SARS1

Summary

SARS1 (seryl-tRNA synthetase 1, HGNC:10537) is a protein-coding gene on chromosome 1p13.3, encoding Serine–tRNA ligase, cytoplasmic (P49591). Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene belongs to the class II amino-acyl tRNA family. The encoded enzyme catalyzes the transfer of L-serine to tRNA (Ser) and is related to bacterial and yeast counterparts. Multiple alternatively spliced transcript variants have been described but the biological validity of all variants is unknown.

Source: NCBI Gene 6301 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary peripheral neuropathy (Strong, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 70 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_006513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10537
Approved symbol	SARS1
Name	seryl-tRNA synthetase 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SERS
Ensembl gene	ENSG00000031698
Ensembl biotype	protein_coding
OMIM	607529
Entrez	6301

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000234677, ENST00000369923, ENST00000468588, ENST00000471705, ENST00000477544, ENST00000482384, ENST00000854545, ENST00000854546, ENST00000854547, ENST00000854548, ENST00000854549, ENST00000854550, ENST00000933281, ENST00000933282, ENST00000933283, ENST00000933284, ENST00000943750, ENST00000943751, ENST00000943752, ENST00000943753, ENST00000943754, ENST00000943755, ENST00000943756

RefSeq mRNA: 2 — MANE Select: NM_006513 NM_001330669, NM_006513

CCDS: CCDS795, CCDS81356

Canonical transcript exons

ENST00000234677 — 11 exons

Exon	Start	End
ENSE00000912997	109237244	109237373
ENSE00000912998	109236391	109236548
ENSE00000913000	109235977	109236106
ENSE00000913003	109231631	109231786
ENSE00000913004	109230878	109231021
ENSE00001068258	109213918	109214128
ENSE00001550658	109237731	109238182
ENSE00003525511	109229414	109229572
ENSE00003534093	109235210	109235431
ENSE00003676323	109228352	109228432
ENSE00003681846	109223978	109224048

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 142.9647 / max 1944.3517, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4393	139.8083	1828
4392	3.1564	1447

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.80	gold quality
body of pancreas	UBERON:0001150	98.55	gold quality
frontal pole	UBERON:0002795	98.54	gold quality
parotid gland	UBERON:0001831	98.44	gold quality
skin of leg	UBERON:0001511	98.28	gold quality
right frontal lobe	UBERON:0002810	98.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.24	gold quality
prefrontal cortex	UBERON:0000451	98.23	gold quality
upper lobe of left lung	UBERON:0008952	98.23	gold quality
mucosa of stomach	UBERON:0001199	98.20	gold quality
skin of abdomen	UBERON:0001416	98.20	gold quality
body of stomach	UBERON:0001161	98.16	gold quality
upper lobe of lung	UBERON:0008948	98.13	gold quality
ganglionic eminence	UBERON:0004023	98.08	gold quality
stromal cell of endometrium	CL:0002255	98.02	gold quality
popliteal artery	UBERON:0002250	98.00	gold quality
tibial artery	UBERON:0007610	98.00	gold quality
cortical plate	UBERON:0005343	97.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.90	gold quality
adenohypophysis	UBERON:0002196	97.89	gold quality
lower esophagus	UBERON:0013473	97.89	gold quality
left lobe of thyroid gland	UBERON:0001120	97.85	gold quality
aorta	UBERON:0000947	97.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.84	gold quality
right lung	UBERON:0002167	97.83	gold quality
cartilage tissue	UBERON:0002418	97.81	gold quality
zone of skin	UBERON:0000014	97.79	gold quality
pancreas	UBERON:0001264	97.74	gold quality
ascending aorta	UBERON:0001496	97.72	gold quality
thoracic aorta	UBERON:0001515	97.71	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting SARS1, 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-6798-5P	100.00	65.77	699
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6787-3P	97.75	66.17	1233

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• SARS regulates endothelial sprouting. These analyses of zebrafish and human endothelial cells reveal a new noncanonical function of Sars in endothelial development. (PMID:19423847)
• Recombinant human cytosolic seryl-tRNA synthetase protein was purified to homogeneity and crystallized. Diffraction data were collected to 3.13 A resolution. (PMID:21045311)
• Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome. (PMID:21255763)
• study identified a nuclear localization signal sequence embedded in UNE-S domain and showed that the essential role of SerRS in vascular development is dependent on UNE-S and its role to mobilize SerRS from the cytoplasm to the nucleus (PMID:22353712)
• Several data support that p.R402H mutation in SARS2 is a new cause of HUPRA syndrome. (PMID:24034276)
• A long-range conformational and functional communication specific to higher eukaryotes is found in human SerRS. (PMID:24095058)
• tRNA recognition mode of SerRS. (PMID:26433229)
• Yin Yang 1 (YY1) interacts with Seryl-tRNA synthetase (SerRS) to form a SerRS/YY1 complex which functions as a negative effector to regulate vegfa transcription through binding a distal segment of the vegfa promoter, while NFKB1 serves as a positive effector through outcompeting SerRS/YY1 for binding at the same distal segment. (PMID:27913726)
• Here, we report on mutations in two aminoacyl-tRNA synthetases that are associated with Intellectual disability (ID) in two unrelated Iranian families. In the first family, we identified a homozygous missense mutation (c.514G>A, p.Asp172Asn) in the cytoplasmic seryl-tRNA synthetase (SARS) gene (PMID:28236339)
• Analyzed the ability of cytosolic SerRS to bind and act on tRNA(Ser), tRNA(Sec), and 10 mutant and chimeric constructs in which elements of tRNA(Ser) were transposed onto tRNA(Sec). We show that SerRS only subtly prefers tRNA(Ser) to tRNA(Sec), and that discrimination occurs at the level of the serylation reaction. (PMID:28808125)
• Herb-sourced emodin inhibits angiogenesis of breast cancer by targeting VEGFA transcription. (PMID:32550907)
• Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer. (PMID:34400610)
• WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly. (PMID:35790048)
• Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery. (PMID:37739431)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sars1	ENSDARG00000008237
mus_musculus	Sars1	ENSMUSG00000068739
rattus_norvegicus	Sars1	ENSRNOG00000020255
drosophila_melanogaster	SerRS	FBGN0031497
caenorhabditis_elegans		WBGENE00005663

Paralogs (1): SARS2 (ENSG00000104835)

Protein

Protein identifiers

Serine–tRNA ligase, cytoplasmic — P49591 (reviewed: P49591)

Alternative names: Seryl-tRNA synthetase, Seryl-tRNA(Ser/Sec) synthetase

All UniProt accessions (2): P49591, Q5T5C7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC. Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at ‘Lys-16’ (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA.

Subunit / interactions. Homodimer. The tRNA molecule may bind across the dimer. Interacts with SIRT2. Interacts with METTL6; interaction is required for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Brain.

Disease relevance. Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709] An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. The disease is caused by variants affecting the gene represented in this entry. A splice site deletion resulting in a five amino acid in-frame insertion in SARS1, is associated with autosomal dominant complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly.

Domain organisation. Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.

Pathway. Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.

RefSeq proteins (2): NP_001317598, NP_006504* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002314	aa-tRNA-synt_IIb	Domain
IPR002317	Ser-tRNA-ligase_type_1	Family
IPR006195	aa-tRNA-synth_II	Domain
IPR010978	tRNA-bd_arm	Homologous_superfamily
IPR015866	Ser-tRNA-synth_1_N	Domain
IPR033729	SerRS_core	Domain
IPR042103	SerRS_1_N_sf	Homologous_superfamily
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily

Pfam: PF00587, PF02403

Enzyme classification (BRENDA):

• EC 6.1.1.11 — serine-tRNA ligase (BRENDA: 32 organisms, 124 substrates, 45 inhibitors, 161 Km, 129 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
TRNASER	—	50
L-SERINE	0.0001–0.9	16
L-SER	0.0061–2.879	15
ATP	0.0001–0.49	12
SER	0.0003–0.45	6
TRNAUTUX	0.0012–0.0072	4
TRNASECUX	0.0037–0.0049	3
TRNASER-I-G-A	0.0008–0.0014	3
TRNASERGCU	0.35–0.37	3
TRNASERUGA	0.22–0.29	3
TRNAUTU1	0.0027–0.0057	3
D-SER	0.2	2
TRNASEC	0.0033–0.031	2
TRNASER(CGA)	0.0029–0.003	2
TRNASER(GCU)	0.0013–0.0053	2

Catalyzed reactions (Rhea), 2 shown:

• tRNA(Ser) + L-serine + ATP = L-seryl-tRNA(Ser) + AMP + diphosphate + H(+) (RHEA:12292)
• tRNA(Sec) + L-serine + ATP = L-seryl-tRNA(Sec) + AMP + diphosphate + H(+) (RHEA:42580)

UniProt features (87 total): mutagenesis site 20, helix 20, strand 20, binding site 7, sequence variant 4, turn 4, modified residue 3, region of interest 2, compositionally biased region 2, sequence conflict 2, chain 1, site 1, short sequence motif 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8P7B	ELECTRON MICROSCOPY	2.42
3VBB	X-RAY DIFFRACTION	2.89
4L87	X-RAY DIFFRACTION	2.9
4RQF	X-RAY DIFFRACTION	3.5
8P7C	ELECTRON MICROSCOPY	3.7
9DPD	ELECTRON MICROSCOPY	3.87
9DPI	ELECTRON MICROSCOPY	3.9
4RQE	X-RAY DIFFRACTION	4
8P7D	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49591-F1	93.48	0.86

Functional residue map

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

Catalytic / active sites (1): 429 (important for serine binding)

Ligand- & substrate-binding residues (7): 325; 391–394; 427; 271; 302–304; 302; 318–321

Post-translational modifications (3): 1, 241, 323

Mutagenesis-validated functional residues (20):

Position	Phenotype
2–14	abolishes dna binding.
9	strongly decreased enzyme activity.
44	abolishes enzyme activity.
51	abolishes enzyme activity.
54	strongly decreased enzyme activity.
55	moderately decreased enzyme activity.
58	moderately decreased enzyme activity.
61	moderately decreased enzyme activity.
75–97	decreased enzyme activity. abolishes dna binding.
104	moderately decreased enzyme activity.
107	moderately decreased enzyme activity.
254–261	mildly decreased enzyme activity. nearly abolishes dna binding.
378	retains nuclear location and abolishes enzyme activity; when associated with v-383.
383	abolishes nuclear location. decreases enzyme activity. retains nuclear location and abolishes enzyme activity; when asso
413–420	abolishes dna binding.
429	catalytically inactive. loss of serine binding. no effect on nuclear location.
482–514	abolishes nuclear localization.
482	abolishes nuclear localization; when associated with a-485 and a-493.
485	abolishes nuclear localization; when associated with a-482 and a-493.
493	abolishes nuclear localization; when associated with a-482 and a-485.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2408557	Selenocysteine synthesis
R-HSA-379716	Cytosolic tRNA aminoacylation
R-HSA-1430728	Metabolism
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-72766	Translation

MSigDB gene sets: 271 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MORF_MTA1, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_AMINO_ACID_ACTIVATION, XU_GH1_AUTOCRINE_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_TRNA_METABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_RNA_METHYLATION, CEBPB_01, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), selenocysteine incorporation (GO:0001514), cytoplasmic translation (GO:0002181), tRNA modification (GO:0006400), translation (GO:0006412), seryl-tRNA aminoacylation (GO:0006434), negative regulation of angiogenesis (GO:0016525), negative regulation of vascular endothelial growth factor production (GO:1904046), tRNA aminoacylation for protein translation (GO:0006418)

GO Molecular Function (13): tRNA binding (GO:0000049), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), serine-tRNA ligase activity (GO:0004828), ATP binding (GO:0005524), enzyme binding (GO:0019899), protein homodimerization activity (GO:0042803), molecular adaptor activity (GO:0060090), selenocysteine-tRNA ligase activity (GO:0098619), nucleotide binding (GO:0000166), DNA binding (GO:0003677), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Selenoamino acid metabolism	1
tRNA Aminoacylation	1
Metabolism of amino acids and derivatives	1
Translation	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
aminoacyl-tRNA ligase activity	2
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
translational readthrough	1
tRNA processing	1
RNA modification	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
conversion of seryl-tRNAsec to selenocys-tRNAsec	1
tRNA aminoacylation for protein translation	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
negative regulation of cytokine production	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
tRNA aminoacylation	1
RNA binding	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1

Protein interactions and networks

STRING

2006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SARS1	PSTK	Q8IV42	990
SARS1	SEPSECS	Q9HD40	965
SARS1	RARS2	Q5T160	930
SARS1	LARS1	Q9P2J5	908
SARS1	RARS1	P54136	903
SARS1	LARS2	Q15031	899
SARS1	IARS2	Q9NSE4	885
SARS1	IARS1	P41252	880
SARS1	CARS2	Q9HA77	864
SARS1	CARS1	P49589	864
SARS1	YARS2	Q9Y2Z4	839
SARS1	YARS1	P54577	838
SARS1	EEFSEC	P57772	833
SARS1	AARS1	P49588	832
SARS1	TARS3	A2RTX5	820

IntAct

139 interactions, top by confidence:

A	B	Type	Score
HRAS	MTHFD2	psi-mi:“MI:0914”(association)	0.730
METTL6	SARS1	psi-mi:“MI:0213”(methylation reaction)	0.700
METTL6	SARS1	psi-mi:“MI:0407”(direct interaction)	0.700
ANXA4	SARS1	psi-mi:“MI:0915”(physical association)	0.560
CDKN1A	SARS1	psi-mi:“MI:0915”(physical association)	0.560
DXO	SARS1	psi-mi:“MI:0915”(physical association)	0.560
PER1	SARS1	psi-mi:“MI:0915”(physical association)	0.560
SARS1	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
LAMTOR5	SARS1	psi-mi:“MI:0915”(physical association)	0.560
SARS1	RASSF1	psi-mi:“MI:0915”(physical association)	0.560
SARS1	SWAP70	psi-mi:“MI:0915”(physical association)	0.560
LARP4B	SARS1	psi-mi:“MI:0915”(physical association)	0.560
POLA2	SARS1	psi-mi:“MI:0915”(physical association)	0.560
WBP1L	SARS1	psi-mi:“MI:0915”(physical association)	0.560
ASIC4	SARS1	psi-mi:“MI:0915”(physical association)	0.560
SARS1	SERTAD4	psi-mi:“MI:0915”(physical association)	0.560
ZKSCAN3	SARS1	psi-mi:“MI:0915”(physical association)	0.560
PRR3	SARS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	SARS1	psi-mi:“MI:0915”(physical association)	0.560
TAF8	SARS1	psi-mi:“MI:0915”(physical association)	0.560
CCDC26	SARS1	psi-mi:“MI:0915”(physical association)	0.560
ADAL	SARS1	psi-mi:“MI:0915”(physical association)	0.560
METTL15	SARS1	psi-mi:“MI:0915”(physical association)	0.560
SARS1	TMEM61	psi-mi:“MI:0915”(physical association)	0.560
SPATS1	SARS1	psi-mi:“MI:0915”(physical association)	0.560
PELI3	SARS1	psi-mi:“MI:0915”(physical association)	0.560
CEP170B	SARS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (161): SARS (Affinity Capture-MS), SARS (Affinity Capture-MS), DUS3L (Affinity Capture-MS), R3HCC1L (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), ARFIP1 (Co-fractionation), ARFIP2 (Co-fractionation), C9orf78 (Co-fractionation), CAD (Co-fractionation), CCDC6 (Co-fractionation), GFPT2 (Co-fractionation), HARS (Co-fractionation), HARS2 (Co-fractionation), HIP1R (Co-fractionation), HSPB1 (Co-fractionation)

ESM2 similar proteins: A0AVT1, A2RTX5, A6QNM8, F4IFC5, O04630, O13914, O13969, O16129, O75879, P04801, P07236, P13642, P21894, P26636, P26638, P26639, P41250, P49588, P49591, P50475, P52709, P87144, Q0V9S0, Q3ZBV8, Q4R4U9, Q4R646, Q54J66, Q5R9K9, Q5RC02, Q5XHY5, Q5ZKA2, Q6DRC0, Q6P799, Q8BGQ7, Q8BGV0, Q8BIJ6, Q8BLY2, Q8CFX8, Q8GZ45, Q8H104

Diamond homologs: A0AM81, A0RTS8, A1RRX4, A1VH35, A2BM70, A2SRC6, A3CTP4, A3DP85, A3MX52, A4J0G4, A4XJH1, A4YI40, A5D6D5, A5IMJ4, A5INQ0, A6LJM6, A6QD48, A6TXF9, A7HN78, A7I890, A7WWP0, A8AB67, A8F3R6, A8FAD7, A8YYT2, A9A4V3, A9BEX3, B0K0Z5, B0KAI8, B1L5G0, B1LBU6, B1Y9Y4, B2VA33, B5Y8D8, B5YEY8, B5YGU2, B6YWW5, B8D3V1, B8DD73, B8E0R9

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
SARS1	“down-regulates activity”	MYC	binding
ATF4	“up-regulates quantity by expression”	SARS1	“transcriptional regulation”
SARS1	“down-regulates quantity”	tRNA(Ser)	“chemical modification”
SARS1	“down-regulates quantity”	serine	“chemical modification”
SARS1	“down-regulates quantity”	ATP(4-)	“chemical modification”
SARS1	“up-regulates quantity”	diphosphate(3-)	“chemical modification”
SARS1	“up-regulates quantity”	AMP	“chemical modification”
SARS1	“up-regulates quantity”	Ser-tRNA(Ser)	“chemical modification”
SARS1	“up-regulates quantity”	alpha-aminoacyl-tRNA	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
DNA Damage/Telomere Stress Induced Senescence	5	14.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	14.1×	6e-03
DNA damage response	8	5.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	43
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
545102	NM_006513.4(SARS1):c.971T>C (p.Ile324Thr)	Pathogenic
3893287	NM_006513.4(SARS1):c.447+1G>A	Likely pathogenic

SpliceAI

1317 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109214124:ACGAT:A	donor_gain	1.0000
1:109214125:CGAT:C	donor_gain	1.0000
1:109214126:GAT:G	donor_gain	1.0000
1:109214126:GATG:G	donor_gain	1.0000
1:109214127:AT:A	donor_gain	1.0000
1:109214129:G:GG	donor_gain	1.0000
1:109214129:GT:G	donor_loss	1.0000
1:109224046:AAGG:A	donor_loss	1.0000
1:109224047:AGG:A	donor_loss	1.0000
1:109224049:G:GC	donor_loss	1.0000
1:109224050:T:G	donor_loss	1.0000
1:109228347:T:A	acceptor_gain	1.0000
1:109228349:CA:C	acceptor_loss	1.0000
1:109228350:A:AG	acceptor_gain	1.0000
1:109228351:G:GT	acceptor_gain	1.0000
1:109228351:GA:G	acceptor_gain	1.0000
1:109228351:GAA:G	acceptor_gain	1.0000
1:109228351:GAAA:G	acceptor_gain	1.0000
1:109228351:GAAAA:G	acceptor_gain	1.0000
1:109228428:TAGCT:T	donor_gain	1.0000
1:109228429:AGCT:A	donor_gain	1.0000
1:109228429:AGCTG:A	donor_loss	1.0000
1:109228430:GCT:G	donor_gain	1.0000
1:109228430:GCTG:G	donor_gain	1.0000
1:109228430:GCTGT:G	donor_loss	1.0000
1:109228431:CT:C	donor_gain	1.0000
1:109228432:TG:T	donor_loss	1.0000
1:109228433:G:GG	donor_gain	1.0000
1:109228433:G:T	donor_loss	1.0000
1:109228438:T:G	donor_gain	1.0000

AlphaMissense

3388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109231766:T:C	F243L	1.000
1:109231767:T:G	F243C	1.000
1:109231768:T:A	F243L	1.000
1:109231768:T:G	F243L	1.000
1:109231779:T:A	L247H	1.000
1:109231779:T:C	L247P	1.000
1:109235265:T:C	L268P	1.000
1:109235271:C:A	A270D	1.000
1:109235355:C:T	S298F	1.000
1:109235362:C:G	C300W	1.000
1:109235363:T:C	F301L	1.000
1:109235365:C:A	F301L	1.000
1:109235365:C:G	F301L	1.000
1:109235366:C:A	R302S	1.000
1:109235366:C:G	R302G	1.000
1:109235367:G:C	R302P	1.000
1:109235423:T:C	F321L	1.000
1:109235425:T:A	F321L	1.000
1:109235425:T:G	F321L	1.000
1:109236464:G:C	E391D	1.000
1:109236464:G:T	E391D	1.000
1:109236485:C:G	C398W	1.000
1:109214123:G:C	R44P	0.999
1:109223992:G:C	D51H	0.999
1:109224022:A:C	S61R	0.999
1:109224024:C:A	S61R	0.999
1:109224024:C:G	S61R	0.999
1:109224035:G:A	G65E	0.999
1:109229536:C:A	N137K	0.999
1:109229536:C:G	N137K	0.999

dbSNP variants (sampled 300 via entrez): RS1000021436 (1:109235717 C>T), RS1000263706 (1:109214305 C>A), RS1000367586 (1:109214974 A>G), RS1000453357 (1:109222404 A>G), RS1000606118 (1:109222087 T>A,C), RS1000749273 (1:109237121 A>G), RS1000845001 (1:109227622 C>T), RS1001490243 (1:109216433 G>A), RS1001590275 (1:109230287 CAAAA>C,CAA,CAAAAA), RS1001610161 (1:109223744 C>G), RS1001748091 (1:109238464 C>T), RS1001885532 (1:109238274 A>C), RS1001960924 (1:109216269 T>C), RS1002096327 (1:109237426 T>C), RS1002143091 (1:109223481 C>A)

Disease associations

OMIM: gene MIM:607529 | disease phenotypes: MIM:617709, MIM:108010, MIM:613845

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary peripheral neuropathy	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal recessive
neurodevelopmental disorder with microcephaly, ataxia, and seizures	Moderate	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly, ataxia, and seizures	Limited	AR

Mondo (6): neurodevelopmental disorder with microcephaly, ataxia, and seizures (MONDO:0060577), hereditary peripheral neuropathy (MONDO:0020127), arteriovenous malformations of the brain (MONDO:0007154), hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (MONDO:0013458), autosomal recessive non-syndromic intellectual disability (MONDO:0019502), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Genetic peripheral neuropathy (Orphanet:98497), Brain arteriovenous malformation (Orphanet:46724), Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Orphanet:363694)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000582	Upslanted palpebral fissure
HP:0000718	Aggressive behavior
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0001533	Slender build
HP:0001763	Pes planus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0002342	Moderate intellectual disability
HP:0003103	Abnormal cortical bone morphology
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007333	Hypoplasia of the frontal lobes
HP:0010864	Severe intellectual disability

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523232 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.66	IC50	2170	nM	CHEMBL1163070

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 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
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2S)-2-amino-3-hydroxypropanoyl]sulfamate	1617086: Inhibition of human N-terminal polyHis-tagged SerRS expressed in Escherichia coli BL21 (DE3) using Ap4A as substrate in presence of serine by leuconostoc mesenteroides hexokinase/glucose 6-Phosphate dehydrogenase coupled UV-visible spectrophotometry	ic50	2.1700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	6
Cyclosporine	increases expression	5
sodium arsenite	decreases expression, increases expression	4
Valproic Acid	affects expression, increases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
perfluorooctanoic acid	increases expression	2
ochratoxin A	decreases expression, increases expression	2
Carbamazepine	affects expression	2
Cisplatin	decreases expression, decreases reaction, increases expression	2
Ethinyl Estradiol	affects expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	affects localization, decreases expression	2
Thapsigargin	increases expression	2
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
beta-lapachone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	decreases expression	1
AM 251	increases expression	1
pterostilbene	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4416636	ADMET	Inhibition of human N-terminal polyHis-tagged SerRS expressed in Escherichia coli BL21 (DE3) using Ap4A as substrate in presence of serine by leuconostoc mesenteroides hexokinase/glucose 6-Phosphate dehydrogenase coupled UV-visible spectrop	Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase. — J Med Chem
CHEMBL5652385	Binding	Binding affinity to human SARS 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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01758211	PHASE3	UNKNOWN	Functional Magnetic Resonance Imagine(fMRI)Navigation in Intracranial Arteriovenous Malformation Surgery
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT04297033	PHASE2	UNKNOWN	Lovastatin for Treatment of Brain Arteriovenous Malformations
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT02314377	PHASE1	COMPLETED	Bevacizumab Therapy for Brain Arteriovenous Malformation
NCT03278093	Not specified	UNKNOWN	Effect of Orthoses and Underfoot Vibration on Balance in Neuropathy
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase