SPRTN (SprT-like N-terminal domain)

Gene

• Entrez ID: 83932
• Gene name: SprT-like N-terminal domain
• Gene symbol: SPRTN
• Synonyms (NCBI Gene): C1orf124, DVC1, PRO4323, spartan
• Chromosome: 1
• Chromosome location: 1q42.2
• Summary: The protein encoded by this gene may play a role in DNA repair during replication of damaged DNA. This protein recruits valosin containing protein (p97) to stalled DNA replication forks where it may prevent excessive translesional DNA synthesis and limit

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs527236212	A>-	Pathogenic	Coding sequence variant, frameshift variant, 3 prime UTR variant
rs527236213	A>G	Pathogenic	Genic upstream transcript variant, upstream transcript variant, coding sequence variant, missense variant, intron variant
rs587593493	GGTA>-	Pathogenic	Coding sequence variant, frameshift variant, splice donor variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016242	hsa-miR-548b-3p	Sequencing	20371350
MIRT021124	hsa-miR-186-5p	Sequencing	20371350
MIRT045975	hsa-miR-125b-5p	CLASH	23622248
MIRT045716	hsa-miR-125a-5p	CLASH	23622248
MIRT713269	hsa-miR-512-5p	HITS-CLIP	19536157
MIRT713273	hsa-miR-548c-3p	HITS-CLIP	19536157
MIRT713272	hsa-miR-7151-5p	HITS-CLIP	19536157
MIRT713271	hsa-miR-3688-3p	HITS-CLIP	19536157
MIRT713270	hsa-miR-4261	HITS-CLIP	19536157
MIRT713269	hsa-miR-512-5p	HITS-CLIP	19536157
MIRT713268	hsa-miR-545-3p	HITS-CLIP	19536157
MIRT713267	hsa-miR-486-5p	HITS-CLIP	19536157
MIRT713266	hsa-miR-7152-5p	HITS-CLIP	19536157
MIRT565490	hsa-miR-124-3p	PAR-CLIP	20371350
MIRT565491	hsa-miR-506-3p	PAR-CLIP	20371350
MIRT565490	hsa-miR-124-3p	PAR-CLIP	20371350
MIRT565489	hsa-miR-3714	PAR-CLIP	20371350
MIRT565488	hsa-miR-3910	PAR-CLIP	20371350
MIRT565487	hsa-miR-5586-3p	PAR-CLIP	20371350
MIRT565486	hsa-miR-29a-3p	PAR-CLIP	20371350
MIRT565485	hsa-miR-29b-3p	PAR-CLIP	20371350
MIRT565484	hsa-miR-29c-3p	PAR-CLIP	20371350
MIRT565483	hsa-miR-6871-3p	PAR-CLIP	20371350
MIRT565482	hsa-miR-875-5p	PAR-CLIP	20371350
MIRT565481	hsa-miR-31-5p	PAR-CLIP	20371350
MIRT565480	hsa-miR-1257	PAR-CLIP	20371350
MIRT565479	hsa-miR-5682	PAR-CLIP	20371350
MIRT565478	hsa-miR-3144-3p	PAR-CLIP	20371350
MIRT560190	hsa-miR-1277-5p	PAR-CLIP	20371350
MIRT560189	hsa-miR-193a-3p	PAR-CLIP	20371350
MIRT560188	hsa-miR-193b-3p	PAR-CLIP	20371350
MIRT560187	hsa-miR-892b	PAR-CLIP	20371350
MIRT560186	hsa-miR-1278	PAR-CLIP	20371350
MIRT560185	hsa-miR-3128	PAR-CLIP	20371350
MIRT560184	hsa-miR-548ao-5p	PAR-CLIP	20371350
MIRT560183	hsa-miR-548ax	PAR-CLIP	20371350
MIRT560182	hsa-miR-5585-5p	PAR-CLIP	20371350
MIRT560181	hsa-miR-4470	PAR-CLIP	20371350
MIRT713269	hsa-miR-512-5p	HITS-CLIP	19536157
MIRT713273	hsa-miR-548c-3p	HITS-CLIP	19536157
MIRT713272	hsa-miR-7151-5p	HITS-CLIP	19536157
MIRT713271	hsa-miR-3688-3p	HITS-CLIP	19536157
MIRT713270	hsa-miR-4261	HITS-CLIP	19536157
MIRT713269	hsa-miR-512-5p	HITS-CLIP	19536157
MIRT713268	hsa-miR-545-3p	HITS-CLIP	19536157
MIRT713267	hsa-miR-486-5p	HITS-CLIP	19536157
MIRT713266	hsa-miR-7152-5p	HITS-CLIP	19536157
MIRT565490	hsa-miR-124-3p	PAR-CLIP	20371350
MIRT565491	hsa-miR-506-3p	PAR-CLIP	20371350
MIRT565490	hsa-miR-124-3p	PAR-CLIP	20371350
MIRT565489	hsa-miR-3714	PAR-CLIP	20371350
MIRT565488	hsa-miR-3910	PAR-CLIP	20371350
MIRT565487	hsa-miR-5586-3p	PAR-CLIP	20371350
MIRT565486	hsa-miR-29a-3p	PAR-CLIP	20371350
MIRT565485	hsa-miR-29b-3p	PAR-CLIP	20371350
MIRT565484	hsa-miR-29c-3p	PAR-CLIP	20371350
MIRT565483	hsa-miR-6871-3p	PAR-CLIP	20371350
MIRT565482	hsa-miR-875-5p	PAR-CLIP	20371350
MIRT565481	hsa-miR-31-5p	PAR-CLIP	20371350
MIRT565480	hsa-miR-1257	PAR-CLIP	20371350
MIRT565479	hsa-miR-5682	PAR-CLIP	20371350
MIRT565478	hsa-miR-3144-3p	PAR-CLIP	20371350
MIRT560190	hsa-miR-1277-5p	PAR-CLIP	20371350
MIRT560189	hsa-miR-193a-3p	PAR-CLIP	20371350
MIRT560188	hsa-miR-193b-3p	PAR-CLIP	20371350
MIRT560187	hsa-miR-892b	PAR-CLIP	20371350
MIRT560186	hsa-miR-1278	PAR-CLIP	20371350
MIRT560185	hsa-miR-3128	PAR-CLIP	20371350
MIRT560184	hsa-miR-548ao-5p	PAR-CLIP	20371350
MIRT560183	hsa-miR-548ax	PAR-CLIP	20371350
MIRT560182	hsa-miR-5585-5p	PAR-CLIP	20371350
MIRT560181	hsa-miR-4470	PAR-CLIP	20371350

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IDA	27852435, 27871365, 27871366, 32649882
GO:0003677	Function	DNA binding	IEA
GO:0003690	Function	Double-stranded DNA binding	IDA	27852435, 27871365, 27871366, 32649882
GO:0003697	Function	Single-stranded DNA binding	IDA	27871365, 32649882
GO:0003697	Function	Single-stranded DNA binding	IEA
GO:0004222	Function	Metalloendopeptidase activity	IDA	27852435, 27871365, 27871366, 32649882, 36608669
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	22681887, 22894931, 22902628, 23042605, 23042607
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	22681887, 22894931, 23042605, 23042607, 27852435
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0006281	Process	DNA repair	IEA
GO:0006508	Process	Proteolysis	IDA	27852435, 27871365, 27871366, 32649882
GO:0006508	Process	Proteolysis	IEA
GO:0006974	Process	DNA damage response	IBA
GO:0006974	Process	DNA damage response	IDA	22681887, 22894931, 22902628, 23042605, 23042607, 27852435, 27871365, 27871366, 32649882, 36608669
GO:0006974	Process	DNA damage response	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0009411	Process	Response to UV	IDA	22681887, 22894931, 22902628
GO:0016540	Process	Protein autoprocessing	IDA	27852435, 27871365, 27871366, 32649882
GO:0016607	Component	Nuclear speck	IDA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019985	Process	Translesion synthesis	IDA	22681887, 22902628
GO:0019985	Process	Translesion synthesis	IMP	23042605, 23042607
GO:0031398	Process	Positive regulation of protein ubiquitination	IDA	22681887
GO:0031593	Function	Polyubiquitin modification-dependent protein binding	IBA
GO:0036297	Process	Interstrand cross-link repair	IDA	36608669
GO:0043130	Function	Ubiquitin binding	IDA	22681887, 22894931, 22902628, 23042605, 23042607
GO:0046872	Function	Metal ion binding	IEA
GO:0070530	Function	K63-linked polyubiquitin modification-dependent protein binding	IDA	22681887, 23042605
GO:0106300	Process	Protein-DNA covalent cross-linking repair	IDA	27852435, 27871365, 27871366, 32152270, 32649882, 36608669
GO:0106300	Process	Protein-DNA covalent cross-linking repair	IEA

Other IDs

• MIM: 616086
• HGNC: 25356
• e!Ensembl: ENSG00000010072

Protein

• UniProt ID: Q9H040
• Protein name: DNA-dependent metalloprotease SPRTN (EC 3.4.24.-) (DNA damage protein targeting VCP) (DVC1) (Protein with SprT-like domain at the N terminus) (Spartan)
• Protein function: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:27852435, PubMed:27871365, PubMed:2787
• PDB: 5IY4, 6MDW, 6MDX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10263	SprT-like	45 → 153	SprT-like family	Domain

• Sequence:

  MDDDLMLALRLQEEWNLQEAERDHAQESLSLVDASWELVDPTPDLQALFVQFNDQFFWGQ
  LEAVEVKWSVRMTLCAGICSYEGKGGMCSIRLSEPLLKLRPRKDLVETLLHEMIHAYLFV
  TNNDKDREGHGPEFCKHMHRINSLTGANITVYHTFHDEVDEYRRHWWRCNGPCQHRPPYY
  GYVKRATNREPSAHDYWWAEHQKTCGGTYIKIKEPENYSKKGKGKAKLGKEPVLAAENKD
  KPNRGEAQLVIPFSGKGYVLGETSNLPSPGKLITSHAINKTQDLLNQNHSANAVRPNSKI
  KVKFEQNGSSKNSHLVSPAVSNSHQNVLSNYFPRVSFANQKAFRGVNGSPRISVTVGNIP
  KNSVSSSSQRRVSSSKISLRNSSKVTESASVMPSQDVSGSEDTFPNKRPRLEDKTVFDNF
  FIKKEQIKSSGNDPKYSTTTAQNSSSSSSQSKMVNCPVCQNEVLESQINEHLDWCLEGDS
  IKVKSEESL

• Sequence length: 489

Pathways

Reactome:

Translesion Synthesis by POLH

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
Progeroid features-hepatocellular carcinoma predisposition syndrome	Pathogenic	rs587593493, rs527236213, rs527236212	RCV000150049 RCV000150050 RCV000150048	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUIJS-AALFS SYNDROME	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPRTN-related disorder	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TERATOZOOSPERMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Carcinogenesis	Carcinogenesis	Pubtator	28053116	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	28053116, 30893605	Associate	★☆☆☆☆ Found in Text Mining only
Clinodactyly	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of fingers	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cockayne Syndrome	Cockayne Syndrome	BEFREE	25352099		★☆☆☆☆ Found in Text Mining only
Cockayne Syndrome	Cockayne Syndrome	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cutis Laxa Autosomal Recessive Type IIB	Cutis laxa	Pubtator	28053116	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Flexion contracture - elbow	Elbow flexion contracture	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lipodystrophy	Lipodystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	25261934, 27852435, 28053116, 28199696		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	CTD_human_DG	25261934		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	30170832, 31316063		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25352099, 27871366		★☆☆☆☆ Found in Text Mining only
Marfan Syndrome	Marfan Syndrome	BEFREE	30959508		★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	BEFREE	31152441, 31340760, 31409292, 31744319		★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	BEFREE	23319060		★☆☆☆☆ Found in Text Mining only
Peripheral Vascular Diseases	Vascular Diseases	BEFREE	23319060		★☆☆☆☆ Found in Text Mining only
Posterior subcapsular cataract	Capsular cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Premature aging syndrome	Premature aging	BEFREE	25352099, 30170832, 31316063		★☆☆☆☆ Found in Text Mining only
Progeria	Progeria	CTD_human_DG	25261934		★☆☆☆☆ Found in Text Mining only
Progeroid features-hepatocellular carcinoma predisposition syndrome	Progeroid features hepatocellular carcinoma predisposition syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
RUIJS-AALFS SYNDROME	RUIJS-AALFS SYNDROME	UNIPROT_DG	25261934		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUIJS-AALFS SYNDROME	RUIJS-AALFS SYNDROME	ORPHANET_DG	25261934		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUIJS-AALFS SYNDROME	RUIJS-AALFS SYNDROME	BEFREE	27852435, 27871366, 28199696		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUIJS-AALFS SYNDROME	RUIJS-AALFS SYNDROME	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RUIJS-AALFS SYNDROME	RUIJS-AALFS SYNDROME	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations