Osteogenesis imperfecta type 11

Summary

Osteogenesis imperfecta type 11 (MONDO:0012592) is a disease caused by FKBP10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FKBP10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 113

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 11
Mondo ID	MONDO:0012592
OMIM	610968
DOID	DOID:0110351
UMLS	C3151218
MedGen	462568
GARD	0012875
Is cancer (heuristic)	no

Also known as: FKBP10 osteogenesis imperfecta · OI type 11 · OI type XI · OI11 · osteogenesis imperfecta caused by mutation in FKBP10 · osteogenesis imperfecta, type XI

Data availability: 113 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › osteogenesis imperfecta › osteogenesis imperfecta and a reduction of bone mineral density. › osteogenesis imperfecta type 11

Related subtypes (32): Cole-Carpenter syndrome 1, calvarial doughnut lesions-bone fragility syndrome, osteogenesis imperfecta type 1, osteogenesis imperfecta type 2, osteogenesis imperfecta type 4, gnathodiaphyseal dysplasia, geroderma osteodysplastica, osteogenesis imperfecta type 3, osteogenesis imperfecta type 9, osteoporosis-pseudoglioma syndrome, Wiedemann-Rautenstrauch syndrome, spondylo-ocular syndrome, Bruck syndrome 2, osteogenesis imperfecta type 7, osteogenesis imperfecta type 8, osteogenesis imperfecta type 5, autosomal recessive cutis laxa type 2B, osteogenesis imperfecta type 10, osteogenesis imperfecta type 12, osteogenesis imperfecta type 6, short stature-optic atrophy-Pelger-Huët anomaly syndrome, osteogenesis imperfecta type 14, osteogenesis imperfecta type 15, osteogenesis imperfecta type 16, Cole-Carpenter syndrome 2, Singleton-Merten syndrome 2, osteogenesis imperfecta type 17, autosomal recessive cutis laxa type 2A, Ehlers-Danlos syndrome, spondylodysplastic type, 1, Singleton-Merten syndrome 1, osteogenesis imperfecta, type 18, osteogenesis imperfecta, type 19

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

113 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 23 conflicting classifications of pathogenicity, 16 likely pathogenic, 9 pathogenic, 9 benign/likely benign, 8 benign, 5 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1380263	NM_021939.4(FKBP10):c.612C>G (p.Tyr204Ter)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
1457018	NM_021939.4(FKBP10):c.21dup (p.Ser8fs)	FKBP10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1490007	NM_021939.4(FKBP10):c.1621C>T (p.Gln541Ter)	FKBP10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222952	NM_021939.4(FKBP10):c.976del (p.Met326fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
30633	NM_021939.4(FKBP10):c.1276dup (p.Gln426fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
30635	NM_021939.4(FKBP10):c.743dup (p.Gln249fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
3581947	NM_021939.4(FKBP10):c.829_841del (p.Pro277fs)	FKBP10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4076410	NM_021939.4(FKBP10):c.46del (p.Leu16fs)	FKBP10	Pathogenic	no assertion criteria provided
41473	NM_021939.4(FKBP10):c.337G>A (p.Glu113Lys)	FKBP10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4291703	NM_021939.4(FKBP10):c.1002C>A (p.Cys334Ter)	FKBP10	Pathogenic	criteria provided, single submitter
438659	NM_021939.4(FKBP10):c.831dup (p.Gly278fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
4796536	NM_021939.4(FKBP10):c.813_814del (p.Glu271fs)	FKBP10	Pathogenic	criteria provided, single submitter
503914	NM_021939.4(FKBP10):c.831del (p.Gly278fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
631496	NM_021939.4(FKBP10):c.890_897dup (p.Gly300Ter)	FKBP10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172574	NM_021939.4(FKBP10):c.391+4A>T	FKBP10	Likely pathogenic	criteria provided, single submitter
2585054	NM_021939.4(FKBP10):c.1034del (p.Pro345fs)	FKBP10	Likely pathogenic	criteria provided, single submitter
2996999	NM_021939.4(FKBP10):c.727+2del	FKBP10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3234921	NM_021939.4(FKBP10):c.1619_1623delinsT (p.Gly540fs)	FKBP10	Likely pathogenic	criteria provided, single submitter
3544390	NM_021939.4(FKBP10):c.1479_1481delinsTCAG (p.Leu494fs)	FKBP10	Likely pathogenic	criteria provided, single submitter
3581945	NM_021939.4(FKBP10):c.726T>G (p.Tyr242Ter)	FKBP10	Likely pathogenic	criteria provided, single submitter
3581946	NM_021939.4(FKBP10):c.743del (p.Pro248fs)	FKBP10	Likely pathogenic	criteria provided, single submitter
3581948	NM_021939.4(FKBP10):c.1400-1G>T	FKBP10	Likely pathogenic	criteria provided, single submitter
3581949	NM_021939.4(FKBP10):c.1499_1502dup (p.Ala503fs)	FKBP10	Likely pathogenic	criteria provided, single submitter
3581950	NM_021939.4(FKBP10):c.1564-2A>T	FKBP10	Likely pathogenic	criteria provided, single submitter
4076407	NM_021939.4(FKBP10):c.1159del (p.Arg387fs)	FKBP10	Likely pathogenic	no assertion criteria provided
4531247	NM_021939.4(FKBP10):c.1A>G (p.Met1Val)	FKBP10	Likely pathogenic	criteria provided, single submitter
684394	NM_021939.4(FKBP10):c.106C>A (p.Pro36Thr)	FKBP10	Likely pathogenic	criteria provided, single submitter
684395	NM_021939.4(FKBP10):c.134T>A (p.Val45Asp)	FKBP10	Likely pathogenic	criteria provided, single submitter
684396	NM_021939.4(FKBP10):c.370G>T (p.Gly124Cys)	FKBP10	Likely pathogenic	criteria provided, single submitter
989304	NM_021939.4(FKBP10):c.918-6T>G	FKBP10	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
FKBP10	Strong	Autosomal recessive	osteogenesis imperfecta type 11	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FKBP10	Orphanet:1149	Kuskokwim syndrome
FKBP10	Orphanet:216812	Osteogenesis imperfecta type 3
FKBP10	Orphanet:216820	Osteogenesis imperfecta type 4
FKBP10	Orphanet:2771	Bruck 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
FKBP10	HGNC:18169	ENSG00000141756	Q96AY3	Peptidyl-prolyl cis-trans isomerase FKBP10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FKBP10	Peptidyl-prolyl cis-trans isomerase FKBP10	PPIases accelerate the folding of proteins during protein synthesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FKBP10	Other/Unknown	no		PPIase_FKBP_dom, EF_hand_dom, EF-hand-dom_pair

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
ascending aorta	1
stromal cell of endometrium	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FKBP10	179	ubiquitous	marker	stromal cell of endometrium, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKBP10	3,473

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKBP10	Q96AY3	89.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
extracellular matrix assembly	1	936.2×	0.003	FKBP10
aorta morphogenesis	1	887.0×	0.003	FKBP10
wound healing	1	227.7×	0.007	FKBP10
collagen fibril organization	1	224.7×	0.007	FKBP10
protein folding	1	103.4×	0.012	FKBP10
in utero embryonic development	1	72.0×	0.014	FKBP10

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FKBP10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FKBP10

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)
FKBP10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.