Osteogenesis imperfecta type 12

Summary

Osteogenesis imperfecta type 12 (MONDO:0013460) is a disease caused by SP7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SP7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 12
Mondo ID	MONDO:0013460
OMIM	613849
DOID	DOID:0110348
UMLS	C3151433
MedGen	462783
GARD	0015722
Is cancer (heuristic)	no

Also known as: OI12 · osteogenesis imperfecta caused by mutation in SP7 · osteogenesis imperfecta, type XII · SP7 osteogenesis imperfecta

Data availability: 22 ClinVar variants · 3 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 12

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, osteogenesis imperfecta type 11, autosomal recessive cutis laxa type 2B, osteogenesis imperfecta type 10, 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

22 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 7 pathogenic, 3 benign, 2 likely pathogenic, 1 likely benign, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
30632	NM_021939.4(FKBP10):c.122_156del (p.Leu41fs)	FKBP10	Pathogenic	no assertion criteria provided
3532	NM_021939.4(FKBP10):c.321_353del (p.Met107_Leu117del)	FKBP10	Pathogenic	criteria provided, single submitter
39842	NM_021939.3(FKBP10):c.1207C>T (p.Arg403Ter)	FKBP10	Pathogenic	no assertion criteria provided
41425	NM_021939.4(FKBP10):c.1271_1272delinsA (p.Ala424fs)	FKBP10	Pathogenic	no assertion criteria provided
41899	NM_021939.4(FKBP10):c.948dup (p.Ile317fs)	FKBP10	Pathogenic	criteria provided, single submitter
438659	NM_021939.4(FKBP10):c.831dup (p.Gly278fs)	FKBP10	Pathogenic	criteria provided, multiple submitters, no conflicts
31854	NM_001173467.3(SP7):c.1052del (p.Glu351fs)	SP7	Pathogenic	no assertion criteria provided
2503440	NM_001173467.3(SP7):c.359_362del (p.Asp120fs)	SP7	Likely pathogenic	no assertion criteria provided
3572974	NM_001173467.3(SP7):c.810C>A (p.Cys270Ter)	SP7	Likely pathogenic	criteria provided, single submitter
282803	NM_001173467.3(SP7):c.1272G>A (p.Glu424=)	SP7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1361090	NM_001173467.3(SP7):c.135_136del (p.Lys46fs)	SP7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1436152	NM_001173467.3(SP7):c.1220G>A (p.Arg407Gln)	SP7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1506437	NM_001173467.3(SP7):c.144C>G (p.Tyr48Ter)	SP7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436268	NM_001173467.3(SP7):c.973G>A (p.Val325Ile)	SP7	Uncertain significance	criteria provided, single submitter
2436269	NM_001173467.3(SP7):c.455G>C (p.Gly152Ala)	SP7	Uncertain significance	criteria provided, multiple submitters, no conflicts
560212	NM_001173467.3(SP7):c.946C>T (p.Arg316Cys)	SP7	Uncertain significance	criteria provided, single submitter
829874	NM_001173467.3(SP7):c.1093C>T (p.Arg365Ter)	SP7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1181435	NM_001173467.3(SP7):c.-47-15del	SP7	Likely benign	criteria provided, multiple submitters, no conflicts
1268320	NM_001173467.3(SP7):c.993C>T (p.Cys331=)	SP7	Benign	criteria provided, multiple submitters, no conflicts
196318	NM_001173467.3(SP7):c.864G>A (p.Leu288=)	SP7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
285778	NM_001173467.3(SP7):c.1098C>T (p.Ser366=)	SP7	Benign	criteria provided, multiple submitters, no conflicts
285779	NM_001173467.3(SP7):c.1128T>C (p.His376=)	SP7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 6 · 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
SP7	Strong	Autosomal recessive	osteogenesis imperfecta type 12	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SP7	Orphanet:1513	Craniodiaphyseal dysplasia
SP7	Orphanet:216820	Osteogenesis imperfecta type 4
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SP7	HGNC:17321	ENSG00000170374	Q8TDD2	Transcription factor Sp7	gencc,clinvar
FKBP10	HGNC:18169	ENSG00000141756	Q96AY3	Peptidyl-prolyl cis-trans isomerase FKBP10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SP7	Transcription factor Sp7	Transcriptional activator essential for osteoblast differentiation.
FKBP10	Peptidyl-prolyl cis-trans isomerase FKBP10	PPIases accelerate the folding of proteins during protein synthesis.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SP7	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
tibia	1
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
SP7	46	tissue_specific	yes	primordial germ cell in gonad, tibia, male germ line stem cell (sensu Vertebrata) in testis
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
SP7	2,310

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKBP10	Q96AY3	89.19
SP7	Q8TDD2	52.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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
RUNX2 regulates bone development	1	815.7×	0.007	SP7
RUNX2 regulates osteoblast differentiation	1	456.8×	0.007	SP7
Transcriptional regulation by RUNX2	1	253.8×	0.008	SP7
RNA Polymerase II Transcription	1	22.5×	0.066	SP7
Gene expression (Transcription)	1	17.8×	0.066	SP7
Generic Transcription Pathway	1	15.1×	0.066	SP7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
diphosphate metabolic process	1	1685.2×	0.005	SP7
cellular response to zinc ion starvation	1	1203.7×	0.005	SP7
cementum mineralization	1	1203.7×	0.005	SP7
cellular response to parathyroid hormone stimulus	1	702.2×	0.006	SP7
positive regulation of stem cell differentiation	1	648.1×	0.006	SP7
extracellular matrix assembly	1	468.1×	0.006	FKBP10
aorta morphogenesis	1	443.5×	0.006	FKBP10
hematopoietic stem cell differentiation	1	383.0×	0.006	SP7
response to mechanical stimulus	1	150.5×	0.013	SP7
response to insulin	1	115.4×	0.013	SP7
wound healing	1	113.9×	0.013	FKBP10
collagen fibril organization	1	112.3×	0.013	FKBP10
osteoblast differentiation	1	60.6×	0.023	SP7
protein folding	1	51.7×	0.025	FKBP10
gene expression	1	39.9×	0.030	SP7
in utero embryonic development	1	36.0×	0.031	FKBP10
positive regulation of transcription by RNA polymerase II	1	7.4×	0.138	SP7
regulation of transcription by RNA polymerase II	1	5.8×	0.164	SP7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SP7	0	0
FKBP10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	SP7, FKBP10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SP7	0	—
FKBP10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.