IL17RA

Chr 22AR

interleukin 17 receptor A

Also known as: CANDF5, CD217, CDw217, IL-17RA, IL17R, IMD51, hIL-17R

NCBI Gene: 23765 ENSG00000177663 UniProt: Q96F46 OMIM: 605461

The IL17RA protein is a cell surface receptor for interleukin-17 cytokines that mediates antimicrobial host defense by promoting neutrophil recruitment and activation against extracellular bacteria and fungi, while also maintaining epithelial barrier integrity. Mutations cause autosomal recessive immunodeficiency 51, characterized by increased susceptibility to infections. The gene is highly constrained against loss-of-function variation (LOEUF 0.632), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 51MIM #613953

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Immunodeficiency 51; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.08

OE 0.38 (0.24–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.79Z-score

OE missense 1.10 (1.02–1.18)

562 obs / 511.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.38 (0.24–0.63)

0≤0.351.4

Missense OE?1.10 (1.02–1.18)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 11 / 28.8Missense obs/exp: 562 / 511.4Syn Z: -1.94

Background carrier burden — how many people carry a rare variant somewhere in IL17RA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,349 rare PASS variants

Rare truncating (LoF)

1 in 1,700

159 rare PASS variants

Rare synonymous (reference)

1 in 86

621 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL17RA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 60	1 in 1,800
South Asian	~43k	1 in 51	1 in 2,200
Remaining (unassigned)	~30k	1 in 35	1 in 3,700
European (Finnish)	~27k	1 in 160	1 in 3,600
Admixed American	~22k	1 in 36	1 in 1,600
African / African American	~21k	1 in 28	1 in 900
East Asian	~20k	1 in 45	1 in 2,600
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 52	≈ 1 in 900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 13.? see exons ↓