POLA1 (DNA polymerase alpha 1, catalytic subunit)

Gene

• Entrez ID: 5422
• Gene name: DNA polymerase alpha 1, catalytic subunit
• Gene symbol: POLA1
• Synonyms (NCBI Gene): NSX, PDR, POLA, VEODS, p180
• Chromosome: X
• Chromosome location: Xp22.11-p21.3
• Summary: This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs774419889	G>A	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs869312979	A>G	Pathogenic	Intron variant
rs1569271378	T>G	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant, intron variant
rs1569271892	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, missense variant
rs1569277866	AAAGCTGTAGACTTGTCCAAGGATGGTCTGCTAGGTGACATTCTACAGGATCTTAACACTGAG>-	Pathogenic	Coding sequence variant, splice acceptor variant, non coding transcript variant
rs1569277899	G>A	Pathogenic	Splice donor variant
rs1569350993	C>T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016282	hsa-miR-193b-3p	Microarray	20304954
MIRT022295	hsa-miR-124-3p	Microarray	18668037
MIRT028969	hsa-miR-26b-5p	Microarray	19088304
MIRT717111	hsa-miR-6882-3p	HITS-CLIP	19536157
MIRT717110	hsa-miR-6885-3p	HITS-CLIP	19536157
MIRT717111	hsa-miR-6882-3p	HITS-CLIP	19536157
MIRT717110	hsa-miR-6885-3p	HITS-CLIP	19536157
MIRT1247157	hsa-miR-1287	CLIP-seq
MIRT1247158	hsa-miR-1296	CLIP-seq
MIRT1247159	hsa-miR-2909	CLIP-seq
MIRT1247160	hsa-miR-3135b	CLIP-seq
MIRT1247161	hsa-miR-3612	CLIP-seq
MIRT1247162	hsa-miR-4443	CLIP-seq
MIRT1247163	hsa-miR-4512	CLIP-seq
MIRT1247164	hsa-miR-4640-5p	CLIP-seq
MIRT1247165	hsa-miR-4726-5p	CLIP-seq
MIRT1247166	hsa-miR-650	CLIP-seq
MIRT1247167	hsa-miR-759	CLIP-seq
MIRT1247168	hsa-miR-765	CLIP-seq
MIRT2300090	hsa-miR-181a	CLIP-seq
MIRT2300091	hsa-miR-181b	CLIP-seq
MIRT2300092	hsa-miR-181c	CLIP-seq
MIRT2300093	hsa-miR-181d	CLIP-seq
MIRT2300094	hsa-miR-3618	CLIP-seq
MIRT2300095	hsa-miR-3663-5p	CLIP-seq
MIRT2300096	hsa-miR-377	CLIP-seq
MIRT2300097	hsa-miR-4262	CLIP-seq
MIRT2300098	hsa-miR-601	CLIP-seq
MIRT2392803	hsa-miR-3921	CLIP-seq
MIRT2392804	hsa-miR-4251	CLIP-seq
MIRT2392805	hsa-miR-4329	CLIP-seq
MIRT2392806	hsa-miR-4653-5p	CLIP-seq
MIRT2392807	hsa-miR-760	CLIP-seq
MIRT2456815	hsa-miR-1267	CLIP-seq
MIRT2456816	hsa-miR-1269	CLIP-seq
MIRT2456817	hsa-miR-1269b	CLIP-seq
MIRT2456818	hsa-miR-4529-3p	CLIP-seq
MIRT2456819	hsa-miR-4711-3p	CLIP-seq
MIRT2456815	hsa-miR-1267	CLIP-seq
MIRT2456816	hsa-miR-1269	CLIP-seq
MIRT2456817	hsa-miR-1269b	CLIP-seq
MIRT2456818	hsa-miR-4529-3p	CLIP-seq
MIRT2456819	hsa-miR-4711-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IDA	3139084
GO:0000166	Function	Nucleotide binding	IEA
GO:0000731	Process	DNA synthesis involved in DNA repair	IMP	11470886
GO:0000785	Component	Chromatin	IDA	9815285
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003677	Function	DNA binding	IDA	16762037
GO:0003677	Function	DNA binding	IEA
GO:0003682	Function	Chromatin binding	IBA
GO:0003682	Function	Chromatin binding	IDA	16762037
GO:0003688	Function	DNA replication origin binding	IBA
GO:0003697	Function	Single-stranded DNA binding	IBA
GO:0003887	Function	DNA-directed DNA polymerase activity	IBA
GO:0003887	Function	DNA-directed DNA polymerase activity	IDA	893425, 3359994, 8026492, 26975377
GO:0003887	Function	DNA-directed DNA polymerase activity	IEA
GO:0003887	Function	DNA-directed DNA polymerase activity	IMP	4084590
GO:0005515	Function	Protein binding	IPI	1311258, 2243771, 7644508, 8380896, 9395244, 9518481, 10518787, 10869558, 16438930, 17666013
GO:0005634	Component	Nucleus	IDA	4084590, 16762037
GO:0005634	Component	Nucleus	IEA
GO:0005635	Component	Nuclear envelope	IDA	9518481
GO:0005654	Component	Nucleoplasm	IDA	7045121
GO:0005654	Component	Nucleoplasm	TAS
GO:0005658	Component	Alpha DNA polymerase:primase complex	IBA
GO:0005658	Component	Alpha DNA polymerase:primase complex	IDA	2175912, 8026492, 22465957, 26975377
GO:0005658	Component	Alpha DNA polymerase:primase complex	IEA
GO:0005658	Component	Alpha DNA polymerase:primase complex	IPI	26975377
GO:0005658	Component	Alpha DNA polymerase:primase complex	TAS	2243771
GO:0005730	Component	Nucleolus	IDA	9518481
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA	27019227
GO:0005829	Component	Cytosol	IEA
GO:0006260	Process	DNA replication	IEA
GO:0006260	Process	DNA replication	IMP	3917431, 4084590, 16762037, 31006512
GO:0006261	Process	DNA-templated DNA replication	IEA
GO:0006269	Process	DNA replication, synthesis of primer	IDA	2175912, 8026492, 27019227
GO:0006270	Process	DNA replication initiation	IDA	2175912, 26975377
GO:0006271	Process	DNA strand elongation involved in DNA replication	IMP	4084590
GO:0006272	Process	Leading strand elongation	IBA
GO:0006272	Process	Leading strand elongation	IDA	2175912, 7910375
GO:0006273	Process	Lagging strand elongation	IBA
GO:0006273	Process	Lagging strand elongation	IDA	2175912, 7910375
GO:0006281	Process	DNA repair	IDA	3335506
GO:0006281	Process	DNA repair	IMP	11470886
GO:0006289	Process	Nucleotide-excision repair	IMP	1508673
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	11470886
GO:0008270	Function	Zinc ion binding	IDA	26975377
GO:0008270	Function	Zinc ion binding	IEA
GO:0016363	Component	Nuclear matrix	IDA	1903085
GO:0016740	Function	Transferase activity	IEA
GO:0016779	Function	Nucleotidyltransferase activity	IEA
GO:0019901	Function	Protein kinase binding	IPI	9506968
GO:0032479	Process	Regulation of type I interferon production	IMP	27019227
GO:0034061	Function	DNA polymerase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:1902975	Process	Mitotic DNA replication initiation	IEA
GO:1904161	Process	DNA synthesis involved in UV-damage excision repair	IMP	1730053

Other IDs

• MIM: 312040
• HGNC: 9173
• e!Ensembl: ENSG00000101868

Protein

• UniProt ID: P09884
• Protein name: DNA polymerase alpha catalytic subunit (EC 2.7.7.7) (DNA polymerase alpha catalytic subunit p180)
• Protein function: Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha compl
• PDB: 1K0P, 1K18, 1N5G, 4Q5V, 4QCL, 4Y97, 5EXR, 5IUD, 6AS7, 7N2M, 7OPL, 7U5C, 8B9D, 8D0B, 8D0K, 8D96, 8D9D, 8QJ7, 8VY3, 9C8V, 9MJ5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12254	DNA_pol_alpha_N	35 → 96	DNA polymerase alpha subunit p180 N terminal	Family
  PF03104	DNA_pol_B_exo1	369 → 711	DNA polymerase family B, exonuclease domain	Family
  PF00136	DNA_pol_B	774 → 1227	DNA polymerase family B	Family
  PF08996	zf-DNA_Pol	1265 → 1455	DNA Polymerase alpha zinc finger	Domain

• Sequence:

  MAPVHGDDSLSDSGSFVSSRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDFTGVYEE
  VDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDADEKGKDGKARNKDK
  RNVKKLAVTKPNNIKSMFIACAGKKTADKAVDLSKDGLLGDILQDLNTETPQITPPPVMI
  LKKKRSIGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDDVQVESTEE
  EQESGAMEFEDGDFDEPMEVEEVDLEPMAAKAWDKESEPAEEVKQEADSGKGTVSYLGSF
  LPDVSCWDIDQEGDSSFSVQEVQVDSSHLPLVKGADEEQVFHFYWLDAYEDQYNQPGVVF
  LFGKVWIESAETHVSCCVMVKNIERTLYFLPREMKIDLNTGKETGTPISMKDVYEEFDEK
  IATKYKIMKFKSKPVEKNYAFEIPDVPEKSEYLEVKYSAEMPQLPQDLKGETFSHVFGTN
  TSSLELFLMNRKIKGPCWLEVKSPQLLNQPVSWCKVEAMALKPDLVNVIKDVSPPPLVVM
  AFSMKTMQNAKNHQNEIIAMAALVHHSFALDKAAPKPPFQSHFCVVSKPKDCIFPYAFKE
  VIEKKNVKVEVAATERTLLGFFLAKVHKIDPDIIVGHNIYGFELEVLLQRINVCKAPHWS
  KIGRLKRSNMPKLGGRSGFGERNATCGRMICDVEISAKELIRCKSYHLSELVQQILKTER
  VVIPMENIQNMYSESSQLLYLLEHTWKDAKFILQIMCELNVLPLALQITNIAGNIMSRTL
  MGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKKGRKKAAYA
  GGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASEAQKVTEDGEQEQIPE
  LPDPSLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLILQYDIRQKALKLTANSMYGCL
  GFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFK
  LGNKVKSEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYVTKQELKGLDIV
  RRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALT
  KDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTASQRAYAPEQLQK
  QDNLTIDTQYYLAQQIHPVVARICEPIDGIDAVLIATWLGLDPTQFRVHHYHKDEENDAL
  LGGPAQLTDEEKYRDCERFKCPCPTCGTENIYDNVFDGSGTDMEPSLYRCSNIDCKASPL
  TFTVQLSNKLIMDIRRFIKKYYDGWLICEEPTCRNRTRHLPLQFSRTGPLCPACMKATLQ
  PEYSDKSLYTQLCFYRYIFDAECALEKLTTDHEKDKLKKQFFTPKVLQDYRKLKNTAEQF
  LSRSGYSEVNLSKLFAGCAVKS

• Sequence length: 1462

Pathways

KEGG:

DNA replication

Reactome:

Inhibition of replication initiation of damaged DNA by RB1/E2F1
Polymerase switching on the C-strand of the telomere
Telomere C-strand synthesis initiation
DNA replication initiation
Activation of the pre-replicative complex
Polymerase switching
Removal of the Flap Intermediate
Processive synthesis on the lagging strand
G1/S-Specific Transcription

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Inherited aplastic anemia	Likely pathogenic	rs2518817148, rs2518693616, rs1930638172	RCV003991543 RCV003991549 RCV003991550
Thyroid cancer, nonmedullary, 1	Pathogenic	rs1569271892	RCV005897367
X-linked intellectual disability, van Esch type	Pathogenic; Likely pathogenic	rs2148341850, rs1569271378, rs1569271892, rs1569350993, rs1569277866, rs1569277899, rs774419889	RCV001786494 RCV000791329 RCV000791333 RCV000791330 RCV000791332 RCV000791331 RCV000995840
X-linked reticulate pigmentary disorder	Pathogenic	rs869312979	RCV000210684

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Agammaglobulinemia	Conflicting classifications of pathogenicity	rs1472724099	RCV005626842
Cholangiocarcinoma	Likely benign	rs778428449	RCV005910736
Congenital heart disease	Benign; Likely benign	rs764912556	RCV005626559
Gastric cancer	Likely benign	rs778428449	RCV005910734
Malignant tumor of esophagus	Likely benign	rs766473136	RCV005925542
Nonpapillary renal cell carcinoma	Uncertain significance	rs1054932634	RCV005932777
Ovarian serous cystadenocarcinoma	Likely benign	rs778428449	RCV005910735
POLA1-related disorder	Benign; Likely benign; Uncertain significance	rs147068943, rs756416451, rs145623455, rs746368334, rs143911626, rs200148911, rs773057698, rs150514156, rs779273587, rs757551355, rs1276294427, rs2518705653, rs781603224, rs2518841905, rs2518761860, rs2518808212, rs1054932634, rs993452973, rs1216566797, rs1397809303, rs2147061696, rs2518834632, rs2518669188, rs2518669432	RCV003963231 RCV003898346 RCV003938686 RCV003940940 RCV003931075 RCV003956127 RCV003903601 RCV003933512 RCV003958537 RCV003918930 RCV003936735 RCV003416780 RCV003394474 RCV003402812 RCV003421033 RCV003403035 RCV003397732 RCV003901253 RCV003909185 RCV004755028 RCV003902231 RCV003912169 RCV003917103 RCV003939746
See cases	Uncertain significance	rs759860811	RCV002252456

Associations from Text Mining
Disease Name	Relationship Type	References
Acidemia isovaleric	Associate	20519759
Carcinoma Hepatocellular	Associate	33188160
Carcinoma Non Small Cell Lung	Associate	32161100
Carcinoma Squamous Cell	Associate	37746664
Colorectal Neoplasms	Associate	1558798, 2328204, 32161100
COVID 19	Associate	34719824
Embryo Loss	Associate	36182037
Endometrial Neoplasms	Associate	1575057, 2470714
Ermine phenotype	Associate	36182037
Glioblastoma	Stimulate	37762371
Glioma	Associate	37349788
Hereditary Autoinflammatory Diseases	Associate	27019227, 31672938
Immune Dysregulation Polyendocrinopathy Enteropathy X Linked Syndrome	Associate	33864888
Leukemia	Inhibit	1696013
Leukemia	Associate	2514170, 8144401
Mental Retardation X Linked	Associate	36182037
Myositis	Associate	2765363
Neoplasm Metastasis	Associate	1558798, 2328204
Neoplasms	Associate	11891323, 1558798
Neuroblastoma	Associate	3146694, 6951191, 9348340
Osteosarcoma	Associate	2188094
Parkinson Disease	Associate	40240887
Pigmentary Disorder Reticulate with Systemic Manifestations	Associate	27019227, 31672938, 36182037
Rectal Neoplasms	Associate	25380052
Retinoblastoma	Associate	34646884
Stomach Neoplasms	Associate	2765363, 35036435
Urinary Bladder Neoplasms	Associate	28320388
Uterine Cervical Neoplasms	Associate	37746664
Virus Diseases	Associate	34719824
Xeroderma Pigmentosum	Associate	866172