CELF1

Chr 11

CUGBP Elav-like family member 1

Also known as: BRUNOL2, CUG-BP, CUGBP, CUGBP1, EDEN-BP, NAB50, NAPOR, hNab50

NCBI Gene: 10658 ENSG00000149187 UniProt: Q92879 OMIM: 601074

CELF1 encodes an RNA-binding protein that regulates alternative splicing, mRNA translation, and stability across multiple tissues including heart and muscle. Mutations cause autosomal dominant myotonic dystrophy type 1, a multisystem disorder affecting skeletal muscle, cardiac conduction, and other organ systems with variable age of onset. The gene is highly constrained against loss-of-function variants, reflecting its essential role in RNA processing.

OMIM ResearchSummary from RefSeq, UniProt

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. This gene may play a role in myotonic dystrophy type 1 (DM1) via interactions with the dystrophia myotonica-protein kinase (DMPK) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.17

Clinical Summary— CELF1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

34 VUS of 59 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.71

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

3.34Z-score

OE missense 0.45 (0.39–0.52)

128 obs / 287.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.45 (0.39–0.52)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 1 / 27.8Missense obs/exp: 128 / 287.5Syn Z: 1.14

This gene — mechanism propensity

0.3594th %ile

GOF

0.3789th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

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

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	0	34
Likely Benign	0	0	0
Benign	0	1	1
Total	34	1	35

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap CELF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →