LGSN

Summary

LGSN (lengsin, lens protein with glutamine synthetase domain, HGNC:21016) is a protein-coding gene on chromosome 6q12, encoding Lengsin (Q5TDP6). May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens.

This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51557 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_016571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21016
Approved symbol	LGSN
Name	lengsin, lens protein with glutamine synthetase domain
Location	6q12
Locus type	gene with protein product
Status	Approved
Aliases	LGS
Ensembl gene	ENSG00000146166
Ensembl biotype	protein_coding
OMIM	611470
Entrez	51557

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000370657, ENST00000370658, ENST00000485906, ENST00000622415

RefSeq mRNA: 2 — MANE Select: NM_016571 NM_001143940, NM_016571

CCDS: CCDS4964, CCDS55027

Canonical transcript exons

ENST00000370657 — 4 exons

Exon	Start	End
ENSE00002151654	63294913	63295045
ENSE00002178279	63275951	63281220
ENSE00002187861	63285587	63285753
ENSE00003893550	63319914	63319983

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 82.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0497 / max 89.7447, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74200	0.0497	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	82.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.23	gold quality
right lobe of liver	UBERON:0001114	65.49	gold quality
liver	UBERON:0002107	62.46	gold quality
placenta	UBERON:0001987	59.82	gold quality
epithelium of bronchus	UBERON:0002031	52.07	silver quality
bronchus	UBERON:0002185	51.63	silver quality
bronchial epithelial cell	CL:0002328	51.59	silver quality
adult mammalian kidney	UBERON:0000082	50.12	gold quality
nephron tubule	UBERON:0001231	49.89	silver quality
colonic epithelium	UBERON:0000397	49.68	gold quality
kidney	UBERON:0002113	49.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.90
E-GEOD-99795	no	16.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting LGSN, 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-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
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-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 5)

• Lengsin is major novel protein of the vertebrate eye lens. (PMID:12107413)
• A potential chaperone-like role of Lengsin was investigated. (PMID:17010935)
• Lengsin belongs to the predominantly prokaryotic class 1 branch of glutamine synthetases but has lost enzyme activity (PMID:17161372)
• Novel spliced form of a lens protein as a novel lung cancer antigen, Lengsin splicing variant 4, is reported. (PMID:19459848)
• In major depressive disorder genome-wide association study, best male-specific SNP was rs9362774 within LGSN gene (PMID:21621269)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lgsn	ENSDARG00000007715
mus_musculus	Lgsn	ENSMUSG00000050217
rattus_norvegicus	Lgsn	ENSRNOG00000012205
caenorhabditis_elegans		WBGENE00001602
caenorhabditis_elegans		WBGENE00001604
caenorhabditis_elegans		WBGENE00001606
caenorhabditis_elegans		WBGENE00001607

Paralogs (1): GLUL (ENSG00000135821)

Protein

Protein identifiers

Lengsin — Q5TDP6 (reviewed: Q5TDP6)

Alternative names: Glutamate-ammonia ligase domain-containing protein 1, Lens glutamine synthase-like

All UniProt accessions (2): Q5TDP6, A0A0A0MTD2

UniProt curated annotations — full annotation on UniProt →

Function. May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens. Does not seem to have enzymatic activity.

Subunit / interactions. Dodecamer. Interacts with BFSP2 and VIM.

Tissue specificity. Abundantly expressed in lens.

Similarity. Belongs to the glutamine synthetase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5TDP6-1	1, LGS_v2	yes
Q5TDP6-2	2, LGS_v1
Q5TDP6-3	3, LGS_v3

RefSeq proteins (2): NP_001137412, NP_057655* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008146	Gln_synth_cat_dom	Domain
IPR008147	Gln_synt_N	Domain
IPR014746	Gln_synth/guanido_kin_cat_dom	Homologous_superfamily
IPR036651	Gln_synt_N_sf	Homologous_superfamily

Pfam: PF00120

UniProt features (13 total): splice variant 4, sequence variant 3, domain 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TDP6-F1	77.35	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, chr6q12, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_GLUTAMINE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GATA6_01, TGACATY_UNKNOWN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, TGGAAA_NFAT_Q4_01

GO Biological Process (1): obsolete glutamine biosynthetic process (GO:0006542)

GO Molecular Function (2): catalytic activity (GO:0003824), glutamine synthetase activity (GO:0004356)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
molecular_function	1
ammonia ligase activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2587 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LGSN	GLUL	P15104	940
LGSN	CRYBA4	P53673	586
LGSN	BFSP2	Q13515	580
LGSN	BFSP1	Q12934	570
LGSN	KHDRBS2	Q5VWX1	557
LGSN	GRIFIN	A4D1Z8	532
LGSN	NOXRED1	Q6NXP6	529
LGSN	CRYZL1	O95825	519
LGSN	SMAP1	Q8IYB5	507
LGSN	CRYBB1	P53674	500
LGSN	CRYGN	Q8WXF5	491
LGSN	CRYBA2	P53672	490
LGSN	LIM2	P55344	475
LGSN	MIP	P30301	472
LGSN	CRYGD	P07320	464

IntAct

3 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): LGSN (Co-fractionation), LGSN (Affinity Capture-MS), LGSN (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JM23, A2RSY6, A6H6X4, A6H8I2, A6NNW6, O60502, O93511, P0CI65, P41320, Q008S8, Q0GA40, Q14AW5, Q1ZZS1, Q2TBM9, Q3U213, Q3UH60, Q496Z9, Q4R3G4, Q4R6C7, Q5R5T0, Q5TDP6, Q692V3, Q6AZT7, Q6K3T2, Q6NVJ5, Q6P2S7, Q6P3V7, Q6P6R7, Q6UXZ4, Q7T2D0, Q7TT51, Q7Z2T5, Q8CIX8, Q8GYY7, Q8TEU7, Q8VIJ5, Q96524, Q96JX3, Q99MV7, Q9BXT8

Diamond homologs: A0R079, I3R176, O08467, O27612, O29313, O58097, O59648, O66514, O87393, P00964, P05457, P07804, P09826, P0A039, P0A040, P0A1P6, P0A1P7, P0A591, P0A9C5, P0A9C6, P0A9C7, P0A9C8, P0C7B6, P10583, P10656, P12425, P13499, P15106, P15124, P19064, P19904, P20805, P21154, P22248, P23794, P25821, P28605, P28786, P31592, P33035

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
6:63285585:A:AC	donor_gain	1.0000
6:63285586:C:CC	donor_gain	1.0000
6:63294929:AT:A	donor_gain	1.0000
6:63294976:T:A	donor_gain	1.0000
6:63294979:T:TA	donor_gain	1.0000
6:63293852:CCTCT:C	acceptor_gain	0.9900
6:63293853:CTCT:C	acceptor_gain	0.9900
6:63293853:CTCTC:C	acceptor_gain	0.9900
6:63293854:TCTCT:T	acceptor_gain	0.9900
6:63293855:CT:C	acceptor_gain	0.9900
6:63293857:C:CC	acceptor_gain	0.9900
6:63294869:G:A	donor_gain	0.9900
6:63294945:T:TA	donor_gain	0.9900
6:63295056:T:TC	acceptor_gain	0.9900
6:63295491:CCTTA:C	acceptor_gain	0.9900
6:63295493:T:C	acceptor_gain	0.9900
6:63295495:A:C	acceptor_gain	0.9900
6:63295975:AGTAT:A	donor_gain	0.9900
6:63319912:ACCT:A	donor_gain	0.9900
6:63319913:CCTC:C	donor_gain	0.9900
6:63319915:T:TA	donor_gain	0.9900
6:63285754:C:CC	acceptor_gain	0.9800
6:63293854:TCT:T	acceptor_gain	0.9800
6:63293855:CTC:C	acceptor_gain	0.9800
6:63293855:CTCT:C	acceptor_loss	0.9800
6:63293856:TCT:T	acceptor_gain	0.9800
6:63293857:CT:C	acceptor_loss	0.9800
6:63293858:T:A	acceptor_loss	0.9800
6:63294930:T:C	donor_gain	0.9800
6:63294980:C:A	donor_gain	0.9800

AlphaMissense

3388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:63285651:C:G	R89P	0.994
6:63280306:G:C	N415K	0.993
6:63280306:G:T	N415K	0.993
6:63280521:A:G	W344R	0.993
6:63280521:A:T	W344R	0.993
6:63281041:A:C	C170W	0.991
6:63285654:A:T	V88E	0.990
6:63281043:A:G	C170R	0.989
6:63280271:C:T	G427D	0.988
6:63280483:G:C	S356R	0.988
6:63280483:G:T	S356R	0.988
6:63280485:T:G	S356R	0.988
6:63285611:C:A	K102N	0.988
6:63285611:C:G	K102N	0.988
6:63285643:C:G	A92P	0.988
6:63285616:A:G	S101P	0.987
6:63280508:A:G	L348P	0.986
6:63281042:C:T	C170Y	0.986
6:63285648:A:G	F90S	0.986
6:63280997:C:A	R185M	0.985
6:63281099:G:C	P151R	0.983
6:63280274:G:T	A426D	0.982
6:63280278:C:G	A425P	0.982
6:63281048:A:T	V168E	0.982
6:63281099:G:T	P151Q	0.982
6:63280997:C:G	R185T	0.981
6:63280967:A:G	L195P	0.980
6:63281054:G:T	A166E	0.980
6:63285636:T:A	D94V	0.980
6:63280715:G:T	A279D	0.979

dbSNP variants (sampled 300 via entrez): RS1000013411 (6:63494193 G>A,T), RS1000023914 (6:63523524 T>C), RS1000028040 (6:63481101 T>A,C), RS1000041265 (6:63392072 G>C), RS1000044776 (6:63414448 T>A,C), RS1000048089 (6:63454534 G>A), RS1000069601 (6:63378208 G>A), RS1000070053 (6:63469385 A>G), RS1000072605 (6:63500096 C>A), RS1000073611 (6:63337097 G>A), RS1000100161 (6:63532841 A>C), RS1000121016 (6:63504462 G>C), RS1000121441 (6:63378515 T>C), RS1000130102 (6:63557357 G>A), RS1000141490 (6:63433567 C>T)

Disease associations

OMIM: gene MIM:611470 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001762_641	Obesity-related traits	5.000000e-06
GCST004735_25	Epstein-Barr virus copy number in lymphoblastoid cell lines	4.000000e-07
GCST009391_76	Metabolite levels	9.000000e-06
GCST90000050_54	Age at first birth	3.000000e-08
GCST90014325_1	Asthma	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
2-methyl-4-isothiazolin-3-one	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
dinophysistoxin 1	decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
licochalcone B	decreases expression	1
Cadmium	decreases expression	1
Hydrogen Peroxide	affects expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	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_D7TK	Ubigene A-549 LGSN KO	Cancer cell line	Male

Clinical trials (associated diseases)

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