SPRTN

SprT-like N-terminal domain

Basic information

Region (hg38): 1:231337103-231355023

Previous symbols: [ "C1orf124" ]

Links

ENSG00000010072 ∙ NCBI:83932 ∙ OMIM:616086 ∙ HGNC:25356 ∙ Uniprot:Q9H040 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progeroid features-hepatocellular carcinoma predisposition syndrome (Supportive), mode of inheritance: AR
• progeroid features-hepatocellular carcinoma predisposition syndrome (Moderate), mode of inheritance: AR
• progeroid features-hepatocellular carcinoma predisposition syndrome (Limited), mode of inheritance: AR

ClinVar

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

• Progeroid features-hepatocellular carcinoma predisposition syndrome (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPRTN 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				7	1	8
missense			19	2	3	24
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			14	7	4	25
Total	1	0	33	16	8

Variants in SPRTN

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

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

Position	Type	Phenotype	Significance	ClinVar
1-231337105-A-C		not specified	Uncertain significance (Dec 14, 2023)
1-231337119-G-C		not specified	Uncertain significance (Jan 09, 2023)
1-231337128-A-G			Likely benign (Nov 27, 2023)
1-231337170-G-A			Benign (Nov 27, 2023)
1-231337189-T-C		not specified	Uncertain significance (Nov 17, 2022)
1-231337236-T-A		not specified	Uncertain significance (Nov 09, 2021)
1-231337292-C-A		not specified	Uncertain significance (Jun 27, 2022)
1-231337294-G-C			Uncertain significance (Sep 13, 2023)
1-231337303-C-T			Uncertain significance (Oct 03, 2023)
1-231337337-C-T		not specified	Uncertain significance (Jun 01, 2023)
1-231337360-C-G		not specified	Uncertain significance (Dec 03, 2021)
1-231337365-C-G			Benign (Dec 22, 2023)
1-231337382-C-G		not specified	Uncertain significance (Mar 07, 2024)
1-231337406-C-T		not specified	Uncertain significance (May 02, 2024)
1-231337425-A-T			Likely benign (Dec 03, 2021)
1-231337426-G-A		not specified	Uncertain significance (Apr 07, 2022)
1-231337508-G-A			Likely benign (Nov 01, 2022)
1-231337508-G-C			Uncertain significance (Nov 08, 2022)
1-231337515-G-T			Likely benign (Oct 11, 2022)
1-231337571-G-A			Likely benign (Jun 21, 2018)
1-231337573-T-C		not specified	Uncertain significance (Mar 30, 2024)
1-231337587-C-A		not specified	Uncertain significance (Jul 05, 2023)
1-231337591-G-T		not specified	Uncertain significance (Mar 30, 2024)
1-231337592-C-G		not specified	Uncertain significance (Mar 30, 2024)
1-231337605-G-A			Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPRTN	protein_coding	protein_coding	ENST00000295050	5	17920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.974	0.0265	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.739	232	266	0.873	0.0000131	3243
Missense in Polyphen		50	86.594	0.57741		963
Synonymous	-0.455	105	99.2	1.06	0.00000511	914
Loss of Function	3.43	1	15.6	0.0641	9.34e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of UV-induced DNA damage response: acts as a 'reader' of ubiquitinated PCNA that enhances RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (TLS). Recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. Acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. {ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607}.
• Disease: DISEASE: Ruijs-Aalfs syndrome (RJALS) [MIM:616200]: A syndrome characterized by genomic instability, progeroid features, and susceptibility toward early onset hepatocellular carcinoma. {ECO:0000269|PubMed:25261934}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA Repair;Translesion Synthesis by POLH;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass (Consensus)

Recessive Scores

• pRec: 0.0968

Intolerance Scores

• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.248
• hipred: N
• hipred_score: 0.355
• ghis: 0.606

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sprtn
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; vision/eye 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Zebrafish Information Network

• Gene name: sprtn
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased life span

Gene ontology

• Biological process: cellular response to DNA damage stimulus;response to UV;translesion synthesis;positive regulation of protein ubiquitination;error-free translesion synthesis
• Cellular component: nucleus;nucleoplasm;chromosome;nuclear speck
• Molecular function: DNA binding;protein binding;ubiquitin binding;metal ion binding;K63-linked polyubiquitin modification-dependent protein binding