IL11RA

Summary

IL11RA (interleukin 11 receptor subunit alpha, HGNC:5967) is a protein-coding gene on chromosome 9p13.3, encoding Interleukin-11 receptor subunit alpha (Q14626). Receptor for interleukin-11 (IL11).

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.

Source: NCBI Gene 3590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): craniosynostosis and dental anomalies (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 129 total — 12 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• MANE Select transcript: NM_001142784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5967
Approved symbol	IL11RA
Name	interleukin 11 receptor subunit alpha
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137070
Ensembl biotype	protein_coding
OMIM	600939
Entrez	3590

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 45 protein_coding, 11 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000318041, ENST00000441545, ENST00000466082, ENST00000478308, ENST00000478802, ENST00000553620, ENST00000553969, ENST00000555003, ENST00000555247, ENST00000555579, ENST00000555981, ENST00000556531, ENST00000556792, ENST00000557298, ENST00000602473, ENST00000684861, ENST00000685278, ENST00000685430, ENST00000685662, ENST00000685768, ENST00000686794, ENST00000687192, ENST00000687770, ENST00000690286, ENST00000692291, ENST00000692530, ENST00000692788, ENST00000902558, ENST00000902559, ENST00000902560, ENST00000902561, ENST00000902562, ENST00000902563, ENST00000902564, ENST00000902565, ENST00000902566, ENST00000902567, ENST00000902568, ENST00000902569, ENST00000902571, ENST00000902572, ENST00000902574, ENST00000926823, ENST00000957047, ENST00000957048, ENST00000957049, ENST00000957050, ENST00000957051, ENST00000957052, ENST00000957053, ENST00000957054, ENST00000957055, ENST00000957056, ENST00000957057, ENST00000957058, ENST00000957059, ENST00000957060, ENST00000957061, ENST00000957062, ENST00000957063, ENST00000957064, ENST00000957065, ENST00000957066

RefSeq mRNA: 1 — MANE Select: NM_001142784 NM_001142784

CCDS: CCDS6567

Canonical transcript exons

ENST00000441545 — 13 exons

Exon	Start	End
ENSE00001700152	34652185	34652233
ENSE00003479810	34657303	34657335
ENSE00003504689	34657035	34657149
ENSE00003506399	34660504	34660600
ENSE00003553867	34661482	34661902
ENSE00003556460	34659759	34659900
ENSE00003590681	34657421	34657587
ENSE00003591471	34660274	34660393
ENSE00003597789	34655605	34655665
ENSE00003659471	34660854	34660936
ENSE00003682706	34656739	34656908
ENSE00003755548	34655218	34655317
ENSE00003788868	34658520	34658683

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.12.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9569 / max 108.5483, expressed in 882 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96529	2.4331	854
96530	0.5238	194

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.12	gold quality
descending thoracic aorta	UBERON:0002345	96.90	gold quality
right atrium auricular region	UBERON:0006631	96.67	gold quality
thoracic aorta	UBERON:0001515	96.49	gold quality
ascending aorta	UBERON:0001496	96.47	gold quality
granulocyte	CL:0000094	96.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.36	gold quality
right coronary artery	UBERON:0001625	96.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.24	gold quality
cardiac atrium	UBERON:0002081	96.10	gold quality
cerebellar hemisphere	UBERON:0002245	95.94	gold quality
left lobe of thyroid gland	UBERON:0001120	95.89	gold quality
left uterine tube	UBERON:0001303	95.85	gold quality
cerebellar cortex	UBERON:0002129	95.73	gold quality
right lobe of thyroid gland	UBERON:0001119	95.69	gold quality
skin of abdomen	UBERON:0001416	95.67	gold quality
skin of leg	UBERON:0001511	95.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.39	gold quality
aorta	UBERON:0000947	95.37	gold quality
mucosa of stomach	UBERON:0001199	95.33	gold quality
body of uterus	UBERON:0009853	95.22	gold quality
right ovary	UBERON:0002118	95.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.01	gold quality
thyroid gland	UBERON:0002046	94.97	gold quality
popliteal artery	UBERON:0002250	94.62	gold quality
tibial artery	UBERON:0007610	94.60	gold quality
left ovary	UBERON:0002119	94.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.32	gold quality
left coronary artery	UBERON:0001626	94.30	gold quality
heart left ventricle	UBERON:0002084	94.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	29.30
E-ANND-3	yes	13.19
E-MTAB-10042	yes	9.26
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

19 targeting IL11RA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-1226-3P	97.51	66.32	1063

Literature-anchored findings (GeneRIF, showing 36)

• IL-11Ralpha was expressed in both epithelial and stromal cells, with epithelial staining being more intense (PMID:12200462)
• expression and function in human endometrium (PMID:12569176)
• the interleukin-11 receptor alpha-chain has evidence of antiapoptotic effects in human colonic epithelial cells (PMID:14701802)
• IL-11Ralpha is a candidate target for translational clinical trials against advanced and metastatic prostate cancer. (PMID:14744752)
• interleukin-11 receptor is expressed in CD38-positive cells from patients with multiple myeloma (PMID:15512823)
• High expression of interleukin-11 receptor alpha is associated with Hodgkin’s lymphoma (PMID:16291580)
• High interleukin 11 receptor is associated with breast cancer (PMID:16614887)
• IL-11/IL-11R pathway plays an important role in the progression of colorectal adenocarcinoma. (PMID:16964382)
• The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric carcinoma. (PMID:17332920)
• binding site of il-11 to IL-11R alpha is characterized (PMID:18941632)
• IL11 inhibits human extravillous trophoblast invasion via STAT3, indicating a likely role for IL11 in the decidual restraint of EVT invasion during normal pregnancy. (PMID:18987331)
• IL11 as well as IL11RA are likely to play a role in the progression of endometrial carcinoma. (PMID:20553623)
• IL11RA promoter polymorphism–rs1061758–may be associated with the risk of papillary thyroid cancer in the Korean population. (PMID:21982075)
• data suggest that IL-11Ralpha-CAR T cells may represent a new therapy for patients with osteosarcoma pulmonary metastases (PMID:22075555)
• Constructed a designer cytokine Hyper IL-11 (H11), which is exclusively composed of naturally existing components. It contains the full length sIL-11Ralpha connected with the mature IL-11 protein, and acts as an agonist on cells expressing the gp130 molec (PMID:22433466)
• These results indicate that IL-11Ralpha is a potential target for the development of molecular targeted therapy and noninvasive tumor imaging in human osteosarcoma. (PMID:25524575)
• Data suggest domains D1-D3, which contain cytokine binding module, determine which cytokine can activate interleukin-6 or interleukin-11 alpha-receptor subunits; stalk, transmembrane, or intracellular regions do not participate in ligand selectivity. (PMID:26551279)
• Proteolysis of the IL-11R represents a molecular switch that controls the IL-11 trans-signaling pathway which is the target in intestinal tumorigenesis, lung carcinomas, and asthma. (PMID:26876177)
• Report IL11RA and MELK amplification in gastric cancer cell lines and primary gastric adenocarcinomas. (PMID:27920471)
• Cancer-associated fibroblasts treated with cisplatin facilitate chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway. (PMID:27922075)
• High IL11RA expression is associated with endometrioid tumours. (PMID:28186993)
• we show by molecular replacement that Arg-112 does not participate in binding of IL-11 to its receptors IL-11R and glycoprotein 130 (gp130). Recombinant IL-11 R112H expressed in E. coli displays a correct four-helix-bundle folding topology, and binds with similar affinity to IL-11R and the IL-11/IL-11R/gp130 complex. (PMID:29237553)
• The results presented here reveal an additional function in classic IL-11 signaling, highlighting the importance of the IL-11R stalk in IL-11 signaling (PMID:29523682)
• The D2 domain of the IL-11R contains two N-linked glycans, which are dispensable for its biological activity, but differentially control maturation and intracellular trafficking of the receptor. (PMID:29533934)
• The results indicate that miR-23b regulates IL-11 and IL-11Ralpha expression, and it might act as an anti-oncogenic agent in the progression of Hepatocellular Carcinoma by directly downregulating IL-11 expression. (PMID:29901200)
• identified six missense mutations in IL11RA, a gene encoding the alpha subunit of interleukin 11 receptor, 4 of them being novel, including 2 in the Ig-like C2-type domain (PMID:29926465)
• IL11RA mutation is associated with craniosynostosis with dental anomalies syndrome. (PMID:30811827)
• Multiple craniosynostosis and facial dysmorphisms with homozygous IL11RA variant caused by maternal uniparental isodisomy of chromosome 9. (PMID:32277509)
• The structure of the extracellular domains of human interleukin 11alpha receptor reveals mechanisms of cytokine engagement. (PMID:32332100)
• Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling. (PMID:33566379)
• IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFbeta-mediated activation of dermal fibroblasts. (PMID:33590875)
• Interleukin-11 receptor expression on monocytes is dispensable for their recruitment and pathogen uptake during Leishmania major infection. (PMID:34530329)
• The outcome of targeted NGS screening in patients with syndromic forms of sagittal and pansynostosis - IL11RA is an emerging core-gene for pansynostosis. (PMID:35331937)
• IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. (PMID:36376885)
• Biophysical insight into protein-protein interactions in the Interleukin-11/Interleukin-11Ralpha/glycoprotein 130 signaling complex. (PMID:37820452)
• Interleukin-11Ralpha2 in the hypothalamic arcuate nucleus affects depression-related behaviors and the AKT-BDNF pathway. (PMID:39341516)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ghrb	ENSDARG00000007671
danio_rerio	il11ra	ENSDARG00000026736
danio_rerio	ghra	ENSDARG00000054771
danio_rerio	il6r	ENSDARG00000104474
mus_musculus	Il11ra3	ENSMUSG00000073876
mus_musculus	Il11ra1	ENSMUSG00000073889
mus_musculus	Il11ra2	ENSMUSG00000078735
rattus_norvegicus	Il11ra1	ENSRNOG00000015068

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CSF3R (ENSG00000119535), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Interleukin-11 receptor subunit alpha — Q14626 (reviewed: Q14626)

All UniProt accessions (11): A0A8I5KTD7, A0A8J9AZZ3, Q14626, G3V2A5, G3V2G0, G3V2J5, G3V3V2, G3V428, G3V571, H0YCS8, Q5VZ79

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for interleukin-11 (IL11). The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. Essential for the normal development of craniofacial bones and teeth. Restricts suture fusion and tooth number. Soluble form of IL11 receptor (sIL11RA) that acts as an agonist of IL11 activity. The IL11:sIL11RA complex binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL11RA in a process called IL11 trans-signaling. Soluble form of IL11 receptor (sIL11RA) that acts as an agonist of IL11 activity. The IL11:sIL11RA complex binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL11RA in a process called IL11 trans-signaling.

Subunit / interactions. On IL11 binding, forms a multimer complex with IL6ST/gp130.

Subcellular location. Membrane Secreted Secreted.

Tissue specificity. Expressed in a number of cell lines, including the myelogenous leukemia cell line K-562, the megakaryocytic leukemia cell line M-07e, the erythroleukemia cell line TF-1, and the osteosarcoma cell lines, MG-63 and SaOS-2. Also expressed in normal and malignant prostate epithelial cell lines. Expression levels are increased in prostate carcinoma.

Post-translational modifications. A short soluble form is also released from the membrane by proteolysis. The sIL11RA is formed either by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, or directly secreted from the cells after alternative mRNA splicing. mIL11RA is cleaved by the proteases ADAM10, ELANE and PRTN3.

Disease relevance. Craniosynostosis and dental anomalies (CRSDA) [MIM:614188] A disorder characterized by craniosynostosis, maxillary hypoplasia, and dental anomalies, including malocclusion, delayed and ectopic tooth eruption, and/or supernumerary teeth. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Lacks the entire cytoplasmic domain.

Similarity. Belongs to the type I cytokine receptor family. Type 3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14626-1	HCR1, Membrane form, mIL11RA	yes
Q14626-2	HCR2, Soluble form, sIL11RA

RefSeq proteins (1): NP_001136256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003530	Hematopoietin_rcpt_L_F3_CS	Conserved_site
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR053073	IL11/IL27_subunit_beta	Family

UniProt features (49 total): strand 21, sequence variant 6, disulfide bond 3, domain 3, chain 2, region of interest 2, glycosylation site 2, topological domain 2, signal peptide 1, short sequence motif 1, compositionally biased region 1, splice variant 1, mutagenesis site 1, turn 1, transmembrane region 1, helix 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8QY4	ELECTRON MICROSCOPY	3.06
6O4P	X-RAY DIFFRACTION	3.43
8DPS	ELECTRON MICROSCOPY	3.47
8DPU	X-RAY DIFFRACTION	3.78
8DPT	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14626-F1	82.01	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 48–94, 120–130, 170–180

Glycosylation sites (2): 127, 194

Mutagenesis-validated functional residues (1):

Position	Phenotype
355	decreases proteolyisis by adam10.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions

MSigDB gene sets: 376 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_PROTEIN_BINDING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, MORF_BRCA1, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOCC_CELL_SURFACE, KYNG_DNA_DAMAGE_DN, GOBP_REGULATION_OF_RECEPTOR_BINDING, CAGCTG_AP4_Q5, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, MORF_RAD51L3, MAHAJAN_RESPONSE_TO_IL1A_DN

GO Biological Process (7): embryo implantation (GO:0007566), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), developmental process (GO:0032502), interleukin-11-mediated signaling pathway (GO:0038154), head development (GO:0060322), cell differentiation (GO:0030154)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), interleukin-11 receptor activity (GO:0004921), interleukin-11 binding (GO:0019970), cytokine receptor activity (GO:0004896), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-6 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine-mediated signaling pathway	2
cytokine binding	2
cellular anatomical structure	2
multicellular organism development	1
female pregnancy	1
reproductive process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
biological_process	1
anatomical structure development	1
cellular developmental process	1
signaling receptor activity	1
cytokine receptor activity	1
interleukin-11 binding	1
interleukin-11-mediated signaling pathway	1
growth factor binding	1
transmembrane signaling receptor activity	1
immune receptor activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
protein-containing complex	1

Protein interactions and networks

STRING

819 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL11RA	IL11	P20809	998
IL11RA	IL6R	P08887	883
IL11RA	IL13RA1	P78552	843
IL11RA	CNTFR	P26992	810
IL11RA	GALT	P07902	803
IL11RA	NUDT2	P50583	777
IL11RA	IL6	P05231	755
IL11RA	LIFR	P42702	698
IL11RA	CTF1	Q16619	696
IL11RA	CNTF	P26441	687
IL11RA	OSM	P13725	657
IL11RA	OSMR	Q99650	631
IL11RA	IL6ST	P40189	606
IL11RA	IL27RA	Q6UWB1	593
IL11RA	TYK2	P29597	592

IntAct

5 interactions, top by confidence:

A	B	Type	Score
IL11RA	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
IL11	IL11RA	psi-mi:“MI:0407”(direct interaction)	0.440
OLFM4	IL11RA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): IL11RA (Two-hybrid), IL11RA (Two-hybrid)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: O35228, O88507, P26992, P51641, P70225, Q08406, Q14213, Q14626, Q5RF19, Q64385, Q71DR4, Q99MF4, O18796, P08887, P22272, P22273, O02744, P29460, P43432, P46282, P46658, P48095, P68220, P68221, Q28234, Q28268, Q28938, Q2PE76, Q61729, Q62959, Q865Y3, Q866G3, Q8CJE6, Q91ZK7, Q9MYL0, Q9XSQ5, D3YYU8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IL11	up-regulates	IL11RA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	9
Uncertain significance	25
Likely benign	32
Benign	24

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1074686	NM_001142784.3(IL11RA):c.709C>T (p.Arg237Ter)	Pathogenic
2022980	NM_001142784.3(IL11RA):c.811-2A>T	Pathogenic
2429382	NM_001142784.3(IL11RA):c.919T>C (p.Trp307Arg)	Pathogenic
30136	NM_001142784.3(IL11RA):c.886C>T (p.Arg296Trp)	Pathogenic
30138	NM_001142784.3(IL11RA):c.734C>G (p.Ser245Cys)	Pathogenic
30139	NM_001142784.3(IL11RA):c.475C>T (p.Gln159Ter)	Pathogenic
30140	NM_001142784.3(IL11RA):c.907ACCTGGAGC[3] (p.Ser308_Pro309insThrTrpSer)	Pathogenic
3355361	NM_001142784.3(IL11RA):c.811-1G>A	Pathogenic
3628326	NM_001142784.3(IL11RA):c.106C>T (p.Gln36Ter)	Pathogenic
3716578	NM_001142784.3(IL11RA):c.874C>T (p.Arg292Ter)	Pathogenic
3719324	NM_001142784.3(IL11RA):c.563G>A (p.Trp188Ter)	Pathogenic
3775771	NM_001142784.3(IL11RA):c.606dup (p.Ala203fs)	Pathogenic
1064613	NM_001142784.3(IL11RA):c.810G>A (p.Thr270=)	Likely pathogenic
2633279	NM_001142784.3(IL11RA):c.162-2A>T	Likely pathogenic
30137	NM_001142784.3(IL11RA):c.662C>G (p.Pro221Arg)	Likely pathogenic
3033581	NM_001142784.3(IL11RA):c.82dup (p.Gln28fs)	Likely pathogenic
3613498	NM_001142784.3(IL11RA):c.1073-1G>C	Likely pathogenic
4081462	NM_001142784.3(IL11RA):c.365del (p.Ala122fs)	Likely pathogenic
4849423	NM_001142784.3(IL11RA):c.1001del (p.Pro334fs)	Likely pathogenic
493489	NM_001142784.3(IL11RA):c.3G>A (p.Met1Ile)	Likely pathogenic
981196	NM_001142784.3(IL11RA):c.281G>T (p.Cys94Phe)	Likely pathogenic

SpliceAI

1860 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34656909:G:GG	donor_gain	1.0000
9:34659753:CCCCA:C	acceptor_loss	1.0000
9:34659756:CA:C	acceptor_loss	1.0000
9:34659758:G:GC	acceptor_loss	1.0000
9:34656904:GGGCT:G	donor_gain	0.9900
9:34656905:GGCT:G	donor_gain	0.9900
9:34656905:GGCTG:G	donor_gain	0.9900
9:34656906:GCT:G	donor_gain	0.9900
9:34656906:GCTG:G	donor_gain	0.9900
9:34657419:AGG:A	acceptor_loss	0.9900
9:34657420:G:GT	acceptor_loss	0.9900
9:34657583:CATCT:C	donor_gain	0.9900
9:34657585:TCT:T	donor_gain	0.9900
9:34657585:TCTGT:T	donor_loss	0.9900
9:34657587:TGTGA:T	donor_loss	0.9900
9:34657588:G:GG	donor_gain	0.9900
9:34657588:GTGAG:G	donor_loss	0.9900
9:34657589:TGAGT:T	donor_loss	0.9900
9:34657590:GAGTA:G	donor_loss	0.9900
9:34657591:AGTAC:A	donor_loss	0.9900
9:34658518:A:AG	acceptor_gain	0.9900
9:34658519:G:GG	acceptor_gain	0.9900
9:34658519:GTGC:G	acceptor_gain	0.9900
9:34659757:A:AG	acceptor_gain	0.9900
9:34659757:AGGT:A	acceptor_gain	0.9900
9:34659757:AGGTG:A	acceptor_gain	0.9900
9:34659758:G:GT	acceptor_gain	0.9900
9:34659758:GGT:G	acceptor_gain	0.9900
9:34659758:GGTG:G	acceptor_gain	0.9900
9:34659758:GGTGG:G	acceptor_gain	0.9900

AlphaMissense

2670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34658639:T:C	F256L	0.997
9:34658641:C:A	F256L	0.997
9:34658641:C:G	F256L	0.997
9:34659870:A:C	S308R	0.997
9:34659872:C:A	S308R	0.997
9:34659872:C:G	S308R	0.997
9:34657099:G:C	W132C	0.996
9:34657099:G:T	W132C	0.996
9:34658591:T:A	W240R	0.996
9:34658591:T:C	W240R	0.996
9:34658593:G:C	W240C	0.996
9:34658593:G:T	W240C	0.996
9:34659787:T:C	I280T	0.996
9:34659861:A:C	S305R	0.996
9:34659863:C:A	S305R	0.996
9:34659863:C:G	S305R	0.996
9:34657538:C:A	N199K	0.995
9:34657538:C:G	N199K	0.995
9:34658535:C:A	P221H	0.995
9:34659862:G:T	S305I	0.995
9:34659869:G:C	W307C	0.994
9:34659869:G:T	W307C	0.994
9:34658640:T:C	F256S	0.993
9:34658651:T:G	Y260D	0.993
9:34657061:T:A	C120S	0.992
9:34657062:G:A	C120Y	0.992
9:34657062:G:C	C120S	0.992
9:34657097:T:A	W132R	0.992
9:34657097:T:C	W132R	0.992
9:34658611:G:C	W246C	0.992

dbSNP variants (sampled 300 via entrez): RS1000378386 (9:34650888 C>T), RS1000409519 (9:34650551 A>G), RS1000460841 (9:34657878 C>A), RS1000557990 (9:34656089 T>C), RS1000645702 (9:34661564 G>A,C), RS1001202581 (9:34656321 G>A), RS1001918221 (9:34654743 G>A,T), RS1002244882 (9:34661229 G>C,T), RS1002266295 (9:34661217 A>C), RS1002584120 (9:34651801 G>A), RS1002636422 (9:34652050 G>GGGTGGA), RS1002639334 (9:34654825 G>A,C), RS1003217063 (9:34653341 G>A), RS1003532521 (9:34659625 C>T), RS1003650052 (9:34653423 TC>T)

Disease associations

OMIM: gene MIM:600939 | disease phenotypes: MIM:614188, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
craniosynostosis and dental anomalies	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
craniosynostosis and dental anomalies	Definitive	AR

Mondo (2): craniosynostosis and dental anomalies (MONDO:0013615), craniosynostosis (MONDO:0015469)

Orphanet (2): Craniosynostosis-dental anomalies (Orphanet:284149), Craniosynostosis (Orphanet:1531)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000262	Turricephaly
HP:0000263	Oxycephaly
HP:0000268	Dolichocephaly
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000340	Sloping forehead
HP:0000348	High forehead
HP:0000381	Stapes ankylosis
HP:0000389	Chronic otitis media
HP:0000405	Conductive hearing impairment
HP:0000444	Convex nasal ridge
HP:0000445	Wide nose
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000678	Dental crowding
HP:0000684	Delayed eruption of teeth
HP:0000689	Dental malocclusion
HP:0001085	Papilledema
HP:0001250	Seizure
HP:0001822	Hallux valgus
HP:0002007	Frontal bossing
HP:0002308	Chiari malformation
HP:0003396	Syringomyelia
HP:0004322	Short stature

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004420_43	CTACK levels	2.000000e-32

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008082	chemokine (C-C motif) ligand 27 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2050 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-6 receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	affects acetylation, affects methylation, affects cotreatment, decreases expression, increases abundance	2
Acetaminophen	increases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
monomethylarsonous acid	affects acetylation, affects methylation	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzene	increases expression	1
Cannabidiol	decreases expression	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6115568	Binding	Binding affinity to CAP chip-immobilized biotinylated recombinant human IL-11Ralpha assessed as dissociation constant by SPR analysis	De novo discovery of cyclic peptide inhibitors of IL-11 signaling. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SS42	HAP1 IL11RA (-) 1	Cancer cell line	Male
CVCL_SS43	HAP1 IL11RA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

17 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT00077831	Not specified	COMPLETED	Child and Infant Learning Project
NCT00106977	Not specified	COMPLETED	Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
NCT00367796	Not specified	COMPLETED	Genetic Analysis of Craniosynostosis, Philadelphia Type
NCT00769847	Not specified	WITHDRAWN	Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
NCT00773643	Not specified	COMPLETED	Osteogenic Profiling of Tissue From Children With Craniosynostosis
NCT01898650	Not specified	COMPLETED	MRI for Non-invasive Evaluation of Brain Stress
NCT02287805	Not specified	COMPLETED	Qualitative and Quantitative Study Which Aims to Determine the Specifics of the Announcement for the Diagnosis of Patients With Craniosynostosis and Their Parents to Better Support Them in Their Care
NCT02561728	Not specified	WITHDRAWN	Hanger Helmet Study
NCT03025763	Not specified	ACTIVE_NOT_RECRUITING	Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
NCT03231085	Not specified	COMPLETED	Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child
NCT04704284	Not specified	COMPLETED	Comparing MRI to CT on Pediatric Craniosynostosis.
NCT05911139	Not specified	ENROLLING_BY_INVITATION	Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
NCT06928727	Not specified	RECRUITING	Ocular Characteristics in Patients With Craniosynostosis