Craniosynostosis and dental anomalies

Summary

Craniosynostosis and dental anomalies (MONDO:0013615) is a disease caused by IL11RA (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: IL11RA (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	craniosynostosis and dental anomalies
Mondo ID	MONDO:0013615
OMIM	614188
Orphanet	284149
UMLS	C3280073
MedGen	481703
GARD	0017309
Is cancer (heuristic)	no

Also known as: craniosynostosis and dental anomalies · CRSDA · Kreiborg-Pakistani syndrome

Data availability: 13 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › craniosynostosis and dental anomalies

Related subtypes (39): Crouzon syndrome, Beare-Stevenson cutis gyrata syndrome, Shprintzen-Goldberg syndrome, acrocephalopolydactyly, Antley-Bixler syndrome, C syndrome, cranioectodermal dysplasia, cardiocranial syndrome, Pfeiffer type, craniosynostosis-fibular aplasia syndrome, Baller-Gerold syndrome, craniotelencephalic dysplasia, Summitt syndrome, X-linked intellectual disability-plagiocephaly syndrome, Lowry-MacLean syndrome, pseudoaminopterin syndrome, craniosynostosis 4, holoprosencephaly-craniosynostosis syndrome, Hunter-McAlpine craniosynostosis, Curry-Jones syndrome, craniomicromelic syndrome, Muenke syndrome, craniosynostosis-anal anomalies-porokeratosis syndrome, craniosynostosis 2, cloverleaf skull-multiple congenital anomalies syndrome, craniosynostosis-intracranial calcifications syndrome, Crouzon syndrome-acanthosis nigricans syndrome, lethal occipital encephalocele-skeletal dysplasia syndrome, TCF12-related craniosynostosis, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, cloverleaf skull-asphyxiating thoracic dysplasia syndrome, craniosynostosis, Philadelphia type, craniosynostosis-cataract syndrome, familial scaphocephaly syndrome, craniosynostosis-hydrocephalus-Arnold-Chiari malformation type I-radioulnar synostosis syndrome, osteosclerosis-developmental delay-craniosynostosis syndrome, craniosynostosis, Herrmann-Opitz type, trigonocephaly-broad thumbs syndrome, acrocephalosyndactyly, Weiss-Kruszka 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

13 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 5 pathogenic, 1 pathogenic/likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
30136	NM_001142784.3(IL11RA):c.886C>T (p.Arg296Trp)	IL11RA	Pathogenic	criteria provided, single submitter
30138	NM_001142784.3(IL11RA):c.734C>G (p.Ser245Cys)	IL11RA	Pathogenic	no assertion criteria provided
30139	NM_001142784.3(IL11RA):c.475C>T (p.Gln159Ter)	IL11RA	Pathogenic	criteria provided, single submitter
30140	NM_001142784.3(IL11RA):c.907ACCTGGAGC[3] (p.Ser308_Pro309insThrTrpSer)	IL11RA	Pathogenic	criteria provided, single submitter
3254791	NM_001142784.3(IL11RA):c.331+6T>G	IL11RA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775771	NM_001142784.3(IL11RA):c.606dup (p.Ala203fs)	IL11RA	Pathogenic	criteria provided, single submitter
1064613	NM_001142784.3(IL11RA):c.810G>A (p.Thr270=)	IL11RA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
30137	NM_001142784.3(IL11RA):c.662C>G (p.Pro221Arg)	IL11RA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081462	NM_001142784.3(IL11RA):c.365del (p.Ala122fs)	IL11RA	Likely pathogenic	criteria provided, single submitter
4849423	NM_001142784.3(IL11RA):c.1001del (p.Pro334fs)	IL11RA	Likely pathogenic	criteria provided, single submitter
981196	NM_001142784.3(IL11RA):c.281G>T (p.Cys94Phe)	IL11RA	Likely pathogenic	criteria provided, single submitter
981195	NM_001142784.3(IL11RA):c.781C>T (p.Arg261Cys)	IL11RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522708	NM_001142784.3(IL11RA):c.331+2T>C	IL11RA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
IL11RA	Definitive	Autosomal recessive	craniosynostosis and dental anomalies	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL11RA	Orphanet:284149	Craniosynostosis-dental anomalies

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
IL11RA	HGNC:5967	ENSG00000137070	Q14626	Interleukin-11 receptor subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL11RA	Interleukin-11 receptor subunit alpha	Receptor for interleukin-11 (IL11).

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)
IL11RA	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_L_F3_CS, Ig_sub, FN3_dom

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
apex of heart	1
descending thoracic aorta	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL11RA	237	broad	marker	apex of heart, descending thoracic aorta, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL11RA	826

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL11RA	Q14626	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
IL-6-type cytokine receptor ligand interactions	1	634.4×	0.002	IL11RA

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
interleukin-11-mediated signaling pathway	1	3370.4×	0.002	IL11RA
head development	1	1203.7×	0.002	IL11RA
developmental process	1	674.1×	0.003	IL11RA
embryo implantation	1	351.1×	0.004	IL11RA
cytokine-mediated signaling pathway	1	130.6×	0.009	IL11RA
positive regulation of cell population proliferation	1	33.6×	0.030	IL11RA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL11RA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IL11RA	2	Binding:2

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	IL11RA
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)
IL11RA	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.