CAPRIN1

Chr 11

cell cycle associated protein 1

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

NCBI Gene: 4076 ENSG00000135387 UniProt: Q14444

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.

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 cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline

UniProtNeurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in CAPRIN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

850 rare PASS variants

Rare truncating (LoF)

1 in 3,500

72 rare PASS variants

Rare synonymous (reference)

1 in 200

362 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CAPRIN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 2,800
South Asian	~43k	1 in 120	1 in 7,200
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 10,000
European (Finnish)	~27k	1 in 230	1 in 2,900
Admixed American	~22k	1 in 140	≈ 1 in 7,400
African / African American	~21k	1 in 130	≈ 1 in 21,000
East Asian	~20k	1 in 170	1 in 2,100
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 18 coding exons well covered in gnomAD exomes; exons 3, 4, 12 marginal. Genomes: 17 of 18 (exon 3 below).? see exons ↓