ERAL1

protein-coding

Era like 12S mitochondrial rRNA chaperone 1

Gene summary

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]

MANE transcript

NM_005702.4

Inheritance

ClinVar variants

P:1U:53B:14

Top phenotype

Perrault syndrome 6

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr17:28,855,010-28,861,061

External References & Databases

Ensembl (ENSG00000132591)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Perrault syndrome 6MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033047

Submitter: PanelApp Australia

Perrault syndrome 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033047

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Perrault syndrome 6AR

Manifestation: Audiologic/Otolaryngologic; Obstetric

Intervention: Audiologic/Otolaryngologic; Obstetric

Rationale: Hearing loss has been described in early childhood, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Genetic knowledge may allow fertility preservation such as by storing eggs in woman with premature ovarian failure

Refs: 28449065

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ERAL1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 51

ERAL1-related disorderTotal: 18

Perrault syndrome 6Total: 4

not providedTotal: 3

Perrault syndromeTotal: 1

Hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005702.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense	1 clinvar		50 clinvar	6 clinvar	1 clinvar	58
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	53	12	2	68

Highest pathogenic variant AF is 0.0000018587614

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005702.4	RefSeq	NP_005693.1	10	MANE Select
ENST00000254928.10	Ensembl	ENSP00000254928.5	10	MANE Select
NM_001317985.2	RefSeq	NP_001304914.1	10	Standard
NM_001317986.2	RefSeq	NP_001304915.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrated Breast Cancer Pathway
Mitochondrial translation initiation
Translation
Metabolism of proteins
Mitochondrial translation elongation

Biological Process

ribosomal small subunit assembly
mitochondrial translational elongation
mitochondrial translational termination

Molecular Function

RNA binding
protein binding
GTP binding
rRNA binding
ribosomal small subunit binding

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254928
Coding exons: 10
Length: 6130
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125748
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.358	222	238	0.935	0.0000117	2831
Missense (PolyPhen)		34	43.646	0.779		514
Synonymous	1.06	83	96.2	0.863	0.00000467	902
Loss of Function	1.47	17	24.9	0.683	0.00000134	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00060	0.00060	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000071	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly. {ECO:0000269|PubMed:20430825, ECO:0000269|PubMed:20604745, ECO:0000269|PubMed:28449065}.;
Disease: DISEASE: Perrault syndrome 6 (PRLTS6) [MIM:617565]: A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. PRLTS6 inheritance is autosomal recessive. {ECO:0000269|PubMed:28449065}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.298
RVIS EVS: 0
RVIS percentile EVS: 53.73

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium