Eiken syndrome

Summary

Eiken syndrome (MONDO:0010803) is a disease caused by PTH1R (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PTH1R (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 97
• Phenotypes (HPO): 23

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0002656	Epiphyseal dysplasia	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0006376	Limited elbow flexion	Very frequent (80-99%)
HP:0001169	Broad palm	Frequent (30-79%)
HP:0001211	Abnormal fingertip morphology	Frequent (30-79%)
HP:0001769	Broad foot	Frequent (30-79%)
HP:0001773	Short foot	Frequent (30-79%)
HP:0001831	Short toe	Frequent (30-79%)
HP:0002663	Delayed epiphyseal ossification	Frequent (30-79%)
HP:0002753	Thin bony cortex	Frequent (30-79%)
HP:0002967	Cubitus valgus	Frequent (30-79%)
HP:0003025	Metaphyseal irregularity	Frequent (30-79%)
HP:0003038	Fibular hypoplasia	Frequent (30-79%)
HP:0003170	Abnormality of the acetabulum	Frequent (30-79%)
HP:0003275	Narrow pelvis bone	Frequent (30-79%)
HP:0004279	Short palm	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0008800	Limited hip movement	Frequent (30-79%)
HP:0008808	High iliac wings	Frequent (30-79%)
HP:0009803	Short phalanx of finger	Frequent (30-79%)
HP:0010305	Absence of the sacrum	Frequent (30-79%)
HP:0011849	Abnormal bone ossification	Frequent (30-79%)
HP:0100671	Abnormal trabecular bone morphology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Eiken syndrome
Mondo ID	MONDO:0010803
MeSH	C564010
OMIM	600002
Orphanet	79106
DOID	DOID:0111732
ICD-11	467339994
SNOMED CT	720863002
UMLS	C1838779
MedGen	325097
GARD	0016698
Is cancer (heuristic)	no

Also known as: bone modelling defect of hands and feet · Eiken syndrome

Data availability: 97 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › Eiken syndrome

Related subtypes (118): osteochondrodysplasia, diaphyseal medullary stenosis-bone malignancy syndrome, fibular aplasia-ectrodactyly syndrome, cerebrocostomandibular syndrome, cleidorhizomelic syndrome, dyschondrosteosis-nephritis syndrome, dysplasia epiphysealis hemimelica, carpotarsal osteochondromatosis, Camurati-Engelmann disease, genochondromatosis, autosomal dominant osteosclerosis, Worth type, coxopodopatellar syndrome, Lenz-Majewski hyperostotic dwarfism, delayed membranous cranial ossification, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, oculodentodigital dysplasia, Ollier disease, osteoglophonic dysplasia, parietal foramina with cleidocranial dysplasia, chondromalacia patellae, Currarino triad, Proteus syndrome, brachydactyly-elbow wrist dysplasia syndrome, tricho-dento-osseous syndrome, bird headed-dwarfism, Montreal type, Yunis-Varon syndrome, split hand-foot malformation 1 with sensorineural hearing loss, ghosal hematodiaphyseal dysplasia, hyperostosis corticalis generalisata, Larsen-like syndrome, B3GAT3 type, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal acroscyphodysplasia, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, familial osteodysplasia, Anderson type, pseudodiastrophic dysplasia, rhizomelic syndrome, Urbach type, Richieri Costa-Pereira syndrome, craniometadiaphyseal dysplasia, wormian bone type, Weaver syndrome, SHOX-related short stature, craniofrontonasal syndrome, 2q37 microdeletion syndrome, skeletal dysplasia-epilepsy-short stature syndrome, rhizomelic dysplasia, Patterson-Lowry type, pelvic dysplasia-arthrogryposis of lower limbs syndrome, Marshall-Smith syndrome, baby rattle pelvis dysplasia, metaphyseal dysplasia, Braun-Tinschert type, genitopatellar syndrome, osteofibrous dysplasia, Larsen-like osseous dysplasia-short stature syndrome, pancreatic insufficiency-anemia-hyperostosis syndrome, microcephalic primordial dwarfism due to ZNF335 deficiency, Hartsfield-Bixler-Demyer syndrome, colobomatous microphthalmia-rhizomelic dysplasia syndrome, Tatton-Brown-Rahman overgrowth syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, Catel-Manzke syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome, complex lethal osteochondrodysplasia, amniotic band syndrome, metaphyseal anadysplasia, syndromic craniosynostosis, thin ribs-tubular bones-dysmorphism syndrome, dysplasia of head of femur, Meyer type, epimetaphyseal skeletal dysplasia, melorheostosis with osteopoikilosis, Cole-Carpenter syndrome, spondylometaphyseal dysplasia, omodysplasia, Bruck syndrome, osteopetrosis, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, chondroectodermal dysplasia with night blindness, TRPV4-related bone disorder, adactyly of foot, short stature-advanced bone age-early-onset osteoarthritis syndrome, McCune-Albright syndrome, parietal foramina, Sotos syndrome, dysspondyloenchondromatosis, autosomal recessive cutis laxa type 2, FGFR3-related chondrodysplasia, filamin-related bone disorder, short rib dysplasia, spondylodysplastic dysplasia, acromelic dysplasia, bent bone dysplasia, chondrodysplasia punctata, primary osteolysis, non-syndromic limb reduction defect, Robinow syndrome, synpolydactyly, acrocoxomesomelic dysplasia, bone dysplasia Moore type, bone dysplasia corpus callosum agenesis, type 2 collagenopathy, LRP5-related primary osteoporosis, SLC26A2-related skeletal dysplasia, COMP-related skeletal dysplasia, primordial dwarfism and slender bone disorder, polydactyly-syndactyly-triphalangism, lysosomal storage disease with skeletal involvement, abnormal mineralization disorder, calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia, de la Chapelle dysplasia, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, proximal femoral focal deficiency, rhizomelic dysplasia, Ain-Naz type, craniotubular dysplasia, Ikegawa type, TRIP11-related skeletal dysplasia, FAM111A-related skeletal dysplasia

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

97 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 9 conflicting classifications of pathogenicity, 7 likely benign, 7 benign/likely benign, 3 likely pathogenic, 2 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13745	NM_000316.3(PTH1R):c.395C>T (p.Pro132Leu)	LOC129936652	Pathogenic	criteria provided, single submitter
13749	NM_000316.3(PTH1R):c.1453C>T (p.Arg485Ter)	PTH1R	Pathogenic	no assertion criteria provided
3589193	NM_000316.3(PTH1R):c.75+1del	PTH1R	Likely pathogenic	criteria provided, single submitter
3589206	NM_000316.3(PTH1R):c.735C>G (p.Tyr245Ter)	PTH1R	Likely pathogenic	criteria provided, single submitter
3589209	NM_000316.3(PTH1R):c.892T>G (p.Trp298Gly)	PTH1R	Likely pathogenic	criteria provided, single submitter
1050981	NM_000316.3(PTH1R):c.1645G>A (p.Glu549Lys)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1410640	NM_000316.3(PTH1R):c.311G>A (p.Arg104Gln)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2707211	NM_000316.3(PTH1R):c.1144G>A (p.Val382Ile)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345577	NM_000316.3(PTH1R):c.128G>A (p.Arg43His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345580	NM_000316.3(PTH1R):c.226G>C (p.Gly76Arg)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345592	NM_000316.3(PTH1R):c.1050-3dup	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345598	NM_000316.3(PTH1R):c.1427G>A (p.Arg476His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899444	NM_000316.3(PTH1R):c.449G>A (p.Arg150His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900527	NM_000316.3(PTH1R):c.137C>A (p.Ala46Asp)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1410602	NM_000316.3(PTH1R):c.364G>A (p.Ala122Thr)	LOC129936652	Uncertain significance	criteria provided, multiple submitters, no conflicts
3589200	NM_000316.3(PTH1R):c.357G>C (p.Pro119=)	LOC129936652	Uncertain significance	criteria provided, single submitter
1014462	NM_000316.3(PTH1R):c.1112T>C (p.Ile371Thr)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1015750	NM_000316.3(PTH1R):c.1672C>T (p.Pro558Ser)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1046655	NM_000316.3(PTH1R):c.543+4C>T	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1309110	NM_000316.3(PTH1R):c.1696G>A (p.Gly566Ser)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1351330	NM_000316.3(PTH1R):c.1531C>G (p.Arg511Gly)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1355105	NM_000316.3(PTH1R):c.1739G>A (p.Arg580Gln)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1355949	NM_000316.3(PTH1R):c.1742C>G (p.Pro581Arg)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1371079	NM_000316.3(PTH1R):c.1198C>T (p.Arg400Trp)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1386566	NM_000316.3(PTH1R):c.1736A>C (p.Glu579Ala)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1401176	NM_000316.3(PTH1R):c.449G>T (p.Arg150Leu)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442623	NM_000316.3(PTH1R):c.629C>T (p.Ala210Val)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1447094	NM_000316.3(PTH1R):c.1366G>A (p.Ala456Thr)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1451055	NM_000316.3(PTH1R):c.749T>C (p.Leu250Pro)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
1515323	NM_000316.3(PTH1R):c.157A>G (p.Lys53Glu)	PTH1R	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 5 · 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
PTH1R	Strong	Autosomal recessive	Eiken syndrome	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTH1R	Orphanet:296	Ollier disease
PTH1R	Orphanet:33067	Metaphyseal chondrodysplasia, Jansen type
PTH1R	Orphanet:412206	Primary failure of tooth eruption
PTH1R	Orphanet:50945	Blomstrand lethal chondrodysplasia
PTH1R	Orphanet:79106	Eiken syndrome

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
PTH1R	HGNC:9608	ENSG00000160801	Q03431	Parathyroid hormone/parathyroid hormone-related peptide receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTH1R	Parathyroid hormone/parathyroid hormone-related peptide receptor	G-protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH).

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTH1R	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_parathyroid_rcpt

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
adult mammalian kidney	1
metanephros cortex	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTH1R	219	broad	marker	adult mammalian kidney, metanephros cortex, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTH1R	1,633

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTH1R	Q03431	48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Class B/2 (Secretin family receptors)	1	190.3×	0.011	PTH1R
G alpha (s) signalling events	1	73.2×	0.014	PTH1R

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
positive regulation of inositol phosphate biosynthetic process	1	2407.4×	0.007	PTH1R
osteoblast development	1	991.3×	0.008	PTH1R
bone resorption	1	581.1×	0.008	PTH1R
cell maturation	1	443.5×	0.008	PTH1R
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	337.0×	0.008	PTH1R
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1	312.1×	0.008	PTH1R
chondrocyte differentiation	1	300.9×	0.008	PTH1R
bone mineralization	1	271.8×	0.008	PTH1R
intracellular calcium ion homeostasis	1	145.3×	0.013	PTH1R
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.013	PTH1R
skeletal system development	1	125.8×	0.013	PTH1R
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.013	PTH1R
cell population proliferation	1	102.8×	0.013	PTH1R
in utero embryonic development	1	72.0×	0.018	PTH1R
cell surface receptor signaling pathway	1	64.1×	0.019	PTH1R
negative regulation of cell population proliferation	1	42.1×	0.027	PTH1R
G protein-coupled receptor signaling pathway	1	36.2×	0.029	PTH1R
positive regulation of cell population proliferation	1	33.6×	0.030	PTH1R

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PTH1R	ABALOPARATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTH1R	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ABALOPARATIDE	4	PTH1R
TERIPARATIDE	4	PTH1R
PCO-371	1	PTH1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PTH1R	59	Functional:42, Binding:17

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
ABALOPARATIDE	4	PTH1R
TERIPARATIDE	4	PTH1R
PCO-371	1	PTH1R

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PTH1R
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.