IL7

Summary

IL7 (interleukin 7, HGNC:6023) is a protein-coding gene on chromosome 8q21.13, encoding Interleukin-7 (P13232). Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintaining lymphoid homeostasis.

The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL7 is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. IL7 plays an essential role in lymphoid cell survival, and in the maintenance of naive and memory T cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their presence in normal tissues has not been confirmed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be a potent inducer of proinflammatory cytokines and chemokines which may defend against the infection, but may also mediate destructive lung injury. Elevated serum IL7 levels, together with several other circulating cytokines and chemokines, has been found to be associated with the severity of Coronavirus Disease 19 (COVID-19).

Source: NCBI Gene 3574 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 98 total — 5 pathogenic
• Phenotypes (HPO): 17
• MANE Select transcript: NM_000880

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6023
Approved symbol	IL7
Name	interleukin 7
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	IL-7
Ensembl gene	ENSG00000104432
Ensembl biotype	protein_coding
OMIM	146660
Entrez	3574

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000263851, ENST00000379113, ENST00000518982, ENST00000519833, ENST00000520215, ENST00000520269, ENST00000520317, ENST00000521323, ENST00000523959, ENST00000541183, ENST00000960091

RefSeq mRNA: 4 — MANE Select: NM_000880 NM_000880, NM_001199886, NM_001199887, NM_001199888

CCDS: CCDS56541, CCDS6224, CCDS75755, CCDS75756

Canonical transcript exons

ENST00000263851 — 6 exons

Exon	Start	End
ENSE00001757516	78798072	78798208
ENSE00002096050	78732772	78733832
ENSE00003538602	78740002	78740082
ENSE00003644128	78736474	78736527
ENSE00003686132	78738504	78738635
ENSE00003850757	78804913	78805463

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 91.47.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9843 / max 57.8589, expressed in 623 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93659	1.1913	392
93658	0.4440	256
93660	0.1977	81
93661	0.1513	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.47	gold quality
male germ cell	CL:0000015	87.90	gold quality
bronchial epithelial cell	CL:0002328	84.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.47	gold quality
calcaneal tendon	UBERON:0003701	82.94	gold quality
jejunal mucosa	UBERON:0000399	82.69	gold quality
epithelium of bronchus	UBERON:0002031	79.75	gold quality
lower lobe of lung	UBERON:0008949	79.41	silver quality
caput epididymis	UBERON:0004358	79.29	gold quality
lymph node	UBERON:0000029	79.07	gold quality
bronchus	UBERON:0002185	78.51	gold quality
right uterine tube	UBERON:0001302	77.40	gold quality
rectum	UBERON:0001052	77.34	gold quality
superficial temporal artery	UBERON:0001614	76.79	gold quality
skin of abdomen	UBERON:0001416	75.74	gold quality
right testis	UBERON:0004534	74.74	gold quality
vermiform appendix	UBERON:0001154	74.30	gold quality
duodenum	UBERON:0002114	74.24	gold quality
left testis	UBERON:0004533	73.90	gold quality
caecum	UBERON:0001153	73.86	gold quality
right lobe of liver	UBERON:0001114	73.67	gold quality
parietal pleura	UBERON:0002400	73.58	gold quality
zone of skin	UBERON:0000014	73.50	gold quality
gall bladder	UBERON:0002110	72.85	gold quality
skin of leg	UBERON:0001511	72.72	gold quality
epithelium of nasopharynx	UBERON:0001951	72.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.37	gold quality
pleura	UBERON:0000977	72.35	gold quality
visceral pleura	UBERON:0002401	72.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	72.15	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DLX4, GFI1, IRF1, IRF2, IRF4, JUN, KLF2, MYB, MYC, NFAT5, PAX5, PREB, SPIB, STAT3, STAT5A, TP63, TXK

miRNA regulators (miRDB)

68 targeting IL7, 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-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494

Literature-anchored findings (GeneRIF, showing 40)

• IL7 downregulates both TGF-beta production and signaling in pulmonary fibroblasts. (PMID:11927620)
• Effects on human thymus function. (PMID:11929775)
• an aromatic residue is required at position 143 of human IL-7 for IL-7R binding and subsequent signal transduction (PMID:12027403)
• increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27(+) thymocytes expressing CXCR4 or CCR5 (PMID:12072494)
• IL-7 may function to regulate the milieu of the microenvironment by modulating IL-6 secretion by the IL-7R-expressing stromal elements (PMID:12149213)
• IL-7 has a role in T cell regeneration that may be useful in enhancing immunity in AIDS infection [review] (PMID:12427286)
• Patients with untreated AML had decreased IL-7 serum levels. Patients in complete remission had intermediate levels and developed adverse effects. IL-7 enhanced in vitro proliferation by clone T-cells and these cells responded to IL-2 and Il-7. (PMID:12433286)
• C-terminal modification alters biological activity (PMID:12441142)
• A role for IL-7-driven inflammation in atherogenesis was suggested and the promotion of clinical instability in coronary artery disease involving interactions between platelets, monocytes, and chemokines (PMID:12742982)
• IL-7 and its downstream signalling complex have roles in some human solid malignancies [review] (PMID:12792903)
• IL-7 regulates homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in T cells that have recently exited from the thymus as well as mature naive and memory T cell subsets. (PMID:12816983)
• IL-7 confers potent survival signals to some but not all subpopulations of human thymocytes in vitro; in contrast, in vivo administration of IL-7 to SCID/hu Thy/Liv mice is not associated with enhanced thymocyte survival or accelerated HIV infection. (PMID:12847229)
• results confirm a role for SDF-1alpha and IL-7 in HIV-1 disease progression, and suggest that these cytokines play a role in the modulation of CXCR4 (PMID:12882655)
• Recombinant human IL-7 induces both a renewal and an expansion of T lymphocytes associated with cell activation in SIVmac-infected macaques without modulation of the other hemopoietic cells and with no increase in the viral load in blood or lymph nodes. (PMID:14530372)
• the drop in CD4 in HIV children would induce an increase of IL-7 as part of a homeostatic mechanism (PMID:14601648)
• Interaction between IL-7 and its receptor has the major role in modulating T-ALL survival within the microenvironment generated by the T-ALL/TEC interaction. (PMID:14607751)
• Human IL-7 has potent effects on the survival and expansion of T cells that are sufficient to significantly increase lethality of murine graft-vs-host disease in the absence of a conditioning regimen. (PMID:14978141)
• IL-7 induced the death of DN STAT5 expressing 697 cells occurs through caspase-dependent and -independent mechanisms that both require mitochondrial activation. (PMID:15048088)
• Interleukin-7 and transforming growth factor-beta play counter-regulatory roles in protein kinase C-delta-dependent control of fibroblast collagen synthesis in pulmonary fibrosis (PMID:15133032)
• Results suggest that the functional interplay between interferon regulatory factors 1 and 2 serves as an elaborate and cooperative mechanism for regulation of interleukin-7 production essential for local immune regulation within human intestinal mucosa. (PMID:15226432)
• Interleukin-7 has a role in rejuvenating the immune system [review] (PMID:15247003)
• interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells requires PI3 kinase (PMID:15353558)
• elevated plasma levels of circulating IL-7 in a subgroup of common variable immunodeficiency (PMID:15598813)
• IL-7 response to T-cell depletion may enhance T-cell production, but at the same time may foster HIV-1 disease progression favoring the emergence of more virulent HIV-1 strains characterized by syncytium-inducing capability and rapid replication rate. (PMID:15911446)
• Transfected into bone marrow stromal cells, protects mice from lukemia following allogeneic T-cell-depleted bone marrow transplantation. (PMID:15964403)
• Anergy induction by IL-7 and restoration of responsiveness by IL-15 suggest novel mechanisms for regulation of helper T-cell responses, induction of peripheral tolerance, and breakdown of T-cell self-tolerance. (PMID:15993713)
• IL-7, which is increased endogenously in HIV-1-infected individuals late in disease, may be involved in the neuronal apoptosis (PMID:16162475)
• findings suggest that higher IL-7 levels may contribute to higher CD4 counts in Hiv-1 infected women (PMID:16284535)
• IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. (PMID:16322477)
• IL-7 plasma levels were higher in centenarian females than males. (PMID:16626395)
• IL-7 promotes the extended survival of both naive and memory CD4+ T cells, whereas cycling of these two subsets is distinct and transient. (PMID:16709829)
• IL-7 plays a major role in the expansion of mature T-cells that occurs during lymphopenia and has a role in immunotherapy [review] (PMID:16923550)
• CD4+ T-cell lymphopenia has an impact on human B-cell development either directly or indirectly via the associated elevation of IL-7 levels (PMID:17053062)
• IL-7 has a distinct inductive effect on APOBEC3G (A3G) deoxycytidine deaminase gene expression and A3G complex assembly that occur in natural cellular targets of human immunodeficiency virus infection. (PMID:17110377)
• showed the capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic patients and to induce osteoclastogenesis in cancer patients without bone involvement (PMID:17205128)
• The level of IL-7-mediated reduction of apoptosis was inversely correlated with the number of circulating CD4+ T cells. The antiapoptotic effect of IL-7 was uncoupled from the induction of cellular proliferation or endogenous HIV-1 replication (PMID:17284597)
• IL-7 has a major role in the enhanced survival mediated by BM stroma both in T-ALL cells and thymocytes (PMID:17296584)
• IL-7 and, to a limited extent, TNFalpha, both of which are produced by activated monocytes and were detected in synovial fluid, abrogated the CD4+,CD25+ Treg-mediated suppression. (PMID:17328044)
• A three base ATC deletion just upstream of an out-of-frame ATG codon in the upstream non-coding region of the IL-7 gene, reduces the efficiency of translation from the upstream, out-of-frame ATG. (PMID:17373935)
• IL-7 levels were found to be strongly associated with ovarian cancer. (PMID:17438097)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il7	ENSMUSG00000040329
rattus_norvegicus	Il7	ENSRNOG00000011973

Protein

Protein identifiers

Interleukin-7 — P13232 (reviewed: P13232)

All UniProt accessions (5): P13232, A0A0A0MTG5, Q5FBX5, Q5FBY3, Q5FBY6

UniProt curated annotations — full annotation on UniProt →

Function. Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintaining lymphoid homeostasis. Mechanistically, exerts its biological effects through a receptor composed of IL7RA subunit and the cytokine receptor common subunit gamma/CSF2RG. Binding to the receptor leads to activation of various kinases including JAK1 or JAK3 depending on the cell type and subsequently propagation of signals through activation of several downstream signaling pathways including the PI3K/Akt/mTOR or the JAK-STAT5.

Subunit / interactions. Interacts with IL7R and CSF2RG.

Subcellular location. Secreted.

Disease relevance. Immunodeficiency 130 with HPV-related verrucosis (IMD130) [MIM:618309] An autosomal recessive immunologic disorder characterized by susceptibility to human papillomavirus (HPV) infections that lead to the development of warts and verrucous or plaque-like skin lesions. There is an increased risk of skin malignancy. Some patients may also suffer from mycobacterial, herpes simplex virus (HSV), or fungal infections. Immunologic workup shows T-cell lymphopenia, particularly affecting CD4+ T cells. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the IL-7/IL-9 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P13232-1	1	yes
P13232-2	2
P13232-3	3

RefSeq proteins (4): NP_000871, NP_001186815, NP_001186816, NP_001186817 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001181	IL-7	Family
IPR018049	IL-7/IL-9_CS	Conserved_site
IPR038325	IL7_sf	Homologous_superfamily

Pfam: PF01415

UniProt features (21 total): helix 6, splice variant 3, glycosylation site 3, disulfide bond 3, turn 2, signal peptide 1, chain 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3DI2	X-RAY DIFFRACTION	2.7
3DI3	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13232-F1	74.68	0.34

Functional residue map

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

Disulfide bonds (3): 27–166, 59–154, 72–117

Glycosylation sites (3): 95, 116, 141

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling

MSigDB gene sets: 357 (showing top): AHRARNT_01, MORF_ITGA2, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH

GO Biological Process (26): positive regulation of cytokine-mediated signaling pathway (GO:0001961), T cell lineage commitment (GO:0002360), humoral immune response (GO:0006959), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), animal organ morphogenesis (GO:0009887), cytokine-mediated signaling pathway (GO:0019221), positive regulation of B cell proliferation (GO:0030890), positive regulation of chemokine production (GO:0032722), organ growth (GO:0035265), interleukin-7-mediated signaling pathway (GO:0038111), B cell proliferation (GO:0042100), negative regulation of apoptotic process (GO:0043066), bone resorption (GO:0045453), positive regulation of B cell differentiation (GO:0045579), positive regulation of T cell differentiation (GO:0045582), positive regulation of organ growth (GO:0046622), homeostasis of number of cells within a tissue (GO:0048873), extrinsic apoptotic signaling pathway (GO:0097191), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), immune response (GO:0006955), signal transduction (GO:0007165), regulation of gene expression (GO:0010468), positive regulation of gene expression (GO:0010628), cellular homeostasis (GO:0019725), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237)

GO Molecular Function (5): cytokine activity (GO:0005125), interleukin-7 receptor binding (GO:0005139), growth factor activity (GO:0008083), cytokine receptor binding (GO:0005126), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

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
cytokine-mediated signaling pathway	2
T cell differentiation	2
cell surface receptor signaling pathway	2
positive regulation of B cell activation	2
tissue homeostasis	2
positive regulation of lymphocyte differentiation	2
receptor ligand activity	2
regulation of cytokine-mediated signaling pathway	1
positive regulation of signal transduction	1
positive regulation of response to cytokine stimulus	1
cell fate commitment	1
immune response	1
cell communication	1
signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
anatomical structure morphogenesis	1
animal organ development	1
cellular response to cytokine stimulus	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
multicellular organismal process	1
developmental growth	1
cellular response to interleukin-7	1
B cell activation	1
lymphocyte proliferation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
bone remodeling	1
B cell differentiation	1
regulation of B cell differentiation	1
regulation of T cell differentiation	1
positive regulation of T cell activation	1
organ growth	1

Protein interactions and networks

STRING

2588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL7	IL7R	P16871	999
IL7	IL4	P05112	998
IL7	IL2	P01585	997
IL7	IL9	P15248	997
IL7	IL2RG	P31785	997
IL7	IL5	P05113	995
IL7	JAK3	P52333	994
IL7	IL3	P08700	988
IL7	IL10	P22301	988
IL7	IL6	P05231	984
IL7	IL15	P40933	966
IL7	STAT5A	P42229	930
IL7	STAT5B	P51692	925
IL7	IL2RA	P01589	924
IL7	HGF	P14210	922

IntAct

14 interactions, top by confidence:

A	B	Type	Score
IL7	IL7R	psi-mi:“MI:0407”(direct interaction)	0.740
IL7	IL7R	psi-mi:“MI:0915”(physical association)	0.740
IL7R	IL7	psi-mi:“MI:0915”(physical association)	0.740
IL2RG	IL7	psi-mi:“MI:0915”(physical association)	0.400
IL7	ZMPSTE24	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): IL7 (Biochemical Activity), IL7 (Affinity Capture-RNA), NOTCH3 (Affinity Capture-MS), QKI (Affinity Capture-MS), ATF6B (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), APP (Reconstituted Complex), IL7 (Two-hybrid)

ESM2 similar proteins: A3QPB9, B0ZE70, B3F0J0, C8AW45, O62757, O77762, O97687, P05113, P07750, P10168, P11052, P13232, P15247, P15248, P20096, P20826, P28773, P40221, P40933, P46685, P48092, P48093, P48346, P55030, P60568, P60569, P68290, P68291, P97604, Q1WM29, Q28028, Q29615, Q3S4V6, Q3Y5G8, Q4GZL1, Q4U0U2, Q5WQV8, Q6EAL8, Q6EBC2, Q75SZ9

Diamond homologs: P10168, P13232, P26895, P56478, Q28540, Q9N2G6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
IL7	up-regulates	IL2RG	binding
IL7	up-regulates	IL7R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	64
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
144237	GRCh38/hg38 8q21.13(chr8:74905308-81339951)x1	Pathogenic
3384148	NM_000880.4(IL7):c.284del (p.Asn95fs)	Pathogenic
3384149	NM_000880.4(IL7):c.3G>A (p.Met1Ile)	Pathogenic
563542	GRCh37/hg19 8q21.11-21.13(chr8:74942333-80413867)x1	Pathogenic
694068	NM_000880.4(IL7):c.205A>T (p.Arg69Ter)	Pathogenic

SpliceAI

2940 predictions. Top by Δscore:

Variant	Effect	Δscore
8:78675861:TTA:T	donor_gain	1.0000
8:78675862:TA:T	donor_gain	1.0000
8:78675864:G:GG	donor_gain	1.0000
8:78678558:A:AG	acceptor_gain	1.0000
8:78678558:AACAG:A	acceptor_loss	1.0000
8:78678559:ACAG:A	acceptor_loss	1.0000
8:78678560:CAGAA:C	acceptor_loss	1.0000
8:78678561:A:AG	acceptor_gain	1.0000
8:78678561:A:C	acceptor_loss	1.0000
8:78678562:G:GG	acceptor_gain	1.0000
8:78678562:GA:G	acceptor_gain	1.0000
8:78678562:GAA:G	acceptor_gain	1.0000
8:78678562:GAAA:G	acceptor_gain	1.0000
8:78678562:GAAAA:G	acceptor_gain	1.0000
8:78678659:G:GG	donor_gain	1.0000
8:78678676:GAGG:G	donor_gain	1.0000
8:78678678:GG:G	donor_gain	1.0000
8:78678679:GG:G	donor_gain	1.0000
8:78686466:GCC:G	acceptor_gain	1.0000
8:78686466:GCCA:G	acceptor_gain	1.0000
8:78686537:C:G	donor_gain	1.0000
8:78686645:A:T	donor_gain	1.0000
8:78689218:ATAG:A	acceptor_loss	1.0000
8:78689219:TA:T	acceptor_loss	1.0000
8:78689220:A:AG	acceptor_gain	1.0000
8:78689220:AGATT:A	acceptor_loss	1.0000
8:78689221:G:GG	acceptor_gain	1.0000
8:78689371:GTG:G	donor_gain	1.0000
8:78689371:GTGGT:G	donor_loss	1.0000
8:78689372:TGGTA:T	donor_loss	1.0000

AlphaMissense

1186 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:78733746:C:A	W167C	0.996
8:78733746:C:G	W167C	0.996
8:78733748:A:G	W167R	0.992
8:78733748:A:T	W167R	0.992
8:78738622:A:G	L81S	0.988
8:78733749:A:C	C166W	0.986
8:78738624:A:C	F80L	0.984
8:78738624:A:T	F80L	0.984
8:78738626:A:G	F80L	0.984
8:78740015:C:G	C72S	0.983
8:78740016:A:T	C72S	0.983
8:78733750:C:T	C166Y	0.981
8:78740015:C:T	C72Y	0.980
8:78798139:C:G	C27S	0.980
8:78798140:A:T	C27S	0.980
8:78733747:C:G	W167S	0.979
8:78738613:G:T	A84D	0.979
8:78738614:C:G	A84P	0.979
8:78740016:A:G	C72R	0.979
8:78733751:A:G	C166R	0.977
8:78798087:G:C	S44R	0.976
8:78798087:G:T	S44R	0.976
8:78798089:T:G	S44R	0.976
8:78733771:A:G	L159P	0.975
8:78738625:A:C	F80C	0.975
8:78740014:A:C	C72W	0.974
8:78738544:A:T	V107D	0.973
8:78798140:A:G	C27R	0.973
8:78798110:A:C	Y37D	0.972
8:78733786:C:G	C154S	0.971

dbSNP variants (sampled 300 via entrez): RS1000012710 (8:78756268 A>T), RS1000052177 (8:78752480 C>G,T), RS1000059242 (8:78731556 T>C), RS1000080875 (8:78756245 A>C), RS1000095322 (8:78709981 C>G,T), RS1000104464 (8:78765984 T>C), RS1000110698 (8:78804003 A>G), RS1000116233 (8:78757107 AT>A,ATT), RS1000147829 (8:78709717 A>G), RS1000148862 (8:78774085 A>G), RS1000170509 (8:78756740 A>G), RS1000192960 (8:78682348 T>A,C), RS1000202661 (8:78714129 A>G), RS1000257066 (8:78766177 C>A,T), RS1000264177 (8:78716996 C>T)

Disease associations

OMIM: gene MIM:146660 | disease phenotypes: MIM:618309

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency	Strong	Autosomal recessive
epidermodysplasia verruciformis	Supportive	Autosomal recessive
epidermodysplasia verruciformis, susceptibility to, 5	Limited	Autosomal recessive

Mondo (3): epidermodysplasia verruciformis, susceptibility to, 5 (MONDO:0032667), epidermodysplasia verruciformis (MONDO:0009176), combined immunodeficiency (MONDO:0015131)

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001051	Seborrheic dermatitis
HP:0001053	Hypopigmented skin patches
HP:0001581	Recurrent skin infections
HP:0001888	Decreased total lymphocyte count
HP:0002715	Abnormality of the immune system
HP:0002860	Squamous cell carcinoma
HP:0005403	Decreased total T cell count
HP:0006739	Squamous cell carcinoma of the skin
HP:0007565	Multiple cafe-au-lait spots
HP:0020114	Persistent human papillomavirus infection
HP:0032160	Cryptococcal meningitis
HP:0100585	Telangiectasia of the skin
HP:0200034	Papule
HP:0200035	Skin plaque
HP:0200039	Pustule
HP:0200043	Verrucae

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001198_67	Multiple sclerosis	2.000000e-07
GCST002699_3	Suicide in bipolar disorder	3.000000e-06
GCST004627_45	Lymphocyte count	7.000000e-32
GCST004632_64	Lymphocyte percentage of white cells	8.000000e-19
GCST004633_78	Neutrophil percentage of white cells	1.000000e-10
GCST006585_1386	Blood protein levels	5.000000e-16
GCST90002388_250	Lymphocyte count	1.000000e-86
GCST90002388_251	Lymphocyte count	2.000000e-41
GCST90002389_180	Lymphocyte percentage of white cells	4.000000e-65
GCST90002394_280	Monocyte percentage of white cells	7.000000e-12
GCST90002399_199	Neutrophil percentage of white cells	5.000000e-39

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004321	attempted suicide
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004819	Epidermodysplasia Verruciformis	C01.925.256.650.810.345; C01.925.825.810.260; C01.925.928.914.345; C17.800.838.790.810.260

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
rs16906115	Toxicity	3	PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors	adverse events

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs16906115	IL7	3	3.50	1	PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	5
Lipopolysaccharides	decreases reaction, increases expression, increases secretion, affects response to substance	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases expression	2
Plant Extracts	decreases reaction, increases abundance, increases expression	2
Dronabinol	increases expression, decreases reaction, increases phosphorylation, increases reaction	2
coagulin-L	decreases reaction, increases expression	1
GSK3235025	decreases phosphorylation, decreases reaction	1
bisphenol F	decreases methylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
5’-methylthioadenosine	decreases phosphorylation, decreases reaction	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
2-butenal	increases expression	1
manganese chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
emamectin benzoate	increases expression	1
monomethylarsonous acid	decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	decreases expression	1
Ethanol	increases expression	1
Arsenic	decreases expression	1
Azathioprine	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_C3HN	RCC-26/CD80/IL-7	Cancer cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02737384	PHASE2	TERMINATED	Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID)
NCT00973856	Not specified	COMPLETED	Evaluation of the Effectiveness of an Alcohol Based Hand Gel for the Reduction of Warts on the Hands
NCT02915406	Not specified	NO_LONGER_AVAILABLE	cliniMACs HUD for T Cell Depletion
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation
NCT06659588	Not specified	RECRUITING	Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency