FARSB

protein-coding

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

Gene summary

This gene encodes a highly conserved enzyme that belongs to the aminoacyl-tRNA synthetase class IIc subfamily. This enzyme comprises the regulatory beta subunits that form a tetramer with two catalytic alpha subunits. In the presence of ATP, this tetramer is responsible for attaching L-phenylalanine to the terminal adenosine of the appropriate tRNA. A pseudogene located on chromosome 10 has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Previous symbols:

FARSLB

MANE transcript

NM_005687.5

Inheritance

ClinVar variants

P:14U:135B:50

Top phenotype

Rajab interstitial lung disease with brain calcifications

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr2:222,566,899-222,656,092

External References & Databases

Ensembl (ENSG00000116120)

Transcript & Mutation Effects

hg38 • Region Span ~89.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Rajab interstitial lung disease with brain calcifications 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100215

Submitter: Orphanet

Rajab interstitial lung disease with brain calcifications 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100215

Submitter: PanelApp Australia

Rajab interstitial lung disease with brain calcifications 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100215

Submitter: Labcorp Genetics (formerly Invitae)

Rajab interstitial lung disease with brain calcifications 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100215

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Rajab interstitial lung disease with brain calcificationsAR

Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary; Renal

Intervention: Cardiovascular; Pulmonary

Rationale: The condition can include vascular aneurysms as well as severe lung disease, and awareness may allow prompt diagnosis and management; lung transplant has been described

Refs: 29573043

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FARSB variants in ClinVar

11 Conditions Cataloged

not providedTotal: 140

Inborn genetic diseasesTotal: 91

FARSB-related disorderTotal: 11

Rajab interstitial lung disease with brain calcifications 1Total: 8

Rajab interstitial lung disease with brain calcificationsTotal: 8

Cirrhosis of liverTotal: 5

Vascular dilatationTotal: 5

Interstitial pneumonitisTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005687.5. 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			1 clinvar	39 clinvar	3 clinvar	43
missense	6 clinvar	2 clinvar	121 clinvar	6 clinvar	2 clinvar	137
nonsense			2 clinvar			2
start loss			1 clinvar			1
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)		2 clinvar	10 clinvar			12
Total	9	5	135	45	5	199

Highest pathogenic variant AF is 0.000022318854

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005687.5	RefSeq	NP_005678.3	17	MANE Select
ENST00000281828.8	Ensembl	ENSP00000281828.6	17	MANE Select
ENST00000875112.1	Ensembl	ENSP00000545171.1	18	Standard
ENST00000875112.2	Ensembl	ENSP00000545171.1	18	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

translation
phenylalanyl-tRNA aminoacylation
protein heterotetramerization

Molecular Function

magnesium ion 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: ENST00000281828
Coding exons: 17
Length: 85802
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125747
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	259	317	0.817	0.0000160	3858
Missense (PolyPhen)		51	91.698	0.55617		1140
Synonymous	0.716	103	113	0.914	0.00000600	1125
Loss of Function	3.43	10	30.4	0.329	0.00000167	384

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00025	rare
Latino/Admixed American	0.000064	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00024	0.00023	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.279
RVIS EVS: -0.38
RVIS percentile EVS: 27.88

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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