FARSA

protein-coding

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

Gene summary

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. This gene encodes a product which is similar to the catalytic subunit of prokaryotic and Saccharomyces cerevisiae phenylalanyl-tRNA synthetases (PheRS). This gene product has been shown to be expressed in a tumor-selective and cell cycle stage- and differentiation-dependent manner, the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression [provided by RefSeq, Jul 2008]

Previous symbols:

FARSL
FARSLA

MANE transcript

NM_004461.3

Inheritance

ClinVar variants

P:4U:83B:15

Top phenotype

Rajab interstitial lung disease with brain calcifications 2

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr19:12,922,479-12,934,037

External References & Databases

Ensembl (ENSG00000179115)

Transcript & Mutation Effects

hg38 • Region Span ~11.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Rajab interstitial lung disease with brain calcifications 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100220

Submitter: PanelApp Australia

Rajab interstitial lung disease with brain calcifications 2LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100220

Submitter: Ambry Genetics

Rajab interstitial lung disease with brain calcifications 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100220

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Rajab interstitial lung disease with brain calcifications 2AR

Manifestation: Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary

Intervention: Endocrine; Pulmonary

Rationale: 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;

Refs: 31355908

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FARSA variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 14

FARSA-related disorderTotal: 11

Rajab interstitial lung disease with brain calcifications 2Total: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004461.3. 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			4 clinvar	9 clinvar	1 clinvar	14
missense	3 clinvar	1 clinvar	76 clinvar	3 clinvar	2 clinvar	85
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	3	1	83	12	3	102

Highest pathogenic variant AF is 0.00012824855

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004461.3	RefSeq	NP_004452.1	13	MANE Select
ENST00000314606.9	Ensembl	ENSP00000320309.3	13	MANE Select
ENST00000423140.6	Ensembl	ENSP00000396548.2	12	Standard
ENST00000423140.7	Ensembl	ENSP00000396548.2	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aminoacyl-tRNA biosynthesis - Homo sapiens (human)
Phenylalanine and Tyrosine Metabolism
Phenylketonuria
Tyrosinemia Type 3 (TYRO3)
Tyrosinemia Type 2 (or Richner-Hanhart syndrome)

Biological Process

phenylalanyl-tRNA aminoacylation
protein heterotetramerization

Molecular Function

tRNA binding
RNA binding
phenylalanine-tRNA ligase activity
protein binding
ATP binding

Cellular Component

cytoplasm
cytosol
phenylalanine-tRNA ligase complex
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314606
Coding exons: 13
Length: 11559
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	268	330	0.811	0.0000222	3283
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.200

Intolerance Scores

LoFtool: 0.672
RVIS EVS: 0.07
RVIS percentile EVS: 58.96

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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