ERAL1

Era like 12S mitochondrial rRNA chaperone 1

Basic information

Region (hg38): 17:28855010-28861061

Links

ENSG00000132591 ∙ NCBI:26284 ∙ OMIM:607435 ∙ HGNC:3424 ∙ Uniprot:O75616 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Perrault syndrome 6 (Moderate), mode of inheritance: AR
• Perrault syndrome (Supportive), mode of inheritance: AR
• Perrault syndrome 6 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Perrault syndrome 6	AR	Audiologic/Otolaryngologic; Obstetric	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	Audiologic/Otolaryngologic; Obstetric	28449065

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERAL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERAL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			25	1		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					7	7
Total	0	0	25	2	8

Variants in ERAL1

This is a list of pathogenic ClinVar variants found in the ERAL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-28855042-C-T		not specified	Uncertain significance (Dec 09, 2023)
17-28855052-G-C		not specified	Uncertain significance (Apr 23, 2024)
17-28855056-G-A		not specified	Uncertain significance (Aug 09, 2021)
17-28855060-C-T		not specified	Uncertain significance (Sep 22, 2023)
17-28855107-G-A		not specified	Uncertain significance (Nov 07, 2024)
17-28855115-G-A		ERAL1-related disorder	Likely benign (Apr 30, 2019)
17-28855167-T-A		not specified	Uncertain significance (Jan 23, 2023)
17-28855185-G-A		Perrault syndrome 6	Uncertain significance (May 01, 2018)
17-28855197-C-A		not specified	Uncertain significance (Aug 30, 2022)
17-28855206-G-A		not specified	Uncertain significance (Jun 10, 2024)
17-28855222-G-T		not specified	Uncertain significance (Aug 08, 2023)
17-28855279-C-T		not specified	Uncertain significance (Sep 06, 2022)
17-28856086-G-A			Benign (May 11, 2021)
17-28856137-C-G			Benign (May 11, 2021)
17-28856336-T-A			Uncertain significance (May 01, 2023)
17-28856444-G-A			Benign (May 12, 2021)
17-28856497-C-T		ERAL1-related disorder	Benign (Jun 27, 2019)
17-28856532-A-G		not specified	Uncertain significance (Mar 16, 2024)
17-28856547-G-A		ERAL1-related disorder	Likely benign (Apr 01, 2022)
17-28856714-CT-C			Benign (May 20, 2021)
17-28857960-A-G		not specified	Uncertain significance (Sep 08, 2024)
17-28857981-A-C		not specified	Uncertain significance (Dec 14, 2024)
17-28858151-A-G		ERAL1-related disorder	Likely benign (Mar 05, 2024)
17-28858205-T-C		not specified	Uncertain significance (Apr 19, 2024)
17-28858376-G-T		not specified	Uncertain significance (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERAL1	protein_coding	protein_coding	ENST00000254928	10	6130

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.11e-9	0.751	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.358	222	238	0.935	0.0000117	2831
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00198	0.00199
East Asian	0.000598	0.000598
Finnish	0.00	0.00
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000598	0.000598
South Asian	0.0000709	0.0000653
Other	0.000326	0.000326

dbNSFP

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.
• Pathway: Integrated Breast Cancer Pathway;Mitochondrial translation initiation;Translation;Metabolism of proteins;Mitochondrial translation elongation;Mitochondrial translation termination;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.298
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.150
• hipred: N
• hipred_score: 0.197
• ghis: 0.543

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eral1

Gene ontology

• Biological process: ribosomal small subunit assembly;mitochondrial translational elongation;mitochondrial translational termination
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix;cytosol
• Molecular function: RNA binding;protein binding;GTP binding;rRNA binding;ribosomal small subunit binding