SPRTN

Chr 1AR

SprT-like N-terminal domain

Also known as: C1orf124, DVC1, PRO4323, spartan

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.301 OMIM phenotype
Clinical SummarySPRTN
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.974
Z-score 3.43
OE 0.06 (0.020.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.74Z-score
OE missense 0.87 (0.780.97)
232 obs / 265.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.020.30)
00.351.4
Missense OE0.87 (0.780.97)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 15.6Missense obs/exp: 232 / 265.9Syn Z: -0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSPRTN-related progeria and hepatocellular carcinomaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3793th %ile
GOF
0.1999th %ile
LOF
0.68top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPRTN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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