IL7R

Chr 5AR

interleukin 7 receptor

Also known as: CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha, ILRA, IMD104

NCBI Gene: 3575 ENSG00000168685 UniProt: P16871 OMIM: 146661

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. [provided by RefSeq, Dec 2015]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.041 OMIM phenotype

Clinical Summary— IL7R

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Gene-Disease Validity (ClinGen)

immunodeficiency 104 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

70 unique Pathogenic / Likely Pathogenic· 212 VUS of 606 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — IL7R

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.43

OE 0.65 (0.42–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.29Z-score

OE missense 1.24 (1.12–1.36)

288 obs / 232.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.42–1.04)

0≤0.351.4

Missense OE?1.24 (1.12–1.36)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 13 / 19.9Missense obs/exp: 288 / 232.7Syn Z: -0.55

This gene — mechanism propensity

0.74top 25%

GOF

0.76top 25%

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

606 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic23

VUS212

Likely Benign233

Benign66

Conflicting18

Pathogenic

Likely Pathogenic

212

VUS

233

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	36	4	6	1	47
Likely Pathogenic	17	5	1	0	23
VUS	3	160	46	3	212
Likely Benign	1	14	91	127	233
Benign	0	9	51	6	66
Conflicting	—				18
Total	57	192	195	137	599

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap IL7R — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →