MRPS22

mitochondrial ribosomal protein S22, the group of Small subunit mitochondrial ribosomal proteins|Mitochondrial ribosomal proteins

Basic information

Region (hg38): 3:139005805-139360497

Links

ENSG00000175110 ∙ NCBI:56945 ∙ OMIM:605810 ∙ HGNC:14508 ∙ Uniprot:P82650 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotonia with lactic acidemia and hyperammonemia (Strong), mode of inheritance: AR
• 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
• hypotonia with lactic acidemia and hyperammonemia (Supportive), mode of inheritance: AR
• hypotonia with lactic acidemia and hyperammonemia (Strong), mode of inheritance: AR
• ovarian dysgenesis 7 (Limited), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 5; Ovarian dysgenesis 7	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Craniofacial; Endocrine; Obstetric; Renal; Musculoskeletal; Neurologic	17873122; 21189481; 29566152

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRPS22 gene.

• not provided (138 variants)
• Inborn genetic diseases (68 variants)
• Hypotonia with lactic acidemia and hyperammonemia (30 variants)
• not specified (14 variants)
• Combined oxidative phosphorylation deficiency (3 variants)
• Ovarian dysgenesis 7 (3 variants)
• Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (1 variants)
• Premature ovarian failure (1 variants)
• Microcephaly 19, primary, autosomal recessive (1 variants)
• Muscular dystrophy, adult-onset, with leukoencephalopathy (1 variants)
• 46 XX gonadal dysgenesis (1 variants)
• Hypotonia with lactic acidemia and hyperammonemia;Ovarian dysgenesis 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRPS22 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				15		15
missense		1	55	2	1	59
nonsense	4	1	2			7
start loss						0
frameshift	3	2	1			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1		1			2
splice region			4	2		6
non coding			49	30	27	106
Total	8	4	110	47	28

Highest pathogenic variant AF is 0.0000329

Variants in MRPS22

This is a list of pathogenic ClinVar variants found in the MRPS22 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-139005818-C-A		not specified	Uncertain significance (Dec 23, 2022)
3-139005884-C-G		not specified	Uncertain significance (Jan 27, 2022)
3-139005923-C-T		not specified	Uncertain significance (Oct 17, 2023)
3-139005991-T-C		not specified	Likely benign (Jun 02, 2023)
3-139006036-A-C		not specified	Uncertain significance (Jun 02, 2023)
3-139006054-G-A		not specified	Uncertain significance (Aug 10, 2021)
3-139006072-C-T		not specified	Uncertain significance (Oct 17, 2023)
3-139006094-A-T		not specified	Uncertain significance (Dec 19, 2023)
3-139006133-C-T		not specified	Uncertain significance (Aug 17, 2022)
3-139006180-C-T		not specified	Uncertain significance (Mar 07, 2024)
3-139006187-G-C		not specified	Uncertain significance (Oct 25, 2022)
3-139006215-C-G		not specified	Uncertain significance (Feb 26, 2024)
3-139006261-C-G		not specified	Uncertain significance (Mar 17, 2023)
3-139019886-C-G		not specified	Uncertain significance (Feb 27, 2024)
3-139019904-C-G		not specified	Uncertain significance (Dec 19, 2022)
3-139019926-C-G		not specified	Uncertain significance (Dec 03, 2021)
3-139019926-C-T		not specified	Uncertain significance (Aug 15, 2023)
3-139019950-A-G		not specified	Likely benign (Mar 25, 2022)
3-139019952-G-A		not specified	Uncertain significance (Feb 21, 2024)
3-139019977-G-T		not specified	Uncertain significance (Dec 14, 2023)
3-139020036-C-G		not specified	Uncertain significance (Oct 20, 2021)
3-139020075-T-C		not specified	Uncertain significance (Mar 14, 2023)
3-139020078-G-C		not specified	Uncertain significance (Mar 14, 2023)
3-139020089-C-A		not specified	Uncertain significance (Jun 07, 2023)
3-139020099-G-C		not specified	Uncertain significance (Sep 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRPS22	protein_coding	protein_coding	ENST00000495075	8	351418

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000148	0.965	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.131	198	203	0.974	0.0000110	2348
Missense in Polyphen		63	74.494	0.8457		849
Synonymous	-1.44	86	70.6	1.22	0.00000350	691
Loss of Function	1.93	11	20.4	0.539	0.00000114	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000547	0.000546
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Combined oxidative phosphorylation deficiency 5 (COXPD5) [MIM:611719]: A mitochondrial disease resulting in severe metabolic acidosis, edema, hypertrophic cardiomyopathy, tubulopathy, and hypotonia. {ECO:0000269|PubMed:17873122}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mitochondrial translation initiation;Translation;Metabolism of proteins;Mitochondrial translation elongation;Mitochondrial translation termination;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.204

Intolerance Scores

• loftool: 0.343
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.0549
• hipred: N
• hipred_score: 0.197
• ghis: 0.477

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0106

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mrps22
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: biological_process;mitochondrial translational elongation;mitochondrial translational termination
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial ribosome;mitochondrial small ribosomal subunit
• Molecular function: structural constituent of ribosome