PAPOLA

Summary

PAPOLA (poly(A) polymerase alpha, HGNC:14981) is a protein-coding gene on chromosome 14q32.2, encoding Poly(A) polymerase alpha (P51003). Polymerase that creates the 3’-poly(A) tail of mRNA’s.

The protein encoded by this gene belongs to the poly(A) polymerase family. It is required for the addition of adenosine residues for the creation of the 3’-poly(A) tail of mRNAs. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10914 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_032632

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14981
Approved symbol	PAPOLA
Name	poly(A) polymerase alpha
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	PAP
Ensembl gene	ENSG00000090060
Ensembl biotype	protein_coding
OMIM	605553
Entrez	10914

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 23 protein_coding, 12 retained_intron, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000216277, ENST00000392990, ENST00000553357, ENST00000553461, ENST00000553689, ENST00000553940, ENST00000554130, ENST00000554135, ENST00000554666, ENST00000554887, ENST00000555021, ENST00000555131, ENST00000555224, ENST00000555508, ENST00000555626, ENST00000555701, ENST00000555912, ENST00000556248, ENST00000556283, ENST00000556459, ENST00000556619, ENST00000556787, ENST00000557320, ENST00000557406, ENST00000557471, ENST00000618976, ENST00000874083, ENST00000874084, ENST00000874085, ENST00000874086, ENST00000874087, ENST00000874088, ENST00000874089, ENST00000874090, ENST00000874091, ENST00000924557, ENST00000924558, ENST00000949669, ENST00000949670, ENST00000949671, ENST00000949672, ENST00000949673

RefSeq mRNA: 10 — MANE Select: NM_032632 NM_001252006, NM_001252007, NM_001293627, NM_001293628, NM_001293632, NM_001363662, NM_001363664, NM_001363665, NM_001363666, NM_032632

CCDS: CCDS58334, CCDS58335, CCDS86431, CCDS9946

Canonical transcript exons

ENST00000216277 — 22 exons

Exon	Start	End
ENSE00001375853	96564955	96567116
ENSE00002461848	96502382	96502600
ENSE00003471177	96542243	96542296
ENSE00003489764	96527430	96527539
ENSE00003504345	96560649	96560711
ENSE00003515186	96562819	96562893
ENSE00003548746	96536976	96537060
ENSE00003570755	96534491	96534563
ENSE00003581686	96544149	96544258
ENSE00003584860	96535879	96535999
ENSE00003595621	96555847	96555947
ENSE00003597360	96527953	96528006
ENSE00003608506	96520055	96520228
ENSE00003611067	96556175	96556413
ENSE00003623999	96525310	96525391
ENSE00003643113	96521006	96521072
ENSE00003647632	96552480	96552622
ENSE00003650700	96547797	96547918
ENSE00003672681	96542774	96542893
ENSE00003680280	96532331	96532420
ENSE00003692268	96532511	96532649
ENSE00003693395	96531475	96531586

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 116.8564 / max 832.8301, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141344	113.2918	1826
207361	1.2880	856
207362	1.2879	818
141345	0.9887	397

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	99.07	gold quality
choroid plexus epithelium	UBERON:0003911	98.78	gold quality
adrenal tissue	UBERON:0018303	98.68	gold quality
ventricular zone	UBERON:0003053	98.57	gold quality
ganglionic eminence	UBERON:0004023	98.44	gold quality
calcaneal tendon	UBERON:0003701	98.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.10	gold quality
embryo	UBERON:0000922	98.00	gold quality
bone marrow cell	CL:0002092	97.99	gold quality
body of pancreas	UBERON:0001150	97.97	gold quality
endometrium	UBERON:0001295	97.97	gold quality
colonic mucosa	UBERON:0000317	97.96	gold quality
jejunal mucosa	UBERON:0000399	97.96	gold quality
cortical plate	UBERON:0005343	97.93	gold quality
skin of hip	UBERON:0001554	97.86	gold quality
islet of Langerhans	UBERON:0000006	97.76	gold quality
left ovary	UBERON:0002119	97.68	gold quality
rectum	UBERON:0001052	97.67	gold quality
lymph node	UBERON:0000029	97.63	gold quality
pancreas	UBERON:0001264	97.61	gold quality
cardia of stomach	UBERON:0001162	97.58	gold quality
tonsil	UBERON:0002372	97.57	gold quality
pylorus	UBERON:0001166	97.53	gold quality
bronchial epithelial cell	CL:0002328	97.50	gold quality
ovary	UBERON:0000992	97.49	gold quality
monocyte	CL:0000576	97.48	gold quality
right ovary	UBERON:0002118	97.47	gold quality
mononuclear cell	CL:0000842	97.46	gold quality
upper leg skin	UBERON:0004262	97.46	gold quality
body of uterus	UBERON:0009853	97.43	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	41.23
E-MTAB-7249	no	3790.27
E-MTAB-8060	no	2494.35
E-CURD-97	no	1275.07
E-MTAB-6386	no	404.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

165 targeting PAPOLA, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 5)

• Observations imply that translational regulation is among the conserved mechanisms regulating PAPOLA expression. (PMID:20174964)
• The ability of PABPN1 to promote splicing requires its RNA binding and, to a lesser extent, poly(A)polymerase (PAP) - stimulatory functions. (PMID:25896913)
• Lack of CstF-64 binding excludes PAPalpha from Star-PAP target pre-mRNA UTRs.CstF-64 and 3’-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding poly A polymerase. (PMID:26496945)
• Whereas PABPN1 strongly increases the activity of its cognate poly(A) polymerase in vitro, Pab2 was unable to stimulate Pla1 to any significant extent. (PMID:28096519)
• PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation. (PMID:33712453)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	papola	ENSDARG00000009585
mus_musculus	Papola	ENSMUSG00000021111
rattus_norvegicus	Papola	ENSRNOG00000004827
drosophila_melanogaster	hrg	FBGN0015949
caenorhabditis_elegans		WBGENE00009658
caenorhabditis_elegans		WBGENE00011791
caenorhabditis_elegans		WBGENE00012528

Paralogs (2): PAPOLG (ENSG00000115421), PAPOLB (ENSG00000218823)

Protein

Protein identifiers

Poly(A) polymerase alpha — P51003 (reviewed: P51003)

Alternative names: Polynucleotide adenylyltransferase alpha

All UniProt accessions (7): P51003, A0A0C4DGK1, G3V3I9, G3V457, G3XAH6, H0YJ00, H0YJL4

UniProt curated annotations — full annotation on UniProt →

Function. Polymerase that creates the 3’-poly(A) tail of mRNA’s. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.

Subunit / interactions. Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with AHCYL1 and FIP1L1; the interaction with AHCYL1 seems to increase interaction with FIP1L1. Interacts with NUDT21; the interaction is diminished by acetylation. Interacts with KPNB1; the interaction promotes PAP nuclear import and is inhibited by acetylation of PAP.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Polysumoylated. Varying sumoylation depending on tissue- and cell-type. Highly sumoylated in bladder and NIH 3T3 cells. Sumoylation is required for nuclear localization and enhances PAP stability. Desumoylated by SENP1. Inhibits polymerase activity. Hyperphosphorylation on multiple CDK2 consensus and non-consensus sites in the C-terminal Ser/Thr-rich region represses PAP activity in late M-phase. Phosphorylation/dephosphorylation may regulate the interaction between PAP and CPSF. Acetylated in the C-terminus. Acetylation decreases interaction with NUDT21 and KPNB1, and inhibits nuclear localization through inhibiting binding to the importin alpha/beta complex.

Cofactor. Binds 2 magnesium ions. Also active with manganese.

Similarity. Belongs to the poly(A) polymerase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51003-1	1	yes
P51003-2	2

RefSeq proteins (10): NP_001238935, NP_001238936, NP_001280556, NP_001280557, NP_001280561, NP_001350591, NP_001350593, NP_001350594, NP_001350595, NP_116021* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007010	PolA_pol_RNA-bd_dom	Domain
IPR007012	PolA_pol_cen_dom	Domain
IPR011068	NuclTrfase_I-like_C	Homologous_superfamily
IPR014492	PolyA_polymerase	Family
IPR043519	NT_sf	Homologous_superfamily
IPR048840	PolA_pol_NTPase	Domain

Pfam: PF04926, PF04928, PF20750

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 (53 total): binding site 12, modified residue 9, compositionally biased region 8, cross-link 6, region of interest 5, site 5, splice variant 2, sequence conflict 2, short sequence motif 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8R8R	ELECTRON MICROSCOPY	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51003-F1	75.46	0.59

Functional residue map

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

Catalytic / active sites (5): 153 (interaction with rna); 158 (interaction with rna); 328 (interaction with rna); 399 (interaction with rna); 524 (interaction with rna)

Ligand- & substrate-binding residues (12): 100–102; 109; 113–115; 113; 113; 115; 115; 167; 167; 228; 237; 246–247

Post-translational modifications (15): 10, 24, 537, 558, 641, 650, 736, 738, 740, 444, 445, 506, 507, 736, 740

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 290 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GNF2_BNIP2, MODULE_255, KAAB_FAILED_HEART_ATRIUM_DN, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, STARK_HYPPOCAMPUS_22Q11_DELETION_UP

GO Biological Process (5): mRNA 3’-end processing (GO:0031124), co-transcriptional mRNA 3’-end processing, cleavage and polyadenylation pathway (GO:0180010), cytosolic mRNA polyadenylation (GO:0180011), mRNA processing (GO:0006397), RNA 3’-end processing (GO:0031123)

GO Molecular Function (10): magnesium ion binding (GO:0000287), RNA binding (GO:0003723), ATP binding (GO:0005524), manganese ion binding (GO:0030145), poly(A) RNA polymerase activity (GO:1990817), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA metabolic process	2
RNA processing	2
cellular anatomical structure	2
mRNA processing	1
RNA 3’-end processing	1
mRNA 3’-end processing	1
co-transcriptional RNA 3’-end processing, cleavage and polyadenylation pathway	1
metal ion binding	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion 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
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2257 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAPOLA	ZCCHC7	Q8N3Z6	995
PAPOLA	MTREX	P42285	994
PAPOLA	SNRNP70	P08621	985
PAPOLA	SYMPK	Q92797	978
PAPOLA	CPSF1	Q10570	968
PAPOLA	TUT1	Q9H6E5	951
PAPOLA	PABPN1	Q86U42	940
PAPOLA	MTPAP	Q9NVV4	936
PAPOLA	CSTF3	Q12996	915
PAPOLA	PARN	O95453	886
PAPOLA	U2AF2	P26368	873
PAPOLA	TUT4	Q5TAX3	872
PAPOLA	TENT2	Q6PIY7	867
PAPOLA	CPEB1	Q9BZB8	862
PAPOLA	CPSF6	Q16630	850

IntAct

32 interactions, top by confidence:

A	B	Type	Score
PAPOLA	Ywhae	psi-mi:“MI:0915”(physical association)	0.590
Ywhae	PAPOLA	psi-mi:“MI:0915”(physical association)	0.590
PAPOLA	Ywhae	psi-mi:“MI:0407”(direct interaction)	0.590
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
AURKB	SMCHD1	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
PKM	PAPOLA	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PAPOLA	NRAS	psi-mi:“MI:0915”(physical association)	0.400
PAPOLA	HSPA2	psi-mi:“MI:0915”(physical association)	0.400
PAPOLA		psi-mi:“MI:0915”(physical association)	0.370
PAPOLA	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
PAPOLA	RSRC1	psi-mi:“MI:0914”(association)	0.350
PAPOLA	SYMPK	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
BACE2	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TGIF2	SAP30	psi-mi:“MI:0914”(association)	0.350
MRPL42	UBA6	psi-mi:“MI:0914”(association)	0.350
ANLN	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
PCBP2	HNRNPL	psi-mi:“MI:0914”(association)	0.350
PCBP2	PAPOLA	psi-mi:“MI:0914”(association)	0.350
NPM1	PAPOLA	psi-mi:“MI:0914”(association)	0.350
CPSF1	PAPOLA	psi-mi:“MI:0914”(association)	0.350
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
RBM15	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
glpD	PAPOLA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (95): PAPOLA (Affinity Capture-MS), GNA11 (Affinity Capture-MS), ADRBK1 (Co-fractionation), CSTF2 (Co-fractionation), CSTF2T (Co-fractionation), CSTF3 (Co-fractionation), HNRNPA1 (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation), PAPOLA (Co-fractionation)

ESM2 similar proteins: F1N2W9, F1QDI9, F1QMB9, O00763, O75909, O88874, O94776, P10276, P11416, P13631, P18514, P18911, P22605, P22681, P22682, P23798, P25500, P25916, P35227, P51003, Q13191, Q14123, Q3TTA7, Q5FBR4, Q5SDR3, Q61183, Q63421, Q640D5, Q64338, Q66JB6, Q69ZT9, Q6NRE7, Q7T3E6, Q7ZTI3, Q80TJ7, Q86UE8, Q8CFK2, Q8IU60, Q8JIR0, Q8K4S7

Diamond homologs: O42617, O82312, P25500, P29468, P51003, P51004, P51005, P51006, Q10295, Q51D88, Q54J73, Q56XM9, Q61183, Q6PCL9, Q8VYW1, Q9BWT3, Q9LMT2, Q9NRJ5, Q9UW26, Q9WVP6

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
FIP1L1	up-regulates	PAPOLA	binding
“CPSF complex”	“up-regulates activity”	PAPOLA	relocalization
PAPOLA	up-regulates	mRNA_polyadenylation
PAPOLA	“up-regulates quantity by stabilization”	“messenger RNA”	“chemical modification”
AHCYL1	“down-regulates activity”	PAPOLA	binding
AHCYL2	“down-regulates activity”	PAPOLA	binding
CDK1	“up-regulates activity”	PAPOLA	phosphorylation
ERK1/2	“up-regulates activity”	PAPOLA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
mRNA Polyadenylation	5	18.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3210 predictions. Top by Δscore:

Variant	Effect	Δscore
14:96502596:CCGTT:C	donor_gain	1.0000
14:96502598:GTT:G	donor_gain	1.0000
14:96502599:TT:T	donor_gain	1.0000
14:96502601:G:GG	donor_gain	1.0000
14:96502602:T:G	donor_loss	1.0000
14:96520051:A:AG	acceptor_gain	1.0000
14:96520052:T:G	acceptor_gain	1.0000
14:96520053:A:AG	acceptor_gain	1.0000
14:96520054:G:GA	acceptor_gain	1.0000
14:96520054:GT:G	acceptor_gain	1.0000
14:96520054:GTC:G	acceptor_gain	1.0000
14:96520054:GTCC:G	acceptor_gain	1.0000
14:96520054:GTCCA:G	acceptor_gain	1.0000
14:96520225:GCAG:G	donor_gain	1.0000
14:96520226:CAGGT:C	donor_loss	1.0000
14:96520227:AGGT:A	donor_loss	1.0000
14:96520229:G:GC	donor_loss	1.0000
14:96520229:G:GG	donor_gain	1.0000
14:96521000:CAACA:C	acceptor_loss	1.0000
14:96521002:ACAG:A	acceptor_loss	1.0000
14:96521003:CA:C	acceptor_loss	1.0000
14:96521004:A:AG	acceptor_gain	1.0000
14:96521004:AG:A	acceptor_gain	1.0000
14:96521005:G:A	acceptor_loss	1.0000
14:96521005:G:GG	acceptor_gain	1.0000
14:96521005:GG:G	acceptor_gain	1.0000
14:96521068:GCAAG:G	donor_gain	1.0000
14:96521069:CAAGG:C	donor_loss	1.0000
14:96521070:AAGG:A	donor_loss	1.0000
14:96521071:AGG:A	donor_loss	1.0000

AlphaMissense

4899 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:96520107:G:C	G21R	1.000
14:96520108:G:A	G21D	1.000
14:96520123:T:A	I26N	1.000
14:96520123:T:C	I26T	1.000
14:96520171:T:C	L42P	1.000
14:96520228:G:C	R61T	1.000
14:96520228:G:T	R61M	1.000
14:96521006:G:C	R61S	1.000
14:96521006:G:T	R61S	1.000
14:96521017:T:C	L65S	1.000
14:96521026:T:C	L68P	1.000
14:96521046:T:A	W75R	1.000
14:96521046:T:C	W75R	1.000
14:96521061:A:C	S80R	1.000
14:96521063:T:A	S80R	1.000
14:96521063:T:G	S80R	1.000
14:96525343:G:A	G95R	1.000
14:96525343:G:C	G95R	1.000
14:96525344:G:A	G95E	1.000
14:96525358:T:A	F100I	1.000
14:96525358:T:C	F100L	1.000
14:96525360:T:A	F100L	1.000
14:96525360:T:G	F100L	1.000
14:96525361:G:A	G101R	1.000
14:96525361:G:C	G101R	1.000
14:96525362:G:A	G101E	1.000
14:96525362:G:C	G101A	1.000
14:96525362:G:T	G101V	1.000
14:96525367:T:G	Y103D	1.000
14:96525371:G:C	R104T	1.000

dbSNP variants (sampled 300 via entrez): RS1000018300 (14:96564154 A>C,G), RS1000023635 (14:96536365 C>T), RS1000051911 (14:96518288 A>G), RS1000124762 (14:96556709 C>T), RS1000167393 (14:96502775 C>A,G), RS1000231992 (14:96530048 T>C), RS1000245686 (14:96549875 G>A), RS1000249659 (14:96539256 A>T), RS1000349541 (14:96508175 G>A), RS1000383170 (14:96549502 C>G), RS1000393383 (14:96532920 C>A,T), RS1000449639 (14:96516347 C>T), RS1000450227 (14:96563841 A>C,T), RS1000497182 (14:96513520 T>A,C), RS1000499262 (14:96543189 T>C)

Disease associations

OMIM: gene MIM:605553 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002938_27	Copper levels	4.000000e-06
GCST005351_4	Carboplatin disposition in epthelial ovarian cancer	6.000000e-06
GCST006742_1	Number of stillbirths in continuous marriage	8.000000e-09
GCST009391_2120	Metabolite levels	2.000000e-06
GCST009391_864	Metabolite levels	4.000000e-06
GCST011742_65	Triglyceride levels in HIV infection	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010382	phosphatidylcholine 36:4 measurement
EFO:0010534	suberic acid measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, affects cotreatment, decreases expression	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Rotenone	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	increases expression	1
3,3’-diindolylmethane	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	increases expression	1
ochratoxin A	decreases expression	1
versicolorin A	increases expression	1
cupric oxide	increases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
AM 251	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3DC	Abcam HEK293T PAPOLA KO	Transformed cell line	Female

Clinical trials (associated diseases)

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