ELAVL4

Chr 1

ELAV like RNA binding protein 4

Also known as: HUD, PNEM

NCBI Gene: 1996 ENSG00000162374 UniProt: P26378 OMIM: 168360

This protein binds to and stabilizes mRNAs involved in neuronal development and function, particularly through binding to AU-rich elements in 3' untranslated regions of target transcripts. Mutations cause autosomal recessive late-onset distal myopathy affecting skeletal muscle, typically presenting in adulthood. The gene is highly constrained against loss-of-function variants, indicating it is essential for normal cellular function.

OMIM ResearchSummary from RefSeq, UniProt

Enables mRNA 3'-UTR AU-rich region binding activity; poly(A) binding activity; and pre-mRNA intronic pyrimidine-rich binding activity. Involved in 3'-UTR-mediated mRNA stabilization; RNA processing; and positive regulation of 3'-UTR-mediated mRNA stabilization. Predicted to be located in axon; cytoplasm; and dendrite. Predicted to be part of ribonucleoprotein complex. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

Clinical Summary— ELAVL4

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

22 VUS of 23 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.908

Z-score 3.31

OE 0.12 (0.05–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.85Z-score

OE missense 0.46 (0.39–0.54)

102 obs / 221.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.38)

0≤0.351.4

Missense OE?0.46 (0.39–0.54)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 16.5Missense obs/exp: 102 / 221.6Syn Z: 0.24

This gene — mechanism propensity

0.4587th %ile

GOF

0.4184th %ile

LOF

0.78top 5%

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

LOFprediction above median · LOEUF 0.38

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

23 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	22	22
Likely Benign	0	0
Benign	0	0
Total	22	22

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ELAVL4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →