CELF4

Chr 18

CUGBP Elav-like family member 4

Also known as: BRUNOL4, CELF-4

This protein regulates pre-mRNA alternative splicing and may also be involved in mRNA editing and translation through its three RNA recognition motif domains. Loss-of-function mutations in CELF4 cause neurodevelopmental disorders with an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, indicating that haploinsufficiency is the likely pathogenic mechanism.

Summary from RefSeq, UniProt, Mechanism
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1
Active trials
14
Pubs (1 yr)
48
P/LP submissions
0%
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryCELF4
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.
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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 81 VUS of 161 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.23LOEUF
pLI 0.998
Z-score 4.48
OE 0.07 (0.030.23)
Highly constrained

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

Missense Constraint
3.16Z-score
OE missense 0.50 (0.440.57)
157 obs / 314.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.030.23)
00.351.4
Missense OE0.50 (0.440.57)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 2 / 27.2Missense obs/exp: 157 / 314.9Syn Z: 1.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateCELF4-related neurodevelopmental disorder with overgrowthLOFAD
DN
0.4090th %ile
GOF
0.3788th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.23

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

161 submitted variants in ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic3
VUS81
Likely Benign20
Benign6
Conflicting2
43
Pathogenic
3
Likely Pathogenic
81
VUS
20
Likely Benign
6
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
3
0
3
VUS
6
55
20
0
81
Likely Benign
0
8
4
8
20
Benign
0
1
2
3
6
Conflicting
2
Total6647211155

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

View in ClinVar →

Protein Context — Lollipop Plot

CELF4 · protein map & ClinVar variants

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

Clinical Literature
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