ITLN2

Summary

ITLN2 (intelectin 2, HGNC:20599) is a protein-coding gene on chromosome 1q23.3, encoding Intelectin-2 (Q8WWU7). May play a role in the defense system against pathogens.

Predicted to enable oligosaccharide binding activity. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 142683 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_080878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20599
Approved symbol	ITLN2
Name	intelectin 2
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HL-2
Ensembl gene	ENSG00000158764
Ensembl biotype	protein_coding
OMIM	609874
Entrez	142683

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000368029, ENST00000490489, ENST00000494442, ENST00000934771, ENST00000934772

RefSeq mRNA: 1 — MANE Select: NM_080878 NM_080878

CCDS: CCDS1212

Canonical transcript exons

ENST00000368029 — 8 exons

Exon	Start	End
ENSE00001133365	160952620	160952733
ENSE00001173765	160954387	160954450
ENSE00001446166	160954727	160954809
ENSE00001843858	160945025	160945292
ENSE00002406851	160951043	160951290
ENSE00003544847	160950553	160950711
ENSE00003572271	160947929	160948032
ENSE00003681455	160950046	160950166

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 98.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5787 / max 115.7402, expressed in 115 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15553	0.2570	75
15554	0.1493	27
15555	0.0926	53
15552	0.0521	34
201782	0.0277	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	98.78	gold quality
small intestine	UBERON:0002108	86.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.77	gold quality
right lung	UBERON:0002167	85.80	gold quality
upper lobe of left lung	UBERON:0008952	83.48	gold quality
lung	UBERON:0002048	79.59	gold quality
right coronary artery	UBERON:0001625	76.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.09	gold quality
omental fat pad	UBERON:0010414	72.51	gold quality
left coronary artery	UBERON:0001626	71.81	gold quality
left ovary	UBERON:0002119	68.35	gold quality
ovary	UBERON:0000992	66.84	gold quality
right ovary	UBERON:0002118	65.58	gold quality
right atrium auricular region	UBERON:0006631	57.50	gold quality
rectum	UBERON:0001052	54.38	gold quality
ascending aorta	UBERON:0001496	50.65	gold quality
thoracic aorta	UBERON:0001515	50.64	gold quality
right lobe of liver	UBERON:0001114	50.28	gold quality
liver	UBERON:0002107	50.17	gold quality
prostate gland	UBERON:0002367	49.65	gold quality
intestine	UBERON:0000160	49.14	gold quality
vermiform appendix	UBERON:0001154	49.05	gold quality
adipose tissue	UBERON:0001013	48.41	gold quality
skin of leg	UBERON:0001511	48.21	gold quality
zone of skin	UBERON:0000014	47.97	gold quality
skin of abdomen	UBERON:0001416	47.75	gold quality
blood	UBERON:0000178	47.56	gold quality
popliteal artery	UBERON:0002250	47.26	gold quality
tibial artery	UBERON:0007610	47.11	gold quality
heart	UBERON:0000948	46.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting ITLN2, 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-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-4474-5P	94.23	67.95	568

Literature-anchored findings (GeneRIF, showing 2)

• Studies indicate that ITLN1 and ITLN2 intelectins are positioned on a single chromosome 1, suggesting mammalian intelectins have been independently expanded by partial gene duplication. (PMID:23643964)
• Human intelectin-2 (ITLN2) is selectively expressed by secretory Paneth cells. (PMID:35182405)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	itln3	ENSDARG00000003523
danio_rerio	itln1	ENSDARG00000007534
danio_rerio	itln2	ENSDARG00000036084
danio_rerio	itln4	ENSDARG00000053630
danio_rerio	zgc:153219	ENSDARG00000054054
danio_rerio	si:ch211-194p6.8	ENSDARG00000093796
danio_rerio	si:ch211-194p6.10	ENSDARG00000105568

Paralogs (1): ITLN1 (ENSG00000179914)

Protein

Protein identifiers

Intelectin-2 — Q8WWU7 (reviewed: Q8WWU7)

Alternative names: Endothelial lectin HL-2

All UniProt accessions (1): Q8WWU7

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the defense system against pathogens.

Subcellular location. Secreted.

Tissue specificity. Expressed only in the small intestine.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WWU7-1	1	yes
Q8WWU7-2	2

RefSeq proteins (1): NP_543154* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR036056	Fibrinogen-like_C	Homologous_superfamily

UniProt features (21 total): binding site 11, disulfide bond 4, sequence variant 2, signal peptide 1, chain 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWU7-F1	91.98	0.86

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): 272; 274–275; 274; 294; 98; 99; 101; 104; 109; 110; 145

Disulfide bonds (4): 53–82, 106–292, 211–271, 263–277

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): MODULE_48, MODULE_95, MODULE_163, GOMF_OLIGOSACCHARIDE_BINDING, BUSSLINGER_DUODENAL_PANETH_CELLS, TRAVAGLINI_LUNG_ALVEOLAR_EPITHELIAL_TYPE_1_CELL, ZHANG_FH_DEFICIENT_RCC_C2_VS_OTHERS_UP, chr1q23, NABA_ECM_AFFILIATED, NABA_MATRISOME_ASSOCIATED, NABA_MATRISOME, GOMF_CARBOHYDRATE_BINDING

GO Biological Process (0):

GO Molecular Function (4): metal ion binding (GO:0046872), oligosaccharide binding (GO:0070492), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cation binding	1
carbohydrate binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITLN2	LTF	P02788	661
ITLN2	LGALS14	Q8TCE9	474
ITLN2	MUC5AC	P98088	438
ITLN2	M0R1X1	M0R1X1	369
ITLN2	ATG7	O95352	368
ITLN2	RHOT1	Q8IXI2	350
ITLN2	ATG12	O94817	350
ITLN2	ZNF776	Q68DI1	348
ITLN2	ZNF586	Q9NXT0	348
ITLN2	RETNLB	Q9BQ08	323
ITLN2	FAM181B	A6NEQ2	313
ITLN2	ZNF551	P17034	310
ITLN2	NUP62CL	Q9H1M0	306
ITLN2	CLCA1	A8K7I4	296
ITLN2	TFF3	Q07654	291

IntAct

11 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
ITLN2	ENDOG	psi-mi:“MI:0915”(physical association)	0.640
ITLN1	HSPA5	psi-mi:“MI:0914”(association)	0.530
ITLN1	TIPRL	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
ITLN1	RAB29	psi-mi:“MI:0914”(association)	0.350
ITLN2	PROS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): COL4A2 (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ITLN2 (Affinity Capture-MS), ITLN2 (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ITLN2 (Synthetic Lethality), ENDOG (Affinity Capture-MS), ITLN2 (Affinity Capture-MS), PIP (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), AZGP1 (Affinity Capture-MS), IGJ (Affinity Capture-MS), APOA1 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS)

ESM2 similar proteins: A4GBX7, A4GCJ7, A4GCL9, A4K143, A4U6V2, A4U7A6, A8C8J4, B4URD6, B8VIU6, O56140, O88310, O89746, P03452, P03453, P09345, P0DMV4, P11132, P11135, P12590, P16060, P18875, P18876, P28730, P28731, P86928, P97259, Q08834, Q09328, Q0HD60, Q289M7, Q2F4V2, Q5PPM0, Q6DPZ9, Q6DQ15, Q6DQ18, Q6DQ19, Q6DQ20, Q6DQ21, Q6DQ22, Q6J8E7

Diamond homologs: O88310, P0DMV4, P86928, Q5PPM0, Q80ZA0, Q8WWA0, Q8WWU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1440 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160947921:AAACT:A	donor_loss	1.0000
1:160947922:AACTC:A	donor_loss	1.0000
1:160947923:ACTCA:A	donor_loss	1.0000
1:160947924:CTC:C	donor_loss	1.0000
1:160947925:T:TC	donor_loss	1.0000
1:160947926:CACAT:C	donor_loss	1.0000
1:160947927:A:AC	donor_gain	1.0000
1:160947927:A:AT	donor_loss	1.0000
1:160947928:C:CC	donor_gain	1.0000
1:160947928:CATG:C	donor_gain	1.0000
1:160950044:A:AC	donor_gain	1.0000
1:160950045:C:CC	donor_gain	1.0000
1:160950164:TTT:T	acceptor_gain	1.0000
1:160950178:C:T	acceptor_gain	1.0000
1:160950548:TGTA:T	donor_loss	1.0000
1:160950549:GTACC:G	donor_loss	1.0000
1:160950550:TAC:T	donor_loss	1.0000
1:160950551:A:T	donor_loss	1.0000
1:160950552:CCT:C	donor_loss	1.0000
1:160950708:GGTT:G	acceptor_gain	1.0000
1:160950709:GTT:G	acceptor_gain	1.0000
1:160950710:TT:T	acceptor_gain	1.0000
1:160950712:C:CC	acceptor_gain	1.0000
1:160951040:AACC:A	donor_loss	1.0000
1:160951042:CCTTG:C	donor_loss	1.0000
1:160951269:G:GC	acceptor_gain	1.0000
1:160945288:CAGTG:C	acceptor_gain	0.9900
1:160945289:AGTG:A	acceptor_gain	0.9900
1:160945291:TG:T	acceptor_gain	0.9900
1:160945293:C:CC	acceptor_gain	0.9900

AlphaMissense

2152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160951043:C:A	K147N	0.994
1:160951043:C:G	K147N	0.994
1:160951079:A:C	F135L	0.990
1:160951079:A:T	F135L	0.990
1:160951081:A:G	F135L	0.990
1:160951150:A:G	W112R	0.990
1:160951150:A:T	W112R	0.990
1:160951213:A:G	W91R	0.988
1:160951213:A:T	W91R	0.988
1:160950709:G:C	N148K	0.987
1:160950709:G:T	N148K	0.987
1:160951097:C:A	W129C	0.987
1:160951097:C:G	W129C	0.987
1:160951148:C:A	W112C	0.987
1:160951148:C:G	W112C	0.987
1:160951196:G:C	S96R	0.984
1:160951196:G:T	S96R	0.984
1:160951198:T:G	S96R	0.984
1:160951099:A:G	W129R	0.983
1:160951099:A:T	W129R	0.983
1:160951239:C:G	C82S	0.983
1:160951240:A:T	C82S	0.983
1:160950669:A:G	W162R	0.982
1:160950669:A:T	W162R	0.982
1:160945233:G:C	F295L	0.979
1:160945233:G:T	F295L	0.979
1:160945235:A:G	F295L	0.979
1:160951211:C:A	W91C	0.978
1:160951211:C:G	W91C	0.978
1:160951239:C:T	C82Y	0.978

dbSNP variants (sampled 300 via entrez): RS1000068043 (1:160952901 C>T), RS1000078008 (1:160952560 G>T), RS1000421685 (1:160954944 T>G), RS1000884163 (1:160949039 G>A), RS1001691437 (1:160945725 G>T), RS1001748067 (1:160951319 C>G,T), RS1001888867 (1:160950447 C>G), RS1001923202 (1:160944769 G>A), RS1002090422 (1:160950331 C>G), RS1002184395 (1:160956233 C>T), RS1002393758 (1:160948626 A>C,T), RS1002517834 (1:160954908 G>A), RS1002568832 (1:160954567 G>T), RS1002617529 (1:160947239 T>G), RS1002672080 (1:160955943 G>T)

Disease associations

OMIM: gene MIM:609874 | 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
GCST004131_64	Inflammatory bowel disease	2.000000e-08
GCST004132_83	Crohn’s disease	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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