POLD3

DNA polymerase delta 3, accessory subunit, the group of Protein phosphatase 1 regulatory subunits|DNA polymerases

Basic information

Region (hg38): 11:74493851-74669117

Links

ENSG00000077514 ∙ NCBI:10714 ∙ OMIM:611415 ∙ HGNC:20932 ∙ Uniprot:Q15054 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLD3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLD3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			14		4	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	15	1	4

Variants in POLD3

This is a list of pathogenic ClinVar variants found in the POLD3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-74493934-T-C			Likely benign (May 01, 2023)
11-74592687-T-C		Immunodeficiency 122	Pathogenic (Jul 02, 2024)
11-74594083-A-G		not specified	Uncertain significance (Sep 26, 2023)
11-74604734-A-G		POLD3-related disorder	Likely benign (Feb 22, 2019)
11-74612989-G-A		not specified	Uncertain significance (Jan 03, 2022)
11-74613007-G-A		not specified	Uncertain significance (Sep 25, 2024)
11-74618593-C-G		not specified	Uncertain significance (Jan 26, 2022)
11-74618593-C-T		POLD3-related disorder	Benign (May 16, 2018)
11-74618668-A-G		not specified	Uncertain significance (Jul 21, 2021)
11-74618697-G-T		not specified	Uncertain significance (Oct 20, 2024)
11-74618773-A-C		not specified	Uncertain significance (Feb 22, 2024)
11-74618796-G-A		POLD3-related disorder	Benign (Sep 05, 2019)
11-74625409-T-G		not specified	Uncertain significance (Sep 27, 2024)
11-74625440-G-A		not specified	Uncertain significance (Oct 29, 2024)
11-74625513-G-C		not specified	Uncertain significance (Aug 12, 2024)
11-74625564-A-C		not specified	Uncertain significance (Mar 20, 2023)
11-74629218-G-C		not specified	Uncertain significance (Jan 19, 2022)
11-74629249-C-T			Benign (May 16, 2018)
11-74629255-A-G		not specified	Uncertain significance (Jul 14, 2024)
11-74629258-C-T		not specified	Uncertain significance (Apr 20, 2024)
11-74634617-G-T		not specified	Uncertain significance (Jan 10, 2023)
11-74634636-C-T		not specified	Uncertain significance (Aug 02, 2021)
11-74634670-C-G		not specified	Uncertain significance (Aug 20, 2023)
11-74634675-C-T		not specified	Uncertain significance (Aug 11, 2022)
11-74634678-G-C		POLD3-related disorder	Benign (Apr 09, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLD3	protein_coding	protein_coding	ENST00000263681	12	175267

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00224	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0857	232	236	0.984	0.0000111	3053
Missense in Polyphen		60	76.05	0.78895		1109
Synonymous	0.485	81	86.7	0.934	0.00000434	877
Loss of Function	4.43	2	26.7	0.0750	0.00000160	314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000972	0.0000909
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000323	0.000323
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000659	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol- delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the POLZ complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the minimal DNA polymerase zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:25628356, ECO:0000269|PubMed:27185888}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Homologous recombination - Homo sapiens (human);Homologous recombination;Retinoblastoma (RB) in Cancer;Pyrimidine metabolism;DNA Replication;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Polymerase switching on the C-strand of the telomere;Purine metabolism;DNA Replication;Pyrimidine metabolism;Polymerase switching;Leading Strand Synthesis;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Recognition of DNA damage by PCNA-containing replication complex;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.199
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.17

Haploinsufficiency Scores

• pHI: 0.610
• hipred: Y
• hipred_score: 0.831
• ghis: 0.519

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.937

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pold3
• Phenotype: limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: telomere maintenance;DNA synthesis involved in DNA repair;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;mismatch repair;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;DNA damage response, detection of DNA damage
• Cellular component: nucleus;nucleoplasm;cytoplasm;delta DNA polymerase complex
• Molecular function: DNA-directed DNA polymerase activity;protein binding