CAPRIN1

Chr 11AD

cell cycle associated protein 1

Also known as: CONDCAC, GPIAP1, GPIP137, GRIP137, M11S1, NEDLAAD, RNG105, p137GPI

NCBI Gene: 4076 ENSG00000135387 UniProt: Q14444 OMIM: 601178

CAPRIN1 encodes an mRNA-binding protein that regulates mRNA transport, translation, and stability through formation of cytoplasmic ribonucleoprotein granules and stress granules, playing essential roles in neurogenesis and synaptic plasticity. Mutations cause autosomal dominant neurodegeneration with childhood-onset cerebellar ataxia and cognitive decline, or neurodevelopmental disorder with language impairment, autism, and ADHD. The gene is highly constrained against loss-of-function mutations (pLI = 0.97), reflecting its critical role in neuronal function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including ATP binding activity; molecular condensate scaffold activity; and signaling adaptor activity. Involved in membraneless organelle assembly; positive regulation of stress granule assembly; and regulation of gene expression. Located in cell leading edge and cytosol. Is active in intracellular membraneless organelle. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.312 OMIM phenotypes

Clinical Summary— CAPRIN1

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Gene-Disease Validity (ClinGen)

neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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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.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.972

Z-score 5.22

OE 0.17 (0.10–0.31)

Highly constrained

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

Missense Constraint?

1.69Z-score

OE missense 0.76 (0.69–0.84)

301 obs / 395.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.31)

0≤0.351.4

Missense OE?0.76 (0.69–0.84)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 46.4Missense obs/exp: 301 / 395.7Syn Z: -0.85

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateCAPRIN1-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

0.2599th %ile

GOF

0.3094th %ile

LOF

0.78top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.31

GOF1 literature citation

Literature Evidence

GOFThese findings associate the gain-of-function Pro512Leu mutation to early-onset ataxia and neurodegeneration, unveiling a critical residue of CAPRIN1 and a key role of RNA-protein interactions.1

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

References