Osteogenesis imperfecta type 8

Summary

Osteogenesis imperfecta type 8 (MONDO:0012581) is a disease caused by P3H1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: P3H1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 852

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 8
Mondo ID	MONDO:0012581
MeSH	C536049
OMIM	610915
DOID	DOID:0110336
UMLS	C1970458
MedGen	410075
GARD	0010152
Is cancer (heuristic)	no

Also known as: OI type VIII · OI8 · osteogenesis imperfecta caused by mutation in P3H1 · osteogenesis imperfecta type 8 · osteogenesis imperfecta, type VIII · P3H1 osteogenesis imperfecta

Data availability: 852 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 8

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 5, osteogenesis imperfecta type 11, 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

600 retrieved; paginated sample, class counts are floors:

327 likely benign, 140 uncertain significance, 66 pathogenic, 30 likely pathogenic, 17 pathogenic/likely pathogenic, 14 conflicting classifications of pathogenicity, 4 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2819440	NM_022356.4(P3H1):c.192_205del (p.Ala66fs)	LOC129930352	Pathogenic	criteria provided, single submitter
2976317	NM_022356.4(P3H1):c.273G>A (p.Trp91Ter)	LOC129930352	Pathogenic	criteria provided, single submitter
1061675	NM_022356.4(P3H1):c.1170+5G>C	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076376	NM_022356.4(P3H1):c.838C>T (p.Gln280Ter)	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1253	NM_022356.4(P3H1):c.1080+1G>T	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1254	NM_022356.4(P3H1):c.1473+1G>T	P3H1	Pathogenic	no assertion criteria provided
1255	NM_022356.4(P3H1):c.747del (p.Tyr250fs)	P3H1	Pathogenic	criteria provided, single submitter
1256	NM_022356.4(P3H1):c.1656C>A (p.Tyr552Ter)	P3H1	Pathogenic	criteria provided, single submitter
1257	NM_022356.4(P3H1):c.1365_1366delinsC (p.Glu455fs)	P3H1	Pathogenic	no assertion criteria provided
1258	NM_022356.4(P3H1):c.1102C>T (p.Arg368Ter)	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1259	NM_022356.4(P3H1):c.2055+18G>A	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332993	NM_022356.4(P3H1):c.1852del (p.Tyr617_Leu618insTer)	P3H1	Pathogenic	no assertion criteria provided
1342297	NM_022356.4(P3H1):c.2051_2054del (p.Glu684fs)	P3H1	Pathogenic	criteria provided, single submitter
1361320	NM_022356.4(P3H1):c.2154dup (p.Glu719fs)	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1384126	NM_022356.4(P3H1):c.933C>G (p.Tyr311Ter)	P3H1	Pathogenic	criteria provided, single submitter
1390172	NM_022356.4(P3H1):c.2101_2102insT (p.Glu701fs)	P3H1	Pathogenic	criteria provided, single submitter
1415316	NM_022356.4(P3H1):c.652G>T (p.Glu218Ter)	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1418473	NM_022356.4(P3H1):c.2055+1G>A	P3H1	Pathogenic	criteria provided, single submitter
1431904	NM_022356.4(P3H1):c.765C>A (p.Tyr255Ter)	P3H1	Pathogenic	criteria provided, single submitter
1457668	NM_022356.4(P3H1):c.377del (p.Pro126fs)	P3H1	Pathogenic	criteria provided, single submitter
1459537	NC_000001.10:g.(?43218172)(43218675_?)del	P3H1	Pathogenic	criteria provided, single submitter
1460006	NM_022356.4(P3H1):c.1223+2T>C	P3H1	Pathogenic	criteria provided, single submitter
1486163	NM_022356.4(P3H1):c.1915-1G>A	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1519163	NM_022356.4(P3H1):c.1345+1G>A	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526256	NM_022356.4(P3H1):c.916del (p.Tyr306fs)	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691307	NM_022356.4(P3H1):c.2143C>T (p.Gln715Ter)	P3H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1702031	NM_022356.4(P3H1):c.1096C>T (p.Arg366Ter)	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1707605	NM_022356.4(P3H1):c.1383_1389dup (p.Lys464fs)	P3H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2002943	NM_022356.4(P3H1):c.1499_1502dup (p.Gly502fs)	P3H1	Pathogenic	criteria provided, single submitter
2035332	NM_022356.4(P3H1):c.922C>T (p.Gln308Ter)	P3H1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
P3H1	Definitive	Autosomal recessive	osteogenesis imperfecta type 8	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
P3H1	Orphanet:216804	Osteogenesis imperfecta type 2
P3H1	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
P3H1	HGNC:19316	ENSG00000117385	Q32P28	Prolyl 3-hydroxylase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
P3H1	Prolyl 3-hydroxylase 1	Basement membrane-associated chondroitin sulfate proteoglycan (CSPG).

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
P3H1	Enzyme (other)	yes	1.14.11.28	Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph, TPR-like_helical_dom_sf

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
adenohypophysis	1
stromal cell of endometrium	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
P3H1	237	ubiquitous	marker	stromal cell of endometrium, adenohypophysis, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
P3H1	1,317

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
P3H1	Q32P28	6

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
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	P3H1

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
negative regulation of post-translational protein modification	1	4213.0×	0.002	P3H1
protein hydroxylation	1	3370.4×	0.002	P3H1
regulation of protein secretion	1	1532.0×	0.002	P3H1
regulation of ossification	1	1203.7×	0.002	P3H1
collagen metabolic process	1	1053.2×	0.002	P3H1
bone development	1	276.3×	0.007	P3H1
collagen fibril organization	1	224.7×	0.008	P3H1
negative regulation of cell growth	1	144.0×	0.010	P3H1
positive regulation of neuron projection development	1	137.0×	0.010	P3H1
protein folding	1	103.4×	0.012	P3H1
protein stabilization	1	66.9×	0.016	P3H1
negative regulation of cell population proliferation	1	42.1×	0.024	P3H1

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
P3H1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P3H1	1.14.11.28, 1.14.11.7	proline 3-hydroxylase, procollagen-proline 3-dioxygenase

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	P3H1
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)
P3H1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.