IL16

Summary

IL16 (interleukin 16, HGNC:5980) is a protein-coding gene on chromosome 15q25.1, encoding Pro-interleukin-16 (Q14005). Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils.

The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 3603 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 242 total
• MANE Select transcript: NM_172217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5980
Approved symbol	IL16
Name	interleukin 16
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	LCF, IL-16, prIL-16, HsT19289, FLJ42735, FLJ16806
Ensembl gene	ENSG00000172349
Ensembl biotype	protein_coding
OMIM	603035
Entrez	3603

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000302987, ENST00000360547, ENST00000394652, ENST00000394660, ENST00000558332, ENST00000558857, ENST00000559342, ENST00000559383, ENST00000559953, ENST00000560115, ENST00000560230, ENST00000560241, ENST00000560989, ENST00000683961, ENST00000706926, ENST00000909975, ENST00000909976

RefSeq mRNA: 6 — MANE Select: NM_172217 NM_001172128, NM_001352684, NM_001352685, NM_001352686, NM_004513, NM_172217

CCDS: CCDS10317, CCDS42069, CCDS53966

Canonical transcript exons

ENST00000683961 — 19 exons

Exon	Start	End
ENSE00001519136	81308605	81314058
ENSE00001654848	81292556	81293037
ENSE00002452465	81273090	81273204
ENSE00002462202	81279558	81279774
ENSE00002463207	81259772	81259880
ENSE00002480848	81285698	81285830
ENSE00002484119	81265659	81265801
ENSE00002495902	81269538	81269648
ENSE00002496510	81282639	81282756
ENSE00002511597	81278817	81278890
ENSE00002608929	81225299	81225711
ENSE00003475289	81305908	81306166
ENSE00003495186	81299380	81300475
ENSE00003507974	81296928	81297078
ENSE00003514993	81301344	81301512
ENSE00003534004	81303549	81303650
ENSE00003651810	81290453	81290540
ENSE00003675168	81306420	81306545
ENSE00003919428	81196879	81197152

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.20.

FANTOM5 (CAGE): breadth broad, TPM avg 28.2483 / max 907.3715, expressed in 739 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148083	20.1825	570
148084	2.5982	244
148082	2.3215	330
148079	0.7487	144
148080	0.6779	132
148067	0.3700	155
148068	0.2771	8
148087	0.2438	71
148064	0.1330	22
148066	0.1325	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.20	gold quality
blood	UBERON:0000178	96.82	gold quality
bone marrow cell	CL:0002092	96.33	gold quality
vermiform appendix	UBERON:0001154	96.15	gold quality
spleen	UBERON:0002106	95.85	gold quality
leukocyte	CL:0000738	95.56	gold quality
monocyte	CL:0000576	95.31	gold quality
mononuclear cell	CL:0000842	95.30	gold quality
lymph node	UBERON:0000029	95.16	gold quality
cerebellar hemisphere	UBERON:0002245	94.85	gold quality
cerebellar cortex	UBERON:0002129	94.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.01	gold quality
tendon of biceps brachii	UBERON:0008188	93.07	gold quality
cerebellum	UBERON:0002037	92.73	gold quality
right lung	UBERON:0002167	92.36	gold quality
superficial temporal artery	UBERON:0001614	92.20	gold quality
sural nerve	UBERON:0015488	91.95	gold quality
bone marrow	UBERON:0002371	91.54	gold quality
caecum	UBERON:0001153	91.53	gold quality
tibial nerve	UBERON:0001323	91.16	gold quality
gall bladder	UBERON:0002110	89.90	gold quality
upper lobe of left lung	UBERON:0008952	89.77	gold quality
left uterine tube	UBERON:0001303	89.54	gold quality
upper lobe of lung	UBERON:0008948	89.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.83	gold quality
tonsil	UBERON:0002372	88.24	gold quality
epithelium of nasopharynx	UBERON:0001951	88.20	gold quality
rectum	UBERON:0001052	88.05	gold quality
omental fat pad	UBERON:0010414	87.81	gold quality
peritoneum	UBERON:0002358	87.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.57
E-CURD-112	yes	3.98
E-MTAB-7381	no	476.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CXCL10	Activation

Upstream regulators (CollecTRI, top): GABPA, GABPB1, TP63

miRNA regulators (miRDB)

116 targeting IL16, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741

Literature-anchored findings (GeneRIF, showing 40)

• cpo has a role in regulating proper nervous system function, including seizure susceptibility (PMID:15687283)
• variation for the diapause phenotype is caused by a single Lys/Ile substitution in one of the six cpo transcripts (PMID:18852464)
• There is no evidence for an association between the cpo I462K polymorphism and ovarian dormancy in Australian fruit flies. (PMID:21689187)
• The results reveal that the downstream cpo SNP does not seem to play any role in diapause induction in European Drosophila populations in contrast to the upstream coding cpo SNP. (PMID:27598401)
• Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family has been reported (PMID:28003515)
• IL-16 released from epidermal Langerhans cells after allergen-mediated activation through Fc epsilon RI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis. (PMID:11714796)
• IL-16 enhances c-kit ligand-mediated expression of tryptase and chymase in mast cells and basophils developed from cord blood and peripheral blood progenitors, is a chemotactic factor for these cells, and inhibits their vulnerability to HIV-1 infection. (PMID:11937573)
• Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus. (PMID:11999883)
• serum level of (IL)-16 was significantly higher in stage III multiple myeloma patients than in healthy controls. The decrease of CD4(+) T cells in MM may be mediated by activation of CD8(+) T cells derived cytokine IL-16. (PMID:12191564)
• The bipartite nuclear localization sequence (NLS) of pro-IL-16 is part of a dual phosphorylation-regulated CcN motif consisting of a protein kinase CK2 substrate site, a cdc2 kinase substrate site, and an NLS. (PMID:12450396)
• binds to Tax in HTLV-1 infected T cells (PMID:12620798)
• identified three closely related myosin phosphatase targeting subunits, MYPT1, MYPT2, and MBS85, as binding partners of the IL-16 precursor proteins (PMID:12923170)
• IL16 genotype was overrepresented among polysensitized individuals (7.0% vs 1.0% in the control group; odds ratio, 7.68; 95% CI, 1.59-48.12) with allergic contact dermatitis to para-substituted aryl compounds (PMID:14657881)
• the cytokine IL-16 plays a role in the disease process underlying rheumatoid arthritis and joint destruction. (PMID:14705216)
• Nuclear IL-16 precursor is identified as a novel regulator of S-phase kinase-associated protein-2 (Skp2) expression and cyclin-dependent kinase inhibitor 1B (p27KIP1) levels, with a role in T cell proliferation. (PMID:14734747)
• Patients with a high level of IL-16 (>430 pg/ml) in multiple myeloma displayed an inferior survival time in comparison to those with lower levels of IL-16. (PMID:14755377)
• recruitment of IL-16+ T cells and microglia/macrophages may represent an innate response to HIV-1 infection in the central nervous system that counterbalances viral stimulatory factors (PMID:15175077)
• IL-16 is constitutively present in peripheral blood monocytes; spontaneous caspase-3 activation (apoptosis) was paralleled by the loss of intracellular IL-16; stimulation with LPS inhibited caspase-3 activation and inhibited the release of IL-16. (PMID:15187155)
• interleukin-16 and its precursor have roles in T lymphocyte activation and growth [review] (PMID:15253385)
• Increased IL-16 levels are associated with hemophagocytic lymphohistiocytosis (PMID:15342983)
• IL-16 is a potent promoter of eosinophil migration through the extracellular matrix components, an effect that is initiated via CD4 and mediated via the release of CCR3 ligand chemokines. (PMID:15383572)
• interleukin-16 production is impaired in monocyte-derived dendritic cells from atopic dermatitis patients but is restored by inflammatory cytokines TNF-alpha and IL-1beta (PMID:15560757)
• IL16 may play an important role in the development of alopecia areata (PMID:15619436)
• Treatment with neutralizing anti-IL-16 antibody successfully reversed paralysis and ameliorated relapsing experimental autoimmune encephalomyelitis (EAE). Relevance for the development of new therapies for relapsing EAE and potentially MS. (PMID:15682385)
• IL-16 in peritoneal fluid may play a role in the pathogenesis of endometriosis by initiating or sustaining inflammatory responses in the peritoneal cavity (PMID:15820794)
• IL-12 and IL-16 may be related to the pathogenesis of periodontal disease, but within the periodontitis sites, IL-16 may be related to disease severity in alcohol drinkers/smokers (PMID:15886011)
• IL-16 activates a PI3K/inositol trisphosphate-dependent signaling pathway in mast cells; CD9 is essential for the IL-16-mediated chemotaxis and activation, acting as an IL-16 receptor in HMC-1, a mast cell line that lacks CD4 (PMID:16144798)
• IL-16, which is up-regulated in macrophages (Mphi), enables Tropheryma whipplei to replicate in monocytes and increases bacterial replication in Mphi; IL-16 down-modulates expression of thioredoxin and up-regulates that of IL-16 and proapoptotic genes (PMID:16177102)
• Suggest that caspase-3 mediated production of IL-16 by infiltrating CD4+ T cells, contributes to ongoing neuroinflammation by chemoattraction of additional waves of CD4+ T cells in relapsing experimental autoimmune encephalomyelitis (EAE). (PMID:16271292)
• determined the effects of IL-16 interaction with CD4 on CXCR3-induced migration (PMID:16455991)
• IL-16 immunoreactivity is a putative marker of a monocytic subset in human gliomas in vivo and may be a novel factor in the regulation of the local inflammatory milieu and tumor progression. (PMID:17221335)
• an influence of genetic variability at the promoter of IL-4 gene (-590C>T) and a coding region of IL-13 gene (R130Q) on the occurrence of allergic asthma and no relationship between IL-16 promoter polymorphism (-295T>C) and this disease. (PMID:17303923)
• an elevation of serum IL16 appears in early trimester of pregnancy of women who later develop preeclampsia, suggesting IL16 plays a role in the pathogenesis of preeclampsia (PMID:17537415)
• Increased levels of circulating IL-16 and apoptosis markers are related to the activity of Whipple’s disease. (PMID:17551575)
• There was no evidence of a statistically significant association in the allelic distribution of IL4, IL10, IL16 and TNF polymorphism that were tested,nor in the haplotype frequencies in patietns with CD. (PMID:17576577)
• A possible prognostic role of IL-16 in lymphoid malignancies. (PMID:17577790)
• pro-IL-16 forms a complex with GABPbeta1 and HDAC3 in suppressing the transcription of Skp2. (PMID:18097041)
• Susceptibility genes CPNE3, IL16 and CDH13 with moderate effects associated with susceptibility to prostate cancer. (PMID:18264096)
• IL-16 gene was significantly associated with susceptibility to Graves’ disease and Graves’ disease associated ophthalmopathy in the Chinese population. (PMID:18394967)
• IL-17 and TLR2 ligands stimulate the production of IL-16 by rheumatoid arthritis fibroblast-like synoviocytes (PMID:18446062)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	il16	ENSDARG00000102908
mus_musculus	Il16	ENSMUSG00000001741
rattus_norvegicus	Il16	ENSRNOG00000011680

Paralogs (1): PDZD2 (ENSG00000133401)

Protein

Protein identifiers

Pro-interleukin-16 — Q14005 (reviewed: Q14005)

All UniProt accessions (8): A0A8C8KBU6, Q14005, H0YKB7, H0YLB1, H0YLH9, H0YLL1, H3BN12, H3BT15

UniProt curated annotations — full annotation on UniProt →

Function. Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4. May act as a scaffolding protein that anchors ion channels in the membrane. Isoform 3 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells.

Subunit / interactions. Homotetramer. According to PubMed:9699630, the formation of a homotetrameric protein complex is not required for the chemo-attractant function. Isoform 3 interacts (via PDZ 3 domain) with PPP1R12A, PPP1R12B and PPP1R12C. Isoform 1 interacts with PPP1R12B. Isoform 3 interacts with GRIN2A. Isoform 3 interacts with GABPB1. Isoform 3 interacts (via PDZ 3 domain) with HDAC3. Isoform 1 interacts with GRIN2D, KCNJ10, KCNJ15 and CACNA1C. (Microbial infection) Isoform 3 interacts with HTLV-1 tax.

Subcellular location. Secreted Cytoplasm Cytoplasm. Nucleus.

Tissue specificity. Expressed in hemopoietic tissues, such as resting T-cells, but undetectable during active T-cell proliferation.

Post-translational modifications. Synthesized as a chemo-attractant inactive precursor in hemopoietic tissues, and proteolytically cleaved by caspase-3 to yield IL-16.

Induction. Down-regulated in T-cells after TCR activation.

Miscellaneous. Produced by alternative promoter usage. Is probably proteolytically processed to yield IL-16. Produced by alternative splicing of isoform 1. Is probably proteolytically processed to yield IL-16. Produced by alternative promoter usage. Is proteolytically processed to yield IL-16.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14005-1	1, nPro-IL-16	yes
Q14005-2	2
Q14005-3	3, Pro-IL-16
Q14005-4	4

RefSeq proteins (6): NP_001165599, NP_001339613, NP_001339614, NP_001339615, NP_004504, NP_757366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR020450	IL-16	Family
IPR036034	PDZ_sf	Homologous_superfamily
IPR055287	IL-16-like	Family

Pfam: PF00595

UniProt features (60 total): strand 15, region of interest 7, compositionally biased region 7, sequence variant 6, sequence conflict 6, mutagenesis site 5, domain 4, helix 4, splice variant 3, chain 2, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5FB8	X-RAY DIFFRACTION	2.07
1I16	SOLUTION NMR
1X6D	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14005-F1	50.24	0.06

Antibody-complex structures (SAbDab): 1 — 5FB8

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): 922

Mutagenesis-validated functional residues (5):

Position	Phenotype
743	reduces phosphorylation and nuclear localization.
757	reduces phosphorylation. enhances nuclear localization.
780–781	reduces nuclear localization of pro-interleukin-16; when associated with 797-aglana-802.
797–802	reduces nuclear localization of pro-interleukin-16; when associated with 780-aa-781.
1211	abolishes proteolytic cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling

MSigDB gene sets: 331 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, WALLACE_PROSTATE_CANCER_RACE_UP, MORF_MSH3, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MORF_BRCA1, GOBP_INDUCTION_OF_POSITIVE_CHEMOTAXIS, KYNG_DNA_DAMAGE_BY_4NQO, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GAURNIER_PSMD4_TARGETS, MORF_ESR1, GOBP_REGULATION_OF_POSITIVE_CHEMOTAXIS, GOBP_INTERLEUKIN_1_PRODUCTION

GO Biological Process (12): immune response (GO:0006955), cytokine-mediated signaling pathway (GO:0019221), leukocyte chemotaxis (GO:0030595), positive regulation of interleukin-1 alpha production (GO:0032730), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-6 production (GO:0032755), positive regulation of inflammatory response (GO:0050729), induction of positive chemotaxis (GO:0050930), immune system process (GO:0002376), chemotaxis (GO:0006935), signal transduction (GO:0007165), regulation of calcium ion transport (GO:0051924)

GO Molecular Function (4): cytokine activity (GO:0005125), CD4 receptor binding (GO:0042609), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), nuclear speck (GO:0016607), Flemming body (GO:0090543), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of cytokine production	2
immune system process	1
response to stimulus	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
leukocyte migration	1
cell chemotaxis	1
interleukin-1 alpha production	1
regulation of interleukin-1 alpha production	1
positive regulation of interleukin-1 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
positive regulation of positive chemotaxis	1
biological_process	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
calcium ion transport	1
regulation of metal ion transport	1
receptor ligand activity	1
signaling receptor binding	1
protein binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
nuclear ribonucleoprotein granule	1
midbody	1

Protein interactions and networks

STRING

1863 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL16	CD4	P01730	976
IL16	IL1A	P01583	947
IL16	CCL27	Q9Y4X3	824
IL16	CCR5	P51681	815
IL16	IL3	P08700	804
IL16	TNF	P01375	782
IL16	IL17A	Q16552	775
IL16	IL1B	P01584	765
IL16	CCL2	P13500	753
IL16	IL18	Q14116	753
IL16	CCL5	P13501	744
IL16	CCL4	P13236	741
IL16	CXCL9	Q07325	702
IL16	IL2RA	P01589	680
IL16	CXCL8	P10145	670

IntAct

1157 interactions, top by confidence:

A	B	Type	Score
E6	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
IL16	GAS2L2	psi-mi:“MI:0407”(direct interaction)	0.440
SCN5A	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
FAM110D	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SLC45A4	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
TANC1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
IL16	SCN4A	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
TANC2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
TAGAP	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
IL16	HTR2C	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2C	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
LNX2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRG	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SEMA4C	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
IL16	KIDINS220	psi-mi:“MI:0407”(direct interaction)	0.440
GUCY1A2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
Tax	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP10	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
RASSF6	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
ADRB1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
MARCHF4	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PRKCA	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (126): USHBP1 (Two-hybrid), SSSCA1 (Two-hybrid), DMRTB1 (Two-hybrid), EFEMP2 (Two-hybrid), IL16 (Proximity Label-MS), IL16 (Two-hybrid), IL16 (Two-hybrid), TRIP6 (Two-hybrid), RNF169 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), IL16 (Affinity Capture-MS), ZNF148 (Affinity Capture-MS), CAMK1 (Affinity Capture-MS), PPP1R12A (Two-hybrid), IL16 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YY25, A0A5K7RLP0, A6NMK8, A8MVX0, B2RQL2, B2RXH4, C9JSJ3, D2J0Y4, O54824, P97303, Q01954, Q05AH6, Q0VET5, Q14005, Q1W617, Q2YDE2, Q3MHT3, Q3U0P1, Q3ULM6, Q3UXL4, Q4R7L6, Q5RC05, Q5T0L3, Q68CR7, Q6GQV1, Q6NS69, Q6NZK5, Q6P1D7, Q6PG16, Q6ZVT6, Q7Z4V0, Q80W88, Q80XI1, Q811R2, Q86T90, Q86YN6, Q8BHP2, Q8BLK9, Q8BP99, Q8BW86

Diamond homologs: A0A140LI67, A5PKA5, A7UA95, E1JIT7, O14910, O15018, O19132, O35274, O35867, O35889, O62666, O62674, O62675, O62676, O62677, O62678, O88951, O88952, P11434, P29475, P29476, P31016, P51140, P55196, P57105, P78352, Q07436, Q0P5F3, Q12923, Q14005, Q29498, Q2KIB6, Q32LM6, Q3T0C9, Q3UHD6, Q4KL35, Q5F425, Q5RAA5, Q62108, Q64512

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	IL16	phosphorylation
MAPK3	up-regulates	IL16	phosphorylation
Gbeta	up-regulates	IL16	phosphorylation
ERK1/2	up-regulates	IL16	phosphorylation
CSNK2A1	“up-regulates activity”	IL16	phosphorylation
CSNK2A2	“up-regulates activity”	IL16	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.8×	4e-05
Neurexins and neuroligins	5	14.1×	2e-03
Deubiquitination	5	8.9×	7e-03
TCF dependent signaling in response to WNT	5	8.4×	9e-03
Signaling by WNT	5	8.0×	1e-02
Cardiac conduction	5	7.8×	1e-02
RHO GTPase cycle	8	6.9×	1e-03
RHOA GTPase cycle	6	6.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of excitatory postsynaptic potential	5	26.6×	2e-04
regulation of synaptic plasticity	5	13.1×	3e-03
learning or memory	5	12.2×	4e-03
sodium ion transmembrane transport	5	10.2×	6e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	7	9.3×	2e-03
chemical synaptic transmission	8	6.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	198
Likely benign	18
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3123 predictions. Top by Δscore:

Variant	Effect	Δscore
15:81265756:G:GT	donor_gain	1.0000
15:81269536:AG:A	acceptor_gain	1.0000
15:81269537:GG:G	acceptor_gain	1.0000
15:81270759:GTT:G	donor_gain	1.0000
15:81270760:TTT:T	donor_gain	1.0000
15:81273088:AG:A	acceptor_gain	1.0000
15:81273089:GG:G	acceptor_gain	1.0000
15:81285693:CACA:C	acceptor_loss	1.0000
15:81285694:ACAG:A	acceptor_gain	1.0000
15:81285695:C:G	acceptor_gain	1.0000
15:81285695:CA:C	acceptor_loss	1.0000
15:81285697:GGT:G	acceptor_gain	1.0000
15:81285697:GGTGT:G	acceptor_gain	1.0000
15:81285826:CACAG:C	donor_loss	1.0000
15:81285827:ACAG:A	donor_loss	1.0000
15:81285829:AGGT:A	donor_loss	1.0000
15:81285830:GGT:G	donor_loss	1.0000
15:81285832:T:G	donor_loss	1.0000
15:81301337:A:AG	acceptor_gain	1.0000
15:81301337:AT:A	acceptor_gain	1.0000
15:81301338:T:G	acceptor_gain	1.0000
15:81301338:T:TA	acceptor_gain	1.0000
15:81301341:A:AG	acceptor_gain	1.0000
15:81301342:A:G	acceptor_gain	1.0000
15:81301343:G:GC	acceptor_gain	1.0000
15:81301343:GC:G	acceptor_gain	1.0000
15:81301511:AG:A	donor_gain	1.0000
15:81301512:GG:G	donor_gain	1.0000
15:81301513:G:GG	donor_gain	1.0000
15:81303544:TGCA:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003034 (15:81262741 G>A), RS1000009007 (15:81194721 G>C,T), RS1000010753 (15:81206022 G>A,T), RS1000039277 (15:81251391 C>A,G), RS1000044332 (15:81298554 T>A), RS1000064483 (15:81227090 T>TA), RS1000096495 (15:81227315 A>G), RS1000121384 (15:81292933 C>T), RS1000152255 (15:81244823 T>C), RS1000159448 (15:81213727 A>G), RS1000205057 (15:81250375 A>G), RS1000226556 (15:81198968 C>T), RS1000227105 (15:81212122 G>C), RS1000230567 (15:81264388 C>T), RS1000252019 (15:81206326 A>G)

Disease associations

OMIM: gene MIM:603035 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000279_10	Inattentive symptoms	4.000000e-06
GCST002816_2	Colorectal cancer (aspirin and/or NSAID use interaction)	8.000000e-09
GCST004302_21	Primary biliary cholangitis	9.000000e-09
GCST004430_6	Interleukin-16 levels	1.000000e-30
GCST005951_10	Body mass index	2.000000e-08
GCST006585_1904	Blood protein levels	7.000000e-83
GCST006989_43	Brown vs. black hair color	3.000000e-11
GCST008839_170	Height	5.000000e-09
GCST009731_36	Blood protein levels in cardiovascular risk	3.000000e-62
GCST90000025_227	Appendicular lean mass	9.000000e-10
GCST90002388_155	Lymphocyte count	4.000000e-17

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007010	drug use measurement
EFO:0007012	NSAID use measurement
EFO:0007013	aspirin use measurement
EFO:0008173	interleukin 16 measurement
EFO:0004340	body mass index
EFO:0003924	hair color
EFO:0010629	pro‐interleukin‐16 measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7170924	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7170924	IL16	3	2.50	1	Platinum compounds
rs11556218	IL16		0.00	0
rs4778889	IL16		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
cinnamaldehyde	increases expression, increases secretion	2
1-hydroxypyrene	affects cotreatment, decreases methylation, increases abundance, increases expression	2
Arsenic	affects methylation, increases expression	2
Eugenol	increases expression, increases secretion	2
Nickel	increases expression, increases secretion	2
Silicon Dioxide	increases expression	2
FR900359	increases phosphorylation	1
methyleugenol	decreases expression	1
geraniol	increases secretion	1
titanium dioxide	affects expression	1
2-methyl-4-isothiazolin-3-one	increases secretion	1
tributyltin	affects cotreatment, decreases secretion	1
sodium arsenite	decreases expression	1
2-tert-butylhydroquinone	increases secretion	1
3-hydroxybenzo(a)pyrene	increases abundance, increases expression	1
perfluorodecanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
thioperamide	decreases reaction, increases expression	1
di-n-butyltin	decreases secretion, affects cotreatment	1
alpha-methylhistamine	increases expression, increases reaction	1
esculentoside A	increases secretion	1
clobenpropit	increases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
3-hydroxybenz(a)anthracene	increases abundance, increases expression	1
Clostridium difficile lethal toxin B	increases secretion	1
brevetoxin 2	increases expression	1
perfluoroundecanoic acid	decreases expression	1
Gemcitabine	increases expression	1
Acetylcysteine	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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