IL11RA

Chr 9AR

interleukin 11 receptor subunit alpha

Also known as: CRSDA

NCBI Gene: 3590 ENSG00000137070 UniProt: Q14626 OMIM: 600939

The IL11RA protein functions as a receptor for interleukin-11 and is essential for normal development of craniofacial bones and teeth, where it restricts suture fusion and controls tooth number. Biallelic mutations cause autosomal recessive craniosynostosis and dental anomalies. The gene shows very low constraint against loss-of-function variants (pLI near zero), which is consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Interleukin 11 is a stromal cell-derived cytokine that belongs to a family of pleiotropic and redundant cytokines that use the gp130 transducing subunit in their high affinity receptors. This gene encodes the IL-11 receptor, which is a member of the hematopoietic cytokine receptor family. This particular receptor is very similar to ciliary neurotrophic factor, since both contain an extracellular region with a 2-domain structure composed of an immunoglobulin-like domain and a cytokine receptor-like domain. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Craniosynostosis and dental anomaliesMIM #614188

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · craniosynostosis and dental anomalies · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.000

Z-score -0.61

OE 1.13 (0.84–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.88 (0.79–0.99)

209 obs / 236.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.13 (0.84–1.54)

0≤0.351.4

Missense OE?0.88 (0.79–0.99)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 29 / 25.7Missense obs/exp: 209 / 236.6Syn Z: 0.12

Background carrier burden — how many people carry a rare variant somewhere in IL11RA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

553 rare PASS variants

Rare truncating (LoF)

1 in 1,100

119 rare PASS variants

Rare synonymous (reference)

1 in 240

205 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL11RA. 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 150	1 in 1,200
South Asian	~43k	1 in 71	1 in 850
Remaining (unassigned)	~30k	1 in 69	1 in 790
European (Finnish)	~27k	1 in 1,600	1 in 2,400
Admixed American	~22k	1 in 87	1 in 720
African / African American	~21k	1 in 130	1 in 950
East Asian	~20k	1 in 97	1 in 920
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 94	1 in 360

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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓