ELAVL2

Chr 9

ELAV like RNA binding protein 2

Also known as: HEL-N1, HELN1, HUB

NCBI Gene: 1993 ENSG00000107105 UniProt: Q12926 OMIM: 601673

ELAVL2 encodes a neuron-specific RNA-binding protein that regulates gene expression by binding to AU-rich elements in the 3' untranslated regions of target mRNAs, including its own transcript and those of FOS, ID, and POU5F1. Mutations cause autosomal dominant or recessive neurodevelopmental disorders with epilepsy, intellectual disability, and movement abnormalities. The gene is highly constrained against loss-of-function variants, indicating that ELAVL2 function is critical for normal neuronal development and function.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

In humans, the ELAV like RNA binding protein gene family has four members (ELAVL1-4). ELAVL RNA binding proteins recognize AU-rich elements in the 3' UTRs of gene transcripts and thereby regulate gene expression post-transcriptionally. The protein encoded by this gene binds to several 3' UTRs, including its own and also that of FOS, ID, and POU5F1. This gene encodes ELAVL2 and, like ELAVL3 and ELAVL4, is expressed specifically in neurons and primarily localizes to the cytoplasm. This protein also forms a cytosolic complex with the normally nuclear-localized ELAVL1 protein. Alternative splicing of this gene results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Jul 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — ELAVL2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.995

Z-score 3.68

OE 0.00 (0.00–0.19)

Highly constrained

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

Missense Constraint?

1.29Z-score

OE missense 0.74 (0.65–0.85)

150 obs / 201.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.74 (0.65–0.85)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 0 / 15.8Missense obs/exp: 150 / 201.5Syn Z: -2.73

Background carrier burden — how many people carry a rare variant somewhere in ELAVL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

480 rare PASS variants

Rare truncating (LoF)

1 in 46,000

14 rare PASS variants

Rare synonymous (reference)

1 in 230

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ELAVL2. 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 360	1 in 46,000
South Asian	~43k	1 in 220	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 180	none seen
European (Finnish)	~27k	1 in 640	none seen
Admixed American	~22k	1 in 300	none seen
African / African American	~21k	1 in 210	none seen
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 820	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 580	≈ 1 in 2,900

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓