POLDIP2

Summary

POLDIP2 (DNA polymerase delta interacting protein 2, HGNC:23781) is a protein-coding gene on chromosome 17q11.2, encoding Polymerase delta-interacting protein 2 (Q9Y2S7). Involved in DNA damage tolerance by regulating translesion synthesis (TLS) of templates carrying DNA damage lesions such as 8oxoG and abasic sites.

This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 26073 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_015584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23781
Approved symbol	POLDIP2
Name	DNA polymerase delta interacting protein 2
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PDIP38, DKFZP586F1524
Ensembl gene	ENSG00000004142
Ensembl biotype	protein_coding
OMIM	611519
Entrez	26073

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000540200, ENST00000618887, ENST00000902297, ENST00000902298, ENST00000902299, ENST00000902300, ENST00000902301, ENST00000902302, ENST00000928257, ENST00000954761, ENST00000954762, ENST00000954763

RefSeq mRNA: 2 — MANE Select: NM_015584 NM_001290145, NM_015584

CCDS: CCDS74018, CCDS76978

Canonical transcript exons

ENST00000540200 — 11 exons

Exon	Start	End
ENSE00002227384	28346633	28348231
ENSE00002245633	28357288	28357527
ENSE00003531888	28351664	28351800
ENSE00003573023	28353241	28353316
ENSE00003576631	28355795	28355876
ENSE00003598798	28350438	28350563
ENSE00003647172	28349083	28349162
ENSE00003655115	28352912	28353019
ENSE00003665141	28350766	28350792
ENSE00003682651	28354488	28354585
ENSE00003688848	28353695	28353791

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.2436 / max 257.0700, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164984	41.2569	1820
164986	1.0043	690
164985	0.9824	704

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.04	gold quality
right adrenal gland	UBERON:0001233	97.72	gold quality
right adrenal gland cortex	UBERON:0035827	97.67	gold quality
left adrenal gland	UBERON:0001234	97.53	gold quality
muscle of leg	UBERON:0001383	97.53	gold quality
apex of heart	UBERON:0002098	97.43	gold quality
left adrenal gland cortex	UBERON:0035825	97.41	gold quality
right lobe of liver	UBERON:0001114	97.20	gold quality
adrenal cortex	UBERON:0001235	97.11	gold quality
heart left ventricle	UBERON:0002084	96.93	gold quality
cardiac ventricle	UBERON:0002082	96.79	gold quality
adrenal gland	UBERON:0002369	96.77	gold quality
muscle organ	UBERON:0001630	96.69	gold quality
right atrium auricular region	UBERON:0006631	96.00	gold quality
islet of Langerhans	UBERON:0000006	95.76	gold quality
adult mammalian kidney	UBERON:0000082	95.68	gold quality
heart	UBERON:0000948	95.53	gold quality
body of pancreas	UBERON:0001150	95.48	gold quality
rectum	UBERON:0001052	95.24	gold quality
liver	UBERON:0002107	95.24	gold quality
skeletal muscle tissue	UBERON:0001134	95.22	gold quality
lower esophagus mucosa	UBERON:0035834	95.18	gold quality
cardiac atrium	UBERON:0002081	94.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.92	gold quality
stromal cell of endometrium	CL:0002255	94.85	gold quality
body of stomach	UBERON:0001161	94.83	gold quality
pancreas	UBERON:0001264	94.75	gold quality
right frontal lobe	UBERON:0002810	94.69	gold quality
mucosa of transverse colon	UBERON:0004991	94.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting POLDIP2, 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-1184	99.99	68.19	1458
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6751-5P	99.56	64.99	1145

Literature-anchored findings (GeneRIF, showing 25)

• PDIP38 might play a role in the pol delta-mediated viral DNA replication (PMID:15811854)
• PDIP38 is located in the mitochondrial matrix. TFAM and mitochondrial single-stranded DNA binding protein (mtSSB) are co-immunoprecipitated with PDIP38 (PMID:16428295)
• PDIP38 can shuttle between the cytoplasmic and the nuclear compartments and that its subcellular localization is regulated by CEACAM1 (PMID:17623671)
• Poldip2 associates with p22phox to activate Nox4, leading to regulation of focal adhesion turnover and vascular smooth muscle cell migration, thus linking reactive oxygen species production and cytoskeletal remodeling. (PMID:19574552)
• suggest that the TNFAIP1/POLDIP2 complex sense-antisense architecture represents a clinically significant transcriptional structural-functional gene module associated with amplification of the genomic region on 17q11.2 in breast cancer. (PMID:20158880)
• We demonstrate that PDIP38 (Poldelta interacting protein of 38kDa) directly interacts with the TLS polymerase Poleta. PDIP38 is able to interact directly not only with Poleta but also with the specialized polymerases Rev1 and Polzeta (via Rev7). (PMID:20554254)
• PDIP38 can respond to genotoxic or transcriptional stresses by undergoing translocation to the spliceosomes, where it is a required participant in the regulation of MDM2 alternative splicing. (PMID:23989611)
• DNA polymerase delta-interacting protein 2 is a processivity factor for DNA polymerase lambda during 8-oxo-7,8-dihydroguanine bypass. (PMID:24191025)
• POLDIP2 plays a crucial role in Tau aggregation via the impairment of autophagy activity, providing insight into Tau aggregation in Tau pathology. (PMID:25930997)
• findings establish that PolDIP2 can regulate the translesion synthesis polymerase and primer extension activities of PrimPol (PMID:26984527)
• Increasing mitochondrial lipoylation by forced expression of Poldip2 increases respiration and reduces the growth rate of cancer cells. Study unveils a regulatory mechanism of catabolic enzymes required for metabolic plasticity and highlights the role of Poldip2 as key during hypoxia and cancer cell metabolic adaptation. (PMID:29434038)
• that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or Epithelial-mesenchymal transition (PMID:29684384)
• Integrin engagement during cell attachment activates Poldip2/Nox4 to oxidize actin, which modulates filamentous actin assembly and its interaction with vinculin. (PMID:30354218)
• Poldip2 and Ect2 are both essential for vascular smooth muscle cell cytokinesis and proliferation. (PMID:30726115)
• The loss of PDIP38 consistently causes a shift in DNA damage tolerance (DDT) from error-prone translesion DNA synthesis (TLS) to error-free template switching (TS) without enhancing cellular sensitivity to DNA damage. We propose that PDIP38 controls the relative usage of TLS and TS increasing usage of TLS without changing the overall capability of DDT. (PMID:30840704)
• Poldip2 deficiency in human aortic vascular smooth muscle in vitro induces the expression of the SRF , myocardin, and MRTFA and dramatically represses KLF4. Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation. Poldip2 deficiency induces a highly differentiated phenotype in VSMCs by regulating metabolism and proteostasis. (PMID:31656131)
• functional interaction of PolDIP2 with human DNA polymerases and the possible functions in DNA damage response (PMID:32383114)
• [PolDIP2 regulates mitochondrial functioning and cellular metabolism].", trans “PolDIP2, une proteine cle de la regulation du fonctionnement mitochondrial et du metabolisme cellulaire. (PMID:33492225)
• Crystal structure and molecular dynamics of human POLDIP2, a multifaceted adaptor protein in metabolism and genome stability. (PMID:33884680)
• Human Polymerase delta-Interacting Protein 2 (PolDIP2) Inhibits the Formation of Human Tau Oligomers and Fibrils. (PMID:34071254)
• MIR31HG regulates the proliferation, migration and invasion of breast cancer by regulating the expression of POLDIP2. (PMID:34076993)
• Endothelial Poldip2 regulates sepsis-induced lung injury via Rho pathway activation. (PMID:34528082)
• Poldip2/Nox4 Mediates Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Lung Epithelial Cells. (PMID:35140544)
• Metabolic regulation of the proteasome under hypoxia by Poldip2 controls fibrotic signaling in vascular smooth muscle cells. (PMID:36596387)
• Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells. (PMID:36795578)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	poldip2	ENSDARG00000092305
mus_musculus	Poldip2	ENSMUSG00000001100
rattus_norvegicus	Poldip2	ENSRNOG00000009252
drosophila_melanogaster	POLDIP2	FBGN0037329
caenorhabditis_elegans		WBGENE00022787

Paralogs (1): FBXO3 (ENSG00000110429)

Protein

Protein identifiers

Polymerase delta-interacting protein 2 — Q9Y2S7 (reviewed: Q9Y2S7)

Alternative names: 38 kDa DNA polymerase delta interaction protein

All UniProt accessions (2): Q9Y2S7, B4DEM9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in DNA damage tolerance by regulating translesion synthesis (TLS) of templates carrying DNA damage lesions such as 8oxoG and abasic sites. May act by stimulating activity of DNA polymerases involved in TLS, such as PRIMPOL and polymerase delta (POLD1).

Subunit / interactions. Interacts with PCNA and POLD2. Interacts with SSBP1. Interacts with PRIMPOL; leading to enhance DNA polymerase activity of PRIMPOL. Interacts with POLH. Interacts with POLD1; leading to stimulate DNA polymerase activity of POLD1.

Subcellular location. Mitochondrion matrix. Nucleus.

RefSeq proteins (2): NP_001277074, NP_056399* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007474	ApaG_domain	Domain
IPR011722	Hemimethylated_DNA-bd_dom	Domain
IPR036623	Hemimethylated_DNA-bd_sf	Homologous_superfamily
IPR036767	ApaG_sf	Homologous_superfamily

Pfam: PF04379, PF08755

UniProt features (29 total): strand 19, helix 3, sequence conflict 2, transit peptide 1, chain 1, domain 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6Z9C	X-RAY DIFFRACTION	2.8
6ZLX	X-RAY DIFFRACTION	3.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2S7-F1	80.96	0.62

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 (1): 292

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_TOLERANCE, chr17q11, GOBP_MACROAUTOPHAGY, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_ERROR_FREE_TRANSLESION_SYNTHESIS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_MITOTIC_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MACROAUTOPHAGY, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (10): DNA repair (GO:0006281), mitochondrion organization (GO:0007005), negative regulation of macroautophagy (GO:0016242), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of focal adhesion assembly (GO:0051894), error-free translesion synthesis (GO:0070987), mitotic spindle assembly (GO:0090307), positive regulation of mitotic cytokinesis (GO:1903490), vascular associated smooth muscle cell proliferation (GO:1990874), DNA damage response (GO:0006974)

GO Molecular Function (3): DNA binding (GO:0003677), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cell-cell junction (GO:0005911), midbody (GO:0030496), mitochondrial nucleoid (GO:0042645), mitotic spindle (GO:0072686)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
mitochondrion	2
DNA metabolic process	1
DNA damage response	1
organelle organization	1
negative regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
positive regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
positive regulation of cell-substrate junction organization	1
positive regulation of cell junction assembly	1
translesion synthesis	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
mitotic cytokinesis	1
positive regulation of cytokinesis	1
regulation of mitotic cytokinesis	1
smooth muscle cell proliferation	1
cellular response to stress	1
nucleic acid binding	1
protein binding	1
molecular adaptor activity	1
binding	1
cytoplasm	1
intracellular organelle lumen	1
anchoring junction	1
cellular anatomical structure	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1
spindle	1

Protein interactions and networks

STRING

1100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLDIP2	CYBA	P13498	994
POLDIP2	NOX4	Q9NPH5	960
POLDIP2	POLD2	P49005	907
POLDIP2	PRIMPOL	Q96LW4	849
POLDIP2	CEACAM1	P13688	794
POLDIP2	NCF2	P19878	765
POLDIP2	NCF1	P14598	762
POLDIP2	CYBB	P04839	744
POLDIP2	POLD1	P28340	713
POLDIP2	NOXA1	Q86UR1	706
POLDIP2	NOX5	Q96PH1	681
POLDIP2	NOXO1	Q8NFA2	674
POLDIP2	NOX1	Q9Y5S8	640
POLDIP2	REV1	Q9UBZ9	623
POLDIP2	SH3PXD2A	Q5TCZ1	620

IntAct

180 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
CHCHD2	POLDIP2	psi-mi:“MI:0915”(physical association)	0.740
POLDIP2	CHCHD2	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
LYRM2	NDUFAB1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
POLDIP2	ALAS1	psi-mi:“MI:0915”(physical association)	0.670
ALAS1	POLDIP2	psi-mi:“MI:0915”(physical association)	0.670
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
GFPT2	GFPT1	psi-mi:“MI:0914”(association)	0.620
MTUS2	POLDIP2	psi-mi:“MI:0915”(physical association)	0.560
DNAAF6	POLDIP2	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	POLDIP2	psi-mi:“MI:0915”(physical association)	0.560
GNLY	YPEL5	psi-mi:“MI:0914”(association)	0.530
GALNS	FBXO21	psi-mi:“MI:0914”(association)	0.530
FAM219A	OBSL1	psi-mi:“MI:0914”(association)	0.530
GPT2	CLPX	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
P/V	IRS4	psi-mi:“MI:0914”(association)	0.530
POLDIP2	E2	psi-mi:“MI:0915”(physical association)	0.490
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420

BioGRID (269): POLDIP2 (Two-hybrid), POLDIP2 (Two-hybrid), POLDIP2 (Affinity Capture-RNA), POLDIP2 (Affinity Capture-RNA), POLDIP2 (Affinity Capture-RNA), POLDIP2 (Affinity Capture-MS), POLDIP2 (Reconstituted Complex), POLDIP2 (Affinity Capture-MS), POLDIP2 (Two-hybrid), POLDIP2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS), POLDIP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A7C9FSB8, A2TLM1, A6H7H7, B8BKI7, B9N1F9, B9SQI7, D2XV59, E0CSI1, F1N9S8, O00178, O08582, O35586, O35760, O48964, O48965, O76031, O81770, P11029, P11497, P58044, P69341, Q0J035, Q13085, Q13907, Q14165, Q1LZ95, Q1LZ96, Q28559, Q2R483, Q38929, Q39471, Q39472, Q39664, Q3UMR5, Q42553, Q4R4W5, Q5NVE1, Q5R8R6, Q5SWU9, Q5U2U0

Diamond homologs: A1K3W2, A1W2Y8, A4TQD9, A4XZJ5, A4Z2J6, A5EA34, A5VXJ4, A6H7H7, A6U5R0, A6UZ95, A6WVX4, A7FMC2, A7HQ48, A7ICI5, A8G9N9, A8ILE7, A9M7Z1, A9QZZ1, A9VZN6, B0CJT2, B0KJ92, B0TV51, B0UC46, B1JE08, B1JKY4, B1LXV0, B1ZJ42, B2III9, B2K486, B2S946, B3PNM4, B3QCE1, B5ENR7, B5ZNW9, B6IPQ9, B6JD70, B7J8G8, B7L060, B7V4H7, B8ELJ0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
Mitochondrial protein import	7	10.4×	7e-04
Mitochondrial protein degradation	9	9.1×	3e-04
Complex I biogenesis	6	8.8×	5e-03
Respiratory electron transport	9	7.6×	7e-04
Aerobic respiration and respiratory electron transport	9	7.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	5	14.0×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1487 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28348230:CC:C	acceptor_gain	1.0000
17:28348231:CC:C	acceptor_gain	1.0000
17:28349082:CCA:C	donor_gain	1.0000
17:28350436:AC:A	donor_gain	1.0000
17:28350437:CC:C	donor_gain	1.0000
17:28350575:G:GC	acceptor_gain	1.0000
17:28350764:AC:A	donor_gain	1.0000
17:28350765:CC:C	donor_gain	1.0000
17:28351659:CATA:C	donor_loss	1.0000
17:28351662:A:C	donor_loss	1.0000
17:28351662:AC:A	donor_gain	1.0000
17:28351663:C:G	donor_loss	1.0000
17:28351663:CC:C	donor_gain	1.0000
17:28351663:CCCT:C	donor_gain	1.0000
17:28351701:A:AC	donor_gain	1.0000
17:28351701:ATGTT:A	donor_gain	1.0000
17:28351796:AGGTG:A	acceptor_gain	1.0000
17:28351797:GGTG:G	acceptor_gain	1.0000
17:28351798:G:GC	acceptor_gain	1.0000
17:28351798:GTG:G	acceptor_loss	1.0000
17:28351799:TG:T	acceptor_gain	1.0000
17:28351800:GCTG:G	acceptor_loss	1.0000
17:28351801:C:CC	acceptor_gain	1.0000
17:28351801:C:CG	acceptor_loss	1.0000
17:28351802:T:C	acceptor_loss	1.0000
17:28352906:GATTA:G	donor_loss	1.0000
17:28352907:ATTAC:A	donor_loss	1.0000
17:28352908:TTA:T	donor_loss	1.0000
17:28352909:TA:T	donor_loss	1.0000
17:28352911:CCTTT:C	donor_loss	1.0000

AlphaMissense

2386 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28348166:A:G	L353P	1.000
17:28348166:A:T	L353Q	1.000
17:28348171:G:C	F351L	1.000
17:28348171:G:T	F351L	1.000
17:28348172:A:G	F351S	1.000
17:28348173:A:G	F351L	1.000
17:28348178:G:C	P349R	1.000
17:28348178:G:T	P349H	1.000
17:28348179:G:T	P349T	1.000
17:28348181:A:C	I348S	1.000
17:28348181:A:G	I348T	1.000
17:28348181:A:T	I348N	1.000
17:28348187:A:T	V346D	1.000
17:28348222:G:C	F334L	1.000
17:28348222:G:T	F334L	1.000
17:28348223:A:G	F334S	1.000
17:28348224:A:G	F334L	1.000
17:28348229:C:A	G332V	1.000
17:28348229:C:T	G332D	1.000
17:28348230:C:A	G332C	1.000
17:28348230:C:G	G332R	1.000
17:28348230:C:T	G332S	1.000
17:28348231:C:A	W331C	1.000
17:28348231:C:G	W331C	1.000
17:28349084:A:G	W331R	1.000
17:28349084:A:T	W331R	1.000
17:28349085:C:A	M330I	1.000
17:28349085:C:G	M330I	1.000
17:28349085:C:T	M330I	1.000
17:28349086:A:C	M330R	1.000

dbSNP variants (sampled 300 via entrez): RS1000469493 (17:28354853 G>A), RS1000812243 (17:28348505 G>A,T), RS1001184079 (17:28355543 C>G,T), RS1001236361 (17:28355303 C>T), RS1001298884 (17:28355934 C>T), RS1001368580 (17:28348961 G>A,T), RS1001654668 (17:28348580 C>G,T), RS1004116065 (17:28350382 G>A), RS1005599175 (17:28350972 C>A,T), RS1005934307 (17:28349281 C>T), RS1005999349 (17:28357489 G>A,C,T), RS1007175438 (17:28350034 G>A), RS1007715709 (17:28356545 A>C), RS1008123200 (17:28356881 G>A), RS1008344242 (17:28359416 C>G,T)

Disease associations

OMIM: gene MIM:611519 | 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
GCST002546_2	Osteoprotegerin levels	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Arsenic Trioxide	increases expression, decreases response to substance	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	affects expression	1
Coumestrol	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE90	HAP1 POLDIP2 (-) 1	Cancer cell line	Male
CVCL_TE91	HAP1 POLDIP2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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