ERAL1

Chr 17AR

Era like 12S mitochondrial rRNA chaperone 1

Also known as: CEGA, ERA, ERA-W, ERAL1A, ERAL1B, H-ERA, HERA-A, HERA-B

NCBI Gene: 26284 ENSG00000132591 UniProt: O75616 OMIM: 607435

The ERAL1 protein is a mitochondrial GTPase that binds to 12S mitochondrial rRNA and is required for proper assembly of the small mitochondrial ribosomal subunit. Mutations cause Perrault syndrome 6, characterized by sensorineural hearing loss and ovarian dysgenesis in females, with autosomal recessive inheritance. This gene shows low constraint to loss-of-function variants (pLI near 0), consistent with its recessive disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a GTPase that localizes to the mitochondrion. The encoded protein binds to the 3' terminal stem loop of 12S mitochondrial rRNA and is required for proper assembly of the 28S small mitochondrial ribosomal subunit. Deletion of this gene has been shown to cause mitochondrial dysfunction, growth retardation, and apoptosis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.021 OMIM phenotype

Clinical Summary— ERAL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 49 VUS of 77 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ERAL1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.47

OE 0.68 (0.47–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.36Z-score

OE missense 0.93 (0.84–1.04)

222 obs / 237.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.47–1.02)

0≤0.351.4

Missense OE?0.93 (0.84–1.04)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 17 / 24.9Missense obs/exp: 222 / 237.5Syn Z: 1.06

This gene — mechanism propensity

0.6842th %ile

GOF

0.5170th %ile

LOF

0.3648th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS49

Likely Benign8

Benign10

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	2	47	0	0	49
Likely Benign	0	5	0	3	8
Benign	0	0	8	2	10
Total	2	53	8	5	68

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ERAL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →