FARSA

Summary

FARSA (phenylalanyl-tRNA synthetase subunit alpha, HGNC:3592) is a protein-coding gene on chromosome 19p13.13, encoding Phenylalanine–tRNA ligase alpha subunit (Q9Y285). It is a common-essential gene (DepMap: required in 93.3% of cancer cell lines).

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

Source: NCBI Gene 2193 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rajab interstitial lung disease with brain calcifications 2 (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 107 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 93.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_004461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3592
Approved symbol	FARSA
Name	phenylalanyl-tRNA synthetase subunit alpha
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	CML33
Ensembl gene	ENSG00000179115
Ensembl biotype	protein_coding
OMIM	602918
Entrez	2193

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000314606, ENST00000423140, ENST00000586146, ENST00000586280, ENST00000587488, ENST00000587981, ENST00000588025, ENST00000588965, ENST00000592662, ENST00000593021, ENST00000908769, ENST00000908770, ENST00000908771, ENST00000941155

RefSeq mRNA: 1 — MANE Select: NM_004461 NM_004461

CCDS: CCDS12287

Canonical transcript exons

ENST00000314606 — 13 exons

Exon	Start	End
ENSE00001252925	12922479	12922886
ENSE00002785501	12933550	12933711
ENSE00003482082	12930223	12930341
ENSE00003495354	12924904	12925003
ENSE00003535080	12928342	12928457
ENSE00003556137	12925090	12925174
ENSE00003579214	12928755	12928847
ENSE00003587090	12924639	12924807
ENSE00003603333	12930429	12930527
ENSE00003604289	12924449	12924526
ENSE00003606464	12930612	12930749
ENSE00003643407	12928535	12928663
ENSE00003785852	12924151	12924265

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 95.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.4665 / max 715.2575, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179422	58.4665	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	95.17	gold quality
mucosa of transverse colon	UBERON:0004991	94.87	gold quality
endometrium epithelium	UBERON:0004811	94.78	gold quality
right frontal lobe	UBERON:0002810	94.77	gold quality
cingulate cortex	UBERON:0003027	93.85	gold quality
anterior cingulate cortex	UBERON:0009835	93.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.15	gold quality
gastrocnemius	UBERON:0001388	92.97	gold quality
neocortex	UBERON:0001950	92.63	gold quality
apex of heart	UBERON:0002098	92.63	gold quality
frontal cortex	UBERON:0001870	92.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.47	gold quality
muscle of leg	UBERON:0001383	92.24	gold quality
ganglionic eminence	UBERON:0004023	92.18	gold quality
ventricular zone	UBERON:0003053	91.75	gold quality
frontal pole	UBERON:0002795	91.71	gold quality
adenohypophysis	UBERON:0002196	91.58	gold quality
stromal cell of endometrium	CL:0002255	91.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.47	gold quality
esophagus mucosa	UBERON:0002469	91.44	gold quality
cortical plate	UBERON:0005343	91.29	gold quality
right adrenal gland	UBERON:0001233	91.09	gold quality
granulocyte	CL:0000094	91.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.04	gold quality
nucleus accumbens	UBERON:0001882	91.00	gold quality
left adrenal gland	UBERON:0001234	90.94	gold quality
body of stomach	UBERON:0001161	90.90	gold quality
heart left ventricle	UBERON:0002084	90.87	gold quality
amygdala	UBERON:0001876	90.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.61
E-CURD-112	yes	9.75
E-ANND-3	yes	7.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting FARSA, 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-7152-3P	99.97	67.47	849
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-6748-3P	97.20	65.66	836

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• 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)
• FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects. (PMID:31355908)
• First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes. (PMID:36675119)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	farsa	ENSDARG00000098825
mus_musculus	Farsa	ENSMUSG00000003808
rattus_norvegicus	Farsa	ENSRNOG00000003149
drosophila_melanogaster	alpha-PheRS	FBGN0030007
caenorhabditis_elegans	fars-1	WBGENE00001497

Paralogs (2): FARS2 (ENSG00000145982), FDXACB1 (ENSG00000255561)

Protein

Protein identifiers

Phenylalanine–tRNA ligase alpha subunit — Q9Y285 (reviewed: Q9Y285)

Alternative names: CML33, Phenylalanyl-tRNA synthetase alpha subunit

All UniProt accessions (7): Q9Y285, K7EK06, K7EPH2, K7ER00, K7ER16, K7ERS0, Q6IBR2

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 2 (RILDBC2) [MIM:619013] An autosomal recessive disorder characterized by interstitial lung disease, growth delay, hypotonia, liver disease, and brain abnormalities including diffuse, symmetrical brain calcifications and periventricular cysts. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y285-1	1	yes
Q9Y285-2	2

RefSeq proteins (1): NP_004452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002319	Phenylalanyl-tRNA_Synthase	Domain
IPR004529	Phe-tRNA-synth_IIc_asu	Family
IPR006195	aa-tRNA-synth_II	Domain
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040586	PheRS_DBD2	Domain
IPR040724	PheRS_DBD1	Domain
IPR040725	PheRS_DBD3	Domain
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily

Pfam: PF01409, PF18552, PF18553, PF18554

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 (68 total): helix 22, strand 19, turn 9, modified residue 5, binding site 5, sequence variant 3, sequence conflict 2, initiator methionine 1, chain 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-Q9Y285-F1	88.43	0.50

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 (5): 329; 372–374; 412; 414; 438

Post-translational modifications (5): 301, 311, 2, 190, 193

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: 226 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_AMINO_ACID_ACTIVATION, GOBP_TRNA_METABOLIC_PROCESS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_TRANSLATION, RICKMAN_METASTASIS_DN, GOBP_PROTEIN_HETEROTETRAMERIZATION, GGAANCGGAANY_UNKNOWN, GARY_CD5_TARGETS_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, LEE_AGING_CEREBELLUM_DN, GOBP_PROTEIN_TETRAMERIZATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, SCHLOSSER_MYC_AND_SERUM_RESPONSE_SYNERGY

GO Biological Process (4): phenylalanyl-tRNA aminoacylation (GO:0006432), protein heterotetramerization (GO:0051290), translation (GO:0006412), tRNA aminoacylation (GO:0043039)

GO Molecular Function (10): tRNA binding (GO:0000049), 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
tRNA aminoacylation for protein translation	1
protein tetramerization	1
protein heterooligomerization	1
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 metabolic process	1
amino acid activation	1
RNA binding	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

2486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FARSA	FARSB	Q9NSD9	991
FARSA	VARS1	P26640	664
FARSA	IARS1	P41252	625
FARSA	WARS1	P23381	588
FARSA	YARS1	P54577	575
FARSA	NARS1	O43776	568
FARSA	FARS2	O95363	565
FARSA	WARS2	Q9UGM6	557
FARSA	QARS1	P47897	552
FARSA	AARS1	P49588	551
FARSA	KARS1	Q15046	543
FARSA	MARS2	Q96GW9	542
FARSA	EPRS1	P07814	542
FARSA	MARS1	P56192	533
FARSA	PARS2	Q7L3T8	484

IntAct

110 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
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
FARSA	ABI3	psi-mi:“MI:0915”(physical association)	0.560
ABI3	FARSA	psi-mi:“MI:0915”(physical association)	0.560
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
COG4	FARSA	psi-mi:“MI:0915”(physical association)	0.560
PDCD10	FARSA	psi-mi:“MI:0915”(physical association)	0.560
FARSA	ECSIT	psi-mi:“MI:0407”(direct interaction)	0.530
ECSIT	FARSA	psi-mi:“MI:0915”(physical association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
FARSA	MLF2	psi-mi:“MI:0915”(physical association)	0.400
FARSA	PSMD2	psi-mi:“MI:0915”(physical association)	0.400
FARSA	A2M	psi-mi:“MI:0915”(physical association)	0.370
CRIPTO	FARSA	psi-mi:“MI:0915”(physical association)	0.370
FARSA	GORAB	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
OFD1	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (226): ABI3 (Two-hybrid), FARSA (Affinity Capture-MS), FARSA (Reconstituted Complex), FARSB (Affinity Capture-MS), CCT6B (Affinity Capture-MS), FARSA (Affinity Capture-MS), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Co-fractionation), FARSA (Affinity Capture-MS)

ESM2 similar proteins: A0B5E9, A0B632, A2SQV5, A2ST81, A3CXN8, A4FXR4, A4FYB1, A6UN84, A6USJ0, A6UVW6, A6UX37, A6VFH1, A7I4Y4, A9AB64, B0K5J0, B0K8E8, B6YWW5, B8GJL9, C3MQH9, C3MW57, C3N6A0, C3NEQ7, C3NGV1, C3NGY7, C4KHR4, C5A226, C6A4A3, O27194, O27545, O30126, O30520, Q0W0T4, Q12TN5, Q12XG0, Q1JPX3, Q2FSR2, Q46AN5, Q46D71, Q505J8, Q58477

Diamond homologs: A0B632, A0M6W9, A1RK14, A1S702, A2SQV5, A2ST81, A3CT76, A3CXN8, A3MUA4, A4FYB1, A4WHY5, A4Y6G8, A5F1W4, A5FLW1, A6USJ0, A6UVW6, A6VJZ5, A6WMK4, A7I4Y4, A7NJ67, A9A794, B8GJL9, C3LLR5, O27545, O30126, P15625, P94282, Q0W0T4, Q12XG0, Q1JPX3, Q2FSR2, Q3K1I9, Q46CQ6, Q46D71, Q4J8P9, Q505J8, Q57911, Q59054, Q5RFA2, Q5ZJQ2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FARSA	“form complex”	“Phenylalanyl-tRNA synthetase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
Activation of NF-kappaB in B cells	6	13.4×	3e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	13.0×	7e-03
Defective CFTR causes cystic fibrosis	5	12.5×	7e-03
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	5	11.6×	8e-03
The role of GTSE1 in G2/M progression after G2 checkpoint	6	11.0×	5e-03
Regulation of RUNX2 expression and activity	5	10.3×	1e-02
Orc1 removal from chromatin	5	10.1×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	75
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1685812	NM_004461.3(FARSA):c.812G>A (p.Arg271His)	Pathogenic
977639	NM_004461.3(FARSA):c.766T>C (p.Phe256Leu)	Pathogenic
977640	NM_004461.3(FARSA):c.1230C>A (p.Asn410Lys)	Pathogenic
3068592	NM_004461.3(FARSA):c.1040C>T (p.Pro347Leu)	Likely pathogenic

SpliceAI

1438 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12922888:T:C	acceptor_gain	1.0000
19:12922888:T:TC	acceptor_gain	1.0000
19:12924146:CTT:C	donor_loss	1.0000
19:12924147:TTACC:T	donor_loss	1.0000
19:12924148:TACC:T	donor_loss	1.0000
19:12924149:A:AC	donor_gain	1.0000
19:12924150:C:CC	donor_gain	1.0000
19:12924150:C:T	donor_loss	1.0000
19:12924150:CCG:C	donor_gain	1.0000
19:12924150:CCGCT:C	donor_gain	1.0000
19:12924261:CAGGC:C	acceptor_gain	1.0000
19:12924262:AGGC:A	acceptor_gain	1.0000
19:12924263:GGC:G	acceptor_gain	1.0000
19:12924264:GC:G	acceptor_gain	1.0000
19:12924265:CC:C	acceptor_gain	1.0000
19:12924266:C:CA	acceptor_loss	1.0000
19:12924266:C:CC	acceptor_gain	1.0000
19:12924269:C:CT	acceptor_gain	1.0000
19:12924275:C:CT	acceptor_gain	1.0000
19:12924276:A:T	acceptor_gain	1.0000
19:12924280:C:CT	acceptor_gain	1.0000
19:12924281:A:T	acceptor_gain	1.0000
19:12924469:T:TA	donor_gain	1.0000
19:12924524:TAC:T	acceptor_gain	1.0000
19:12924524:TACCT:T	acceptor_loss	1.0000
19:12924525:ACCTG:A	acceptor_loss	1.0000
19:12924536:G:C	acceptor_gain	1.0000
19:12924536:G:GC	acceptor_gain	1.0000
19:12924633:GCTCA:G	donor_loss	1.0000
19:12924634:CTCAC:C	donor_loss	1.0000

AlphaMissense

3331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12924724:G:C	F370L	1.000
19:12924724:G:T	F370L	1.000
19:12924726:A:G	F370L	1.000
19:12924738:G:C	H366D	1.000
19:12924167:C:G	G458R	0.999
19:12924170:A:G	W457R	0.999
19:12924170:A:T	W457R	0.999
19:12924232:C:T	G436E	0.999
19:12924233:C:A	G436W	0.999
19:12924237:G:C	N434K	0.999
19:12924237:G:T	N434K	0.999
19:12924241:C:T	G433E	0.999
19:12924474:G:C	S416R	0.999
19:12924474:G:T	S416R	0.999
19:12924476:T:G	S416R	0.999
19:12924492:G:C	N410K	0.999
19:12924492:G:T	N410K	0.999
19:12924725:A:G	F370S	0.999
19:12924781:G:C	F351L	0.999
19:12924781:G:T	F351L	0.999
19:12924783:A:G	F351L	0.999
19:12924934:G:C	S332R	0.999
19:12924934:G:T	S332R	0.999
19:12924936:T:G	S332R	0.999
19:12928454:G:C	F243L	0.999
19:12928454:G:T	F243L	0.999
19:12928456:A:G	F243L	0.999
19:12922854:A:T	I474N	0.998
19:12924152:G:T	R463S	0.998
19:12924166:C:T	G458D	0.998

dbSNP variants (sampled 300 via entrez): RS1000185743 (19:12927963 A>G), RS1000288063 (19:12934041 C>T), RS1000614335 (19:12931303 G>A), RS1000662199 (19:12927765 G>A,T), RS1000687918 (19:12931514 G>A), RS1001349643 (19:12934116 C>A), RS1001542285 (19:12933291 G>A), RS1001582477 (19:12928183 A>G), RS1001712873 (19:12927364 C>T), RS1001923605 (19:12922083 G>A), RS1001970285 (19:12932922 C>CT), RS1002182100 (19:12926543 G>A), RS1002355847 (19:12932846 C>T), RS1002621324 (19:12926786 A>C,T), RS1002714253 (19:12926028 G>T)

Disease associations

OMIM: gene MIM:602918 | disease phenotypes: MIM:619013

GenCC curated gene-disease

Disease	Classification	Inheritance
Rajab interstitial lung disease with brain calcifications 2	Strong	Autosomal recessive

Mondo (1): Rajab interstitial lung disease with brain calcifications 2 (MONDO:0100220)

Orphanet (0):

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000490	Deeply set eye
HP:0000821	Hypothyroidism
HP:0001166	Arachnodactyly
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001397	Hepatic steatosis
HP:0001433	Hepatosplenomegaly
HP:0001562	Oligohydramnios
HP:0001935	Microcytic anemia
HP:0002091	Restrictive ventilatory defect
HP:0002155	Hypertriglyceridemia
HP:0002650	Scoliosis
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003199	Decreased muscle mass
HP:0003546	Exercise intolerance
HP:0004322	Short stature
HP:0004428	Elfin facies
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0007109	Periventricular cysts
HP:0008872	Feeding difficulties in infancy
HP:0011461	Fetal onset
HP:0012735	Cough
HP:0040075	Hypopituitarism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001765_24	Red blood cell traits	8.000000e-20
GCST002595_9	Clozapine-induced agranulocytosis	1.000000e-06
GCST004601_187	Red blood cell count	6.000000e-14
GCST008059_184	Estimated glomerular filtration rate	1.000000e-12
GCST009379_231	Type 2 diabetes	8.000000e-06
GCST009379_232	Type 2 diabetes	6.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725072 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.38	Kd	41.94	nM	CHEMBL3752910
7.38	ED50	41.94	nM	CHEMBL3752910
7.10	Kd	80.11	nM	CHEMBL5653589
7.10	ED50	80.11	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148371: Binding affinity to human FARSA incubated for 45 mins by Kinobead based pull down assay	kd	0.0419	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148371: Binding affinity to human FARSA incubated for 45 mins by Kinobead based pull down assay	kd	0.0801	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Estradiol	affects expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment	2
Smoke	increases expression, decreases expression, increases abundance	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651413	Binding	Binding affinity to human FARSA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05514470	Not specified	WITHDRAWN	Impact of Mutations in Aminoacyl tRNA Synthetases on Protein Translation and Cellular Stress