LACTB2

Summary

LACTB2 (lactamase beta 2, HGNC:18512) is a protein-coding gene on chromosome 8q13.3, encoding Endoribonuclease LACTB2 (Q53H82). Endoribonuclease; cleaves preferentially 3’ to purine-pyrimidine dinucleotide motifs in single-stranded RNA.

Enables RNA endonuclease activity; single-stranded RNA binding activity; and zinc ion binding activity. Located in mitochondrial matrix.

Source: NCBI Gene 51110 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_016027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18512
Approved symbol	LACTB2
Name	lactamase beta 2
Location	8q13.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-83
Ensembl gene	ENSG00000147592
Ensembl biotype	protein_coding
OMIM	618921
Entrez	51110

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000276590, ENST00000517601, ENST00000522447, ENST00000522558, ENST00000879329, ENST00000879330, ENST00000879331, ENST00000879332

RefSeq mRNA: 1 — MANE Select: NM_016027 NM_016027

CCDS: CCDS6208

Canonical transcript exons

ENST00000276590 — 7 exons

Exon	Start	End
ENSE00000980760	70661734	70661897
ENSE00000980761	70657756	70657882
ENSE00000980762	70644065	70644243
ENSE00000980763	70640902	70641050
ENSE00000980764	70638548	70638629
ENSE00001090270	70637266	70637903
ENSE00002128554	70668999	70669185

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.3195 / max 655.2508, expressed in 1812 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93527	39.1587	1811
93528	0.1607	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	94.37	gold quality
right adrenal gland cortex	UBERON:0035827	94.10	gold quality
adult organism	UBERON:0007023	93.87	gold quality
nephron tubule	UBERON:0001231	93.66	gold quality
left adrenal gland	UBERON:0001234	93.60	gold quality
jejunal mucosa	UBERON:0000399	93.45	gold quality
adrenal cortex	UBERON:0001235	93.04	gold quality
left adrenal gland cortex	UBERON:0035825	93.04	gold quality
heart right ventricle	UBERON:0002080	92.96	gold quality
right lobe of liver	UBERON:0001114	92.58	gold quality
left testis	UBERON:0004533	92.55	gold quality
right testis	UBERON:0004534	92.42	gold quality
jejunum	UBERON:0002115	92.29	gold quality
adrenal gland	UBERON:0002369	92.21	gold quality
gall bladder	UBERON:0002110	92.08	gold quality
caput epididymis	UBERON:0004358	91.59	gold quality
biceps brachii	UBERON:0001507	91.32	gold quality
testis	UBERON:0000473	91.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.11	gold quality
adult mammalian kidney	UBERON:0000082	90.94	gold quality
liver	UBERON:0002107	90.82	gold quality
cortex of kidney	UBERON:0001225	90.12	gold quality
sperm	CL:0000019	90.02	gold quality
metanephros cortex	UBERON:0010533	90.02	gold quality
renal medulla	UBERON:0000362	89.94	gold quality
duodenum	UBERON:0002114	89.81	gold quality
kidney	UBERON:0002113	89.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.54	gold quality
islet of Langerhans	UBERON:0000006	89.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting LACTB2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 4)

• Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer (PMID:25823027)
• this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells. (PMID:26826708)
• This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers the XKR9 and LACTB2 genes, which both could have related functions in cadmium absorption and metabolism (PMID:27005419)
• LACTB2 renders radioresistance by activating PINK1/Parkin-dependent mitophagy in nasopharyngeal carcinoma. (PMID:34271102)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lactb2	ENSMUSG00000025937
rattus_norvegicus	Lactb2	ENSRNOG00000007829
drosophila_melanogaster	CG12375	FBGN0031987
caenorhabditis_elegans		WBGENE00013176

Protein

Protein identifiers

Endoribonuclease LACTB2 — Q53H82 (reviewed: Q53H82)

Alternative names: Beta-lactamase-like protein 2

All UniProt accessions (2): Q53H82, A0A024R811

UniProt curated annotations — full annotation on UniProt →

Function. Endoribonuclease; cleaves preferentially 3’ to purine-pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage product contains a free 3’ -OH group. Has no activity with double-stranded RNA or DNA. Required for normal mitochondrial function and cell viability.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion matrix.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Miscellaneous. RNAi-mediated down-regulation results in rapid cell death. The reason for this is not clear; there are only minor changes in mitochondrial mRNA levels.

Similarity. Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

RefSeq proteins (1): NP_057111* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001279	Metallo-B-lactamas	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily
IPR041516	LACTB2_WH	Domain
IPR047921	LACTB2-like_MBL-fold	Domain
IPR050662	Sec-metab_biosynth-thioest	Family

Pfam: PF00753, PF17778

UniProt features (54 total): strand 16, binding site 10, mutagenesis site 8, helix 8, turn 5, modified residue 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4AD9	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53H82-F1	95.85	0.93

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 (10): 77; 199; 79; 81; 82; 118; 118; 145; 164; 164

Post-translational modifications (4): 102, 235, 273, 282

Mutagenesis-validated functional residues (8):

Position	Phenotype
77–82	loss of endoribonuclease activity.
81	loss of endoribonuclease activity.
110	mildly decreases endoribonuclease activity. no effect on rna-binding.
116	loss of endoribonuclease activity. no effect on rna-binding.
118	loss of endoribonuclease activity. no effect on rna-binding.
164	loss of endoribonuclease activity.
216–217	loss of endoribonuclease activity. strongly decreases rna-binding.
220	loss of endoribonuclease activity. strongly decreases rna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WEI_MYCN_TARGETS_WITH_E_BOX, YOKOE_CANCER_TESTIS_ANTIGENS, ONKEN_UVEAL_MELANOMA_UP, GOMF_RNA_ENDONUCLEASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, LEE_LIVER_CANCER_DENA_DN, chr8q13, HOWLIN_CITED1_TARGETS_2_UP, GOCC_MITOCHONDRIAL_MATRIX, GOMF_SINGLE_STRANDED_RNA_BINDING

GO Biological Process (0):

GO Molecular Function (9): single-stranded RNA binding (GO:0003727), RNA endonuclease activity (GO:0004521), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), RNA binding (GO:0003723), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	1
endonuclease activity	1
RNA nuclease activity	1
transition metal ion binding	1
catalytic activity	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LACTB2	MBLAC1	A4D2B0	642
LACTB2	SUPV3L1	Q8IYB8	637
LACTB2	XKR9	Q5GH70	621
LACTB2	PDE12	Q6L8Q7	544
LACTB2	HAGHL	Q6PII5	544
LACTB2	ELAC2	Q9BQ52	506
LACTB2	YBEY	P58557	502
LACTB2	ELAC1	Q9H777	476
LACTB2	JSRP1	Q96MG2	473
LACTB2	REXO2	Q9Y3B8	460
LACTB2	HAGH	Q16775	455
LACTB2	DCLRE1A	Q6PJP8	423
LACTB2	PNPT1	Q8TCS8	416
LACTB2	SLIRP	Q9GZT3	414
LACTB2	LSS	P48449	406

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SIAH1	LACTB2	psi-mi:“MI:0915”(physical association)	0.560
LACTB2	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
LACTB2	OGA	psi-mi:“MI:0915”(physical association)	0.400
LACTB2	NAGK	psi-mi:“MI:0915”(physical association)	0.370
ACP6	NME4	psi-mi:“MI:0914”(association)	0.350
rep	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LACTB2	CKM	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): LACTB2 (Two-hybrid), MGEA5 (Affinity Capture-MS), GPI (Co-fractionation), LACTB2 (Co-fractionation), LACTB2 (Co-fractionation), LACTB2 (Co-fractionation), LACTB2 (Co-fractionation), LACTB2 (Co-fractionation), LACTB2 (Co-fractionation), PDCD6IP (Co-fractionation), MGEA5 (Affinity Capture-MS), LACTB2 (Co-fractionation), ABHD11 (Co-fractionation), LACTB2 (Co-fractionation), GLRX5 (Co-fractionation)

ESM2 similar proteins: B0BN85, B4G0F3, B8BKI7, C6JS30, O00244, O08997, O74735, O76003, O81187, P07178, P07311, P13439, P19356, P22907, P24540, P31754, P38636, P41500, P55142, P55143, P56376, Q0V9A9, Q28C69, Q28ID3, Q2KIK0, Q2R483, Q3T0E0, Q53H82, Q54PZ2, Q5R514, Q5RAL9, Q5XGR8, Q5XJ54, Q5XK67, Q61035, Q6DBT3, Q8L8T2, Q8W1X2, Q94BT9, Q96EK6

Diamond homologs: A0A067XMV3, A0A1L9WLF1, A0A2I1C3U0, A0A411PQM3, A0A4P8DJU1, A0A5B8YUX5, A0A7R7ZLL0, A0KIK2, A1D8J2, A1S6T3, A2QX23, A4SPI6, A7Z4X7, B2FR57, B7VB64, C5FM60, D4AWH0, D4CZZ5, D7PHZ8, E1ACR1, E4V2N5, F2PWS8, F2S702, F2T0M3, G3KLH5, M1WCF7, M3ANL0, O94250, P0CU68, Q0A751, Q0CCY4, Q0V9A9, Q1LZ83, Q2NVG1, Q31ND6, Q3IIR9, Q4W945, Q4WA58, Q4WQZ6, Q53H82

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
8:70637900:CTAA:C	acceptor_gain	1.0000
8:70638546:A:AC	donor_gain	1.0000
8:70638547:C:CC	donor_gain	1.0000
8:70638628:TT:T	acceptor_gain	1.0000
8:70644062:CAC:C	donor_loss	1.0000
8:70644063:A:C	donor_loss	1.0000
8:70644064:C:G	donor_loss	1.0000
8:70644239:GAACT:G	acceptor_gain	1.0000
8:70644240:AACT:A	acceptor_gain	1.0000
8:70644241:ACTC:A	acceptor_loss	1.0000
8:70644242:CT:C	acceptor_gain	1.0000
8:70644244:C:CC	acceptor_gain	1.0000
8:70644244:C:CG	acceptor_loss	1.0000
8:70644245:T:A	acceptor_loss	1.0000
8:70644248:T:C	acceptor_gain	1.0000
8:70644248:T:TC	acceptor_gain	1.0000
8:70657883:C:CC	acceptor_gain	1.0000
8:70657888:C:CT	acceptor_gain	1.0000
8:70657889:A:C	acceptor_gain	1.0000
8:70661661:G:C	donor_gain	1.0000
8:70661700:T:A	donor_gain	1.0000
8:70661805:T:TA	donor_gain	1.0000
8:70661893:TTCTC:T	acceptor_gain	1.0000
8:70637901:TAA:T	acceptor_gain	0.9900
8:70637904:C:CC	acceptor_gain	0.9900
8:70638540:ATAC:A	donor_loss	0.9900
8:70638541:TAC:T	donor_loss	0.9900
8:70638542:AC:A	donor_loss	0.9900
8:70638543:C:CA	donor_loss	0.9900
8:70638544:T:TG	donor_loss	0.9900

AlphaMissense

1895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:70644166:T:A	D164V	0.997
8:70644165:A:C	D164E	0.995
8:70644165:A:T	D164E	0.995
8:70640992:T:A	R217S	0.994
8:70640992:T:G	R217S	0.994
8:70644166:T:C	D164G	0.993
8:70644166:T:G	D164A	0.993
8:70644222:G:C	H145Q	0.993
8:70644222:G:T	H145Q	0.993
8:70641046:A:C	H199Q	0.992
8:70641046:A:T	H199Q	0.992
8:70661774:A:C	H82Q	0.992
8:70661774:A:T	H82Q	0.992
8:70661789:G:C	H77Q	0.992
8:70661789:G:T	H77Q	0.992
8:70669025:G:C	N32K	0.992
8:70669025:G:T	N32K	0.992
8:70644167:C:G	D164H	0.991
8:70661776:G:C	H82D	0.991
8:70644175:A:G	F161S	0.990
8:70644224:G:C	H145D	0.990
8:70644226:C:T	G144D	0.990
8:70661884:C:G	D46H	0.990
8:70640984:C:G	R220P	0.989
8:70640993:C:G	R217T	0.989
8:70641044:C:T	G200D	0.989
8:70641048:G:C	H199D	0.989
8:70661778:T:G	D81A	0.989
8:70661889:A:G	L44P	0.989
8:70661777:A:C	D81E	0.988

dbSNP variants (sampled 300 via entrez): RS1000058707 (8:70656779 C>A), RS1000176961 (8:70645457 C>T), RS1000177649 (8:70671072 C>T), RS1000335099 (8:70666840 G>A), RS1000414536 (8:70639916 G>A), RS1000520757 (8:70647555 G>A), RS1000529015 (8:70639688 C>T), RS1000598970 (8:70646156 G>A), RS1000694634 (8:70653672 C>T), RS1000725410 (8:70653365 G>A), RS1000728777 (8:70654065 G>A), RS1000834065 (8:70660216 G>A), RS1001278825 (8:70652126 A>G), RS1001513073 (8:70665664 A>G), RS1001551822 (8:70652875 T>C)

Disease associations

OMIM: gene MIM:618921 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003448_1	Erythrocyte cadmium concentration in never smokers	3.000000e-11
GCST006479_5	Diverticular disease	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	increases expression	2
Valproic Acid	affects expression, decreases expression, decreases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benztropine	increases expression	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9I6	Ubigene HEK293 LACTB2 KO	Transformed cell line	Female
CVCL_SV23	HAP1 LACTB2 (-) 1	Cancer cell line	Male
CVCL_SV24	HAP1 LACTB2 (-) 2	Cancer cell line	Male
CVCL_SV25	HAP1 LACTB2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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