RIMKLB

Summary

RIMKLB (ribosomal modification protein rimK like family member B, HGNC:29228) is a protein-coding gene on chromosome 12p13.31, encoding Beta-citrylglutamate synthase B (Q9ULI2). Catalyzes the synthesis of beta-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate.

Predicted to enable N-acetyl-L-aspartate-L-glutamate ligase activity and citrate-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 57494 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001297776

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29228
Approved symbol	RIMKLB
Name	ribosomal modification protein rimK like family member B
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1238, NAAGS, NAAGS-I
Ensembl gene	ENSG00000166532
Ensembl biotype	protein_coding
OMIM	614054
Entrez	57494

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 24 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000299673, ENST00000357529, ENST00000504495, ENST00000510357, ENST00000535829, ENST00000537189, ENST00000538135, ENST00000538758, ENST00000539923, ENST00000541044, ENST00000542232, ENST00000544257, ENST00000619374, ENST00000910594, ENST00000910595, ENST00000910596, ENST00000910597, ENST00000910598, ENST00000910599, ENST00000910600, ENST00000910601, ENST00000910602, ENST00000910603, ENST00000922852, ENST00000922853, ENST00000941851, ENST00000941852, ENST00000941853, ENST00000941854, ENST00000941855

RefSeq mRNA: 7 — MANE Select: NM_001297776 NM_001297776, NM_001352267, NM_001352268, NM_001352269, NM_001352270, NM_001352271, NM_020734

CCDS: CCDS41748

Canonical transcript exons

ENST00000535829 — 6 exons

Exon	Start	End
ENSE00001789554	8773321	8777191
ENSE00002242458	8697991	8698297
ENSE00003540305	8753890	8754093
ENSE00003587193	8713811	8714041
ENSE00003588573	8751957	8752043
ENSE00003593151	8749862	8750092

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9708 / max 517.9376, expressed in 1714 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123987	8.2740	1642
123986	2.0128	953
123981	0.6404	151
123988	0.1956	63
123990	0.1852	66
123989	0.1694	66
123982	0.1452	53
123985	0.1417	42
123984	0.1092	36
123980	0.0973	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	99.01	gold quality
right uterine tube	UBERON:0001302	99.00	gold quality
popliteal artery	UBERON:0002250	97.36	gold quality
tibial artery	UBERON:0007610	97.36	gold quality
ascending aorta	UBERON:0001496	97.27	gold quality
aorta	UBERON:0000947	97.25	gold quality
thoracic aorta	UBERON:0001515	97.24	gold quality
body of uterus	UBERON:0009853	97.12	gold quality
cerebellar hemisphere	UBERON:0002245	97.06	gold quality
right coronary artery	UBERON:0001625	97.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.00	gold quality
descending thoracic aorta	UBERON:0002345	96.98	gold quality
right testis	UBERON:0004534	96.96	gold quality
cerebellar cortex	UBERON:0002129	96.94	gold quality
left testis	UBERON:0004533	96.93	gold quality
cortical plate	UBERON:0005343	96.73	gold quality
nerve	UBERON:0001021	96.67	gold quality
tibial nerve	UBERON:0001323	96.67	gold quality
endocervix	UBERON:0000458	96.51	gold quality
left coronary artery	UBERON:0001626	96.39	gold quality
mucosa of stomach	UBERON:0001199	96.32	gold quality
sural nerve	UBERON:0015488	96.27	gold quality
left ovary	UBERON:0002119	96.20	gold quality
fallopian tube	UBERON:0003889	96.19	gold quality
left uterine tube	UBERON:0001303	96.14	gold quality
ventricular zone	UBERON:0003053	96.08	gold quality
sperm	CL:0000019	96.03	gold quality
coronary artery	UBERON:0001621	95.95	gold quality
cerebellum	UBERON:0002037	95.78	gold quality
omental fat pad	UBERON:0010414	95.67	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	3729.04
E-MTAB-10287	yes	1594.63
E-MTAB-6701	yes	18.45
E-ANND-3	yes	9.98
E-GEOD-124858	no	1774.82
E-MTAB-6058	no	294.65
E-MTAB-7303	no	113.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

253 targeting RIMKLB, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Literature-anchored findings (GeneRIF, showing 1)

• ribosomal modification protein rimK-like family member A (Rimkla) gene is a NAAG synthetase (NAAGS-II), which synthesizes the N-acetylated tripeptide N-acetylaspartylglutamylglutamate (NAAG(2)) (PMID:21454531)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rimklb	ENSMUSG00000040649
rattus_norvegicus	Rimklbl1	ENSRNOG00000036910
rattus_norvegicus	Rimklb	ENSRNOG00000064238

Paralogs (1): RIMKLA (ENSG00000177181)

Protein

Protein identifiers

Beta-citrylglutamate synthase B — Q9ULI2 (reviewed: Q9ULI2)

Alternative names: N-acetyl-aspartylglutamate synthetase B, Ribosomal protein S6 modification-like protein B

All UniProt accessions (4): Q9ULI2, F5GZH5, F5H3V4, F5H552

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of beta-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate. Beta-citryl-L-glutamate is synthesized more efficiently than N-acetyl-L-aspartyl-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). Beta-citryl-L-glutamate, a structural analog of NAAG, is present in testis and immature brain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the RimK family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULI2-1	1	yes
Q9ULI2-2	2

RefSeq proteins (7): NP_001284705, NP_001339196, NP_001339197, NP_001339198, NP_001339199, NP_001339200, NP_065785 (=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)
• citrate + L-glutamate + ATP = beta-citrylglutamate + ADP + phosphate + H(+) (RHEA:40043)

UniProt features (17 total): binding site 11, splice variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULI2-F1	81.30	0.63

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): 277; 277; 277; 279; 279; 158; 193–203; 219; 264; 264; 277

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964539	Glutamate and glutamine metabolism

MSigDB gene sets: 209 (showing top): FISCHER_G1_S_CELL_CYCLE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, YAMAZAKI_TCEB3_TARGETS_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, GOMF_ADENYL_NUCLEOTIDE_BINDING

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), citrate-L-glutamate ligase activity (GO:0072591), nucleotide binding (GO:0000166), 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
ligase activity, forming carbon-nitrogen bonds	2
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
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMKLB	ASPNAT	Q8N9F0	653
RIMKLB	GSG1	Q2KHT4	491
RIMKLB	PEPD	P12955	407
RIMKLB	NOP9	Q86U38	397
RIMKLB	CELF2	O95319	394
RIMKLB	SLITRK5	O94991	393
RIMKLB	CRELD2	Q6UXH1	387
RIMKLB	ALDH18A1	P54886	379
RIMKLB	FOLH1	Q04609	372
RIMKLB	NAALAD2	Q9Y3Q0	370
RIMKLB	GLOD4	Q9HC38	361
RIMKLB	C9K0I3	C9K0I3	349
RIMKLB	MRPS6	P82932	349
RIMKLB	SLC9D1	Q6UWJ1	349
RIMKLB	C19orf44	Q9H6X5	348
RIMKLB	IYD	Q6PHW0	348

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RIMKLB	EGR2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
POC5	PDHX	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): RIMKLB (Affinity Capture-MS), RIMKLB (Affinity Capture-RNA), RIMKLB (Affinity Capture-RNA), RIMKLB (Affinity Capture-RNA), RIMKLB (Affinity Capture-MS), RIMKLB (Cross-Linking-MS (XL-MS)), RIMKLB (Cross-Linking-MS (XL-MS)), RIMKLB (Cross-Linking-MS (XL-MS)), RIMKLB (Cross-Linking-MS (XL-MS)), RIMKLB (Cross-Linking-MS (XL-MS)), RIMKLB (Affinity Capture-RNA), RIMKLB (Affinity Capture-RNA), RIMKLB (Proximity Label-MS), RIMKLB (Affinity Capture-MS), RIMKLB (Two-hybrid)

ESM2 similar proteins: A0QX93, A1L4V7, A2XNK3, A2Y8B9, A3AZW5, F4JHA2, K7WIZ6, O94582, P00895, P00898, P00899, P09785, P0DKG8, P15395, P21689, P22099, P32068, P32069, P67002, P9WFX2, P9WFX3, Q0JCU7, Q0VCE9, Q3U213, Q40412, Q44598, Q44695, Q44697, Q5JN42, Q5K2C4, Q5VS72, Q6NQJ6, Q6TAS3, Q84W56, Q84ZX8, Q8BH55, Q8LEV3, Q8LPN3, Q8S2E5, Q93YN4

Diamond homologs: A0KFE0, A4SSJ2, A4VG93, A4W8L7, A4XP70, A5VX27, A8GCA7, B0KI00, B1JET8, B1XQE7, B5XYN4, B7LN16, C1DJI2, C3KE61, P47258, P75097, Q0VCE9, Q1IGK6, Q3KJQ0, Q48BZ2, Q4KK09, Q500C6, Q6D3R5, Q7TUG9, Q80WS1, Q88AZ9, Q88R85, Q9ULI2, A1SAF6, Q0HMU1, Q0HQZ0, Q66HZ2, Q6PFX8, Q8IXN7, A1A991, A1U360, A1WTM6, A5IHI0, A5UCC6, A5UEH4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1658 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8707164:C:G	donor_gain	1.0000
12:8713805:A:AG	acceptor_gain	1.0000
12:8713806:T:G	acceptor_gain	1.0000
12:8713806:TCTA:T	acceptor_loss	1.0000
12:8713807:CTAG:C	acceptor_loss	1.0000
12:8713808:TAG:T	acceptor_loss	1.0000
12:8713809:A:AG	acceptor_gain	1.0000
12:8713809:A:T	acceptor_loss	1.0000
12:8713809:AG:A	acceptor_gain	1.0000
12:8713810:G:GT	acceptor_gain	1.0000
12:8713810:GG:G	acceptor_gain	1.0000
12:8713810:GGT:G	acceptor_gain	1.0000
12:8713810:GGTA:G	acceptor_gain	1.0000
12:8714037:CCTGG:C	donor_gain	1.0000
12:8714038:CTGG:C	donor_gain	1.0000
12:8714039:TGG:T	donor_gain	1.0000
12:8714040:GG:G	donor_gain	1.0000
12:8714040:GGG:G	donor_gain	1.0000
12:8714041:GG:G	donor_gain	1.0000
12:8714042:G:GG	donor_gain	1.0000
12:8714043:T:A	donor_loss	1.0000
12:8749856:TTTCA:T	acceptor_loss	1.0000
12:8749857:TTCA:T	acceptor_loss	1.0000
12:8749859:CAGGT:C	acceptor_loss	1.0000
12:8750089:TATGG:T	donor_loss	1.0000
12:8750091:TGGTG:T	donor_loss	1.0000
12:8750092:GGT:G	donor_loss	1.0000
12:8750093:G:GA	donor_loss	1.0000
12:8750093:G:GG	donor_gain	1.0000
12:8750094:T:G	donor_loss	1.0000

AlphaMissense

2536 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8752022:A:G	K158E	1.000
12:8752024:G:C	K158N	1.000
12:8752024:G:T	K158N	1.000
12:8753908:C:A	A171D	1.000
12:8753998:G:A	G201E	1.000
12:8753998:G:T	G201V	1.000
12:8754083:C:A	N229K	1.000
12:8754083:C:G	N229K	1.000
12:8773369:C:A	A249D	1.000
12:8773414:A:C	D264A	1.000
12:8773414:A:G	D264G	1.000
12:8773414:A:T	D264V	1.000
12:8773415:T:A	D264E	1.000
12:8773415:T:G	D264E	1.000
12:8773417:T:C	L265P	1.000
12:8773447:T:A	V275D	1.000
12:8773450:G:A	C276Y	1.000
12:8773451:T:G	C276W	1.000
12:8773453:A:T	E277V	1.000
12:8749964:G:C	R93P	0.999
12:8749970:T:C	L95P	0.999
12:8749998:C:A	N104K	0.999
12:8749998:C:G	N104K	0.999
12:8750022:C:G	C112W	0.999
12:8750027:A:T	N114I	0.999
12:8750028:T:A	N114K	0.999
12:8750028:T:G	N114K	0.999
12:8750029:A:C	K115Q	0.999
12:8750029:A:G	K115E	0.999
12:8750030:A:T	K115M	0.999

dbSNP variants (sampled 300 via entrez): RS1000006522 (12:8746086 T>C), RS1000029722 (12:8697597 AC>A,ACC,ACCC), RS1000040783 (12:8682229 G>A,C), RS1000044081 (12:8759351 T>G), RS1000044568 (12:8691533 C>G), RS1000106727 (12:8739836 C>T), RS1000117051 (12:8700186 C>T), RS1000147896 (12:8695191 G>A,C), RS1000163663 (12:8767211 A>G), RS1000196385 (12:8761453 A>G), RS1000198725 (12:8722513 C>G,T), RS1000239499 (12:8682541 G>A), RS1000247283 (12:8724003 GTTTTGTTTTT>G), RS1000257931 (12:8685390 T>C), RS1000259808 (12:8741359 CAG>C)

Disease associations

OMIM: gene MIM:614054 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004611_186	High light scatter reticulocyte count	4.000000e-15
GCST004612_120	High light scatter reticulocyte percentage of red cells	5.000000e-15
GCST004619_136	Reticulocyte fraction of red cells	2.000000e-15
GCST004622_116	Reticulocyte count	3.000000e-15
GCST009391_551	Metabolite levels	9.000000e-06
GCST90002385_221	High light scatter reticulocyte count	1.000000e-22
GCST90002386_317	High light scatter reticulocyte percentage of red cells	2.000000e-22
GCST90002387_118	Immature fraction of reticulocytes	1.000000e-12
GCST90002405_299	Reticulocyte count	3.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0010496	hippuric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance	2
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
acetochlor	affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1

Clinical trials (associated diseases)

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