SARS2

seryl-tRNA synthetase 2, mitochondrial, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 19:38915265-38930763

Previous symbols: [ "SARSM" ]

Links

ENSG00000104835 ∙ NCBI:54938 ∙ OMIM:612804 ∙ HGNC:17697 ∙ Uniprot:Q9NP81 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Supportive), mode of inheritance: AR
• hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Limited), mode of inheritance: AR
• hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Strong), mode of inheritance: AR
• hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome	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	Endocrine; Neurologic; Renal	21255763

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARS2 gene.

• not provided (177 variants)
• Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome (86 variants)
• not specified (33 variants)
• Inborn genetic diseases (20 variants)
• SARS2-associated condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARS2 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			5	26	2	33
missense		1	73	2	1	77
nonsense		1	1			2
start loss						0
frameshift			2			2
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			4	10	1	15
non coding			11	44	26	81
Total	1	3	93	72	30

Highest pathogenic variant AF is 0.0000131

Variants in SARS2

This is a list of pathogenic ClinVar variants found in the SARS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-38915356-T-C		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Jan 13, 2018)
19-38915373-AGCCCAGAC-A			Likely benign (Jul 09, 2018)
19-38915382-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Jan 13, 2018)
19-38915466-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Jan 13, 2018)
19-38915475-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Mar 02, 2018)
19-38915490-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Likely benign (Jul 26, 2018)
19-38915507-A-C		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Likely benign (Jan 12, 2018)
19-38915527-C-G		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Benign (Jun 23, 2018)
19-38915584-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Jan 13, 2018)
19-38915584-G-T		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Jan 12, 2018)
19-38915616-GCAGGCTGGC-G			Uncertain significance (Mar 08, 2022)
19-38915617-C-G			Uncertain significance (Mar 04, 2022)
19-38915622-T-A			Uncertain significance (Mar 02, 2016)
19-38915624-G-C			Likely benign (Mar 02, 2016)
19-38915624-G-GCCAGGCAGC		not specified • SARS2-related disorder	Benign/Likely benign (Jan 22, 2024)
19-38915626-C-T		not specified	Uncertain significance (Feb 16, 2023)
19-38915644-G-A			Uncertain significance (Mar 17, 2022)
19-38915644-G-C		not specified	Uncertain significance (Sep 27, 2022)
19-38915660-G-A			Likely benign (Jan 04, 2024)
19-38915662-T-C		not specified	Uncertain significance (Feb 05, 2024)
19-38915670-A-G			Uncertain significance (Feb 28, 2022)
19-38915682-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Uncertain significance (Apr 27, 2017)
19-38915691-G-A			Uncertain significance (Apr 17, 2022)
19-38915697-C-T			Uncertain significance (Jun 05, 2022)
19-38915708-G-A			Likely benign (Oct 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SARS2	protein_coding	protein_coding	ENST00000600042	17	34590

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.77e-10	0.913	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.249	310	323	0.961	0.0000209	3329
Missense in Polyphen		96	115.98	0.82771		1198
Synonymous	-0.935	142	129	1.10	0.00000786	1064
Loss of Function	1.87	19	30.1	0.631	0.00000157	320

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.00105
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000217	0.000217
Finnish	0.0000476	0.0000462
European (Non-Finnish)	0.000330	0.000316
Middle Eastern	0.000217	0.000217
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). {ECO:0000250|UniProtKB:Q9N0F3}.
• Disease: DISEASE: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome (HUPRAS) [MIM:613845]: A multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely. {ECO:0000269|PubMed:21255763}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Selenium Metabolism and Selenoproteins;tRNA Aminoacylation;Translation;Metabolism of proteins;selenocysteine biosynthesis;tRNA charging;Mitochondrial tRNA aminoacylation;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.681
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.0868
• hipred: N
• hipred_score: 0.403
• ghis: 0.543

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sars2

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;seryl-tRNA aminoacylation;selenocysteinyl-tRNA(Sec) biosynthetic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix
• Molecular function: RNA binding;serine-tRNA ligase activity;ATP binding