Osteogenesis imperfecta type 10

Summary

Osteogenesis imperfecta type 10 (MONDO:0013459) is a disease caused by SERPINH1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SERPINH1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 10
Mondo ID	MONDO:0013459
OMIM	613848
DOID	DOID:0110346
UMLS	C3151211
MedGen	462561
GARD	0012874
Is cancer (heuristic)	no

Also known as: OI type 10 · OI type X · OI10 · osteogenesis imperfecta caused by mutation in SERPINH1 · osteogenesis imperfecta, type X · SERPINH1 osteogenesis imperfecta

Data availability: 69 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 10

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 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

69 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 15 conflicting classifications of pathogenicity, 14 benign, 3 pathogenic, 2 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
599217	NC_000011.10:g.75554407_75559680del	LOC110121439	Pathogenic	no assertion criteria provided
265865	NM_001235.5(SERPINH1):c.710T>C (p.Met237Thr)	SERPINH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30141	NM_001235.5(SERPINH1):c.233T>C (p.Leu78Pro)	SERPINH1	Pathogenic	no assertion criteria provided
599349	NM_001235.5(SERPINH1):c.1233dup (p.Asp412Ter)	SERPINH1	Pathogenic	no assertion criteria provided
195143	NM_001235.5(SERPINH1):c.580C>A (p.Arg194Ser)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196324	NM_001235.5(SERPINH1):c.721+9T>C	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197191	NM_001235.5(SERPINH1):c.744C>T (p.Asp248=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290775	NM_001235.5(SERPINH1):c.92G>C (p.Gly31Ala)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306097	NM_001235.5(SERPINH1):c.298G>A (p.Glu100Lys)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306101	NM_001235.5(SERPINH1):c.481A>C (p.Ile161Leu)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306103	NM_001235.5(SERPINH1):c.492C>T (p.Arg164=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306106	NM_001235.5(SERPINH1):c.600A>C (p.Leu200=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306114	NM_001235.5(SERPINH1):c.*4C>G	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
440263	NM_001235.5(SERPINH1):c.565A>G (p.Thr189Ala)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
717684	NM_001235.5(SERPINH1):c.1119C>T (p.Arg373=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
732927	NM_001235.5(SERPINH1):c.160T>C (p.Leu54=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
880604	NM_001235.5(SERPINH1):c.1059C>T (p.His353=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
880605	NM_001235.5(SERPINH1):c.1152C>T (p.Ala384=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
883119	NM_001235.5(SERPINH1):c.588C>T (p.Asp196=)	SERPINH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435816	NM_001235.5(SERPINH1):c.1020G>A (p.Met340Ile)	SERPINH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435817	NM_001235.5(SERPINH1):c.119C>T (p.Ala40Val)	SERPINH1	Uncertain significance	criteria provided, single submitter
2585085	NM_001235.5(SERPINH1):c.1244G>A (p.Arg415Gln)	SERPINH1	Uncertain significance	criteria provided, single submitter
306091	NM_001235.3(SERPINH1):c.-211G>A	SERPINH1	Uncertain significance	criteria provided, single submitter
306092	NM_001235.3(SERPINH1):c.-191A>G	SERPINH1	Uncertain significance	criteria provided, single submitter
306094	NM_001235.3(SERPINH1):c.-185T>C	SERPINH1	Uncertain significance	criteria provided, single submitter
306098	NM_001235.5(SERPINH1):c.336C>T (p.Gly112=)	SERPINH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
306100	NM_001235.5(SERPINH1):c.480G>C (p.Lys160Asn)	SERPINH1	Uncertain significance	criteria provided, single submitter
306102	NM_001235.5(SERPINH1):c.486C>G (p.Asn162Lys)	SERPINH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
306104	NM_001235.5(SERPINH1):c.573C>A (p.Asp191Glu)	SERPINH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
306108	NM_001235.5(SERPINH1):c.807C>T (p.Ile269=)	SERPINH1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SERPINH1	Strong	Autosomal recessive	osteogenesis imperfecta type 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPINH1	Orphanet:216812	Osteogenesis imperfecta type 3

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
SERPINH1	HGNC:1546	ENSG00000149257	P50454	Serpin H1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINH1	Serpin H1	Binds specifically to collagen.

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)
SERPINH1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_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
endometrium epithelium	1
smooth muscle tissue	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINH1	265	ubiquitous	marker	stromal cell of endometrium, endometrium epithelium, smooth muscle tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINH1	705

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINH1	P50454	91.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Collagen formation	1	456.8×	0.006	SERPINH1
Attenuation phase	1	407.9×	0.006	SERPINH1
HSF1 activation	1	380.7×	0.006	SERPINH1
HSF1-dependent transactivation	1	317.2×	0.006	SERPINH1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.008	SERPINH1
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	SERPINH1
Extracellular matrix organization	1	63.1×	0.016	SERPINH1

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
chondrocyte development involved in endochondral bone morphogenesis	1	8426.0×	6e-04	SERPINH1
collagen biosynthetic process	1	1053.2×	0.002	SERPINH1
response to unfolded protein	1	300.9×	0.006	SERPINH1
collagen fibril organization	1	224.7×	0.006	SERPINH1
protein maturation	1	163.6×	0.006	SERPINH1

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
SERPINH1	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
SERPINH1	1	Binding:1

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	SERPINH1

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)
SERPINH1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.