LXN

Summary

LXN (latexin, HGNC:13347) is a protein-coding gene on chromosome 3q25.32, encoding Latexin (Q9BS40). Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4.

This gene encodes the only known protein inhibitor of zinc-dependent metallocarboxypeptidases. The encoded protein, latexin, downregulates the population size of hematopoietic stem cells. This protein is found to be downregulated in cancer cells because of promoter hypermethylation.

Source: NCBI Gene 56925 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• MANE Select transcript: NM_020169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13347
Approved symbol	LXN
Name	latexin
Location	3q25.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000079257
Ensembl biotype	protein_coding
OMIM	609305
Entrez	56925

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000264265, ENST00000482640

RefSeq mRNA: 1 — MANE Select: NM_020169 NM_020169

CCDS: CCDS3183

Canonical transcript exons

ENST00000264265 — 6 exons

Exon	Start	End
ENSE00000453467	158670957	158671019
ENSE00000453469	158668996	158669132
ENSE00000779944	158667012	158667074
ENSE00000801685	158672350	158672648
ENSE00000968161	158669433	158669610
ENSE00001268981	158666414	158666744

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2994 / max 1156.4856, expressed in 1501 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45330	31.2368	1501
45329	0.0625	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	97.92	gold quality
bronchial epithelial cell	CL:0002328	97.18	gold quality
pericardium	UBERON:0002407	97.09	gold quality
epithelium of bronchus	UBERON:0002031	96.64	gold quality
palpebral conjunctiva	UBERON:0001812	96.42	gold quality
bronchus	UBERON:0002185	96.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.20	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.88	gold quality
colonic mucosa	UBERON:0000317	95.12	gold quality
parietal pleura	UBERON:0002400	95.00	gold quality
pleura	UBERON:0000977	94.66	gold quality
gall bladder	UBERON:0002110	94.24	gold quality
nasal cavity mucosa	UBERON:0001826	94.17	gold quality
rectum	UBERON:0001052	93.88	gold quality
omental fat pad	UBERON:0010414	93.77	gold quality
peritoneum	UBERON:0002358	93.75	gold quality
visceral pleura	UBERON:0002401	93.74	gold quality
left adrenal gland cortex	UBERON:0035825	93.63	gold quality
mucosa of urinary bladder	UBERON:0001259	93.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.39	gold quality
left adrenal gland	UBERON:0001234	93.27	gold quality
eye	UBERON:0000970	93.12	gold quality
right adrenal gland	UBERON:0001233	93.07	gold quality
left ovary	UBERON:0002119	92.90	gold quality
mucosa of transverse colon	UBERON:0004991	92.43	gold quality
parotid gland	UBERON:0001831	92.30	gold quality
duodenum	UBERON:0002114	92.24	gold quality
prostate gland	UBERON:0002367	92.09	gold quality
trabecular bone tissue	UBERON:0002483	92.03	gold quality
caput epididymis	UBERON:0004358	91.91	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1482.50
E-HCAD-6	yes	49.79
E-MTAB-8142	yes	14.74
E-HCAD-1	yes	12.79
E-HCAD-9	yes	12.63
E-MTAB-9388	yes	7.75
E-MTAB-5061	yes	6.00
E-HCAD-13	no	568.77
E-MTAB-8271	no	522.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXN1, KLF4, NANOG, NFKB, SOX9

miRNA regulators (miRDB)

23 targeting LXN, 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-153-5P	99.89	73.86	6317
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-127-5P	97.78	67.64	869

Literature-anchored findings (GeneRIF, showing 12)

• downregulated expression in gastric carcinomas; tumor suppressor (PMID:21466706)
• Latexin expression is lost or greatly reduced in approximately 50% of human leukemia/lymphoma cell lines. (PMID:21567403)
• These results are consistent with a tumor suppressor role for latexin. (PMID:23028717)
• The hematopoietic stem cell regulatory gene latexin has tumor-suppressive properties in malignant melanoma. (PMID:23364479)
• CD146 and Lxn increased tumor migration and invasion of thyroid cancer. (PMID:23712706)
• latexin is markedly downregulated in hepatocellular carcinoma specimens, compared to adjacent non-cancerous tissues. (PMID:24399246)
• Lxn protein and mRNA expression levels in CD133+ miapaca-2 cells were significantly lower than those in CD133- cells. (PMID:25551472)
• Results show that Lxn expression was clearly decreased in the pancreatic ductal adenocarcinoma tissues suggesting it that as a tumor suppressor that targets CD133-positive cancer cells. (PMID:26530530)
• Results identified that LXN expression inversely modulates taxane-chemoresistance in the PC-3 prostate cancer cell line. Inhibition of LXN expression in the bone microenvironment promotes chemoresistance, in part through a methylation-dependent mechanism. (PMID:28087740)
• Deletion of latexin in vivo increases HSC repopulation capacity and survival, expands the entire hematopoietic system, and mitigates myelosuppression. Latexin inactivation downregulates thrombospondin 1 (Thbs1). It inhibits nuclear translocation of ribosomal protein subunit 3 (Rps3), a novel latexin-binding protein, and sensitizes hematopoietic cells to radiation-induced cell death. (PMID:29608488)
• The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy. (PMID:30914656)
• Circ_0002715 promotes the development of osteoarthritis through regulating LXN by sponging miR-127-5p. (PMID:36949500)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lxn	ENSDARG00000043102
mus_musculus	Lxn	ENSMUSG00000047557
rattus_norvegicus	Lxn	ENSRNOG00000013572

Paralogs (1): RARRES1 (ENSG00000118849)

Protein

Protein identifiers

Latexin — Q9BS40 (reviewed: Q9BS40)

Alternative names: Endogenous carboxypeptidase inhibitor, Protein MUM, Tissue carboxypeptidase inhibitor

All UniProt accessions (2): Q9BS40, H7C5A4

UniProt curated annotations — full annotation on UniProt →

Function. Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4. May play a role in inflammation.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in heart, prostate, ovary, kidney, pancreas, and colon, moderate or low in other tissues including brain.

Similarity. Belongs to the protease inhibitor I47 (latexin) family.

RefSeq proteins (1): NP_064554* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009684	Latexin	Family
IPR046350	Cystatin_sf	Homologous_superfamily
IPR049897	CYSTATIN_LXN	Domain

Pfam: PF06907

UniProt features (24 total): strand 10, turn 4, helix 3, domain 2, sequence variant 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2BO9	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BS40-F1	95.97	0.96

Functional residue map

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

Post-translational modifications (1): 55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 258 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, HORIUCHI_WTAP_TARGETS_DN, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_INFLAMMATORY_RESPONSE, GOLDRATH_ANTIGEN_RESPONSE, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, WANG_LMO4_TARGETS_DN, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN

GO Biological Process (2): inflammatory response (GO:0006954), detection of temperature stimulus involved in sensory perception of pain (GO:0050965)

GO Molecular Function (5): metalloendopeptidase inhibitor activity (GO:0008191), heparin binding (GO:0008201), enzyme inhibitor activity (GO:0004857), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
metalloendopeptidase activity	1
endopeptidase inhibitor activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LXN	CPA4	Q9UI42	935
LXN	CPA2	P48052	809
LXN	CPA1	P15085	669
LXN	NTNG2	Q96CW9	576
LXN	DAB2IP	Q5VWQ8	556
LXN	AGBL2	Q5U5Z8	546
LXN	RPS3	P23396	516
LXN	GNG2	P59768	487
LXN	CUX2	O14529	486
LXN	PIR	O00625	459
LXN	CPA5	Q8WXQ8	427
LXN	CDKN2B	P42772	426
LXN	DOT1L	Q8TEK3	426
LXN	RNF2	Q99496	424
LXN	ATRX	P46100	423
LXN	RORB	Q92753	423

IntAct

92 interactions, top by confidence:

A	B	Type	Score
LXN	ZKSCAN4	psi-mi:“MI:0915”(physical association)	0.720
ZKSCAN4	LXN	psi-mi:“MI:0915”(physical association)	0.720
LXN	MAGEA8	psi-mi:“MI:0915”(physical association)	0.560
DPYD	LXN	psi-mi:“MI:0915”(physical association)	0.560
GSG1L	LXN	psi-mi:“MI:0915”(physical association)	0.560
TRIM39	LXN	psi-mi:“MI:0915”(physical association)	0.560
TMEM14A	LXN	psi-mi:“MI:0915”(physical association)	0.560
MAGEA8	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	DPYD	psi-mi:“MI:0915”(physical association)	0.560
LXN	TRIM39	psi-mi:“MI:0915”(physical association)	0.560
LXN	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
BOC	LXN	psi-mi:“MI:0915”(physical association)	0.560
CA3	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	TRAIP	psi-mi:“MI:0915”(physical association)	0.560
IGSF11	LXN	psi-mi:“MI:0915”(physical association)	0.560
SPAG7	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	DNAJC11	psi-mi:“MI:0915”(physical association)	0.560
PAX6	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	PPP1R3C	psi-mi:“MI:0915”(physical association)	0.560
ZNF679	LXN	psi-mi:“MI:0915”(physical association)	0.560
NSMF	LXN	psi-mi:“MI:0915”(physical association)	0.560
ZNF430	LXN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (43): LXN (Two-hybrid), LXN (Two-hybrid), LXN (Two-hybrid), LXN (Two-hybrid), GSG1L (Two-hybrid), ZKSCAN4 (Two-hybrid), LXN (Affinity Capture-MS), CEP162 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), CIRBP (Affinity Capture-MS), CLASP2 (Affinity Capture-MS), LXN (Affinity Capture-MS), LXN (Affinity Capture-MS), LXN (Two-hybrid)

ESM2 similar proteins: A0A1S3PBB7, E3P6N3, E3P6N4, E3P6N5, E3P6N7, E3P6N9, G1SRW8, O60676, O70159, O88969, P01036, P01042, P01044, P01045, P01048, P02765, P08932, P0C7P3, P12763, P24090, P29699, P32766, P70202, P97515, Q02955, Q08CH6, Q0IHI3, Q29RH0, Q58D62, Q5W188, Q64361, Q6T6T4, Q6X784, Q6X786, Q80ZN5, Q8HDG8, Q8K5A3, Q8VIH8, Q8VII2, Q8VII3

Diamond homologs: P49788, P70202, Q64361, Q90YI1, Q9BS40

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2224 predictions. Top by Δscore:

Variant	Effect	Δscore
3:158646298:G:GG	donor_gain	1.0000
3:158649158:G:GG	donor_gain	1.0000
3:158652090:TCTTA:T	acceptor_loss	1.0000
3:158652091:CTTA:C	acceptor_loss	1.0000
3:158652092:TTA:T	acceptor_loss	1.0000
3:158652093:TA:T	acceptor_loss	1.0000
3:158652094:A:AG	acceptor_gain	1.0000
3:158652094:AG:A	acceptor_loss	1.0000
3:158652095:G:GG	acceptor_gain	1.0000
3:158652095:GTC:G	acceptor_gain	1.0000
3:158652095:GTCA:G	acceptor_gain	1.0000
3:158652214:G:GT	donor_gain	1.0000
3:158652243:AAAG:A	donor_loss	1.0000
3:158652244:AAG:A	donor_loss	1.0000
3:158652245:AG:A	donor_loss	1.0000
3:158652246:GG:G	donor_loss	1.0000
3:158652247:GCA:G	donor_loss	1.0000
3:158652249:AAGT:A	donor_loss	1.0000
3:158653305:T:A	acceptor_gain	1.0000
3:158653308:A:AG	acceptor_gain	1.0000
3:158653309:G:GG	acceptor_gain	1.0000
3:158653309:GC:G	acceptor_gain	1.0000
3:158653309:GCT:G	acceptor_gain	1.0000
3:158653309:GCTA:G	acceptor_gain	1.0000
3:158653463:GAGGA:G	donor_gain	1.0000
3:158653464:AGGA:A	donor_gain	1.0000
3:158653465:GGA:G	donor_gain	1.0000
3:158653465:GGAG:G	donor_gain	1.0000
3:158653466:GA:G	donor_gain	1.0000
3:158653466:GAG:G	donor_gain	1.0000

AlphaMissense

1479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:158666714:A:G	W201R	0.954
3:158666714:A:T	W201R	0.954
3:158669589:C:G	A72P	0.904
3:158670981:A:C	F56L	0.900
3:158670981:A:T	F56L	0.900
3:158670983:A:G	F56L	0.900
3:158666712:C:A	W201C	0.895
3:158666712:C:G	W201C	0.895
3:158669588:G:T	A72D	0.892
3:158666732:A:G	W195R	0.890
3:158666732:A:T	W195R	0.890
3:158670995:A:C	Y52D	0.877
3:158672383:A:C	F32L	0.877
3:158672383:A:T	F32L	0.877
3:158672385:A:G	F32L	0.877
3:158667057:A:C	F175L	0.874
3:158667057:A:T	F175L	0.874
3:158667059:A:G	F175L	0.874
3:158672403:C:A	G26W	0.870
3:158669049:A:G	S152P	0.862
3:158666713:C:G	W201S	0.855
3:158669577:A:C	Y76D	0.852
3:158670994:T:G	Y52S	0.845
3:158669006:A:T	V166D	0.844
3:158670988:A:G	L54P	0.840
3:158669058:A:G	W149R	0.835
3:158669058:A:T	W149R	0.835
3:158667049:A:G	L178S	0.831
3:158669087:A:G	L139S	0.830
3:158669084:G:T	A140D	0.825

dbSNP variants (sampled 300 via entrez): RS1000319395 (3:158668351 G>A), RS1000758125 (3:158672869 A>T), RS1000997325 (3:158674048 T>C), RS1001372130 (3:158670430 G>A), RS1003190056 (3:158674593 G>A,T), RS1003242369 (3:158674410 A>G), RS1003790151 (3:158667285 A>G), RS1004340839 (3:158674444 C>A,T), RS1004547324 (3:158668133 A>G), RS1004779078 (3:158666361 C>T), RS1005210271 (3:158671765 G>C), RS1005259613 (3:158671375 G>A), RS1006183024 (3:158669949 C>T), RS1006211133 (3:158669993 A>G), RS1006846806 (3:158673158 T>C)

Disease associations

OMIM: gene MIM:609305 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007611_15	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	6
Valproic Acid	increases methylation, affects expression, decreases expression	4
sodium arsenite	decreases expression	2
Benzo(a)pyrene	affects expression, affects methylation	2
Dexamethasone	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	2
biochanin A	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
glycidyl methacrylate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
o,p’-DDT	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	decreases expression, increases expression	1
NSC 689534	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Azathioprine	increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Diclofenac	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1W9	Abcam HeLa LXN KO	Cancer cell line	Female

Clinical trials (associated diseases)

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