FARSB

Summary

FARSB (phenylalanyl-tRNA synthetase subunit beta, HGNC:17800) is a protein-coding gene on chromosome 2q36.1, encoding Phenylalanine–tRNA ligase beta subunit (Q9NSD9). It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

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.

Source: NCBI Gene 10056 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rajab interstitial lung disease with brain calcifications 1 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 249 total — 9 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_005687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17800
Approved symbol	FARSB
Name	phenylalanyl-tRNA synthetase subunit beta
Location	2q36.1
Locus type	gene with protein product
Status	Approved
Aliases	PheHB, FRSB
Ensembl gene	ENSG00000116120
Ensembl biotype	protein_coding
OMIM	609690
Entrez	10056

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000281828, ENST00000568928, ENST00000875112, ENST00000875113, ENST00000875114, ENST00000875115, ENST00000938935, ENST00000938936, ENST00000938937, ENST00000938938, ENST00000938939, ENST00000938940, ENST00000958636, ENST00000958637

RefSeq mRNA: 1 — MANE Select: NM_005687 NM_005687

CCDS: CCDS2454

Canonical transcript exons

ENST00000281828 — 17 exons

Exon	Start	End
ENSE00000786316	222628837	222628888
ENSE00000786317	222630113	222630174
ENSE00000786318	222631604	222631674
ENSE00000786319	222633199	222633307
ENSE00000843675	222619645	222619737
ENSE00000843676	222623650	222623730
ENSE00000843678	222624714	222624775
ENSE00000843683	222634391	222634541
ENSE00000843684	222639580	222639695
ENSE00001071416	222613811	222613928
ENSE00001071421	222599928	222600083
ENSE00001199527	222656016	222656092
ENSE00001241909	222624272	222624479
ENSE00002616840	222566899	222572022
ENSE00003625245	222648740	222648795
ENSE00003640618	222640862	222640931
ENSE00003658509	222642851	222643005

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.0994 / max 1307.4279, expressed in 1814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34144	79.0994	1814

Top tissues by expression

265 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.44	gold quality
gingival epithelium	UBERON:0001949	98.29	gold quality
epithelial cell of pancreas	CL:0000083	97.43	gold quality
gingiva	UBERON:0001828	96.77	gold quality
pancreatic ductal cell	CL:0002079	96.60	gold quality
upper arm skin	UBERON:0004263	96.47	gold quality
myocardium	UBERON:0002349	96.41	gold quality
middle temporal gyrus	UBERON:0002771	96.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.14	gold quality
sperm	CL:0000019	95.51	gold quality
kidney epithelium	UBERON:0004819	95.37	gold quality
epithelium of nasopharynx	UBERON:0001951	95.13	gold quality
nasopharynx	UBERON:0001728	95.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.94	gold quality
deltoid	UBERON:0001476	94.83	gold quality
dorsal root ganglion	UBERON:0000044	94.34	gold quality
esophagus squamous epithelium	UBERON:0006920	94.33	gold quality
quadriceps femoris	UBERON:0001377	94.25	gold quality
pons	UBERON:0000988	94.14	gold quality
vastus lateralis	UBERON:0001379	94.10	gold quality
germinal epithelium of ovary	UBERON:0001304	93.87	gold quality
heart right ventricle	UBERON:0002080	93.85	gold quality
oocyte	CL:0000023	93.82	gold quality
entorhinal cortex	UBERON:0002728	93.81	gold quality
tibialis anterior	UBERON:0001385	93.73	silver quality
pharyngeal mucosa	UBERON:0000355	93.59	gold quality
body of tongue	UBERON:0011876	93.53	gold quality
superior vestibular nucleus	UBERON:0007227	93.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	3.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): QRICH1

miRNA regulators (miRDB)

22 targeting FARSB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-4508	90.37	59.62	240

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns (PMID:20223217)
• Human PheRS recognizes C74, the G1-C72 base pair, and the “discriminator” base A73, proposed to contribute to tRNA(Phe) identity in the yeast mitochondrial enzyme. (PMID:22137894)
• Expression studies using fibroblasts isolated from the proband revealed a severe depletion of both FARSB and FARSA protein levels. These data indicate that the FARSB variants destabilize total phenylalanyl-tRNA synthetase levels, thus causing a loss-of-function effect. (PMID:29573043)
• This study further implicates FARSB mutations in a multisystem, recessive, neurodevelopmental phenotype that share clinical features with the previously known aminoacyl-tRNA synthetase-related diseases. (PMID:30014610)
• FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects. (PMID:31355908)
• Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer. (PMID:34159625)
• FARSB Facilitates Hepatocellular Carcinoma Progression by Activating the mTORC1 Signaling Pathway. (PMID:38069034)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	farsb	ENSDARG00000016864
mus_musculus	Farsb	ENSMUSG00000026245
rattus_norvegicus	Farsb	ENSRNOG00000014119
drosophila_melanogaster	beta-PheRS	FBGN0039175
caenorhabditis_elegans		WBGENE00001498

Paralogs (1): LRRC47 (ENSG00000130764)

Protein

Protein identifiers

Phenylalanine–tRNA ligase beta subunit — Q9NSD9 (reviewed: Q9NSD9)

Alternative names: Phenylalanyl-tRNA synthetase beta subunit

All UniProt accessions (1): Q9NSD9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Heterotetramer; dimer of two heterodimers formed by FARSA and FARSB.

Subcellular location. Cytoplasm.

Disease relevance. Rajab interstitial lung disease with brain calcifications 1 (RILDBC1) [MIM:613658] An autosomal recessive, lethal neurodevelopmental disorder characterized by multiple clinical manifestations including intrauterine growth restriction, failure to thrive, developmental delay, hypotonia, interstitial lung disease, and liver dysfunction. Brain imaging shows abnormal periventricular white matter, basal ganglia echogenicity, cerebral volume loss, incomplete closure of the Sylvian fissures, and normal myelination. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NSD9-1	1	yes
Q9NSD9-2	2

RefSeq proteins (1): NP_005678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004531	Phe-tRNA-synth_IIc_bsu_arc_euk	Family
IPR005146	B3/B4_tRNA-bd	Domain
IPR005147	tRNA_synthase_B5-dom	Domain
IPR009061	DNA-bd_dom_put_sf	Homologous_superfamily
IPR020825	Phe-tRNA_synthase-like_B3/B4	Homologous_superfamily
IPR040659	PhetRS_B1	Domain
IPR041616	PheRS_beta_core	Domain
IPR045060	Phe-tRNA-ligase_IIc_bsu	Family
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily

Pfam: PF03483, PF03484, PF17759, PF18262

Enzyme classification (BRENDA):

• EC 6.1.1.20 — phenylalanine-tRNA ligase (BRENDA: 45 organisms, 151 substrates, 239 inhibitors, 149 Km, 73 kcat entries)

Substrate kinetics (BRENDA)

22 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-PHENYLALANINE	0.0003–11	28
TRNAPHE	0.0001–0.018	27
ATP	0.0058–2.5	26
PHE	0.0004–0.083	12
L-PHE	0.0018–0.05	11
2-CHLOROADENOSINE 5’-TRIPHOSPHATE	0.05–0.2	8
L-TYROSINE	0.32–3	7
2’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.085–0.4	4
3,4-DIHYDROXY-L-PHENYLALANINE	0.38–0.65	3
3’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.82–1	2
DL-M-TYROSINE	0.012–0.13	2
(S-PA)TRNAPHE	0.0002	1
(S-PG)TRNAPHE	0.0002	1
2-DEOXYADENOSINE 5’-TRIPHOSPHATE	1.54	1
2-L-NAPHTHYLALANINE	2	1

Catalyzed reactions (Rhea), 1 shown:

• tRNA(Phe) + L-phenylalanine + ATP = L-phenylalanyl-tRNA(Phe) + AMP + diphosphate + H(+) (RHEA:19413)

UniProt features (73 total): strand 28, helix 21, sequence variant 9, turn 6, binding site 4, sequence conflict 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3L4G	X-RAY DIFFRACTION	3.3
9UDM	X-RAY DIFFRACTION	3.33
9UDL	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSD9-F1	94.71	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 357; 363; 366; 367

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-379716	Cytosolic tRNA aminoacylation
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 258 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_AMINO_ACID_ACTIVATION, TSENG_IRS1_TARGETS_UP, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_PROTEIN_HETEROTETRAMERIZATION, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, ZHANG_BREAST_CANCER_PROGENITORS_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_PROTEIN_TETRAMERIZATION, DURCHDEWALD_SKIN_CARCINOGENESIS_DN

GO Biological Process (3): translation (GO:0006412), phenylalanyl-tRNA aminoacylation (GO:0006432), protein heterotetramerization (GO:0051290)

GO Molecular Function (9): magnesium ion binding (GO:0000287), RNA binding (GO:0003723), phenylalanine-tRNA ligase activity (GO:0004826), ATP binding (GO:0005524), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), phenylalanine-tRNA ligase complex (GO:0009328), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
tRNA Aminoacylation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
tRNA aminoacylation for protein translation	1
protein tetramerization	1
protein heterooligomerization	1
metal ion binding	1
nucleic acid binding	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
catalytic complex	1

Protein interactions and networks

STRING

3097 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FARSB	FARSA	Q9Y285	991
FARSB	FARS2	O95363	766
FARSB	YARS1	P54577	595
FARSB	PAX3	P23760	587
FARSB	VARS1	P26640	574
FARSB	IARS1	P41252	564
FARSB	ARSB	P15848	527
FARSB	WARS1	P23381	524
FARSB	TARS1	P26639	523
FARSB	MARS2	Q96GW9	522
FARSB	KARS1	Q15046	518
FARSB	DARS2	Q6PI48	506
FARSB	EPRS1	P07814	493
FARSB	NARS1	O43776	492
FARSB	MARS1	P56192	491

IntAct

94 interactions, top by confidence:

A	B	Type	Score
FARSA	FARSB	psi-mi:“MI:0407”(direct interaction)	0.890
FARSA	FARSB	psi-mi:“MI:0915”(physical association)	0.890
FARSB	FARSA	psi-mi:“MI:0915”(physical association)	0.890
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
HTT	FARSB	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	FARSB	psi-mi:“MI:0915”(physical association)	0.560
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
APBA3	DUSP11	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
APBA3	CLSTN1	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
ACTB	DDX3X	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
FOXR1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
GLI1	IFT56	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (201): FARSB (Affinity Capture-RNA), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSA (Co-fractionation), FARSB (Co-fractionation), FARSB (Co-fractionation), IARS (Co-fractionation), OGT (Co-fractionation), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS), FARSB (Affinity Capture-MS)

ESM2 similar proteins: B0FRF9, B1PVZ9, B9N1F9, C7E3T4, O80526, P00949, P36871, P38652, P42932, P43490, P54577, P55931, Q004B5, Q08DP0, Q16134, Q29465, Q2KIG0, Q2QNG7, Q2QZ86, Q3ZCI9, Q4KM49, Q4R5E4, Q52I78, Q5PQL4, Q5R614, Q5R7F7, Q5R8T5, Q5RCW2, Q5RDD3, Q5RFI8, Q5ZJ08, Q5ZMA6, Q6EE31, Q6UPE1, Q7TSV4, Q80Z29, Q8K1R3, Q8TCS8, Q91WQ3, Q921G7

Diamond homologs: A0B993, A1QZU9, A1RYS1, A2ST82, A3CT77, A4FWS3, A4YIL0, A6UPQ4, A6UWT1, A6VGJ4, A7I615, A9AA58, B0R807, B1L7C0, B2S0L6, B5RM71, B5RPL7, B6YTJ3, B7J278, B8GEX4, B9LU47, C3MJ88, C3MYY0, C3N028, C3N8B1, C3NMS5, C4KJ68, C5A5Z0, C6A237, O26864, O28848, O42849, O73984, P57694, P94283, P95960, Q0W0X4, Q12YP2, Q19713, Q2FLL1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
QRICH1	“up-regulates quantity by expression”	FARSB	“transcriptional regulation”
FARSB	“form complex”	“Phenylalanyl-tRNA synthetase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ALK fusions and activated point mutants	6	11.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell motility	5	20.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

249 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	3
Uncertain significance	123
Likely benign	66
Benign	14

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1685813	NM_005687.5(FARSB):c.1408del (p.Leu470fs)	Pathogenic
1685814	NM_005687.5(FARSB):c.460A>G (p.Arg154Gly)	Pathogenic
2200254	NM_005687.5(FARSB):c.499_500del (p.Leu167fs)	Pathogenic
487456	NM_005687.5(FARSB):c.1486delinsAA (p.His496fs)	Pathogenic
545642	NM_005687.5(FARSB):c.1381A>C (p.Thr461Pro)	Pathogenic
545655	NM_005687.5(FARSB):c.784A>G (p.Lys262Glu)	Pathogenic
545664	NM_005687.5(FARSB):c.1202G>A (p.Arg401Gln)	Pathogenic
545694	NM_005687.5(FARSB):c.755T>C (p.Phe252Ser)	Pathogenic
545695	NM_005687.5(FARSB):c.226T>C (p.Cys76Arg)	Pathogenic
2797522	NM_005687.5(FARSB):c.58+2T>C	Likely pathogenic
4845835	NM_005687.5(FARSB):c.37del (p.Gln13fs)	Likely pathogenic
545502	NM_005687.5(FARSB):c.914G>A (p.Arg305Gln)	Likely pathogenic

SpliceAI

2682 predictions. Top by Δscore:

Variant	Effect	Δscore
2:222599922:TCTTA:T	donor_loss	1.0000
2:222599923:CTTA:C	donor_loss	1.0000
2:222599924:TTA:T	donor_loss	1.0000
2:222599925:TA:T	donor_loss	1.0000
2:222599927:C:CG	donor_loss	1.0000
2:222599927:CCTT:C	donor_gain	1.0000
2:222600079:TACAT:T	acceptor_gain	1.0000
2:222600081:CAT:C	acceptor_gain	1.0000
2:222600084:C:CC	acceptor_gain	1.0000
2:222613805:TCTTA:T	donor_loss	1.0000
2:222613806:CTTAC:C	donor_loss	1.0000
2:222613807:TTACC:T	donor_loss	1.0000
2:222613808:TA:T	donor_loss	1.0000
2:222613809:ACCTG:A	donor_loss	1.0000
2:222619640:CTTA:C	donor_loss	1.0000
2:222619641:TTAC:T	donor_loss	1.0000
2:222619642:TACCT:T	donor_loss	1.0000
2:222619643:ACC:A	donor_loss	1.0000
2:222619644:CCTG:C	donor_loss	1.0000
2:222619733:GAGCA:G	acceptor_gain	1.0000
2:222619734:AGCA:A	acceptor_gain	1.0000
2:222619735:GCAC:G	acceptor_loss	1.0000
2:222619736:CA:C	acceptor_gain	1.0000
2:222619738:C:CC	acceptor_gain	1.0000
2:222619739:T:A	acceptor_loss	1.0000
2:222623726:GGAAA:G	acceptor_gain	1.0000
2:222623731:C:CC	acceptor_gain	1.0000
2:222624270:A:AC	donor_gain	1.0000
2:222624271:C:CC	donor_gain	1.0000
2:222624475:TTTCT:T	acceptor_gain	1.0000

AlphaMissense

3890 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:222642908:C:G	R71T	0.999
2:222613897:A:G	L459P	0.998
2:222613922:G:T	R451S	0.998
2:222619648:A:C	F447L	0.998
2:222619648:A:T	F447L	0.998
2:222619650:A:G	F447L	0.998
2:222623651:A:G	L417P	0.998
2:222623699:C:G	R401P	0.998
2:222624336:G:T	A369D	0.998
2:222642907:T:A	R71S	0.998
2:222642907:T:G	R71S	0.998
2:222571956:C:T	G562E	0.997
2:222571957:C:A	G562W	0.997
2:222571965:C:T	G559E	0.997
2:222571966:C:A	G559W	0.997
2:222619673:A:T	I439K	0.997
2:222623663:A:G	L413P	0.997
2:222624337:C:G	A369P	0.997
2:222624377:T:A	R355S	0.997
2:222624377:T:G	R355S	0.997
2:222639582:G:C	C151W	0.997
2:222642899:A:G	L74P	0.997
2:222642908:C:A	R71I	0.997
2:222571907:G:C	C578W	0.996
2:222571957:C:G	G562R	0.996
2:222571957:C:T	G562R	0.996
2:222600050:G:T	A499D	0.996
2:222613841:A:G	S478P	0.996
2:222613921:C:G	R451P	0.996
2:222623651:A:T	L417Q	0.996

dbSNP variants (sampled 300 via entrez): RS1000038366 (2:222621918 C>T), RS1000050669 (2:222574767 T>C), RS1000089851 (2:222639138 C>G), RS1000110225 (2:222590695 C>G,T), RS1000129298 (2:222649819 C>T), RS1000143125 (2:222638193 A>C), RS1000238962 (2:222604747 A>C,T), RS1000294833 (2:222604843 G>C), RS1000312041 (2:222628595 A>T), RS1000320094 (2:222597147 C>T), RS1000335460 (2:222604583 C>T), RS1000357466 (2:222587050 A>G), RS1000371245 (2:222582690 C>T), RS1000378672 (2:222654800 T>A,C), RS1000402126 (2:222574395 A>G)

Disease associations

OMIM: gene MIM:609690 | disease phenotypes: MIM:613658, MIM:618007, MIM:615486

GenCC curated gene-disease

Disease	Classification	Inheritance
Rajab interstitial lung disease with brain calcifications 1	Strong	Autosomal recessive

Mondo (4): Rajab interstitial lung disease with brain calcifications 1 (MONDO:0100215), severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (MONDO:0014206), Rajab interstitial lung disease with brain calcifications (MONDO:0100214), cirrhosis of liver (MONDO:0005155)

Orphanet (2): Interstitial lung disease-brain calcification syndrome (Orphanet:178506), Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Orphanet:440427)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000046	Small scrotum
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000490	Deeply set eye
HP:0000601	Hypotelorism
HP:0000767	Pectus excavatum
HP:0000938	Osteopenia
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001328	Specific learning disability
HP:0001382	Joint hypermobility
HP:0001394	Cirrhosis
HP:0001396	Cholestasis
HP:0001397	Hepatic steatosis
HP:0001408	Bile duct proliferation
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001533	Slender build
HP:0001541	Ascites
HP:0001562	Oligohydramnios
HP:0001876	Pancytopenia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002812_2	Schizophrenia (inflammation and infection response interaction)	2.000000e-06
GCST003989_15	Chin dimples	2.000000e-17
GCST009391_1198	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007050	HSV1 seropositivity
EFO:0009765	alanine measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008103	Liver Cirrhosis	C06.552.630; C23.550.355.412

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105969 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,367 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL124660	TANDUTINIB	2	2,530
CHEMBL1230607	PHA-793887	1	299

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	PHA-793887
8.22	Kd	6	nM	TANDUTINIB
7.01	Kd	97.1	nM	CHEMBL3752910
7.01	ED50	97.1	nM	CHEMBL3752910
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 248 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1425000: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	1425000: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148372: Binding affinity to human FARSB incubated for 45 mins by Kinobead based pull down assay	kd	0.0971	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178720: Inhibition of FARSB (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases activity, decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
4-phenylbutyric acid	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
tanespimycin	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	increases expression	1
STA 9090	increases expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991713	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00108355	PHASE4	COMPLETED	Vasoconstrictors as Alternatives to Albumin After Large-Volume Paracentesis (LVP) in Cirrhosis
NCT00179413	PHASE4	COMPLETED	Study of Long-term Peg Intron vs. Colchicine in Non-responders.
NCT00287664	PHASE4	SUSPENDED	Treatment of Hepatorenal Syndrome With Terlipressin Plus Albumin vs Albumin
NCT00347009	PHASE4	COMPLETED	Adefovir Dipivoxil For The Treatment Of Patients With Chronic Hepatitis B Related Advanced Fibrosis Or Cirrhosis
NCT00359853	PHASE4	COMPLETED	Norfloxacin In The Primary Prophylaxis Of Spontaneous Bacterial Peritonitis
NCT00414713	PHASE4	UNKNOWN	Transfusion Requirements in Gastrointestinal (GI) Bleeding
NCT00450164	PHASE4	COMPLETED	Secondary Prophylaxis After Variceal Bleeding in Non-Responders
NCT00513201	PHASE4	COMPLETED	Lyspro Insulin vs Regular Insulin in Cirrhotic Patients
NCT00534677	PHASE4	COMPLETED	The Safety & Efficacy of Terlipressin vs Octreotide for the Control of Variceal Bleed
NCT00570622	PHASE4	COMPLETED	Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis
NCT00570973	PHASE4	COMPLETED	Band Ligation Versus Transjugular Intrahepatic Portosystemic Stent Shunt (TIPS) in Cirrhotics With Recurrent Variceal Bleeding Non Responding to Medical Therapy
NCT00596414	PHASE4	COMPLETED	Sedation and Analgesia for Transjugular Liver Biopsy: A Randomized Double Blind Placebo Controlled Trial
NCT00741663	PHASE4	COMPLETED	Spironolactone Versus Spironolactone Plus Furosemide (SVSSF)
NCT00760032	PHASE4	WITHDRAWN	Lipopolysaccharide Binding Protein and Development of Infectious Events in Cirrhotic Patients
NCT00761098	PHASE4	UNKNOWN	Randomized Comparison of Two Albumin Administration Schedules for Spontaneous Bacterial Peritonitis (SBP)
NCT00906139	PHASE4	UNKNOWN	Propofol and Fentanyl Versus Midazolam and Fentanyl for Endoscopy Sedation in Cirrhotic Patients
NCT00921349	PHASE4	COMPLETED	A Trial of Ligation Plus Nadolol Versus Nadolol Alone in the Prophylaxis of First Variceal Bleeding in Cirrhosis
NCT00965900	PHASE4	UNKNOWN	Endoscopic Band Ligation (EBL) Versus Propranolol for Primary Prophylaxis of Variceal Bleeding
NCT00966082	PHASE4	UNKNOWN	EBL Versus EBL and Propranolol for the Prevention of Variceal Rebleeding in Pts With Previous Variceal Treatment
NCT00966121	PHASE4	UNKNOWN	Endoscopic Band Ligation (EBL) Versus Endoscopic Band Ligation and Propranolol for the Prevention of Variceal Rebleeding
NCT00968695	PHASE4	COMPLETED	Effects of Long Term Albumin 20% Administration in Patients With Cirrhosis and Ascites.
NCT01292304	PHASE4	COMPLETED	Tolvaptan for Ascites in Cirrhotic Patients
NCT01530711	PHASE4	UNKNOWN	Treatment of Hepatorenal Syndrome With Terlipressin Infusion Adjusted to Hemodynamic Response
NCT01686698	PHASE4	COMPLETED	Effect of VSL#3 (Original De Simone Formulation) on Cognitive Function, Risk of Falls and Quality of Life in Patients With Cirrhosis
NCT01722578	PHASE4	COMPLETED	L-ornithine L-aspartate in Overt Hepatic Encephalopathy
NCT01820026	PHASE4	UNKNOWN	Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis
NCT01842581	PHASE4	COMPLETED	The Safety/Efficacy of Rifaximin With/Without Lactulose in Participants With A History of Recurrent Hepatic Encephalopathy
NCT01847651	PHASE4	COMPLETED	Brain Muscle Axis During Treatment of Hepatic Encephalopathy With L-ornithine L-aspartate
NCT01893541	PHASE4	COMPLETED	PROPRANOLOL PLUS LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES?
NCT02074280	PHASE4	UNKNOWN	Rifaximin Predicts the Complications of Decompensated Cirrhosis
NCT02190357	PHASE4	UNKNOWN	Rifaximin Reduces the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial
NCT02238444	PHASE4	UNKNOWN	Warfarin Prevents Portal Vein Thrombosis in Liver Cirrhotic Patients With Hypersplenism After Laparoscopic Splenectomy
NCT02247414	PHASE4	COMPLETED	Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection
NCT02249741	PHASE4	COMPLETED	Prospective Study of Profile of Hepatic Osteodystrophy in Patients With Non-Choleastatic Liver Cirrhosis and Impact of Bisphosphonate Supplementation
NCT02304159	PHASE4	COMPLETED	Study to Evaluate the Safety and Efficacy of Daclatasvir/Sofosbuvir/Ribavirin for 16 Versus 24 Weeks for HCV Genotype 3 Cirrhotics
NCT02321202	PHASE4	COMPLETED	Omega-3 Fatty Acid-Based Parenteral Nutrition Improves Postoperative Recovery for Cirrhotic Patients With Liver Cancer
NCT02344719	PHASE4	COMPLETED	Effect of Taurine on Portal Hemodynamics in Patients With Advanced Liver Cirrhosis
NCT02344823	PHASE4	UNKNOWN	Effect of Vardenafil on Erectile Dysfunction and Portal Hemodynamics in Patients With Liver Cirrhosis
NCT02401490	PHASE4	UNKNOWN	Albumin Infusion Effects in Mortality in Patients With Cirrhosis and Hepatic Encephalopathy
NCT02533934	PHASE4	COMPLETED	Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant