FARSA

phenylalanyl-tRNA synthetase subunit alpha, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 19:12922479-12934037

Previous symbols: [ "FARSL", "FARSLA" ]

Links

ENSG00000179115 ∙ NCBI:2193 ∙ OMIM:602918 ∙ HGNC:3592 ∙ Uniprot:Q9Y285 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Rajab interstitial lung disease with brain calcifications 2 (Limited), mode of inheritance: AR
• Rajab interstitial lung disease with brain calcifications 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rajab interstitial lung disease with brain calcifications 2	AR	Endocrine; Pulmonary	An individual has been described with endocrine manifestations, including panhypopituitarism and hypothyroidism, and awareness may allow early diagnosis and medical management (eg, with hormone replacement therapy); The condition can include severe lung disease, and awareness may allow prompt diagnosis and management;	Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary	31355908

ClinVar

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

• Rajab interstitial lung disease with brain calcifications 2 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FARSA 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	3	8
missense	2	1	26	1	4	34
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	2	1	27	6	9

Highest pathogenic variant AF is 0.0000131

Variants in FARSA

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

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

Position	Type	Phenotype	Significance	ClinVar
19-12922762-G-C		not specified	Uncertain significance (Jan 09, 2024)
19-12922863-A-G		FARSA-related disorder	Benign (May 28, 2019)
19-12924192-G-A		FARSA-related disorder	Benign (Nov 19, 2019)
19-12924214-A-G		not specified	Uncertain significance (Oct 26, 2021)
19-12924492-G-T		Rajab interstitial lung disease with brain calcifications 2	Pathogenic (Sep 08, 2020)
19-12924511-C-T		Rajab interstitial lung disease with brain calcifications 2	Uncertain significance (Dec 12, 2022)
19-12924700-C-T			Likely benign (Mar 01, 2022)
19-12924703-C-T		FARSA-related disorder	Benign (Feb 20, 2019)
19-12924708-C-A		FARSA-related disorder	Benign (Feb 28, 2019)
19-12924709-G-A		FARSA-related disorder	Likely benign (Aug 08, 2019)
19-12924777-T-C		not specified	Uncertain significance (Apr 04, 2024)
19-12924794-G-A		Rajab interstitial lung disease with brain calcifications 2	Likely pathogenic (Dec 23, 2022)
19-12924800-A-G		not specified	Uncertain significance (Mar 17, 2023)
19-12924824-A-G			Benign (Nov 06, 2019)
19-12924908-T-C		FARSA-related disorder	Benign (Jul 19, 2019)
19-12924912-C-G		not specified	Uncertain significance (Dec 16, 2023)
19-12924918-G-A		not specified • FARSA-related disorder	Uncertain significance (Jun 17, 2024)
19-12924923-A-G		not specified	Uncertain significance (Apr 08, 2024)
19-12925074-G-GT			Benign (Nov 06, 2019)
19-12925100-C-T		Rajab interstitial lung disease with brain calcifications 2	Uncertain significance (Apr 04, 2024)
19-12925167-C-T		FARSA-related disorder	Benign (Sep 19, 2019)
19-12925168-G-A		not specified	Uncertain significance (Dec 02, 2022)
19-12928370-A-G		FARSA-related disorder	Likely benign (Jul 19, 2019)
19-12928371-C-T		Rajab interstitial lung disease with brain calcifications 2	Pathogenic (May 04, 2022)
19-12928403-G-A			Likely benign (Aug 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FARSA	protein_coding	protein_coding	ENST00000314606	13	11559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0141	0.986	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	268	330	0.811	0.0000222	3283
Missense in Polyphen		85	131.06	0.64855		1351
Synonymous	-0.0618	138	137	1.01	0.00000927	1001
Loss of Function	3.54	9	29.9	0.301	0.00000175	289

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000478
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000476	0.0000462
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Phenylalanine and Tyrosine Metabolism;Phenylketonuria;Tyrosinemia Type 3 (TYRO3);Tyrosinemia Type 2 (or Richner-Hanhart syndrome);tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.672
• rvis_EVS: 0.07
• rvis_percentile_EVS: 58.96

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.639
• ghis: 0.614

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Farsa
• 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); skeleton phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: phenylalanyl-tRNA aminoacylation;protein heterotetramerization
• Cellular component: cytoplasm;cytosol;phenylalanine-tRNA ligase complex;membrane
• Molecular function: tRNA binding;RNA binding;phenylalanine-tRNA ligase activity;protein binding;ATP binding