IL7R

Summary

IL7R (interleukin 7 receptor, HGNC:6024) is a protein-coding gene on chromosome 5p13.2, encoding Interleukin-7 receptor subunit alpha (P16871). Receptor for interleukin-7.

The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found.

Source: NCBI Gene 3575 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 104 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 43 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 622 total — 47 pathogenic, 17 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 12 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 59
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_002185
• Interaction hub: 3,030 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6024
Approved symbol	IL7R
Name	interleukin 7 receptor
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD127, IL7RA, lnc-IL7R, IL-7Ralpha, IL7Ralpha, sIL-7R, CDw127
Ensembl gene	ENSG00000168685
Ensembl biotype	protein_coding
OMIM	146661
Entrez	3575

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000303115

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000303115, ENST00000505093, ENST00000505875, ENST00000506850, ENST00000508941, ENST00000509668, ENST00000511031, ENST00000511982, ENST00000514217, ENST00000515665, ENST00000877114, ENST00001042026, ENST00001110206, ENST00001128373, ENST00001138970

RefSeq mRNA: 4 — MANE Select: NM_002185 NM_001410734, NM_001437963, NM_001437964, NM_002185

CCDS: CCDS3911

Canonical transcript exons

ENST00000303115 — 8 exons

Exon	Start	End
ENSE00001130269	35873480	35873648
ENSE00001130274	35871056	35871213
ENSE00001130282	35867306	35867463
ENSE00001805007	35875983	35879603
ENSE00002047686	35856891	35857059
ENSE00003475448	35875512	35875587
ENSE00003666759	35874449	35874542
ENSE00003667135	35860852	35860990

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.0899 / max 3672.3247, expressed in 1029 samples.

Highest expression (Bgee): lung, granulocyte, lymph node, lower lobe of lung, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IL7R is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	3.6e-47	-1.02	5:35874473:C:T
Lung	sqtl	2.5e-36	+0.94	5:35874473:C:T
Testis	eqtl	3.1e-17	-0.45	5:35856528:G:A
Whole Blood	sqtl	7.8e-07	+0.35	5:35874473:C:T
Cells Cultured fibroblasts	eqtl	1.8e-06	-0.15	5:35920156:T:C
Esophagus Mucosa	eqtl	4.0e-04	-0.10	5:35845546:A:G
Esophagus Muscularis	eqtl	5.7e-03	+0.17	5:35828018:T:C
Testis	sqtl	5.9e-03	+0.39	5:35953847:G:A
Colon Sigmoid	eqtl	7.1e-03	-0.24	5:35762490:G:A
Ovary	eqtl	1.4e-02	-1.79	5:35276148:C:T
Muscle Skeletal	eqtl	1.7e-02	-0.83	5:35386952:G:C
Skin Sun Exposed Lower leg	eqtl	2.3e-02	+0.10	5:35828018:T:C
Brain Caudate basal ganglia	eqtl	2.7e-02	-0.83	5:35331268:G:A
Esophagus Gastroesophageal Junction	sqtl	3.7e-02	+1.59	5:35374739:T:G
Esophagus Gastroesophageal Junction	eqtl	3.7e-02	-0.57	5:35124793:T:C
Small Intestine Terminal Ileum	eqtl	4.2e-02	+0.16	5:35828018:T:C
Brain Hypothalamus	eqtl	4.6e-02	+1.22	5:35021766:T:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
56110	27.3324	686
56111	19.0782	898
56112	1.9516	204
56109	0.7694	234
56108	0.6947	230
56104	0.6290	151
56113	0.5137	57
56105	0.1210	59

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	97.85	gold quality
granulocyte	CL:0000094	97.14	gold quality
lymph node	UBERON:0000029	96.99	gold quality
lower lobe of lung	UBERON:0008949	96.62	gold quality
epithelium of nasopharynx	UBERON:0001951	96.15	gold quality
nasopharynx	UBERON:0001728	96.13	gold quality
vermiform appendix	UBERON:0001154	95.94	gold quality
blood	UBERON:0000178	95.38	gold quality
thymus	UBERON:0002370	95.07	gold quality
upper lobe of left lung	UBERON:0008952	94.78	gold quality
upper lobe of lung	UBERON:0008948	94.73	gold quality
gall bladder	UBERON:0002110	94.10	gold quality
lung	UBERON:0002048	93.39	gold quality
caecum	UBERON:0001153	92.89	gold quality
spleen	UBERON:0002106	92.74	gold quality
visceral pleura	UBERON:0002401	92.74	gold quality
colonic epithelium	UBERON:0000397	92.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.93	gold quality
amniotic fluid	UBERON:0000173	91.05	gold quality
small intestine	UBERON:0002108	90.20	gold quality
jejunal mucosa	UBERON:0000399	90.08	gold quality
bone marrow	UBERON:0002371	89.41	gold quality
tonsil	UBERON:0002372	88.92	gold quality
rectum	UBERON:0001052	88.85	gold quality
trabecular bone tissue	UBERON:0002483	88.16	gold quality
superficial temporal artery	UBERON:0001614	87.91	gold quality
bone marrow cell	CL:0002092	87.57	gold quality
ileal mucosa	UBERON:0000331	87.32	gold quality
pleura	UBERON:0000977	87.23	gold quality
parietal pleura	UBERON:0002400	86.59	gold quality
mucosa of urinary bladder	UBERON:0001259	84.65	gold quality
duodenum	UBERON:0002114	84.38	gold quality
cartilage tissue	UBERON:0002418	84.23	gold quality
omental fat pad	UBERON:0010414	83.33	gold quality
peritoneum	UBERON:0002358	83.28	gold quality
adult organism	UBERON:0007023	83.23	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.77	gold quality
left uterine tube	UBERON:0001303	82.00	gold quality
mucosa of transverse colon	UBERON:0004991	81.49	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.80	gold quality
pylorus	UBERON:0001166	80.69	gold quality
intestine	UBERON:0000160	80.66	gold quality
body of stomach	UBERON:0001161	80.62	gold quality
urinary bladder	UBERON:0001255	80.57	gold quality
colonic mucosa	UBERON:0000317	80.22	gold quality
tibia	UBERON:0000979	80.05	gold quality
stomach	UBERON:0000945	79.67	gold quality
transverse colon	UBERON:0001157	79.53	gold quality
jejunum	UBERON:0002115	79.31	gold quality
fundus of stomach	UBERON:0001160	79.14	gold quality
vagina	UBERON:0000996	78.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.91	gold quality
large intestine	UBERON:0000059	77.85	gold quality
oral cavity	UBERON:0000167	77.67	gold quality
colon	UBERON:0001155	77.39	gold quality
thyroid gland	UBERON:0002046	76.83	gold quality
left lobe of thyroid gland	UBERON:0001120	76.82	gold quality
tongue squamous epithelium	UBERON:0006919	76.48	gold quality
cardia of stomach	UBERON:0001162	76.35	gold quality
right lobe of thyroid gland	UBERON:0001119	76.04	gold quality
cervix epithelium	UBERON:0004801	76.01	silver quality
adipose tissue	UBERON:0001013	75.84	gold quality
connective tissue	UBERON:0002384	75.81	gold quality
stromal cell of endometrium	CL:0002255	75.77	gold quality
palpebral conjunctiva	UBERON:0001812	75.70	gold quality
lower esophagus mucosa	UBERON:0035834	75.52	gold quality
left adrenal gland	UBERON:0001234	75.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.46	gold quality
ectocervix	UBERON:0012249	75.27	gold quality
mammalian vulva	UBERON:0000997	75.10	gold quality
right adrenal gland cortex	UBERON:0035827	75.00	gold quality
pericardium	UBERON:0002407	74.98	gold quality
left adrenal gland cortex	UBERON:0035825	74.93	gold quality
adrenal gland	UBERON:0002369	74.82	gold quality
mammary duct	UBERON:0001765	74.72	silver quality
uterine cervix	UBERON:0000002	74.69	gold quality
prostate gland	UBERON:0002367	74.68	gold quality
decidua	UBERON:0002450	74.63	silver quality
esophagus mucosa	UBERON:0002469	74.58	gold quality
minor salivary gland	UBERON:0001830	74.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.44	gold quality
right coronary artery	UBERON:0001625	74.42	gold quality
thoracic mammary gland	UBERON:0005200	73.93	gold quality
smooth muscle tissue	UBERON:0001135	73.84	gold quality
mammary gland	UBERON:0001911	73.81	gold quality
oviduct epithelium	UBERON:0004804	73.80	silver quality
adrenal cortex	UBERON:0001235	73.74	gold quality
left coronary artery	UBERON:0001626	73.59	gold quality
fallopian tube	UBERON:0003889	73.59	gold quality
cervix squamous epithelium	UBERON:0006922	73.58	gold quality
mouth mucosa	UBERON:0003729	73.37	gold quality
right adrenal gland	UBERON:0001233	73.28	gold quality
skin of hip	UBERON:0001554	73.15	gold quality
coronary artery	UBERON:0001621	73.05	gold quality
squamous epithelium	UBERON:0006914	73.02	silver quality
epithelium of mammary gland	UBERON:0003244	72.87	silver quality
urethra	UBERON:0000057	72.54	gold quality
gingiva	UBERON:0001828	72.21	silver quality
endocervix	UBERON:0000458	72.19	gold quality

Single-cell (SCXA)

Detected in 48 experiment(s), a significant marker in 37.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	3376.74
E-MTAB-8142	yes	3013.77
E-CURD-120	yes	2795.48
E-MTAB-10553	yes	2745.88
E-CURD-112	yes	2710.99
E-CURD-88	yes	2530.67
E-CURD-122	yes	2472.53
E-GEOD-150728	yes	2351.19
E-HCAD-36	yes	2323.57
E-MTAB-6678	yes	2064.91
E-MTAB-10042	yes	1976.12
E-MTAB-9221	yes	1957.26
E-HCAD-1	yes	1893.19
E-MTAB-10855	yes	1829.62
E-HCAD-15	yes	1803.04

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	171.2	high
Lymph node	tissue	130.9	medium
Appendix	tissue	129.9	low
Tonsil	tissue	115.5	medium
Spleen	tissue	66.1	medium
Lung	tissue	60.3	not detected
Small intestine	tissue	53.5	not detected
Urinary bladder	tissue	44.9	not detected
Stomach 1	tissue	32.1	not detected
Gallbladder	tissue	30.5	not detected
Rectum	tissue	19.2	not detected
Breast	tissue	19.0	not detected
Choroid plexus	tissue	18.8
Nucleus accumbens	tissue	18.4
Hippocampus	tissue	18.2	not detected
Postcentral gyrus	tissue	17.2
Colon	tissue	16.2	not detected
Locus coeruleus	tissue	15.4
Duodenum	tissue	14.1	not detected
Adrenal gland	tissue	13.6	not detected
Bone marrow	tissue	13.1	medium
Liver	tissue	11.7	not detected
Cervix	tissue	11.2	not detected
Esophagus	tissue	10.4	not detected
Prostate	tissue	8.2	not detected
Vagina	tissue	6.9	not detected
Adipose tissue	tissue	6.4	not detected
Smooth muscle	tissue	5.2	not detected
Pancreas	tissue	5.0	not detected
Testis	tissue	4.4	not detected
Thyroid gland	tissue	4.1	not detected
Skeletal muscle	tissue	3.9	not detected
Endometrium 1	tissue	3.8	not detected
Skin 1	tissue	3.6	not detected
Seminal vesicle	tissue	2.9	not detected
Kidney	tissue	2.9	not detected
Fallopian tube	tissue	2.9	not detected
Salivary gland	tissue	2.6	not detected
Placenta	tissue	2.6	not detected
Ovary	tissue	2.0	not detected
Heart muscle	tissue	1.7	not detected
Pituitary gland	tissue	1.6
Tongue	tissue	1.6
Epididymis	tissue	1.5
Spinal cord	tissue	1.3
Substantia nigra	tissue	0.9
Retina	tissue	0.8
Parathyroid gland	tissue	0.7	not detected
Medulla oblongata	tissue	0.7
Pons	tissue	0.6
Thalamus	tissue	0.6
Corpus callosum	tissue	0.5
Olfactory bulb	tissue	0.5
Hypothalamus	tissue	0.4
Superior colliculi	tissue	0.4
Hippocampal formation	tissue	0.4
Entorhinal cortex	tissue	0.4
Periaqueductal gray	tissue	0.4
Septum	tissue	0.4
Cerebral cortex	tissue	0.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (31.6), Vermis (29.1), Parieto-temporal junction (white matter) (28.0), Anterior thalamic nucleus, ventral (27.9), Cerebellar cortex (26.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BRD2, BRD4, ETS1, FOS, FOXO1, FOXP1, GABPA, GATA3, GFI1, IKZF1, JUN, MAFB, MYC, NOTCH1, NR3C1, RELA, RUNX1, SPI1, STAT5A, TCF3, ZBTB17

Functional genomics

gnomAD constraint: pLI 2.53e-08, LOEUF 0.981, missense Z -1.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000303115 — one region, missense o/e 1.18.

Literature-anchored findings (GeneRIF, showing 40)

• 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-2 signaling can diminish IL-7Ralpha expression via a phosphatidylinositol 3-kinase/Akt-dependent mechanism. (PMID:12354940)
• IL-7R has a role in some human solid malignancies [review] (PMID:12792903)
• 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)
• Expansion of CD8 positive, CD127 negative effector-like T cells is identified as a novel feature of HIV-associated immune perturbation. (PMID:15728501)
• Maturation of memory CD4 and CD8 T cells is associated with a CD127high phenotype and the expression of CD127 serves as a predictor of the functional quality of antiviral T cells. (PMID:15879083)
• Virus-specific IL-7Ralpha+ cells proliferated vigorously in response to IL-7, IL-15, or peptide, whereas IL-7Ralpha- cells required both peptide and helper-cell activation or IL-2 or IL-15 for optimal expansion (PMID:15947093)
• Altogether, we show that gamma(c) is the target of an ubiquitination mechanism and its expression level can be regulated through the activities of a couple of ubiquitin-ligase/ubiquitin-hydrolase enzymes, namely c-Cbl/DUB-2. (PMID:16004964)
• The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. (PMID:16075257)
• Aging affects IL-7Ralpha expression by T cells, leading to impaired signaling and survival responses to IL-7. (PMID:16357322)
• HIV infection produces the Tat protein, which in turn may up-regulate IL-7R in a paracrine manner, which ultimately promotes early events in HIV replication. (PMID:16614257)
• Transcription of the IL-7R alpha subunit is suppressed in both naive and memory T cells following IL-7 stimulation. (PMID:16709829)
• Cell surface expression of CD127 therefore allows accurate estimation of regulatory T cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases. (PMID:16818676)
• CD127 can be used to quantitate regulatory T (Treg) cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human Treg cells. (PMID:16818678)
• CD127 expression on T cells remains low in HIV-infected patients despite antiretroviral therapy (PMID:16837861)
• IL-7 receptor and Notch1 pathways cooperate to synchronize cell proliferation and suppression of non-T lineage choices in primitive intrathymic progenitors. (PMID:16951331)
• CD127 uniquely enables the purification of FOXP3+ Treg cells and, potentially, also “adaptive” regulatory T-cell subsets from the CD4+CD25- T-cell population. (PMID:17045841)
• A large fraction of peripheral HCV-specific CD8+ T cells were CD127+ and KLRG1-. Intrahepatic virus-specific CD8+ T cells displayed significantly reduced levels of CD127 expression but similar levels of KLRG1 expression compared to the peripheral blood. (PMID:17079288)
• CD4+ regulatory T-cells exhibiting suppressive activity in vitro display distinctly lower surface expression of CD127, irrespective of their level of CD25 expression. (PMID:17173927)
• results confirm that signal transduction via the IL-15R, and hence NK ontogeny, is preferentially retained relative to the IL-7R as gammac expression becomes limiting. (PMID:17363735)
• These findings suggest that DNA methylation is involved in regulating IL-7Ralpha expression in T cells via affecting IL-7Ralpha gene promoter activity. (PMID:17442928)
• gene encoding the IL-7Ralpha chain is polymorphic, and investigation of inhalation allergic patients compared with controls showed significant association with two alleles at position +1237 and +2087 (PMID:17504502)
• A subset of naive CD8-positive cells characterized by low interleukin-7 receptor alpha message and protein expression may encompass cells that have recently received homeostatic signals. (PMID:17579041)
• CD4(+)CD25(+)CD45RO(+)IL-7Ralpha(high) cell population contained allospecific CD4 T cells and secreted effector cytokines. (PMID:17591854)
• Increased constitutive interleukin-7 receptor alpha expression has minimal effects on the numbers or function of effector and memory CD8 T cells formed. (PMID:17609371)
• Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis. (PMID:17660530)
• Results provide compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor alpha chain (IL7Ralpha), indeed contribute to the non-HLA genetic risk in multiple sclerosis. (PMID:17660816)
• Results show allelic association of a polymorphism in interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets. (PMID:17660817)
• Immunolocalization of IL-7, IL-7Ralpha, SDF-1alpha, and CXCR4 resulted in a diffuse but specific labeling. RT-PCR analysis confirmed the expression of the above-mentioned transcripts. (PMID:17894415)
• Stimulation of the IL-7 pathway begins with IL-7 binding to unglycosylated and glycosylated forms of its alpha-receptor, IL-7 receptor alpha. (PMID:17909291)
• Haplotypes of the IL7R gene are correlated with altered expression in whole blood cells in multiple sclerosis. (PMID:17928869)
• IL-7 reduced CD127-surface expression and shedding by CD8+ T cells; results support a role for IL-7 in the down-regulation of CD127 expression and impairment of CTL function observed in HIV infection (PMID:17956896)
• We report that loss of CD127 defines terminally differentiated B cell-helping effector T cells in human tonsils. (PMID:18025189)
• The association between rs6897932 and multiple sclerosis in the Olmsted County collection appeared to be much stronger than anticipated on the basis of recent studies (PMID:18272905)
• Expression of transgenic IL-7 receptor alpha by itself does not support increased survival of effector antigen-specific CD4 or CD8 T cells into the memory phase following infection with Listeria monocytogenes. (PMID:18292507)
• IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. (PMID:18354419)
• IL-7- and TCR/CD28-mediated signaling data show that differentially regulate IL-7Ralpha expression on human T cells with a transient and chronic effect, respectively. (PMID:18390701)
• during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression (PMID:18390743)
• Independent replication of the association between the CAPSL and IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients. (PMID:18563381)
• Association studies between IL7RA rs6897932 and multiple sclerosis. (PMID:18721276)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il7r	ENSMUSG00000003882
rattus_norvegicus	Il7r	ENSRNOG00000065741

Paralogs (7): IL4R (ENSG00000077238), CSF2RB (ENSG00000100368), IL2RB (ENSG00000100385), IL21R (ENSG00000103522), MPL (ENSG00000117400), IL9R (ENSG00000124334), EPOR (ENSG00000187266)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96562) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 38 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased thymocyte number	3
spleen hypoplasia	2
thymus hypoplasia	2
decreased B cell number	2
decreased T cell number	2
decreased double-positive T cell number	2
decreased CD8-positive, alpha-beta T cell number	2
decreased leukocyte cell number	1
decreased bone marrow cell number	1
small thymus	1
increased thymocyte number	1
arrested B cell differentiation	1
arrested T cell differentiation	1
abnormal B cell differentiation	1
abnormal T cell differentiation	1
absent Peyer’s patches	1
abnormal T cell subpopulation ratio	1
decreased B-1 B cell number	1
increased B cell number	1
decreased lymphocyte cell number	1
increased double-negative T cell number	1
increased double-positive T cell number	1
abnormal T cell proliferation	1
decreased T cell proliferation	1
abnormal CD4-positive, alpha-beta T cell physiology	1

+13 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q38IC7	97.2%	Diamond
Callithrix jacchus	A5HJM1	86.3%	Diamond
Equus caballus	A0MSX9	78.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
UGT3A1	protein-coding	133688
CAPSL	protein-coding	133690
UGT3A2	protein-coding	167127
SPEF2	protein-coding	79925
PRLR	protein-coding	5618
CAPSL-DT	ncRNA	100506406

Protein

Protein identifiers

Interleukin-7 receptor subunit alpha — P16871 (reviewed: P16871)

Alternative names: CDw127

All UniProt accessions (6): P16871, B8YG18, D6RCR9, D6RDM4, D6RG28, H0YA41

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).

Subunit / interactions. The IL7 receptor is a heterodimer of IL7R and IL2RG. The TSLP receptor is a heterodimer of CRLF2 and IL7R. Interacts with CD53.

Subcellular location. Cell membrane Cell membrane Secreted.

Post-translational modifications. N-glycosylated IL-7Ralpha binds IL7 300-fold more tightly than the unglycosylated form. Ubiquitinated by MARCHF8; leading to lysosomal degradation.

Disease relevance. Immunodeficiency 104, severe combined (IMD104) [MIM:608971] A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. The disease is caused by variants affecting the gene represented in this entry. Multiple sclerosis 3 (MS3) [MIM:612595] A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. A polymorphism at position 244 strongly influences susceptibility to multiple sclerosis. Overtransmission of the major ‘C’ allele coding for Thr-244 is detected in offspring affected with multiple sclerosis. In vitro analysis of transcripts from minigenes containing either ‘C’ allele (Thr-244) or ‘T’ allele (Ile-244) shows that the ‘C’ allele results in an approximately two-fold increase in the skipping of exon 6, leading to increased production of a soluble form of IL7R. Thus, the multiple sclerosis associated ‘C’ risk allele of IL7R would probably decrease membrane-bound expression of IL7R. As this risk allele is common in the general population, some additional triggers are probably required for the development and progression of MS.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.

Similarity. Belongs to the type I cytokine receptor family. Type 4 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P16871-1	1, H20	yes
P16871-2	3, H1
P16871-3	4, H6, Secreted
P16871-4	2, Secreted

RefSeq proteins (4): NP_001397663, NP_001424892, NP_001424893, NP_002176* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003531	Hempt_rcpt_S_F1_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR040997	FN3_7	Domain

Pfam: PF00041, PF18447

UniProt features (58 total): strand 17, sequence variant 7, helix 7, glycosylation site 6, splice variant 4, sequence conflict 4, disulfide bond 3, topological domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1, turn 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
7OPB	IL7R in complex with an antagonist	X-RAY DIFFRACTION	2.14
3UP1	Crystal structure of the unliganded human interleukin-7 receptor extracellular domain	X-RAY DIFFRACTION	2.15
5J11	Structure of human TSLP in complex with TSLPR and IL-7Ralpha	X-RAY DIFFRACTION	2.56
3DI2	Crystal structure of the complex of human interleukin-7 with unglycosylated human …	X-RAY DIFFRACTION	2.7
3DI3	Crystal structure of the complex of human interleukin-7 with glycosylated human …	X-RAY DIFFRACTION	2.9
6P50	Crystal Structure of a Complex of human IL-7Ralpha with an anti-IL-7Ralpha Fab 4A10	X-RAY DIFFRACTION	2.9
6P67	Crystal Structure of a Complex of human IL-7Ralpha with an anti-IL-7Ralpha 2B8 Fab	X-RAY DIFFRACTION	2.9
9XEA	Structure of the transmembrane domain dimer of human IL-7R V253G mutant	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16871-F1	68.52	0.42

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 6P50, 6P67

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Cancer-related genes, Mutated cancer genes, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH supported · IF supported

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)

Type	Positions
Phosphothreonine	282

Disulfide bonds (3)

Type	Positions
Disulfide bond	42–57, 74–82, 108–118

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	65, 151, 182, 232, 233, 49

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-1266695	Interleukin-7 signaling	electronic
R-HSA-199991	Membrane Trafficking	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 775 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_169, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_B_CELL_ACTIVATION

GO Biological Process (18): regulation of DNA recombination (GO:0000018), leukocyte homeostasis (GO:0001776), immune response (GO:0006955), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), cellular homeostasis (GO:0019725), hemopoiesis (GO:0030097), interleukin-7-mediated signaling pathway (GO:0038111), negative regulation of tyrosine phosphorylation of STAT protein (GO:0042532), negative regulation of apoptotic process (GO:0043066), positive regulation of T cell differentiation (GO:0045582), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), defense response to Gram-positive bacterium (GO:0050830), negative regulation of Fas signaling pathway (GO:1902045), positive regulation of receptor signaling pathway via STAT (GO:1904894), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (4): antigen binding (GO:0003823), cytokine receptor activity (GO:0004896), interleukin-7 receptor activity (GO:0004917), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), clathrin-coated endocytic vesicle membrane (GO:0030669), membrane (GO:0016020)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Signaling by Interleukins	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Immune System	1
Vesicle-mediated transport	1
Cytokine Signaling in Immune system	1

GO top-level categories

57 GO namespaces:

Category	Terms
immune system process	2
cell surface receptor signaling pathway via STAT	2
cytokine-mediated signaling pathway	2
binding	2
cellular anatomical structure	2
DNA recombination	1
regulation of DNA metabolic process	1
homeostasis of number of cells	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
homeostatic process	1
cell development	1
cellular response to interleukin-7	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
negative regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of peptidyl-tyrosine phosphorylation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
defense response to bacterium	1
negative regulation of signal transduction	1
Fas signaling pathway	1
regulation of Fas signaling pathway	1
positive regulation of signal transduction	1
regulation of receptor signaling pathway via STAT	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
cytokine receptor activity	1
interleukin-7 binding	1
interleukin-7-mediated signaling pathway	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
cellular homeostasis	BP	direct assay
interleukin-7-mediated signaling pathway	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of receptor signaling pathway via STAT	BP	direct assay
plasma membrane	CC	direct assay
cytokine receptor activity	MF	direct assay
interleukin-7 receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,030 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL7R	IL7	P13232	960
IL7R	CD8A	P01732	936
IL7R	CD4	P01730	925
IL7R	IL2RG	P31785	887
IL7R	IL2	P01585	863
IL7R	PTPRC	P08575	859
IL7R	IL2RA	P01589	857
IL7R	FOXP3	Q9BZS1	857
IL7R	KLRG1	Q96E93	855
IL7R	IL2RB	P14784	850
IL7R	CRLF2	Q9HC73	850
IL7R	TSLP	Q969D9	848
IL7R	IL15	P40933	832
IL7R	IFNG	P01579	831
IL7R	FLT3	P36888	822

IntAct

Human interaction partners of IL7R in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
IL7	direct interaction	0.740	10
AGTRAP	physical association	0.560	3
APOL3	physical association	0.560	3
ATP6V0C	physical association	0.560	3
CD302	physical association	0.560	3
FAM3C	physical association	0.560	3
MALL	physical association	0.560	3
MS4A1	physical association	0.560	3
SDC4	physical association	0.560	3
TMEM120B	physical association	0.560	3
TMEM60	physical association	0.560	3
VAMP5	physical association	0.560	3
SPOP	proximity	0.470	5
IL2RG	physical association	0.400	1
NPM1	physical association	0.400	1
BRI3	physical association	0.370	1
FAM171A2	association	0.350	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SMARCA4	proximity	0.270	4
AKT1	proximity	0.270	1
BRAF	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (135 interactions; top human partners by supporting records): CISH (Affinity Capture-Western; 3 records), KIT (Affinity Capture-Western; 2 records), AGTRAP (Two-hybrid), ALYREF (Protein-RNA), AMPD2 (Affinity Capture-MS), APOL3 (Two-hybrid), C17orf80 (Affinity Capture-MS), CBL (Affinity Capture-Western), CCDC51 (Affinity Capture-MS), CIRBP (Protein-RNA), CPSF1 (Protein-RNA), DDX21 (Protein-RNA), DDX39B (Protein-RNA), DDX3X (Protein-RNA), DDX5 (Protein-RNA)

SIGNOR signaling

showing 4 of 5 signaling interactions:

A	Effect	B	Mechanism
IL7	up-regulates	IL7R	binding
IL7R	up-regulates	JAK1	binding
NOTCH1	“up-regulates quantity by expression”	IL7R	“transcriptional regulation”
NOTCH	“up-regulates quantity by expression”	IL7R	“transcriptional regulation”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ CRLF2-Il7R-TSLP complex	3	CRLF2, IL7R, TSLP

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
IL7R;IL2RG		Signaling by Interleukin
IL7R;CRLF2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	6	9.1×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — ALL, ESCA, HCC, STAD.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for IL7R: 622 ClinVar records (64 pathogenic / likely pathogenic); 44 ClinGen expert-panel interpretations; 43 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	17
Uncertain significance	220
Likely benign	234
Benign	61

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 64 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
224841	NM_002185.5(IL7R):c.361dup (p.Ile121fs)	Pathogenic	reviewed by expert panel	12
36392	NM_002185.5(IL7R):c.353G>A (p.Cys118Tyr)	Pathogenic	reviewed by expert panel	7
353259	NM_002185.5(IL7R):c.83-2A>T	Pathogenic	reviewed by expert panel	7
1298987	NM_002185.5(IL7R):c.616C>T (p.Arg206Ter)	Pathogenic	reviewed by expert panel	7
265195	NM_002185.5(IL7R):c.221+2T>G	Pathogenic	reviewed by expert panel	6
134528	NM_002185.5(IL7R):c.662G>T (p.Ser221Ile)	Pathogenic	reviewed by expert panel	5
14841	NM_002185.5(IL7R):c.538-1G>A	Pathogenic	reviewed by expert panel	3
624613	NM_002185.5(IL7R):c.537+1G>A	Pathogenic	reviewed by expert panel	3
1339483	NM_002185.5(IL7R):c.379G>A (p.Val127Ile)	Pathogenic	reviewed by expert panel	3
830061	NM_002185.5(IL7R):c.221+1G>A	Pathogenic	reviewed by expert panel	2
804345	NM_002185.5(IL7R):c.265C>T (p.Gln89Ter)	Likely pathogenic	reviewed by expert panel	5
578174	NM_002185.5(IL7R):c.704C>G (p.Ser235Ter)	Likely pathogenic	reviewed by expert panel	3
14843	NM_002185.5(IL7R):c.394C>T (p.Pro132Ser)	Likely pathogenic	reviewed by expert panel	2
642787	NM_002185.5(IL7R):c.355A>T (p.Lys119Ter)	Likely pathogenic	reviewed by expert panel	2
1323115	NM_002185.5(IL7R):c.235G>T (p.Glu79Ter)	Likely pathogenic	reviewed by expert panel	2

Per-variant reference — Sugi Variant

Explore IL7R’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (44)

Expert ACMG interpretations from Severe Combined Immunodeficiency Disease VCEP for severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	12
Likely Pathogenic	5
Uncertain Significance	10
Likely Benign	9
Benign	8

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 716):

Position(s)	Effect	Δscore	Sites
5:35871054–35871055	acceptor_loss	1.0000	5
5:35857060–35857061	donor_loss	0.9900	5
5:35860850–35860851	acceptor_loss	0.9900	6
5:35860991–35860992	donor_loss	0.9900	6
5:35860997	donor_gain	0.9900
5:35871055	acceptor_loss	0.9900
5:35871214–35871215	donor_loss	0.9900	5
5:35867464–35867465	donor_loss	0.9800	6
5:35876083	donor_gain	0.9800
5:35867466	donor_loss	0.9700	2

AlphaMissense

592 missense substitutions predicted likely pathogenic (of 3,037 scored), across 156 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
S218	8	0.893	0.995
H165	8	0.891	0.975
F298	8	0.884	0.981
F226	8	0.881	0.984
D145	8	0.877	0.951
M452	8	0.873	0.962
W220	7	0.981	0.998
C57	7	0.976	0.992
C42	7	0.975	0.991
F150	7	0.960	0.993
W217	7	0.950	0.988
F213	7	0.936	0.969
S221	7	0.931	0.997
F146	7	0.930	0.987
C74	7	0.924	0.952
W178	7	0.913	0.987
C82	7	0.904	0.953
F455	7	0.903	0.982
W273	7	0.839	0.946
F303	7	0.839	0.941

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:146661 | disease phenotypes: MIM:608971, MIM:612595, MIM:603554

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 104	Definitive	Autosomal recessive	4
T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency	Supportive	Autosomal recessive
Omenn syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
immunodeficiency 104	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (6): immunodeficiency 104 (MONDO:0012163), T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency (MONDO:0015701), severe combined immunodeficiency (MONDO:0015974), breast neoplasm (MONDO:0021100), multiple sclerosis, susceptibility to, 3 (MONDO:0012957), Omenn syndrome (MONDO:0011338)

Orphanet (3): T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency (Orphanet:169154), Severe combined immunodeficiency (Orphanet:183660), Omenn syndrome (Orphanet:39041)

HPO phenotypes

59 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000100	Nephrotic syndrome
HP:0000155	Oral ulcer
HP:0000388	Otitis media
HP:0000403	Recurrent otitis media
HP:0000821	Hypothyroidism
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000969	Edema
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001072	Thickened skin
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001875	Decreased total neutrophil count
HP:0001880	Increased total eosinophil count
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0001945	Fever
HP:0001973	Autoimmune thrombocytopenia
HP:0001974	Increased total leukocyte count
HP:0002014	Diarrhea
HP:0002020	Gastroesophageal reflux
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002240	Hepatomegaly
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002728	Recurrent mucocutaneous candidiasis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002960	Autoimmunity
HP:0003212	Increased circulating IgE concentration
HP:0003237	Increased circulating IgG concentration
HP:0003261	Increased circulating IgA concentration
HP:0003593	Infantile onset
HP:0004332	Abnormal lymphocyte morphology
HP:0004429	Recurrent viral infections
HP:0004430	Severe combined immunodeficiency
HP:0005390	Recurrent opportunistic infections
HP:0005401	Recurrent Candida infection
HP:0005403	Decreased total T cell count
HP:0005415	Decreased total CD8+ T cell proportion
HP:0007549	Desquamation of skin soon after birth
HP:0008866	Failure to thrive secondary to recurrent infections
HP:0010702	Increased circulating immunoglobulin concentration
HP:0025526	Psoriasiform lesion
HP:0031381	Decreased mitogen-induced T-cell proliferation
HP:0032218	Decreased total CD4+ T cell proportion
HP:0040187	Neonatal sepsis
HP:0100646	Thyroiditis
HP:0100806	Sepsis
HP:0100827	Increased total lymphocyte count
HP:0100840	Aplasia/Hypoplasia of the eyebrow

GWAS associations

showing 30 of 43 associations:

Study	Trait	p-value
GCST90002388_160	Lymphocyte count	5e-108
GCST90002389_47	Lymphocyte percentage of white cells	1e-63
GCST90002399_389	Neutrophil percentage of white cells	4e-44
GCST004627_150	Lymphocyte count	2e-43
GCST005038_53	Allergic disease (asthma, hay fever or eczema)	9e-36
GCST006409_22	Allergic rhinitis	4e-32
GCST004632_111	Lymphocyte percentage of white cells	3e-29
GCST009597_222	Multiple sclerosis	2e-28
GCST010042_129	Asthma	1e-19
GCST004633_52	Neutrophil percentage of white cells	2e-19
GCST90002407_296	White blood cell count	6e-19
GCST009719_8	Allergic rhinitis	8e-19
GCST006585_2274	Blood protein levels	1e-18
GCST005531_118	Multiple sclerosis	4e-17
GCST009720_22	Asthma	3e-16
GCST007563_11	Allergic disease (asthma, hay fever or eczema)	3e-15
GCST007564_4	Asthma or allergic disease (pleiotropy)	2e-14
GCST003184_20	Atopic dermatitis	3e-14
GCST007799_44	Asthma (adult onset)	9e-14
GCST005581_29	Primary biliary cirrhosis	2e-13
GCST007798_130	Asthma	2e-13
GCST001010_2	Primary biliary cholangitis	1e-11
GCST003129_22	Primary biliary cholangitis	5e-11
GCST008916_82	Asthma	1e-10
GCST90002380_38	Basophil percentage of white cells	1e-10
GCST003184_28	Atopic dermatitis	2e-10
GCST009718_8	Eczema	3e-10
GCST90014325_68	Asthma	5e-10
GCST007941_20	Medication use (adrenergics, inhalants)	9e-10
GCST90002394_383	Monocyte percentage of white cells	1e-9

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C563822	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell Negative, B Cell Positive, NK Cell Positive *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-2 receptor family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
lusvertikimab	Antagonist	11.4	pEC50
bempikibart	Binding	9.0	pEC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression, increases expression	8
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	6
bisphenol A	decreases expression, decreases methylation, increases expression	3
Estradiol	affects expression, affects cotreatment, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
nickel sulfate	increases expression	2
Bortezomib	increases expression, increases response to substance	2
Arsenic	increases expression, affects expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression, increases expression	2
Calcitriol	decreases expression	2
Copper	affects binding, decreases expression, increases expression	2
Nickel	increases expression	2
Ozone	increases abundance, increases expression, affects cotreatment	2
Dronabinol	decreases reaction, increases expression	2
Cadmium Chloride	increases expression	2
Nanotubes, Carbon	increases expression	2
Particulate Matter	increases cleavage, increases expression, increases reaction, affects expression, decreases expression (+2 more)	2
Glupearl 19S	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
captax	increases expression	1
geraniol	increases expression	1
lead acetate	decreases expression	1
trichostatin A	increases expression	1
cinnamaldehyde	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8II	Abcam HCT 116 IL7R KO	Cancer cell line	Male
CVCL_B8XG	Abcam MCF-7 IL7R KO	Cancer cell line	Female
CVCL_B9KS	Abcam A-549 IL7R KO	Cancer cell line	Male
CVCL_D9H7	Ubigene HEK293 IL7R KO	Transformed cell line	Female
CVCL_E0F7	Ubigene HeLa IL7R KO	Cancer cell line	Female
CVCL_E8EI	HEK-Blue IL-7	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT00092183	Phase 4	COMPLETED	An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778	Phase 4	COMPLETED	Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120	Phase 4	UNKNOWN	The MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606	Phase 4	UNKNOWN	Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240	Phase 4	COMPLETED	Chlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752	Phase 4	TERMINATED	Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354	Phase 4	COMPLETED	Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968	Phase 4	TERMINATED	Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135	Phase 4	COMPLETED	Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090	Phase 4	COMPLETED	A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285	Phase 4	TERMINATED	Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916	Phase 4	COMPLETED	Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400	Phase 4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380	Phase 4	UNKNOWN	Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936	Phase 4	COMPLETED	Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960	Phase 4	COMPLETED	Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544	Phase 4	COMPLETED	Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064	Phase 4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02004834	Phase 4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02372305	Phase 4	WITHDRAWN	Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347	Phase 4	COMPLETED	Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677	Phase 4	COMPLETED	Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870	Phase 4	UNKNOWN	Sienna+® Injection Time Study 4 Arms
NCT02627560	Phase 4	COMPLETED	The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932	Phase 4	COMPLETED	Fertility Preservation in Breast Cancer Patients
NCT02781259	Phase 4	UNKNOWN	Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921	Phase 4	TERMINATED	Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178	Phase 4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944	Phase 4	COMPLETED	A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154	Phase 4	COMPLETED	Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196	Phase 4	COMPLETED	A Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615	Phase 4	COMPLETED	ARTISS a Single-centre Randomised Control Study
NCT05033769	Phase 4	UNKNOWN	Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005	Phase 4	UNKNOWN	Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05452213	Phase 4	RECRUITING	Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031	Phase 4	RECRUITING	Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT05949333	Phase 4	UNKNOWN	Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT07158164	Phase 4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259	Phase 4	NOT_YET_RECRUITING	Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT00220766	Phase 3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	Phase 3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	Phase 3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000611	Phase 3	COMPLETED	Women’s Health Initiative (WHI)
NCT00001338	Phase 3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00021255	Phase 3	COMPLETED	Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
NCT00034125	Phase 3	COMPLETED	Phase 3 Study of LY353381 Vs Tamoxifen in Women With Locally Advanced or Metastatic Breast Cancer.
NCT00036270	Phase 3	COMPLETED	Randomized Phase III Study Of Exemestane (Aromasin) For 5 Years Versus Tamoxifen for 2.5 to 3 Years Followed By Exemestane
NCT00038467	Phase 3	COMPLETED	Randomized Trial Of Exemestane Versus Continued Tamoxifen In Postmenopausal Women With Early Breast Cancer
NCT00039780	Phase 3	COMPLETED	Evaluation of BNP7787 for the Prevention of Neurotoxicity in Metastatic Breast Cancer Patients Receiving Weekly Paclitaxel
NCT00044291	Phase 3	COMPLETED	Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
NCT00046527	Phase 3	COMPLETED	Study of ABI-007 and Taxol in Patients With Metastatic Breast Cancer
NCT00050011	Phase 3	COMPLETED	Zoledronic Acid - Letrozole Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy
NCT00073528	Phase 3	COMPLETED	Study Comparing Lapatinib (GW572016) And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
NCT00083993	Phase 3	TERMINATED	Study Evaluating CCI-779 and Letrozole in Post-menopausal Women With Breast Cancer
NCT00092196	Phase 3	COMPLETED	Study of MK0869 for the Prevention of Chemotherapy-Induced Nausea and Vomiting (0869-071)(COMPLETED)
NCT00097344	Phase 3	TERMINATED	The CAT Study: Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
NCT00115713	Phase 3	COMPLETED	Effects of Aerobic Exercise Versus Weight Training in Breast Cancer Survivors During Chemotherapy
NCT00121992	Phase 3	COMPLETED	Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment
NCT00138814	Phase 3	UNKNOWN	Boost Use in Breast Conservation Radiotherapy
NCT00143390	Phase 3	COMPLETED	Aromasin Vs Arimidex Study As Initial Hormonal Therapy In Postmenopausal Women With Advanced/Recurrent Breast Cancer