SPRTN

Chr 1AR

SprT-like N-terminal domain

Also known as: C1orf124, DVC1, PRO4323, spartan

NCBI Gene: 83932 ENSG00000010072 UniProt: Q9H040 OMIM: 616086

The protein functions as a DNA-dependent metalloendopeptidase that cleaves toxic DNA-protein cross-links during DNA replication to maintain genomic integrity. Mutations cause Ruijs-Aalfs progeroid syndrome, an autosomal recessive disorder characterized by premature aging features and chromosomal instability. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.30), consistent with its essential role in DNA repair.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ruijs-Aalfs progeroid syndromeMIM #616200

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted