RIMKLA

Summary

RIMKLA (ribosomal modification protein rimK like family member A, HGNC:28725) is a protein-coding gene on chromosome 1p34.2, encoding N-acetylaspartylglutamate synthase A (Q8IXN7). Catalyzes the synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and N-acetyl-L-aspartyl-L-glutamyl-L-glutamate.

Predicted to enable N-acetyl-L-aspartate-L-glutamate ligase activity. Predicted to be involved in glutamine family amino acid metabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 284716 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_173642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28725
Approved symbol	RIMKLA
Name	ribosomal modification protein rimK like family member A
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC47816, RP11-157D18.1, NAAGS-II
Ensembl gene	ENSG00000177181
Ensembl biotype	protein_coding
OMIM	618949
Entrez	284716

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000410070, ENST00000431473, ENST00000910105

RefSeq mRNA: 1 — MANE Select: NM_173642 NM_173642

CCDS: CCDS466

Canonical transcript exons

ENST00000431473 — 5 exons

Exon	Start	End
ENSE00001265874	42409984	42410187
ENSE00001299279	42404511	42404597
ENSE00001458123	42380792	42381097
ENSE00001585281	42414484	42424232
ENSE00003613413	42399404	42399634

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 94.05.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2620 / max 101.3910, expressed in 627 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2451	3.0925	622
2453	0.1050	64
2452	0.0645	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.05	gold quality
oocyte	CL:0000023	82.54	gold quality
prefrontal cortex	UBERON:0000451	81.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.09	gold quality
pancreatic ductal cell	CL:0002079	78.98	silver quality
frontal cortex	UBERON:0001870	78.27	gold quality
cortical plate	UBERON:0005343	77.98	gold quality
middle temporal gyrus	UBERON:0002771	77.61	gold quality
neocortex	UBERON:0001950	77.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.88	gold quality
right frontal lobe	UBERON:0002810	76.62	gold quality
tibialis anterior	UBERON:0001385	76.36	silver quality
Brodmann (1909) area 9	UBERON:0013540	76.23	gold quality
primary visual cortex	UBERON:0002436	75.84	gold quality
anterior cingulate cortex	UBERON:0009835	75.69	gold quality
endothelial cell	CL:0000115	75.63	silver quality
islet of Langerhans	UBERON:0000006	75.52	gold quality
superior frontal gyrus	UBERON:0002661	75.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.32	gold quality
cerebral cortex	UBERON:0000956	75.18	gold quality
postcentral gyrus	UBERON:0002581	74.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	73.51	silver quality
heart right ventricle	UBERON:0002080	73.12	gold quality
colonic mucosa	UBERON:0000317	72.47	gold quality
parietal lobe	UBERON:0001872	72.39	gold quality
occipital lobe	UBERON:0002021	72.17	gold quality
mucosa of transverse colon	UBERON:0004991	72.17	gold quality
deltoid	UBERON:0001476	72.08	silver quality
ileal mucosa	UBERON:0000331	71.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

284 targeting RIMKLA, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 1)

• Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis. (PMID:39117631)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rimkla	ENSDARG00000016830
mus_musculus	Rimkla	ENSMUSG00000048899
rattus_norvegicus	Rimkla	ENSRNOG00000008625

Paralogs (1): RIMKLB (ENSG00000166532)

Protein

Protein identifiers

N-acetylaspartylglutamate synthase A — Q8IXN7 (reviewed: Q8IXN7)

Alternative names: N-acetylaspartylglutamylglutamate synthase A, Ribosomal protein S6 modification-like protein A

All UniProt accessions (2): Q8IXN7, X1WI25

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and N-acetyl-L-aspartyl-L-glutamyl-L-glutamate.

Subcellular location. Cytoplasm.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Miscellaneous. N-acetyl-L-aspartyl-L-glutamate (NAAG) is the most abundant dipeptide present in vertebrate central nervous system (CNS).

Similarity. Belongs to the RimK family.

RefSeq proteins (1): NP_775913* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004666	Rp_bS6_RimK/Lys_biosynth_LsyX	Family
IPR011761	ATP-grasp	Domain
IPR013651	ATP-grasp_RimK-type	Domain
IPR013815	ATP_grasp_subdomain_1	Homologous_superfamily

Pfam: PF08443

Catalyzed reactions (Rhea), 2 shown:

• N-acetyl-L-aspartate + L-glutamate + ATP = N-acetyl-L-aspartyl-L-glutamate + ADP + phosphate + H(+) (RHEA:40035)
• N-acetyl-L-aspartate + 2 L-glutamate + 2 ATP = N-acetyl-L-aspartyl-L-glutamyl-L-glutamate + 2 ADP + 2 phosphate + 2 H(+) (RHEA:40039)

UniProt features (16 total): binding site 11, chain 1, domain 1, modified residue 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXN7-F1	81.15	0.65

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 (11): 273; 273; 273; 275; 275; 154; 189–199; 215; 260; 260; 273

Post-translational modifications (1): 319

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964539	Glutamate and glutamine metabolism

MSigDB gene sets: 104 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, AREB6_03, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, chr1p34, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, CERVERA_SDHB_TARGETS_1_UP, TTTGCAC_MIR19A_MIR19B, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_ADENYL_NUCLEOTIDE_BINDING, MEISSNER_NPC_HCP_WITH_H3K4ME2

GO Biological Process (3): obsolete glutamine family amino acid metabolic process (GO:0009064), L-amino acid metabolic process (GO:0170033), protein modification process (GO:0036211)

GO Molecular Function (6): ATP binding (GO:0005524), metal ion binding (GO:0046872), N-acetyl-L-aspartate-L-glutamate ligase activity (GO:0072590), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
amino acid metabolic process	1
carboxylic acid metabolic process	1
protein metabolic process	1
macromolecule modification	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
ligase activity, forming carbon-nitrogen bonds	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMKLA	ASPNAT	Q8N9F0	603
RIMKLA	CCDC30	Q5VVM6	527
RIMKLA	CFAP96	A7E2U8	522
RIMKLA	RAB20	Q9NX57	437
RIMKLA	SAP30L	Q9HAJ7	409
RIMKLA	CCDC184	Q52MB2	409
RIMKLA	ACOT12	Q8WYK0	408
RIMKLA	MSRA	Q9UJ68	408
RIMKLA	USP31	Q70CQ4	403
RIMKLA	PXMP4	Q9Y6I8	389
RIMKLA	CFAP144	A6NL82	380
RIMKLA	C1orf50	Q9BV19	372
RIMKLA	MCCD1	P59942	372
RIMKLA	SNX29	Q8TEQ0	372
RIMKLA	ZGRF1	Q86YA3	366

IntAct

18 interactions, top by confidence:

A	B	Type	Score
RIMKLA	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
RIMKLA	GSN	psi-mi:“MI:0915”(physical association)	0.560
RIMKLA	HRAS	psi-mi:“MI:0915”(physical association)	0.560
HTT	RIMKLA	psi-mi:“MI:0915”(physical association)	0.560
RIMKLA	ZNG1C	psi-mi:“MI:0914”(association)	0.530
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (12): MOCOS (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), DHTKD1 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), DHTKD1 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), RIMKLA (Affinity Capture-RNA), CBWD3 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), RIMKLA (Proximity Label-MS), RIMKLA (Proximity Label-MS), RIMKLA (Proximity Label-MS)

ESM2 similar proteins: A2XLG5, A2XM23, A7MB78, B2RR83, B4YB07, B8A4F4, I1MGE5, O49934, P06593, P06594, P13807, P13834, P14712, P14713, P15001, P19862, P29130, P30733, P33530, P34094, P36505, P42496, P42499, P42500, P93526, P93673, Q0VCE9, Q10003, Q10CQ8, Q10DU0, Q14BI7, Q3MHU3, Q5F3R2, Q5R746, Q5R9H0, Q66HZ2, Q6IQX0, Q6K881, Q6PFX8, Q80WS1

Diamond homologs: A1SAF6, A4W8L7, B1XQE7, P47258, P75097, Q0HMU1, Q0HQZ0, Q0VCE9, Q66HZ2, Q6PFX8, Q80WS1, Q8IXN7, Q9ULI2, A0KFE0, A1A991, A1U360, A1WTM6, A4SSJ2, A5IHI0, A5UCC6, A5UEH4, A7ZJS0, A7ZYF5, A8AIR5, A8GCA7, A9MSM9, B1IWS0, B1LN04, B1X7Z3, B2TUM8, B4T0D6, B4TCX3, B4TRM8, B5BBW2, B5F0Z4, B5FBB1, B5FPY9, B5QYJ7, B5R861, B5XYN4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1178 predictions. Top by Δscore:

Variant	Effect	Δscore
1:42381094:CTCGG:C	donor_loss	1.0000
1:42381097:GGT:G	donor_loss	1.0000
1:42381098:G:GG	donor_gain	1.0000
1:42381099:T:A	donor_loss	1.0000
1:42399399:TGCA:T	acceptor_loss	1.0000
1:42399400:GCA:G	acceptor_loss	1.0000
1:42399401:CAGGC:C	acceptor_loss	1.0000
1:42399402:A:AG	acceptor_gain	1.0000
1:42399403:G:GG	acceptor_gain	1.0000
1:42399403:GGC:G	acceptor_gain	1.0000
1:42399632:ATGGT:A	donor_loss	1.0000
1:42399635:G:GG	donor_gain	1.0000
1:42399635:G:T	donor_loss	1.0000
1:42399636:T:G	donor_loss	1.0000
1:42409979:TAAA:T	acceptor_loss	1.0000
1:42409980:A:AG	acceptor_gain	1.0000
1:42409982:A:AG	acceptor_gain	1.0000
1:42409982:A:G	acceptor_loss	1.0000
1:42409983:G:GA	acceptor_loss	1.0000
1:42409983:G:GG	acceptor_gain	1.0000
1:42409983:GGA:G	acceptor_gain	1.0000
1:42409983:GGAAA:G	acceptor_gain	1.0000
1:42410069:GAA:G	donor_gain	1.0000
1:42410072:G:GG	donor_gain	1.0000
1:42410185:TCGGT:T	donor_loss	1.0000
1:42381034:G:GT	donor_gain	0.9900
1:42381093:CCTCG:C	donor_gain	0.9900
1:42381095:TCG:T	donor_gain	0.9900
1:42399401:CAGG:C	acceptor_gain	0.9900
1:42399402:AG:A	acceptor_gain	0.9900

AlphaMissense

2558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:42414580:T:C	L261P	1.000
1:42414616:A:T	E273V	1.000
1:42399564:C:G	C108W	0.999
1:42399593:T:C	L118P	0.999
1:42404571:T:A	V152E	0.999
1:42404574:T:A	V153E	0.999
1:42404576:A:G	K154E	0.999
1:42404578:G:C	K154N	0.999
1:42404578:G:T	K154N	0.999
1:42409984:G:A	G161E	0.999
1:42410069:G:C	Q189H	0.999
1:42410069:G:T	Q189H	0.999
1:42410092:G:T	G197V	0.999
1:42410097:G:C	D199H	0.999
1:42414532:C:A	A245D	0.999
1:42414577:A:C	D260A	0.999
1:42414577:A:T	D260V	0.999
1:42414578:T:A	D260E	0.999
1:42414578:T:G	D260E	0.999
1:42414583:T:C	L262P	0.999
1:42414613:G:A	C272Y	0.999
1:42414614:T:G	C272W	0.999
1:42399570:C:A	N110K	0.998
1:42399570:C:G	N110K	0.998
1:42399571:A:G	K111E	0.998
1:42399572:A:T	K111I	0.998
1:42399573:A:C	K111N	0.998
1:42399573:A:T	K111N	0.998
1:42399617:C:A	P126Q	0.998
1:42399617:C:G	P126R	0.998

dbSNP variants (sampled 300 via entrez): RS1000188427 (1:42390002 A>G), RS1000209217 (1:42410558 G>T), RS1000444222 (1:42422142 A>G), RS1000533227 (1:42394781 G>C), RS1000576480 (1:42415836 G>A,T), RS1000628854 (1:42415567 C>A,T), RS1000683894 (1:42408909 A>C,G), RS1000812459 (1:42401275 C>T), RS1000963044 (1:42422573 A>G), RS1001075641 (1:42394770 C>T), RS1001139657 (1:42395431 C>A), RS1001157515 (1:42407079 C>T), RS1001165309 (1:42409610 T>C), RS1001182898 (1:42383587 A>G), RS1001229171 (1:42410367 G>A)

Disease associations

OMIM: gene MIM:618949 | 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: yes

ChEMBL targets (1): CHEMBL6196108 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.10	Ki	8	nM	CHEMBL46005

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
tungsten carbide	affects cotreatment, increases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
nickel chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
cobalt oxide	increases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cobalt	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Oxygen	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6187730	Binding	Binding affinity to NAAG synthetase A (unknown origin) assessed as inhibition constant	Prodrugs Targeting Prostate-Specific Membrane Antigen against Prostate Cancer. — J Med Chem

Clinical trials (associated diseases)

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