FARSB

Chr 2

phenylalanyl-tRNA synthetase subunit beta

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

NCBI Gene: 10056ENSG00000116120UniProt: Q9NSD9

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]

Primary Disease Associations & Inheritance

UniProtRajab interstitial lung disease with brain calcifications 1
252
ClinVar variants
45
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FARSB
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 123 VUS of 252 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.16Z-score
OE missense 0.82 (0.74–0.91)
259 obs / 317.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.20–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.74–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 10 / 30.4Missense obs/exp: 259 / 317.1Syn Z: 0.72

ClinVar Variant Classifications

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic5
VUS123
Likely Benign68
Benign14
Conflicting2
40
Pathogenic
5
Likely Pathogenic
123
VUS
68
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
6
31
0
40
Likely Pathogenic
2
2
1
0
5
VUS
0
117
6
0
123
Likely Benign
0
4
27
37
68
Benign
0
3
7
4
14
Conflicting
—2
Total51327241252

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

View in ClinVar →

Protein Context — Lollipop Plot

FARSB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
Exercise-related immune gene signature for hepatocellular carcinoma: machine learning and multi-omics analysis.
Pu C et al.·Front Immunol
2025
Compound heterozygosity for loss-of-function FARSB variants in a patient with classic features of recessive aminoacyl-tRNA synthetase-related disease.
Antonellis A et al.·Hum Mutat
2018Case report
Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review.
Guo R et al.·BMC Med Genomics
2023Review
[FARSB stratifies prognosis and cold tumor microenvironment across different cancer types: an integrated single cell and bulk RNA sequencing analysis].
Zhang Z et al.·Nan Fang Yi Ke Da Xue Xue Bao
2023
FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects.
Krenke K et al.·Clin Genet
2019Case report
Systemic inflammatory syndrome in children with FARSA deficiency.
Charbit-Henrion F et al.·Clin Genet
2022
Homozygosity for FARSB mutation leads to Phe-tRNA synthetase-related disease of growth restriction, brain calcification, and interstitial lung disease.
Zadjali F et al.·Hum Mutat
2018
Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules.
Ahn HS et al.·Endocrinol Metab (Seoul)
2025
Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer.
Gao X et al.·J Gastroenterol Hepatol
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools