SPRTN

protein-coding

SprT-like N-terminal domain

Gene 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 the number of DNA-damage induced mutations. It may also be involved in replication-related G2/M-checkpoint regulation. Deficiency of a similar protein in mouse causes chromosomal instability and progeroid phenotypes. Mutations in this gene have been associated with Ruijs-Aalfs syndrome (RJALS). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

Previous symbols:

C1orf124

MANE transcript

NM_032018.7

Inheritance

ClinVar variants

P:4U:49B:15

Top phenotype

progeroid features-hepatocellular carcinoma predisposition syndrome

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr1:231,337,104-231,355,023

External References & Databases

Ensembl (ENSG00000010072)

Transcript & Mutation Effects

hg38 • Region Span ~17.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

progeroid features-hepatocellular carcinoma predisposition syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014527

Submitter: G2P

progeroid features-hepatocellular carcinoma predisposition syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014527

Submitter: Labcorp Genetics (formerly Invitae)

progeroid features-hepatocellular carcinoma predisposition syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014527

Submitter: Orphanet

progeroid features-hepatocellular carcinoma predisposition syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014527

Submitter: PanelApp Australia

progeroid features-hepatocellular carcinoma predisposition syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014527

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPRTN variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 49

not providedTotal: 15

SPRTN-related disorderTotal: 3

Progeroid features-hepatocellular carcinoma predisposition syndromeTotal: 3

Abnormal sperm morphologyTotal: 1

Reduced sperm motilityTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032018.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				8 clinvar	2 clinvar	10
missense	1 clinvar		49 clinvar	3 clinvar	2 clinvar	55
nonsense						0
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	3	1	49	11	4	68

Highest pathogenic variant AF is 0.000014372104

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032018.7	RefSeq	NP_114407.3	5	MANE Select
ENST00000295050.12	Ensembl	ENSP00000295050.7	5	MANE Select
NM_001010984.4	RefSeq	NP_001010984.1	4	Standard
NM_001261462.3	RefSeq	NP_001248391.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sprtn	Danio rerio	Structure: whole organism Quality: decreased life span abnormal

Gene / Model

Organism

Observed Phenotype

sprtn

Danio rerio

Structure: whole organism

Quality: decreased life span

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DNA Repair
Translesion Synthesis by POLH
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
DNA Damage Bypass

Biological Process

cellular response to DNA damage stimulus
response to UV
translesion synthesis
positive regulation of protein ubiquitination
error-free translesion synthesis

Molecular Function

DNA binding
protein binding
ubiquitin binding
metal ion binding
K63-linked polyubiquitin modification-dependent protein binding

Cellular Component

nucleus
nucleoplasm
chromosome
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295050
Coding exons: 5
Length: 17920
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.739	232	266	0.873	0.0000131	3243
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0968

Intolerance Scores

RVIS EVS: -0.58
RVIS percentile EVS: 18.72

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E

Gene Damage Prediction

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