-end processing	1
positive regulation of gene expression	1
3’-UTR-mediated mRNA stabilization	1
regulation of 3’-UTR-mediated mRNA stabilization	1
mRNA metabolic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
RNA binding	1
adenylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
nuclear lumen	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENT4B	ZCCHC7	Q8N3Z6	995
TENT4B	MTREX	P42285	969
TENT4B	MTPAP	Q9NVV4	798
TENT4B	PAPOLG	Q9BWT3	777
TENT4B	PAPOLA	P51003	773
TENT4B	PAPOLB	Q9NRJ5	773
TENT4B	TUT4	Q5TAX3	756
TENT4B	TUT1	Q9H6E5	741
TENT4B	EXOSC10	Q01780	717
TENT4B	PARN	O95453	716
TENT4B	ZCCHC8	Q6NZY4	678
TENT4B	RBM7	Q9Y580	661
TENT4B	ZCCHC14	Q8WYQ9	648
TENT4B	RAD21	O60216	648
TENT4B	ZFC3H1	O60293	607

IntAct

149 interactions, top by confidence:

A	B	Type	Score
C1D	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
EXOSC5	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NPM1	NVL	psi-mi:“MI:0914”(association)	0.610
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
PPAN	PPM1G	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
MPHOSPH6	ZFC3H1	psi-mi:“MI:0914”(association)	0.530

BioGRID (168): PAPD5 (Affinity Capture-MS), PAPD5 (Affinity Capture-MS), PAPD5 (Affinity Capture-MS), PAPD5 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), KRT6A (Affinity Capture-MS), KRT6B (Affinity Capture-MS), NUMA1 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), BCL7B (Affinity Capture-MS), MED17 (Affinity Capture-MS), RCL1 (Affinity Capture-MS), RBM6 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PRR9, B2RX14, F4I443, F4JNY0, F4KIX0, F6RIX4, I3XHK1, O22199, O82175, O82312, P0DOY1, P51004, P93831, Q0P4S5, Q0WNR6, Q0WUR5, Q10MI4, Q336N8, Q3UWM4, Q53NI2, Q5QJC2, Q5TAX3, Q5VN06, Q60GC1, Q68ED3, Q6EU49, Q6NQ79, Q6NRM6, Q6PCL9, Q6ZMT4, Q84UI6, Q86W56, Q8L6Z7, Q8NDF8, Q8S4P4, Q8S4P5, Q8S4P6, Q8VYU4, Q8VYW1, Q9BWT3

Diamond homologs: G5EFL0, P48561, P53632, Q5XG87, Q68ED3, Q6PB75, Q7KVS9, Q8NDF8, Q9HFW3, Q9UTN3, Q9VC07, Q5K9E2, O74518, Q9VD44, Q503I9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TENT4B	“form complex”	“NEXT complex, TENT4B-ZCCHC7 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	40.5×	1e-06
Peptide chain elongation	21	32.1×	7e-25
Viral mRNA Translation	21	32.1×	7e-25
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	21	31.8×	7e-25
Selenocysteine synthesis	21	30.4×	1e-24
Eukaryotic Translation Termination	21	30.4×	1e-24
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	21	29.8×	1e-24
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	21	29.8×	1e-24

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	6	54.4×	6e-08
chromosome condensation	5	34.0×	2e-05
cytoplasmic translation	22	32.9×	4e-25
ribosomal large subunit biogenesis	9	32.2×	7e-10
rRNA processing	16	18.3×	6e-14
translation	22	18.2×	2e-19
ribosomal small subunit biogenesis	9	16.5×	3e-07
RNA processing	7	12.3×	6e-05

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	67
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1879 predictions. Top by Δscore:

Variant	Effect	Δscore
16:50161132:GCTT:G	donor_gain	1.0000
16:50211320:CA:C	acceptor_gain	1.0000
16:50211321:A:AG	acceptor_gain	1.0000
16:50211321:A:G	acceptor_loss	1.0000
16:50211321:AG:A	acceptor_gain	1.0000
16:50211321:AGTCT:A	acceptor_gain	1.0000
16:50211322:G:GA	acceptor_gain	1.0000
16:50211322:GT:G	acceptor_gain	1.0000
16:50211322:GTC:G	acceptor_gain	1.0000
16:50211322:GTCT:G	acceptor_gain	1.0000
16:50211322:GTCTG:G	acceptor_gain	1.0000
16:50211442:CTGAC:C	donor_gain	1.0000
16:50211443:TGAC:T	donor_gain	1.0000
16:50211444:GAC:G	donor_gain	1.0000
16:50211444:GACG:G	donor_gain	1.0000
16:50211445:AC:A	donor_gain	1.0000
16:50211447:G:C	donor_loss	1.0000
16:50211447:G:GG	donor_gain	1.0000
16:50211448:TGAGT:T	donor_loss	1.0000
16:50214215:TTTCA:T	acceptor_loss	1.0000
16:50214216:TTCA:T	acceptor_loss	1.0000
16:50214217:TCAG:T	acceptor_loss	1.0000
16:50214219:A:AG	acceptor_gain	1.0000
16:50214220:G:GG	acceptor_gain	1.0000
16:50214268:G:T	donor_loss	1.0000
16:50216056:ATAT:A	acceptor_gain	1.0000
16:50216057:T:G	acceptor_gain	1.0000
16:50216059:T:G	acceptor_gain	1.0000
16:50216073:A:AG	acceptor_gain	1.0000
16:50216074:G:GT	acceptor_gain	1.0000

AlphaMissense

4683 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007685 (16:50169022 C>G,T), RS1000038375 (16:50162194 A>G), RS1000047653 (16:50153180 C>A,G,T), RS1000059914 (16:50168775 A>G), RS1000125420 (16:50162040 T>C), RS1000163749 (16:50156420 C>A), RS1000203456 (16:50229562 T>C), RS1000256162 (16:50186304 G>A,C,T), RS1000269548 (16:50168194 T>C), RS1000273800 (16:50205844 G>A), RS1000322183 (16:50198120 A>T), RS1000398744 (16:50211950 A>C,G,T), RS1000409397 (16:50192434 T>G), RS1000496769 (16:50173725 G>A,C), RS1000504440 (16:50216500 C>T)

Disease associations

OMIM: gene MIM:605540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003050_21	Schizophrenia	4.000000e-06
GCST007429_123	Lung function (FVC)	2.000000e-12
GCST007432_59	FEV1	1.000000e-08
GCST008362_59	Birth weight	1.000000e-08
GCST90002389_309	Lymphocyte percentage of white cells	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0004344	birth weight
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4680036 (SINGLE PROTEIN), CHEMBL6066029 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.03	IC50	94	nM	CHEMBL5573474
6.07	IC50	850	nM	CHEMBL6143667

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(6S)-2-methoxy-3-(3-methoxypropoxy)-10-oxo-6-propan-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid	2098383: Inhibition of recombinant human PAPD5 expressed in Escherichia coli BL21 (DE3) using 5’-GCCUUUCAUCUC UAACUGCGAAAAAAAAAA-3’ as RNA substrate incubated for 3 hrs in presence of ATP by ATP depletion based kinase-glo luminescent assay	ic50	0.0940	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
perfluorooctane sulfonic acid	decreases expression	2
(+)-JQ1 compound	increases expression	2
Valproic Acid	affects expression, increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, affects methylation	1
TAK-243	increases sumoylation	1
kojic acid	decreases expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
scriptaid	increases expression	1
jinfukang	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Bleomycin	decreases expression	1
Deoxyglucose	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4672539	Binding	Binding affinity to PAPD5 in human HePAD38 cells infected with HBV assessed as protein labelling at 20 uM after 1 hr by photoaffinity labelling in-situ fluorescence gel-based LC-MS/MS analysis	Development of DHQ-based chemical biology probe to profile cellular targets for HBV. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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