T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

Summary

T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency (MONDO:0015701) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.15	Worldwide	Validated
Prevalence at birth	<1 / 1 000 000	0.04	Chile	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001888	Lymphopenia	Frequent (30-79%)
HP:0004429	Recurrent viral infections	Frequent (30-79%)
HP:0005403	Decreased total T cell count	Frequent (30-79%)
HP:0005415	Decreased proportion of CD8-positive T cells	Frequent (30-79%)
HP:0031381	Decreased lymphocyte proliferation in response to mitogen	Frequent (30-79%)
HP:0032218	Decreased proportion of CD4-positive T cells	Frequent (30-79%)
HP:0045080	Decreased proportion of CD3-positive T cells	Frequent (30-79%)
HP:0000155	Oral ulcer	Occasional (5-29%)
HP:0001019	Erythroderma	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001596	Alopecia	Occasional (5-29%)
HP:0001875	Decreased total neutrophil count	Occasional (5-29%)
HP:0001880	Eosinophilia	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0001973	Autoimmune thrombocytopenia	Occasional (5-29%)
HP:0002028	Chronic diarrhea	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0002783	Recurrent lower respiratory tract infections	Occasional (5-29%)
HP:0002788	Recurrent upper respiratory tract infections	Occasional (5-29%)
HP:0003212	Increased circulating IgE level	Occasional (5-29%)
HP:0003237	Increased circulating IgG level	Occasional (5-29%)
HP:0003261	Increased circulating IgA level	Occasional (5-29%)
HP:0005401	Recurrent candida infections	Occasional (5-29%)
HP:0010702	Increased circulating antibody level	Occasional (5-29%)
HP:0025526	Psoriasiform lesion	Occasional (5-29%)
HP:0040187	Neonatal sepsis	Occasional (5-29%)
HP:0100827	Lymphocytosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency
Mondo ID	MONDO:0015701
Orphanet	169154
DOID	DOID:0060015
UMLS	C5679577
MedGen	1842915
GARD	0017051
Is cancer (heuristic)	no

Also known as: IL-7R · IL-7Ralpha deficiency · T-B+ SCID due to IL-7Ralpha deficiency

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

Related subtypes (189): precocious puberty, complex cortical dysplasia with other brain malformations, imperforate anus, microcephaly, demyelinating disease, hypospadias, bone development disease, primary basilar invagination, familial bicuspid aortic valve, camptodactyly of fingers, isolated congenital digital clubbing, aorta coarctation, gingival fibromatosis-progressive deafness syndrome, Eng-Strom syndrome, Morgagni-Stewart-Morel syndrome, familial partial lipodystrophy, Dunnigan type, megalodactyly, odontomatosis-aortae esophagus stenosis syndrome, otodental syndrome, oculodental syndrome, Rutherfurd type, spina bifida, steatocystoma multiplex-natal teeth syndrome, distal symphalangism, thumb deformity-alopecia-pigmentation anomaly syndrome, double uterus-hemivagina-renal agenesis syndrome, amelogenesis imperfecta type 1G, Bloom syndrome, cardiac valvular defect, developmental, isolated cerebellar hypoplasia/agenesis, cleft palate-stapes fixation-oligodontia syndrome, Jalili syndrome, craniodiaphyseal dysplasia, craniofacial dyssynostosis, deafness-oligodontia syndrome, duodenal atresia, Fowler syndrome, multiple intestinal atresia, natal teeth-intestinal pseudoobstruction-patent ductus syndrome, atresia of small intestine, mulibrey nanism, oculocerebral hypopigmentation syndrome, Cross type, familial osteodysplasia, Anderson type, pancreatic agenesis, postaxial polydactyly-dental and vertebral anomalies syndrome, familial primary pulmonary hypoplasia, renal tubular dysgenesis of genetic origin, Rothmund-Thomson syndrome, familial isolated congenital asplenia, subaortic stenosis, membranous, non-eruption of teeth-maxillary hypoplasia-genu valgum syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, CK syndrome, Ogden syndrome, Nance-Horan syndrome, colonic atresia, Aicardi syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, 46,XY complete gonadal dysgenesis, loose anagen syndrome, lung agenesis-heart defect-thumb anomalies syndrome, Chudley-McCullough syndrome, macrocephaly-autism syndrome, DNA ligase IV deficiency, horizontal gaze palsy with progressive scoliosis, cataract - congenital heart disease - neural tube defect syndrome, autosomal recessive frontotemporal pachygyria, craniofacial dysplasia - osteopenia syndrome, porencephaly-microcephaly-bilateral congenital cataract syndrome, congenital short bowel syndrome, familial median cleft of the upper and lower lips, progeroid features-hepatocellular carcinoma predisposition syndrome, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, aneurysm of sinus of Valsalva, blepharoptosis-cleft palate-ectrodactyly-dental anomalies syndrome, medullary sponge kidney, isolated congenital syngnathia, cleft lip and alveolus, diprosopus, high anorectal malformation, intermediate anorectal malformation, low anorectal malformation, microcephaly-polymicrogyria-corpus callosum agenesis syndrome, cordiform uterus, septate uterus, bicornuate uterus, uterine hypoplasia, agenesis and aplasia of uterine body, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, axial mesodermal dysplasia spectrum, multicystic dysplastic kidney, diabetic embryopathy, congenital microgastria, isolated cleft lip, cleft lip/palate, hereditary gingival fibromatosis, congenital bronchobiliary fistula, congenital hydrocephalus, maternal hyperthermia induced birth defects, diphallia, epibulbar lipodermoid-preauricular appendage-polythelia syndrome, bronchogenic cyst, duplication of urethra, hypohidrotic ectodermal dysplasia, Lowe-Kohn-Cohen syndrome, biliary atresia with splenic malformation syndrome, congenital pulmonary airway malformation, familial intestinal malrotation-facial anomalies syndrome, megalencephaly, cephalocele, cerebral cortical dysplasia, L1 syndrome, familial omphalocele syndrome with facial dysmorphism, penoscrotal transposition, pericardial and diaphragmatic defect, hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome, congenital deformities of limbs, familial isolated clinodactyly of fingers, congenital shoulder dislocation, congenital elbow dislocation, congenital knee dislocation, congenital patella dislocation, macrodactyly of fingers, macrodactyly of toes, upper limb hypertrophy, lower limb hypertrophy, duplication of the pituitary gland, diencephalic-mesencephalic junction dysplasia, steroid dehydrogenase deficiency-dental anomalies syndrome, congenital achiasma, tracheal agenesis, renal agenesis, hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome, isolated splenogonadal fusion, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, congenital bilateral absence of vas deferens, congenital portosystemic shunt, lissencephaly spectrum disorders, Berardinelli-Seip congenital lipodystrophy, congenital primary megaureter, craniorachischisis, vaginal atresia, bronchopulmonary dysplasia, dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome, aniridia, atypical Werner syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, anterior segment dysgenesis, congenital esophageal diverticulum, renal hypoplasia, renal dysplasia, overgrowth syndrome, developmental defect during embryogenesis, acalvaria, congenital aortic valve insufficiency, congenital anomaly of superior vena cava, congenital anomaly of hepatic vein, posterior hypospadias, isolated micropenis, isolated partial vaginal agenesis, anorectal malformation, pulmonary agenesis, congenital tricuspid malformation, Noonan syndrome and Noonan-related syndrome, coronary sinus stenosis, coronary sinus atresia, cartilage development disorder, syndactyly, polydactyly, brachydactyly, neurocristopathy, congenital absence of septum pellucidum, branchial arch disease, congenital anomaly of cardiovascular system, atelencephaly, aprosencephaly, aortic valve stenosis, hereditary lethal multiple congenital anomalies/dysmorphic syndrome, congenital agenesis of the scrotum, keratinization disease, lactation disease, COACH syndrome, constitutional delay of growth and puberty, isolated congenital femoral bifurcation, congenital peritoneal encapsulation, isolated short stature, congenital high airway obstruction syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1298987	NM_002185.5(IL7R):c.616C>T (p.Arg206Ter)	IL7R	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
IL7R	Definitive	Autosomal recessive	immunodeficiency 104	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL7R	Orphanet:169154	T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency
IL7R	Orphanet:39041	Omenn syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL7R	HGNC:6024	ENSG00000168685	P16871	Interleukin-7 receptor subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL7R	Interleukin-7 receptor subunit alpha	Receptor for interleukin-7.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL7R	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
lymph node	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL7R	220	ubiquitous	marker	right lung, granulocyte, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL7R	3,412

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL7R	P16871	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-7 signaling	1	317.2×	0.009	IL7R
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.012	IL7R
Clathrin-mediated endocytosis	1	85.2×	0.012	IL7R

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of DNA recombination	1	4213.0×	0.003	IL7R
negative regulation of T cell mediated cytotoxicity	1	2106.5×	0.003	IL7R
interleukin-7-mediated signaling pathway	1	2106.5×	0.003	IL7R
negative regulation of T cell apoptotic process	1	1685.2×	0.003	IL7R
positive regulation of receptor signaling pathway via STAT	1	1685.2×	0.003	IL7R
positive regulation of T cell differentiation in thymus	1	1532.0×	0.003	IL7R
T cell mediated cytotoxicity	1	1123.5×	0.003	IL7R
cellular homeostasis	1	802.5×	0.003	IL7R
lymph node development	1	802.5×	0.003	IL7R
regulation of cell size	1	766.0×	0.003	IL7R
B cell homeostasis	1	561.7×	0.004	IL7R
B cell proliferation	1	481.5×	0.004	IL7R
T cell homeostasis	1	455.5×	0.004	IL7R
positive regulation of receptor signaling pathway via JAK-STAT	1	432.1×	0.004	IL7R
T cell differentiation in thymus	1	411.0×	0.004	IL7R
hemopoiesis	1	267.5×	0.006	IL7R
cell morphogenesis	1	157.5×	0.009	IL7R
defense response to Gram-positive bacterium	1	127.7×	0.010	IL7R
gene expression	1	79.9×	0.016	IL7R
cell surface receptor signaling pathway	1	64.1×	0.019	IL7R
immune response	1	47.1×	0.024	IL7R
positive regulation of gene expression	1	38.7×	0.028	IL7R
positive regulation of cell population proliferation	1	33.6×	0.031	IL7R
signal transduction	1	16.1×	0.062	IL7R

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL7R	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	IL7R
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IL7R	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.