DNA2 (DNA replication helicase/nuclease 2)

Gene

• Entrez ID: 1763
• Gene name: DNA replication helicase/nuclease 2
• Gene symbol: DNA2
• Synonyms (NCBI Gene): DNA2L, RTS4, hDNA2
• Chromosome: 10
• Chromosome location: 10q21.3
• Summary: This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progres

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs181679245	G>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs201999986	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs376624048	G>A,T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs587777614	G>-	Pathogenic	Intron variant
rs746522359	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs768077989	GTCT>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs777604935	CA>-,CACA	Likely-pathogenic	Stop gained, coding sequence variant, frameshift variant, upstream transcript variant, inframe indel, genic upstream transcript variant, non coding transcript variant
rs1554911807	TCACAGCTCCGC>-	Likely-pathogenic	Genic upstream transcript variant, intron variant, non coding transcript variant, splice donor variant, coding sequence variant
rs1590045526	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1590054876	G>A	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1590055107	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT691417	hsa-miR-548an	HITS-CLIP	23313552
MIRT691416	hsa-miR-18a-3p	HITS-CLIP	23313552
MIRT691415	hsa-miR-18b-3p	HITS-CLIP	23313552
MIRT691414	hsa-miR-3157-3p	HITS-CLIP	23313552
MIRT691413	hsa-miR-508-5p	HITS-CLIP	23313552
MIRT691412	hsa-miR-1273g-3p	HITS-CLIP	23313552
MIRT691411	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT691410	hsa-miR-939-3p	HITS-CLIP	23313552
MIRT691409	hsa-miR-766-3p	HITS-CLIP	23313552
MIRT691408	hsa-miR-4793-3p	HITS-CLIP	23313552
MIRT691407	hsa-miR-4486	HITS-CLIP	23313552
MIRT691406	hsa-miR-661	HITS-CLIP	23313552
MIRT691405	hsa-miR-4649-5p	HITS-CLIP	23313552
MIRT691404	hsa-miR-6729-5p	HITS-CLIP	23313552
MIRT691403	hsa-miR-6512-3p	HITS-CLIP	23313552
MIRT691402	hsa-miR-6720-5p	HITS-CLIP	23313552
MIRT691401	hsa-miR-7703	HITS-CLIP	23313552
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23313552
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23313552
MIRT671448	hsa-miR-4284	HITS-CLIP	23313552
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23313552
MIRT671446	hsa-miR-3178	HITS-CLIP	23313552
MIRT671445	hsa-miR-7977	HITS-CLIP	23313552
MIRT688491	hsa-miR-548c-3p	HITS-CLIP	23313552
MIRT688490	hsa-miR-3613-3p	HITS-CLIP	23313552
MIRT688489	hsa-miR-4684-5p	HITS-CLIP	23313552
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT524118	hsa-let-7c-5p	PAR-CLIP	23446348
MIRT524117	hsa-miR-4458	PAR-CLIP	23446348
MIRT524116	hsa-let-7i-5p	PAR-CLIP	23446348
MIRT524115	hsa-let-7d-5p	PAR-CLIP	23446348
MIRT524114	hsa-let-7g-5p	PAR-CLIP	23446348
MIRT524113	hsa-let-7e-5p	PAR-CLIP	23446348
MIRT524112	hsa-let-7f-5p	PAR-CLIP	23446348
MIRT524111	hsa-let-7b-5p	PAR-CLIP	23446348
MIRT524110	hsa-let-7a-5p	PAR-CLIP	23446348
MIRT524109	hsa-miR-98-5p	PAR-CLIP	23446348
MIRT524108	hsa-miR-4500	PAR-CLIP	23446348
MIRT524107	hsa-miR-6888-5p	PAR-CLIP	23446348
MIRT524105	hsa-miR-3929	PAR-CLIP	23446348
MIRT524106	hsa-miR-4419b	PAR-CLIP	23446348
MIRT524104	hsa-miR-4478	PAR-CLIP	23446348
MIRT524103	hsa-miR-7162-3p	PAR-CLIP	23446348
MIRT524102	hsa-miR-485-5p	PAR-CLIP	23446348
MIRT524101	hsa-miR-6884-5p	PAR-CLIP	23446348
MIRT524100	hsa-miR-202-3p	PAR-CLIP	23446348
MIRT524099	hsa-miR-7160-5p	PAR-CLIP	23446348
MIRT524098	hsa-miR-665	PAR-CLIP	23446348
MIRT691417	hsa-miR-548an	HITS-CLIP	23313552
MIRT691416	hsa-miR-18a-3p	HITS-CLIP	23313552
MIRT691415	hsa-miR-18b-3p	HITS-CLIP	23313552
MIRT691414	hsa-miR-3157-3p	HITS-CLIP	23313552
MIRT691413	hsa-miR-508-5p	HITS-CLIP	23313552
MIRT691412	hsa-miR-1273g-3p	HITS-CLIP	23313552
MIRT691411	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT691410	hsa-miR-939-3p	HITS-CLIP	23313552
MIRT691409	hsa-miR-766-3p	HITS-CLIP	23313552
MIRT691408	hsa-miR-4793-3p	HITS-CLIP	23313552
MIRT691407	hsa-miR-4486	HITS-CLIP	23313552
MIRT691406	hsa-miR-661	HITS-CLIP	23313552
MIRT691405	hsa-miR-4649-5p	HITS-CLIP	23313552
MIRT691404	hsa-miR-6729-5p	HITS-CLIP	23313552
MIRT691403	hsa-miR-6512-3p	HITS-CLIP	23313552
MIRT691402	hsa-miR-6720-5p	HITS-CLIP	23313552
MIRT691401	hsa-miR-7703	HITS-CLIP	23313552
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23313552
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23313552
MIRT671448	hsa-miR-4284	HITS-CLIP	23313552
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23313552
MIRT671446	hsa-miR-3178	HITS-CLIP	23313552
MIRT671445	hsa-miR-7977	HITS-CLIP	23313552
MIRT688491	hsa-miR-548c-3p	HITS-CLIP	23313552
MIRT688490	hsa-miR-3613-3p	HITS-CLIP	23313552
MIRT688489	hsa-miR-4684-5p	HITS-CLIP	23313552
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT671450	hsa-miR-6499-5p	HITS-CLIP	23824327
MIRT671449	hsa-miR-1199-3p	HITS-CLIP	23824327
MIRT671448	hsa-miR-4284	HITS-CLIP	23824327
MIRT671447	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671446	hsa-miR-3178	HITS-CLIP	23824327
MIRT671445	hsa-miR-7977	HITS-CLIP	23824327
MIRT524118	hsa-let-7c-5p	PAR-CLIP	23446348
MIRT524117	hsa-miR-4458	PAR-CLIP	23446348
MIRT524116	hsa-let-7i-5p	PAR-CLIP	23446348
MIRT524115	hsa-let-7d-5p	PAR-CLIP	23446348
MIRT524114	hsa-let-7g-5p	PAR-CLIP	23446348
MIRT524113	hsa-let-7e-5p	PAR-CLIP	23446348
MIRT524112	hsa-let-7f-5p	PAR-CLIP	23446348
MIRT524111	hsa-let-7b-5p	PAR-CLIP	23446348
MIRT524110	hsa-let-7a-5p	PAR-CLIP	23446348
MIRT524109	hsa-miR-98-5p	PAR-CLIP	23446348
MIRT524108	hsa-miR-4500	PAR-CLIP	23446348
MIRT524107	hsa-miR-6888-5p	PAR-CLIP	23446348
MIRT524105	hsa-miR-3929	PAR-CLIP	23446348
MIRT524106	hsa-miR-4419b	PAR-CLIP	23446348
MIRT524104	hsa-miR-4478	PAR-CLIP	23446348
MIRT524103	hsa-miR-7162-3p	PAR-CLIP	23446348
MIRT524102	hsa-miR-485-5p	PAR-CLIP	23446348
MIRT524101	hsa-miR-6884-5p	PAR-CLIP	23446348
MIRT524100	hsa-miR-202-3p	PAR-CLIP	23446348
MIRT524099	hsa-miR-7160-5p	PAR-CLIP	23446348
MIRT524098	hsa-miR-665	PAR-CLIP	23446348
MIRT939512	hsa-let-7a	CLIP-seq
MIRT939513	hsa-let-7b	CLIP-seq
MIRT939514	hsa-let-7c	CLIP-seq
MIRT939515	hsa-let-7d	CLIP-seq
MIRT939516	hsa-let-7e	CLIP-seq
MIRT939517	hsa-let-7f	CLIP-seq
MIRT939518	hsa-let-7g	CLIP-seq
MIRT939519	hsa-let-7i	CLIP-seq
MIRT939520	hsa-miR-1914	CLIP-seq
MIRT939521	hsa-miR-200b	CLIP-seq
MIRT939522	hsa-miR-200c	CLIP-seq
MIRT939523	hsa-miR-202	CLIP-seq
MIRT939524	hsa-miR-217	CLIP-seq
MIRT939525	hsa-miR-218	CLIP-seq
MIRT939526	hsa-miR-297	CLIP-seq
MIRT939527	hsa-miR-3149	CLIP-seq
MIRT939528	hsa-miR-320a	CLIP-seq
MIRT939529	hsa-miR-320b	CLIP-seq
MIRT939530	hsa-miR-320c	CLIP-seq
MIRT939531	hsa-miR-320d	CLIP-seq
MIRT939532	hsa-miR-34b	CLIP-seq
MIRT939533	hsa-miR-3672	CLIP-seq
MIRT939534	hsa-miR-3927	CLIP-seq
MIRT939535	hsa-miR-3973	CLIP-seq
MIRT939536	hsa-miR-429	CLIP-seq
MIRT939537	hsa-miR-4418	CLIP-seq
MIRT939538	hsa-miR-4429	CLIP-seq
MIRT939539	hsa-miR-4643	CLIP-seq
MIRT939540	hsa-miR-4650-3p	CLIP-seq
MIRT939541	hsa-miR-4760-3p	CLIP-seq
MIRT939542	hsa-miR-4803	CLIP-seq
MIRT939543	hsa-miR-509-3-5p	CLIP-seq
MIRT939544	hsa-miR-509-5p	CLIP-seq
MIRT939545	hsa-miR-513a-3p	CLIP-seq
MIRT939546	hsa-miR-520d-5p	CLIP-seq
MIRT939547	hsa-miR-520g	CLIP-seq
MIRT939548	hsa-miR-520h	CLIP-seq
MIRT939549	hsa-miR-524-5p	CLIP-seq
MIRT939550	hsa-miR-548u	CLIP-seq
MIRT939551	hsa-miR-561	CLIP-seq
MIRT939552	hsa-miR-636	CLIP-seq
MIRT939553	hsa-miR-98	CLIP-seq
MIRT1547987	hsa-miR-4640-3p	CLIP-seq
MIRT1547988	hsa-miR-4765	CLIP-seq
MIRT1547989	hsa-miR-548a-3p	CLIP-seq
MIRT1547990	hsa-miR-548e	CLIP-seq
MIRT1547991	hsa-miR-548f	CLIP-seq
MIRT1977899	hsa-miR-128	CLIP-seq
MIRT1977900	hsa-miR-27a	CLIP-seq
MIRT1977901	hsa-miR-27b	CLIP-seq
MIRT1977902	hsa-miR-369-3p	CLIP-seq
MIRT1977903	hsa-miR-374a	CLIP-seq
MIRT1977904	hsa-miR-374b	CLIP-seq
MIRT1977905	hsa-miR-410	CLIP-seq
MIRT1977906	hsa-miR-4328	CLIP-seq
MIRT1977907	hsa-miR-4494	CLIP-seq
MIRT1977908	hsa-miR-4798-5p	CLIP-seq
MIRT1977909	hsa-miR-499a-5p	CLIP-seq
MIRT1977910	hsa-miR-5096	CLIP-seq
MIRT1977911	hsa-miR-513a-5p	CLIP-seq
MIRT1977899	hsa-miR-128	CLIP-seq
MIRT939520	hsa-miR-1914	CLIP-seq
MIRT939521	hsa-miR-200b	CLIP-seq
MIRT939522	hsa-miR-200c	CLIP-seq
MIRT939525	hsa-miR-218	CLIP-seq
MIRT1977900	hsa-miR-27a	CLIP-seq
MIRT1977901	hsa-miR-27b	CLIP-seq
MIRT2213291	hsa-miR-3125	CLIP-seq
MIRT2213292	hsa-miR-3150b-3p	CLIP-seq
MIRT2213293	hsa-miR-3916	CLIP-seq
MIRT939536	hsa-miR-429	CLIP-seq
MIRT1977906	hsa-miR-4328	CLIP-seq
MIRT2213294	hsa-miR-4427	CLIP-seq
MIRT2213295	hsa-miR-4661-5p	CLIP-seq
MIRT2213296	hsa-miR-4698	CLIP-seq
MIRT2213297	hsa-miR-4724-5p	CLIP-seq
MIRT2213298	hsa-miR-4784	CLIP-seq
MIRT1977908	hsa-miR-4798-5p	CLIP-seq
MIRT1977911	hsa-miR-513a-5p	CLIP-seq
MIRT939552	hsa-miR-636	CLIP-seq
MIRT2213299	hsa-miR-877	CLIP-seq
MIRT2679308	hsa-miR-2117	CLIP-seq
MIRT2679309	hsa-miR-4273	CLIP-seq
MIRT2679310	hsa-miR-4457	CLIP-seq
MIRT2679311	hsa-miR-513b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000076	Process	DNA replication checkpoint signaling	IMP	22570476
GO:0000166	Function	Nucleotide binding	IEA
GO:0000723	Process	Telomere maintenance	IEA
GO:0000723	Process	Telomere maintenance	ISS	23604072
GO:0000729	Process	DNA double-strand break processing	IDA	21325134
GO:0000781	Component	Chromosome, telomeric region	IEA
GO:0000781	Component	Chromosome, telomeric region	ISS	23604072
GO:0003677	Function	DNA binding	IDA	20019387, 22570407
GO:0003677	Function	DNA binding	IEA
GO:0003678	Function	DNA helicase activity	IDA	16595799
GO:0003678	Function	DNA helicase activity	IDA	16595800
GO:0003723	Function	RNA binding	IBA
GO:0003824	Function	Catalytic activity	IEA
GO:0004386	Function	Helicase activity	IEA
GO:0004386	Function	Helicase activity	TAS	18995831
GO:0004518	Function	Nuclease activity	IDA	21325134
GO:0004518	Function	Nuclease activity	IEA
GO:0004518	Function	Nuclease activity	IMP	31478350
GO:0004519	Function	Endonuclease activity	IEA
GO:0005515	Function	Protein binding	IPI	20019387, 21325134
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	19487465
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005760	Component	Gamma DNA polymerase complex	IDA	18995831
GO:0006260	Process	DNA replication	IEA
GO:0006260	Process	DNA replication	IMP	22570476
GO:0006264	Process	Mitochondrial DNA replication	IDA	18995831, 19487465
GO:0006281	Process	DNA repair	IEA
GO:0006284	Process	Base-excision repair	IDA	18995831
GO:0006284	Process	Base-excision repair	IMP	37055165
GO:0006974	Process	DNA damage response	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IMP	31478350
GO:0016887	Function	ATP hydrolysis activity	TAS	18995831
GO:0017108	Function	5'-flap endonuclease activity	IBA
GO:0017108	Function	5'-flap endonuclease activity	IDA	16595799, 16595800, 18995831, 20019387, 22570407
GO:0017108	Function	5'-flap endonuclease activity	IEA
GO:0017108	Function	5'-flap endonuclease activity	TAS
GO:0017116	Function	Single-stranded DNA helicase activity	IDA	16595799, 16595800
GO:0032201	Process	Telomere maintenance via semi-conservative replication	IEA
GO:0032201	Process	Telomere maintenance via semi-conservative replication	TAS
GO:0032392	Process	DNA geometric change	TAS	27918544
GO:0033567	Process	DNA replication, Okazaki fragment processing	IDA	22570407
GO:0033892	Function	Deoxyribonuclease (pyrimidine dimer) activity	IDA	18995831
GO:0042645	Component	Mitochondrial nucleoid	IDA	19487465
GO:0043137	Process	DNA replication, removal of RNA primer	IDA	18995831
GO:0043139	Function	5'-3' DNA helicase activity	IDA	20019387
GO:0043504	Process	Mitochondrial DNA repair	IDA	19487465
GO:0045740	Process	Positive regulation of DNA replication	IDA	18995831
GO:0046872	Function	Metal ion binding	IEA
GO:0051536	Function	Iron-sulfur cluster binding	IEA
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IEA
GO:0071932	Process	Replication fork reversal	IBA
GO:0090656	Process	T-circle formation	TAS	27918544
GO:1902990	Process	Mitotic telomere maintenance via semi-conservative replication	IEA
GO:1902990	Process	Mitotic telomere maintenance via semi-conservative replication	ISS	23604072

Other IDs

• MIM: 601810
• HGNC: 2939
• e!Ensembl: ENSG00000138346

Protein

• UniProt ID: P51530
• Protein name: DNA replication ATP-dependent helicase/nuclease DNA2 (hDNA2) (DNA replication ATP-dependent helicase-like homolog) [Includes: DNA replication nuclease DNA2 (EC 3.1.-.-); DNA replication ATP-dependent helicase DNA2 (EC 3.6.4.12)]
• Protein function: Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A c
• PDB: 5EAY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08696	Dna2	71 → 282	DNA replication factor Dna2	Family
  PF13086	AAA_11	625 → 736	AAA domain	Domain
  PF13086	AAA_11	722 → 798	AAA domain	Domain
  PF13087	AAA_12	805 → 1017	AAA domain	Domain

• Sequence:

  MEQLNELELLMEKSFWEEAELPAELFQKKVVASFPRTVLSTGMDNRYLVLAVNTVQNKEG
  NCEKRLVITASQSLENKELCILRNDWCSVPVEPGDIIHLEGDCTSDTWIIDKDFGYLILY
  PDMLISGTSIASSIRCMRRAVLSETFRSSDPATRQMLIGTVLHEVFQKAINNSFAPEKLQ
  ELAFQTIQEIRHLKEMYRLNLSQDEIKQEVEDYLPSFCKWAGDFMHKNTSTDFPQMQLSL
  PSDNSKDNSTCNIEVVKPMDIEESIWSPRFGLKGKIDVTVGVKIHRGYKTKYKIMPLELK
  TGKESNSIEHRSQVVLYTLLSQERRADPEAGLLLYLKTGQMYPVPANHLDKRELLKLRNQ
  MAFSLFHRISKSATRQKTQLASLPQIIEEEKTCKYCSQIGNCALYSRAVEQQMDCSSVPI
  VMLPKIEEETQHLKQTHLEYFSLWCLMLTLESQSKDNKKNHQNIWLMPASEMEKSGSCIG
  NLIRMEHVKIVCDGQYLHNFQCKHGAIPVTNLMAGDRVIVSGEERSLFALSRGYVKEINM
  TTVTCLLDRNLSVLPESTLFRLDQEEKNCDIDTPLGNLSKLMENTFVSKKLRDLIIDFRE
  PQFISYLSSVLPHDAKDTVACILKGLNKPQRQAMKKVLLSKDYTLIVGMPGTGKTTTICT
  LVRILYACGFSVLLTSYTHSAVDNILLKLAKFKIGFLRLGQIQKVHPAIQQFTEQEICRS
  KSIKSLALLEELYNSQLIVATTCMGINHPIFSRKIFDFCIVDEASQISQPICLGPLFFSR
  RFVLVGDHQQLPPLVLNREARALGMSESLFKRLEQNKSAVVQLTVQYRMNSKIMSLSNKL
  TYEGKLECGSDKVANAVINLRHFKDVKLELEFYADYSDNPWLMGVFEPNNPVCFLNTDKV
  PAPEQVEKGGVSNVTEAKLIVFLTSIFVKAGCSPSDIGIIAPYRQQLKIINDLLARSIGM
  VEVNTVDKYQGRDKSIVLVSFVRSNKDGTVGELLKDWRRLNVAITRAKHKLILLGCVPSL
  NCYPPLEKLLNHLNSEKLIIDLPSREHESLCHILGDFQRE

• Sequence length: 1060

Pathways

KEGG:

DNA replication

Reactome:

Removal of the Flap Intermediate from the C-strand
HDR through Single Strand Annealing (SSA)
HDR through Homologous Recombination (HRR)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
Resolution of D-loop Structures through Holliday Junction Intermediates
Homologous DNA Pairing and Strand Exchange
Processing of DNA double-strand break ends
Presynaptic phase of homologous DNA pairing and strand exchange
Regulation of TP53 Activity through Phosphorylation
Removal of the Flap Intermediate
G2/M DNA damage checkpoint

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Ateleiotic dwarfism	Likely pathogenic; Pathogenic	rs587777614	RCV000162161	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial DNA deletion syndrome with progressive myopathy	Likely pathogenic	rs1554911807, rs376624048, rs1590054876	RCV005357794 RCV000626157 RCV000995534	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rothmund-Thomson syndrome	Pathogenic; Likely pathogenic	rs2493999571, rs2494019349, rs1469135249	RCV003154066 RCV003154242 RCV003154243	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rothmund-Thomson syndrome type 4	Pathogenic; Likely pathogenic	rs2493999571, rs2494019349, rs1469135249	RCV004545280 RCV004545281 RCV004545282	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seckel syndrome 8	Likely pathogenic; Pathogenic	rs587777614, rs2494022602, rs2493927502	RCV000133461 RCV004542241 RCV004544248	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital myopathy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DNA2-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DNA2-RELATED MITOCHONDRIAL DNA DELETION SYNDROME	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOGONADOTROPIC HYPOGONADISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IDIOPATHIC GROWTH HORMONE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KALLMANN SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Long QT syndrome	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL MYOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANHYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY DWARFISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY DWARFISM I	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY SHORT STATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ROTHMUND-THOMSON SYNDROME, TYPE 4	—	ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SECKEL SYNDROME	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SHEEHAN SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alternating hemiplegia of childhood	Alternating hemiplegia of childhood	Pubtator	24413054	Associate	★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	12680237		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	BEFREE	28554558		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom Syndrome	BEFREE	12826610, 31153714		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	25909997		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33574966	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	12680237		★☆☆☆☆ Found in Text Mining only
Chronic myeloproliferative disorder	Myeloproliferative disorder	BEFREE	31045292		★☆☆☆☆ Found in Text Mining only
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	23951239	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms Hereditary Nonpolyposis	Lynch syndrome	Pubtator	23951239	Associate	★☆☆☆☆ Found in Text Mining only
Compression of spinal cord	Spinal cord compression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ptosis	Congenital ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
DNA2-related mitochondrial DNA deletion syndrome	Mitochondrial DNA Deletion Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Ectopic kidney	Ectopic kidney	HPO_DG			★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	36916001	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	34047877	Stimulate	★☆☆☆☆ Found in Text Mining only
External Ophthalmoplegia	External Ophthalmoplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Facial paralysis	Facial paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi Anemia	BEFREE	22987153		★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi anemia	Pubtator	22987153, 24626199	Associate	★☆☆☆☆ Found in Text Mining only
FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder)	Anemia	BEFREE	22987153		★☆☆☆☆ Found in Text Mining only
Generalized amyotrophy	Amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	11955677		★☆☆☆☆ Found in Text Mining only
Li-Fraumeni Syndrome	Li-Fraumeni Syndrome	BEFREE	15526362		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	25909997		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	25238049		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	31297881		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	12680237		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28414320, 28718810, 28903076, 31754720		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	BEFREE	23352259, 31478350		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Myopathies	Mitochondrial myopathy	Pubtator	23352259, 31478350	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Myopathies	Mitochondrial myopathy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple System Atrophy	Multiple system atrophy	Pubtator	36064591	Associate	★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	23352259, 28554558, 31478350		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31754720		★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia Chronic Progressive External	Progressive external ophthalmoplegia	Pubtator	23352259	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	37756561	Stimulate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	31297881		★☆☆☆☆ Found in Text Mining only
PITUITARY DWARFISM I	Pituitary dwarfism	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 6	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	ORPHANET_DG	23352259		★☆☆☆☆ Found in Text Mining only
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 6	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	UNIPROT_DG	23352259		★☆☆☆☆ Found in Text Mining only
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 6	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	GENOMICS_ENGLAND_DG	23352259		★☆☆☆☆ Found in Text Mining only
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 6	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 6	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Progressive ophthalmoplegia	Ophthalmoplegia	BEFREE	28554558		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	BEFREE	28554558		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seckel syndrome	Seckel Syndrome	BEFREE	24389050, 31045292		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seckel syndrome	Seckel Syndrome	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seckel syndrome 1	Seckel syndrome	Pubtator	24389050, 31045292	Associate	★☆☆☆☆ Found in Text Mining only
Seckel syndrome 2	Seckel syndrome	Pubtator	31045292	Associate	★☆☆☆☆ Found in Text Mining only
SECKEL SYNDROME 8	Seckel Syndrome	GENOMICS_ENGLAND_DG	24389050		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SECKEL SYNDROME 8	Seckel Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sleep Apnea, Obstructive	Sleep Apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Visceral myopathy familial external ophthalmoplegia	Visceral neuropathy	Pubtator	23352259, 36064591	Associate	★☆☆☆☆ Found in Text Mining only
Werner Syndrome	Werner Syndrome	BEFREE	28640365		★☆☆☆☆ Found in Text Mining only