FARSB

Chr 2AR

phenylalanyl-tRNA synthetase subunit beta

Also known as: FARSLB, FRSB, HSPC173, NEDBLLA, PheHB, PheRS, RILDBC, RILDBC1

NCBI Gene: 10056 ENSG00000116120 UniProt: Q9NSD9 OMIM: 609690

The FARSB gene encodes the regulatory beta subunit of phenylalanyl-tRNA synthetase, which attaches phenylalanine to its corresponding tRNA during protein synthesis. Mutations cause Rajab interstitial lung disease with brain calcifications 1, an autosomal recessive disorder affecting the lungs and central nervous system. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.558).

OMIM ResearchSummary from RefSeq, OMIM

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.561 OMIM phenotype

Clinical Summary— FARSB

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

📋

ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 124 VUS of 250 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.003

Z-score 3.43

OE 0.33 (0.20–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.16Z-score

OE missense 0.82 (0.74–0.91)

259 obs / 317.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.20–0.56)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 10 / 30.4Missense obs/exp: 259 / 317.1Syn Z: 0.72

This gene — mechanism propensity

0.6744th %ile

GOF

0.5464th %ile

LOF

0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

250 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic5

VUS124

Likely Benign68

Benign14

Conflicting2

Pathogenic

Likely Pathogenic

124

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	6	0	0	9
Likely Pathogenic	3	2	0	0	5
VUS	1	119	4	0	124
Likely Benign	0	4	27	37	68
Benign	0	3	7	4	14
Conflicting	—				2
Total	7	134	38	41	222

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap FARSB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →