AARSD1

Summary

AARSD1 (alanyl-tRNA synthetase domain containing 1, HGNC:28417) is a protein-coding gene on chromosome 17q21.31, encoding Alanyl-tRNA editing protein Aarsd1 (Q9BTE6). Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala).

Predicted to enable Ser-tRNA(Ala) deacylase activity. Predicted to be involved in regulation of translational fidelity. Located in nucleus.

Source: NCBI Gene 80755 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_001261434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28417
Approved symbol	AARSD1
Name	alanyl-tRNA synthetase domain containing 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC2744, AlaXp
Ensembl gene	ENSG00000266967
Ensembl biotype	protein_coding
OMIM	613212
Entrez	80755

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 14 protein_coding, 12 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000416949, ENST00000427569, ENST00000430739, ENST00000436545, ENST00000441280, ENST00000450475, ENST00000474578, ENST00000478040, ENST00000483535, ENST00000483774, ENST00000486493, ENST00000486664, ENST00000491665, ENST00000492036, ENST00000587023, ENST00000591096, ENST00000591910, ENST00000592136, ENST00000593123, ENST00000871338, ENST00000871339, ENST00000871340, ENST00000871341, ENST00000871342, ENST00000871343, ENST00000871344, ENST00000871345, ENST00000935094, ENST00000935095, ENST00000935096, ENST00000935097

RefSeq mRNA: 1 — MANE Select: NM_001261434 NM_001261434

CCDS: CCDS58552

Canonical transcript exons

ENST00000427569 — 12 exons

Exon	Start	End
ENSE00001728788	42964402	42964454
ENSE00003464439	42961192	42961351
ENSE00003477264	42953724	42953778
ENSE00003507788	42954876	42954967
ENSE00003537500	42955158	42955224
ENSE00003624248	42964106	42964237
ENSE00003629943	42950526	42950728
ENSE00003639431	42951800	42951894
ENSE00003649302	42956404	42956560
ENSE00003654136	42957138	42957195
ENSE00003686589	42956204	42956320
ENSE00003689923	42955842	42955972

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.9323 / max 258.4927, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166193	26.8702	1813
166192	0.0621	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.20	gold quality
right testis	UBERON:0004534	98.08	gold quality
testis	UBERON:0000473	97.23	gold quality
cerebellar hemisphere	UBERON:0002245	96.35	gold quality
pituitary gland	UBERON:0000007	96.34	gold quality
cerebellar cortex	UBERON:0002129	96.33	gold quality
cerebellum	UBERON:0002037	96.29	gold quality
adenohypophysis	UBERON:0002196	96.29	gold quality
right ovary	UBERON:0002118	96.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.12	gold quality
left ovary	UBERON:0002119	96.09	gold quality
ovary	UBERON:0000992	95.97	gold quality
body of pancreas	UBERON:0001150	95.87	gold quality
gastrocnemius	UBERON:0001388	95.55	gold quality
skeletal muscle tissue	UBERON:0001134	95.49	gold quality
nucleus accumbens	UBERON:0001882	95.49	gold quality
apex of heart	UBERON:0002098	95.42	gold quality
putamen	UBERON:0001874	95.39	gold quality
muscle of leg	UBERON:0001383	95.36	gold quality
body of uterus	UBERON:0009853	95.36	gold quality
prostate gland	UBERON:0002367	95.33	gold quality
cortical plate	UBERON:0005343	95.32	gold quality
right lobe of thyroid gland	UBERON:0001119	95.28	gold quality
caudate nucleus	UBERON:0001873	95.22	gold quality
myometrium	UBERON:0001296	95.21	gold quality
muscle tissue	UBERON:0002385	95.17	gold quality
right frontal lobe	UBERON:0002810	95.17	gold quality
tibial artery	UBERON:0007610	95.13	gold quality
popliteal artery	UBERON:0002250	95.12	gold quality
left uterine tube	UBERON:0001303	95.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66
E-MTAB-7249	no	57.11

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Aarsd1 inhibits the activity of a paradigmatic Hsp90 client protein. (PMID:26884463)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	aarsd1	ENSDARG00000015747
mus_musculus	Aarsd1	ENSMUSG00000075528
rattus_norvegicus	Aarsd1	ENSRNOG00000020658
drosophila_melanogaster	CG10802	FBGN0029664

Paralogs (2): AARS1 (ENSG00000090861), AARS2 (ENSG00000124608)

Protein

Protein identifiers

Alanyl-tRNA editing protein Aarsd1 — Q9BTE6 (reviewed: Q9BTE6)

Alternative names: Alanyl-tRNA synthetase domain-containing protein 1

All UniProt accessions (6): Q9BTE6, H7C1K1, K7EQ85, K7N799, L7N2F4, L7N2F5

UniProt curated annotations — full annotation on UniProt →

Function. Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala).

Subcellular location. Cytoplasm.

Cofactor. Binds 1 zinc ion per subunit.

Miscellaneous. Based on a readthrough transcript which may produce a PTGES3L-AARSD1 fusion protein. Based on a readthrough transcript which may produce a PTGES3L-AARSD1 fusion protein.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BTE6-1	1	yes
Q9BTE6-2	2
Q9BTE6-3	3

RefSeq proteins (1): NP_001248363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR012947	tRNA_SAD	Domain
IPR018163	Thr/Ala-tRNA-synth_IIc_edit	Homologous_superfamily
IPR018165	Ala-tRNA-synth_IIc_core	Domain
IPR051335	Alanyl-tRNA_Editing_Enzymes	Family

Pfam: PF07973

UniProt features (8 total): binding site 4, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTE6-F1	93.77	0.84

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): 109; 113; 209; 213

Post-translational modifications (1): 174

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_AMINO_ACID_ACTIVATION, MYOGENIN_Q6, GCANCTGNY_MYOD_Q6, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, CAGCTG_AP4_Q5, SRF_Q5_01, GOBP_TRANSLATION, SRF_C, HIF1_Q3, GOBP_REGULATION_OF_TRANSLATIONAL_FIDELITY, RFX1_02, TGGAAA_NFAT_Q4_01

GO Biological Process (6): alanyl-tRNA aminoacylation (GO:0006419), regulation of translational fidelity (GO:0006450), translation (GO:0006412), biological_process (GO:0008150), tRNA aminoacylation (GO:0043039), aminoacyl-tRNA metabolism involved in translational fidelity (GO:0106074)

GO Molecular Function (9): Ser-tRNA(Ala) deacylase activity (GO:0002196), nucleic acid binding (GO:0003676), alanine-tRNA ligase activity (GO:0004813), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), aminoacyl-tRNA deacylase activity (GO:0002161), molecular_function (GO:0003674), aminoacyl-tRNA ligase activity (GO:0004812)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA metabolic process	2
catalytic activity, acting on a tRNA	2
tRNA aminoacylation for protein translation	1
regulation of biological quality	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
amino acid activation	1
regulation of translational fidelity	1
aminoacyl-tRNA deacylase activity	1
binding	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
carboxylic ester hydrolase activity	1
aminoacyl-tRNA metabolism involved in translational fidelity	1
deacylase activity	1
ligase activity, forming carbon-oxygen bonds	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AARSD1	AARS1	P49588	876
AARSD1	KARS1	Q15046	694
AARSD1	ADAT1	Q9BUB4	650
AARSD1	PTGES2	Q9H7Z7	508
AARSD1	RPA1	P27694	497
AARSD1	SRRM1	Q8IYB3	461
AARSD1	NME2	P22392	458
AARSD1	A2M	P01023	452
AARSD1	CNOT11	Q9UKZ1	444
AARSD1	EEF1A2	P54266	422
AARSD1	H4C16	P02304	410
AARSD1	POU5F1	P31359	408
AARSD1	ISG15	P05161	408
AARSD1	MTUS2	Q5JR59	407
AARSD1	LRRC71	Q8N4P6	381

IntAct

44 interactions, top by confidence:

A	B	Type	Score
RGS20	GLRX3	psi-mi:“MI:0914”(association)	0.810
MED22	MED19	psi-mi:“MI:0914”(association)	0.790
PARVG	LIMS1	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
USP10	ANKRD28	psi-mi:“MI:0914”(association)	0.610
YKT6	C1QL1	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
YKT6	NAPA	psi-mi:“MI:0914”(association)	0.530
PYCR3	RPL23	psi-mi:“MI:0914”(association)	0.530
TAT	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
RHOJ	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	AARSD1	psi-mi:“MI:0915”(physical association)	0.370
CFTR	AARSD1	psi-mi:“MI:0915”(physical association)	0.370
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DPPA3	TBKBP1	psi-mi:“MI:0914”(association)	0.350
JADE2	MYO9A	psi-mi:“MI:0914”(association)	0.350
MED22	DCTN6	psi-mi:“MI:0914”(association)	0.350
RGS20	KIF3B	psi-mi:“MI:0914”(association)	0.350
AARSD1	MAP3K7	psi-mi:“MI:0914”(association)	0.350
ELP4	HSPA8	psi-mi:“MI:0914”(association)	0.350
GNA13	HSPA8	psi-mi:“MI:0914”(association)	0.350
PYCR3	PCMT1	psi-mi:“MI:0914”(association)	0.350
UBL4B	FECH	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	GPD2	psi-mi:“MI:0914”(association)	0.350
TXK	HSP90AB4P	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
DNAJB6	SCAMP1	psi-mi:“MI:0914”(association)	0.350
DERL2	SNX3	psi-mi:“MI:0914”(association)	0.350
GDPD5	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (191): AARSD1 (Affinity Capture-MS), AARSD1 (Affinity Capture-MS), AARSD1 (Affinity Capture-MS), AARSD1 (Affinity Capture-MS), PTGES3L-AARSD1 (Co-fractionation), AARSD1 (Co-fractionation), PPP1R14B (Co-fractionation), PPP1R14B (Co-fractionation), SBDS (Co-fractionation), SBDS (Co-fractionation), SEPT2 (Co-fractionation), SEPT2 (Co-fractionation), SEPT8 (Co-fractionation), SEPT8 (Co-fractionation), SRM (Co-fractionation)

ESM2 similar proteins: A2RTX5, A9S3D3, B8B4H5, B9FSH5, B9HQZ6, B9RUN8, B9SQR9, C5Z7K4, F4IFC5, F4KE63, O01541, O13914, O23627, O43011, O48593, O62431, O82413, P21894, P26639, P36428, P40825, P41250, P49079, P49588, P50475, P93648, Q08B09, Q0V9S0, Q3THG9, Q3ZBV8, Q54Y20, Q5A8K2, Q5AQL1, Q5I0G4, Q5RBL1, Q5RC02, Q6DEJ5, Q7ZYJ9, Q8BGQ7, Q8CFX8

Diamond homologs: A0B6X3, A0RX10, A1RT13, A1RWQ1, A2BN65, A2ST90, A3CVP2, A3DNI3, A3MXP1, A4FZA5, A4WN07, A4YH91, A5UKU6, A6US09, A6UUN3, A6VJ32, A7I7S4, A8A8X8, A8MBI2, A9A565, A9A6Q2, B0R7I0, B1L762, B1YDH4, B9LUG4, C3MR87, C3MXH6, C3MZC2, C3N7E3, C3NG91, C4KIK1, O27718, O28029, O57848, O58035, O58307, P24075, P35029, P61710, P96041

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1730 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42955154:TCA:T	donor_loss	1.0000
17:42955156:A:C	donor_loss	1.0000
17:42955157:C:CA	donor_loss	1.0000
17:42955157:CCTT:C	donor_gain	1.0000
17:42955160:T:A	donor_gain	1.0000
17:42955840:A:AC	donor_gain	1.0000
17:42955841:C:CC	donor_gain	1.0000
17:42956316:CTCAC:C	acceptor_gain	1.0000
17:42956398:CCTTA:C	donor_loss	1.0000
17:42956399:CTTA:C	donor_loss	1.0000
17:42956400:TTA:T	donor_loss	1.0000
17:42956401:TACC:T	donor_loss	1.0000
17:42956401:TACCT:T	donor_loss	1.0000
17:42956402:A:AT	donor_loss	1.0000
17:42956403:C:T	donor_loss	1.0000
17:42956403:CCT:C	donor_loss	1.0000
17:42961253:T:TA	donor_gain	1.0000
17:42961347:TCAGG:T	acceptor_gain	1.0000
17:42961348:CAGG:C	acceptor_gain	1.0000
17:42961348:CAGGC:C	acceptor_gain	1.0000
17:42961349:AGG:A	acceptor_gain	1.0000
17:42961349:AGGC:A	acceptor_loss	1.0000
17:42961349:AGGCT:A	acceptor_loss	1.0000
17:42961350:GG:G	acceptor_gain	1.0000
17:42961350:GGC:G	acceptor_loss	1.0000
17:42961351:GC:G	acceptor_loss	1.0000
17:42961351:GCT:G	acceptor_loss	1.0000
17:42961352:C:CA	acceptor_loss	1.0000
17:42961352:C:CC	acceptor_gain	1.0000
17:42961353:T:G	acceptor_loss	1.0000

AlphaMissense

2703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42964124:G:C	F51L	0.998
17:42964124:G:T	F51L	0.998
17:42964126:A:G	F51L	0.998
17:42961218:C:A	R102M	0.997
17:42955916:A:C	F240L	0.996
17:42955916:A:T	F240L	0.996
17:42955918:A:G	F240L	0.996
17:42957188:A:C	H113Q	0.996
17:42957188:A:T	H113Q	0.996
17:42957190:G:C	H113D	0.996
17:42961196:A:C	H109Q	0.996
17:42961196:A:T	H109Q	0.996
17:42961344:T:A	D60V	0.996
17:42961345:C:G	D60H	0.996
17:42954939:G:T	A297D	0.995
17:42954940:C:G	A297P	0.995
17:42957139:A:G	W130R	0.995
17:42957139:A:T	W130R	0.995
17:42957186:A:G	L114P	0.995
17:42961198:G:C	H109D	0.995
17:42961218:C:G	R102T	0.995
17:42961344:T:G	D60A	0.995
17:42955908:C:A	G243V	0.994
17:42956242:A:G	C209R	0.994
17:42957195:C:T	G111E	0.994
17:42961192:C:A	G111W	0.994
17:42961217:C:A	R102S	0.994
17:42961217:C:G	R102S	0.994
17:42964106:C:A	Q57H	0.994
17:42964106:C:G	Q57H	0.994

dbSNP variants (sampled 300 via entrez): RS1000007514 (17:42959844 A>G), RS1000038702 (17:42960086 T>C,G), RS1000390826 (17:42952959 A>C,G), RS1000995900 (17:42951410 G>A,T), RS1001147961 (17:42955501 C>G,T), RS1001420615 (17:42958552 TTTTA>T), RS1001435354 (17:42955177 G>A), RS1001536186 (17:42964768 T>C), RS1002028846 (17:42963946 A>C,G), RS1002583645 (17:42965225 G>C), RS1002591453 (17:42966332 G>A,T), RS1002648963 (17:42951243 G>A,C), RS1003182404 (17:42960254 C>T), RS1003288091 (17:42962799 G>C), RS1003340526 (17:42962447 G>A)

Disease associations

OMIM: gene MIM:613212 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Ethyl Methanesulfonate	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Vanadates	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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