POLR1G

Summary

POLR1G (RNA polymerase I subunit G, HGNC:24219) is a protein-coding gene on chromosome 19q13.32, encoding DNA-directed RNA polymerase I subunit RPA34 (O15446). Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. It is a selective cancer dependency (DepMap: 39.7% of cell lines).

Enables RNA binding activity. Involved in transcription initiation at RNA polymerase I promoter. Located in cytosol; mitochondrion; and nuclear lumen. Part of RNA polymerase I complex. Implicated in multiple myeloma.

Source: NCBI Gene 10849 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 39.7% of screened cell lines
• MANE Select transcript: NM_012099

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24219
Approved symbol	POLR1G
Name	RNA polymerase I subunit G
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	ASE-1, CAST, PAF49, RPA34, A34.5
Ensembl gene	ENSG00000117877
Ensembl biotype	protein_coding
OMIM	107325
Entrez	10849

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000309424, ENST00000589804, ENST00000590794, ENST00000592852

RefSeq mRNA: 2 — MANE Select: NM_012099 NM_001297590, NM_012099

CCDS: CCDS12661, CCDS74397

Canonical transcript exons

ENST00000309424 — 3 exons

Exon	Start	End
ENSE00000793899	45407094	45407235
ENSE00001271430	45408133	45410737
ENSE00001291541	45406644	45406718

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 85.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7895 / max 59.0521, expressed in 1657 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176411	8.0273	1650
176410	0.3946	160
208862	0.3676	224

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.67	gold quality
oocyte	CL:0000023	84.01	gold quality
diaphragm	UBERON:0001103	82.14	silver quality
secondary oocyte	CL:0000655	80.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.73	gold quality
mucosa of urinary bladder	UBERON:0001259	79.15	silver quality
tibialis anterior	UBERON:0001385	78.56	silver quality
buccal mucosa cell	CL:0002336	77.89	gold quality
gingival epithelium	UBERON:0001949	76.19	silver quality
gastrocnemius	UBERON:0001388	76.07	gold quality
gingiva	UBERON:0001828	75.40	silver quality
type B pancreatic cell	CL:0000169	75.33	gold quality
olfactory bulb	UBERON:0002264	75.30	gold quality
muscle of leg	UBERON:0001383	75.26	gold quality
muscle organ	UBERON:0001630	74.55	gold quality
endothelial cell	CL:0000115	74.34	silver quality
male germ cell	CL:0000015	73.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.61	gold quality
sperm	CL:0000019	73.51	gold quality
prefrontal cortex	UBERON:0000451	73.28	gold quality
squamous epithelium	UBERON:0006914	73.15	silver quality
quadriceps femoris	UBERON:0001377	72.87	silver quality
vastus lateralis	UBERON:0001379	72.63	silver quality
ileal mucosa	UBERON:0000331	72.12	silver quality
heart left ventricle	UBERON:0002084	72.00	gold quality
cortical plate	UBERON:0005343	71.99	gold quality
skeletal muscle tissue	UBERON:0001134	71.89	gold quality
stromal cell of endometrium	CL:0002255	71.86	gold quality
cardiac ventricle	UBERON:0002082	71.78	gold quality
esophagus mucosa	UBERON:0002469	71.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.88
E-GEOD-111727	no	498.47
E-CURD-53	no	409.52
E-MTAB-4850	no	60.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting POLR1G, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• model for CAST/hPAF49 function in which the network of interactions of Pol I-specific subunits with UBF facilitates conformational changes of the polymerase, leading to stabilization of the Pol I-template complex and, thereby, activation of transcription (PMID:16809778)
• The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06-1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15-2.39) (PMID:16817948)
• ASE-1 polymorphisms and the previously identified ASE-1 haplotype are not associated with risk of colorectal cancer. (PMID:18289367)
• A SNP in the 5’ noncoding region of exon 1 at position -21 from the first codon, which does not affect the final AA sequence but may affect transcription/translation, was associated with drug sensitivity in the NC160 human cancer cell line panel. (PMID:19396015)
• Polymorphism in RAI and CD3EAP are associated with outcome of myeloma patients treated with high dose treatment. (PMID:21046104)
• variant alleles of PPP1R13L rs1970764 and CD3EAP rs967591 may contribute to risk factors of lung cancer. (PMID:22335888)
• In nonsmoking Chinese women CD3EAP rs967591 variant allele carriers are at increased risk of lung cancer. (PMID:23624123)
• There was no interaction between NFKB1 polymorphisms and PPP1R13L and CD3EAP and smoking status in relation to lung cancer risk (PMID:25917613)
• we were able to reproduce previously found associations between PPP1R13L and CD3EAP polymorphisms and lung cancer risk in an increased study group, and we found interactions between NFKB1 rs28362491-PPP1R13L rs1970764 and smoking duration and between CD3EAP rs735482 and smoking duration (PMID:26563375)
• a genetic variant in the CD3EAP gene is associated with outcome of patients treated for multiple myeloma (PMID:26568154)
• These findings demonstrate that 19p13.3-GADD45B rs7354 variant and interaction between 19p13.3-GADD45B rs3783501 and 19q13.3-CD3EAP rs967591 may play a role in association with smoke-exposed lung cancer among Chinese. (PMID:28870783)
• The expression of CD3EAP exon 1 was demonstrated to be significantly associated with PPP1R13L exon 1, while CD3EAP exon 3 was significantly associated with ERCC1 exon 11 in normal and non-small cell lung cancer (NSCLC) tissues. It was observed that short transcripts of ERCC1, CD3EAP and PPP1R13L are co-expressed in A549 NSCLC cell line. (PMID:29620255)
• Haplotypes consisting of PPP1R13L, CD3EAP and GLTSCR1 SNPs on Chr19q13.3 may associate with lung cancer risk in the Chinese population. (PMID:30128886)
• TP53 common variants and interaction with PPP1R13L and CD3EAP SNPs and lung cancer risk and smoking behavior in a Chinese population. (PMID:35351459)
• STAT3 potentiates RNA polymerase I-directed transcription and tumor growth by activating RPA34 expression. (PMID:36526675)
• Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese. (PMID:37147350)
• PAF49: An RNA Polymerase I subunit essential for rDNA transcription and stabilization of PAF53. (PMID:37356716)
• ASE-1 co-localises with the RNA polymerase I transcription initiation factor UBF/NOR-90 throughout all stages of the cell cycle and these two proteins associate with each other in vitro. (PMID:9426281)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr1g	ENSDARG00000090386
mus_musculus	Polr1g	ENSMUSG00000047649
rattus_norvegicus	Polr1g	ENSRNOG00000016825

Protein

Protein identifiers

DNA-directed RNA polymerase I subunit RPA34 — O15446 (reviewed: O15446)

Alternative names: A34.5, Antisense to ERCC-1 protein, CD3-epsilon-associated protein, DNA-directed RNA polymerase I subunit G, RNA polymerase I-associated factor PAF49

All UniProt accessions (3): O15446, K7EMH2, K7EQC8

UniProt curated annotations — full annotation on UniProt →

Function. Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. Has been described as a component of preformed T-cell receptor (TCR) complex.

Subunit / interactions. Component of the RNA polymerase I (Pol I) complex consisting of 13 subunits: a ten-subunit catalytic core composed of POLR1A/RPA1, POLR1B/RPA2, POLR1C/RPAC1, POLR1D/RPAC2, POLR1H/RPA12, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk subunit POLR1F/RPA43 protruding from the core and additional subunits homologous to general transcription factors POLR1E/RPA49 and POLR1G/RPA34. Forms a heterodimer with POLR1E/RPA49. Part of Pol I pre-initiation complex (PIC), in which Pol I core assembles with RRN3 and promoter-bound UTBF and SL1/TIF-IB complex. Interacts with TAF1A thereby associates with the SL1/TIF-IB complex. Interacts with UBTF. Interacts with POLR1E/PRAF1 through its N-terminal region. Interacts with CD3E.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Post-translational modifications. Undergoes tyrosine phosphorylation upon T-cell receptor (TCR) stimulation. This phosphorylation has not been confirmed by other groups. Phosphorylated on tyrosine residues in initiation-competent Pol I-beta complexes but not in Pol I-alpha complexes.

Miscellaneous. It is in an antisense orientation to and overlaps the gene of the DNA repair enzyme ERCC1. This gene overlap is conserved in mouse, suggesting an important biological function. Has sharply different functional characteristics.

Similarity. Belongs to the eukaryotic RPA34 RNA polymerase subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15446-1	1	yes
O15446-2	2, CAST

RefSeq proteins (2): NP_001284519, NP_036231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013240	DNA-dir_RNA_pol1_su_RPA34	Family

Pfam: PF08208

UniProt features (44 total): modified residue 11, strand 8, sequence variant 6, compositionally biased region 6, cross-link 4, region of interest 3, sequence conflict 2, turn 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7OB9	ELECTRON MICROSCOPY	2.7
7VBB	ELECTRON MICROSCOPY	2.81
7VBA	ELECTRON MICROSCOPY	2.89
7VBC	ELECTRON MICROSCOPY	3.01
7OBA	ELECTRON MICROSCOPY	3.1
7OBB	ELECTRON MICROSCOPY	3.3
8A43	ELECTRON MICROSCOPY	4.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15446-F1	55.68	0.15

Functional residue map

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

Post-translational modifications (15): 1, 27, 80, 128, 136, 172, 205, 285, 287, 309, 490, 270, 270, 314, 314

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 581 (showing top): WENDT_COHESIN_TARGETS_UP, RNGTGGGC_UNKNOWN, E2F_Q4, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, E2F4DP1_01, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, ROVERSI_GLIOMA_COPY_NUMBER_UP, HSIAO_HOUSEKEEPING_GENES, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (4): transcription initiation at RNA polymerase I promoter (GO:0006361), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), rRNA transcription (GO:0009303), transcription by RNA polymerase I (GO:0006360)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (10): RNA polymerase I transcription regulator complex (GO:0000120), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), RNA polymerase I complex (GO:0005736), mitochondrion (GO:0005739), cytosol (GO:0005829), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RNA Polymerase I Promoter Clearance	2
RNA Polymerase I Transcription	2
Gene expression (Transcription)	2
Epigenetic regulation of gene expression	2
Negative epigenetic regulation of rRNA expression	1
Positive epigenetic regulation of rRNA expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleolus	3
cellular anatomical structure	3
DNA-templated transcription	2
nuclear protein-containing complex	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
intracellular membrane-bounded organelle	2
DNA-templated transcription initiation	1
transcription by RNA polymerase I	1
enzyme-linked receptor protein signaling pathway	1
rRNA metabolic process	1
nucleic acid binding	1
binding	1
transcription regulator complex	1
DNA-directed RNA polymerase complex	1
RNA polymerase complex	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR1G	POLR1E	Q9GZS1	979
POLR1G	TAF1A	Q15573	922
POLR1G	RRN3	Q9NYV6	854
POLR1G	POLR1H	Q9P1U0	842
POLR1G	ERCC1	P07992	827
POLR1G	UBTF	P17480	806
POLR1G	POLR1C	O15160	725
POLR1G	POLR1D	P0DPB6	721
POLR1G	POLI	Q9UNA4	698
POLR1G	POLR2K	P53803	675
POLR1G	ERCC2	P18074	674
POLR1G	PPP1R13L	Q8WUF5	657
POLR1G	POLR1F	Q3B726	644
POLR1G	POLR2E	P19388	637
POLR1G	POLR2L	P52436	603

IntAct

83 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR1A	POLR1C	psi-mi:“MI:0914”(association)	0.730
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR1B	POLR1C	psi-mi:“MI:0914”(association)	0.530
SCRN1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
GPN3	POLR3A	psi-mi:“MI:0914”(association)	0.530
POLR1C	POLR3A	psi-mi:“MI:0914”(association)	0.530
POLR1D	POLR3A	psi-mi:“MI:0914”(association)	0.530
SSRP1	POLR1G	psi-mi:“MI:0914”(association)	0.430
SSRP1	POLR1G	psi-mi:“MI:0403”(colocalization)	0.430
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
SUPT16H	POLR1G	psi-mi:“MI:0915”(physical association)	0.400
POLR1G	XPA	psi-mi:“MI:0915”(physical association)	0.370
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR1A	POLR2H	psi-mi:“MI:0914”(association)	0.350
NBN	POLR1G	psi-mi:“MI:0914”(association)	0.350
ARRB1		psi-mi:“MI:0914”(association)	0.350

BioGRID (565): CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), POLR1E (Co-fractionation), CD3EAP (Affinity Capture-RNA), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS), CD3EAP (Affinity Capture-MS)

ESM2 similar proteins: A2A3V1, A2A995, A5D7J3, B1AX39, O15446, O60303, O88573, P0DPK0, P23497, Q14684, Q1ED39, Q2KIN0, Q3KRF1, Q3TFK5, Q3UY34, Q4R2Z8, Q566R3, Q58CQ0, Q5I034, Q5PQK4, Q5PQN4, Q5SU73, Q5XG69, Q66H19, Q66LM6, Q68A65, Q6IR42, Q6NTE8, Q6P1D7, Q6P9P0, Q76KJ5, Q7L190, Q80YR5, Q8BI29, Q8BVK9, Q8C0X0, Q8C753, Q8IY92, Q8IYF1, Q8K4R9

Diamond homologs: O15446, Q76KJ5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR1G	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
RNA Polymerase III Chain Elongation	8	86.0×	4e-13
Positive epigenetic regulation of rRNA expression	13	76.2×	1e-19
RNA Polymerase III Transcription Termination	8	67.3×	4e-12
RNA Polymerase I Transcription Termination	12	66.4×	9e-18
RNA Polymerase I Promoter Clearance	13	64.5×	7e-19
RNA Polymerase III Transcription Initiation From Type 2 Promoter	9	64.5×	3e-13
FGFR2 mutant receptor activation	5	64.5×	1e-07
RNA Polymerase I Transcription	13	62.9×	7e-19

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	5	13.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45408131:A:AG	acceptor_gain	0.9800
19:45408132:G:GG	acceptor_gain	0.9800
19:45406696:G:GT	donor_gain	0.9700
19:45407166:T:TA	acceptor_gain	0.9700
19:45407231:GAATG:G	donor_gain	0.9700
19:45408132:GCTTC:G	acceptor_gain	0.9700
19:45409641:A:AC	donor_gain	0.9700
19:45408130:TA:T	acceptor_loss	0.9600
19:45408131:A:AC	acceptor_loss	0.9600
19:45408132:G:GA	acceptor_loss	0.9600
19:45408132:GCTT:G	acceptor_gain	0.9600
19:45409232:A:T	acceptor_gain	0.9600
19:45409656:T:TA	donor_gain	0.9500
19:45407236:G:GG	donor_gain	0.9400
19:45409645:CA:C	donor_gain	0.9400
19:45409723:GGCC:G	acceptor_loss	0.9400
19:45409724:GCC:G	acceptor_loss	0.9400
19:45409725:CCTG:C	acceptor_loss	0.9400
19:45409726:CTGG:C	acceptor_loss	0.9400
19:45409727:T:G	acceptor_loss	0.9400
19:45407235:GGTGA:G	donor_loss	0.9300
19:45407237:TGAGT:T	donor_loss	0.9300
19:45407238:GAGTG:G	donor_loss	0.9300
19:45407239:AGTGG:A	donor_loss	0.9300
19:45407240:G:C	donor_loss	0.9300
19:45409594:TG:T	donor_gain	0.9300
19:45406868:A:T	donor_gain	0.9200
19:45407168:G:C	acceptor_gain	0.9200
19:45408132:GC:G	acceptor_gain	0.9200
19:45408128:T:TA	acceptor_gain	0.9100

AlphaMissense

3282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45408413:T:C	F149L	0.996
19:45408415:C:A	F149L	0.996
19:45408415:C:G	F149L	0.996
19:45407198:T:A	W43R	0.994
19:45407198:T:C	W43R	0.994
19:45407222:T:C	F51L	0.993
19:45407224:T:A	F51L	0.993
19:45407224:T:G	F51L	0.993
19:45408318:T:C	I117T	0.993
19:45408422:T:C	F152L	0.993
19:45408424:T:A	F152L	0.993
19:45408424:T:G	F152L	0.993
19:45407205:T:C	I45T	0.992
19:45407123:T:C	F18L	0.990
19:45407125:T:A	F18L	0.990
19:45407125:T:G	F18L	0.990
19:45407223:T:C	F51S	0.989
19:45407200:G:C	W43C	0.987
19:45407200:G:T	W43C	0.987
19:45407205:T:A	I45N	0.987
19:45407223:T:G	F51C	0.986
19:45407105:T:C	F12L	0.985
19:45407107:C:A	F12L	0.985
19:45407107:C:G	F12L	0.985
19:45408206:T:G	Y80D	0.983
19:45408414:T:C	F149S	0.983
19:45407205:T:G	I45S	0.982
19:45408318:T:G	I117S	0.980
19:45408213:T:A	V82D	0.978
19:45407199:G:C	W43S	0.977

dbSNP variants (sampled 300 via entrez): RS1000892061 (19:45404731 C>A), RS1001039735 (19:45406114 G>T), RS1001385997 (19:45408747 A>C), RS1001386363 (19:45410917 G>A), RS1002206319 (19:45410383 C>T), RS1002395179 (19:45409923 G>A), RS1002426274 (19:45410084 TCAC>T), RS1002771970 (19:45404649 C>T), RS1002901802 (19:45407309 A>C,G), RS1003138740 (19:45407805 C>T), RS1004498119 (19:45409900 T>A), RS1004790821 (19:45406249 C>G), RS1004869770 (19:45409712 A>G), RS1005165 (19:45405792 C>G,T), RS1005166 (19:45405937 T>C)

Disease associations

OMIM: gene MIM:107325 | 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
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067043 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3212986	Efficacy	3	Platinum compounds	Ovarian Neoplasms
rs3212986	Efficacy	3	cisplatin;gemcitabine	Mesothelioma
rs3212986	Toxicity	3	doxorubicin	Infectious disease;Leukopenia;Osteosarcoma

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs735482	ERCC1, POLR1G, PPP1R13L	3	2.00	1	thalidomide
rs967591	POLR1G, PPP1R13L		0.00	0
rs3212986	ERCC1, POLR1G, PPP1R13L	3	4.00	11	cisplatin;Platinum compounds;docetaxel;paclitaxel;cisplatin;gemcitabine;bleomycin;cisplatin;etoposide;cyclophosphamide;doxorubicin;fluorouracil;granisetron;palonosetron;doxorubicin
rs4572514	POLR1G, PPP1R13L		0.00	0

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
5.83	Kd	1495	nM	CHEMBL5653589
5.83	ED50	1495	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148028: Binding affinity to human CD3EAP incubated for 45 mins by Kinobead based pull down assay	kd	1.4947	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
Aflatoxin B1	decreases methylation, increases expression	2
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	affects phosphorylation	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
NSC 689534	decreases expression, affects binding	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Estradiol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651070	Binding	Binding affinity to human CD3EAP incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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