Osteogenesis imperfecta type 6

Summary

Osteogenesis imperfecta type 6 (MONDO:0013515) is a disease caused by SERPINF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SERPINF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 93

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 6
Mondo ID	MONDO:0013515
MeSH	C536047
OMIM	613982
DOID	DOID:0110350
UMLS	C3279564
MedGen	481194
GARD	0008700
Is cancer (heuristic)	no

Also known as: OI type 6 · OI type VI · OI6 · osteogenesis imperfecta caused by mutation in SERPINF1 · osteogenesis imperfecta type · osteogenesis imperfecta, type VI · SERPINF1 osteogenesis imperfecta · SERPINFI- related osteogenesis imperfecta

Data availability: 93 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 6

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 12, 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

93 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 20 pathogenic, 16 conflicting classifications of pathogenicity, 12 likely pathogenic, 11 benign, 4 benign/likely benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1224470	NM_002615.7(SERPINF1):c.262GCCCTCTCG[3] (p.88ALS[3])	LOC130059892	Pathogenic	criteria provided, multiple submitters, no conflicts
1299366	NM_002615.7(SERPINF1):c.278C>A (p.Ser93Ter)	LOC130059892	Pathogenic	criteria provided, multiple submitters, no conflicts
4076401	NM_002615.7(SERPINF1):c.283+2T>C	LOC130059892	Pathogenic	criteria provided, multiple submitters, no conflicts
1064530	NM_002615.7(SERPINF1):c.838_839del (p.Leu280fs)	SERPINF1	Pathogenic	criteria provided, single submitter
1299422	NM_002615.7(SERPINF1):c.907C>T (p.Arg303Ter)	SERPINF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342706	NM_002615.7(SERPINF1):c.77dup (p.Glu27fs)	SERPINF1	Pathogenic	criteria provided, single submitter
1388059	NM_002615.7(SERPINF1):c.77del (p.Pro26fs)	SERPINF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1962411	NM_002615.7(SERPINF1):c.553C>T (p.Gln185Ter)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
224879	NM_002615.7(SERPINF1):c.1152_1170del (p.Phe384fs)	SERPINF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3069167	NM_002615.7(SERPINF1):c.532C>T (p.Gln178Ter)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
31851	NM_002615.7(SERPINF1):c.696C>G (p.Tyr232Ter)	SERPINF1	Pathogenic	criteria provided, single submitter
31852	NM_002615.7(SERPINF1):c.324_325dup (p.Tyr109fs)	SERPINF1	Pathogenic	no assertion criteria provided
31853	NM_002615.7(SERPINF1):c.1132C>T (p.Gln378Ter)	SERPINF1	Pathogenic	no assertion criteria provided
3581692	NM_002615.7(SERPINF1):c.857_868del (p.Leu286_Glu290delinsTer)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
3906952	NM_002615.7(SERPINF1):c.250dup (p.Ser84fs)	SERPINF1	Pathogenic	criteria provided, single submitter
41892	NM_002615.7(SERPINF1):c.119_120del (p.Val40fs)	SERPINF1	Pathogenic	no assertion criteria provided
41893	NM_002615.7(SERPINF1):c.-9+2dup	SERPINF1	Pathogenic	no assertion criteria provided
41894	NM_002615.7(SERPINF1):c.653del (p.Val218fs)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
426454	NM_002615.7(SERPINF1):c.295C>T (p.Arg99Ter)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
4531286	NM_002615.7(SERPINF1):c.397C>T (p.Gln133Ter)	SERPINF1	Pathogenic	criteria provided, single submitter
684387	NM_002615.7(SERPINF1):c.1217_1253del (p.Leu406fs)	SERPINF1	Pathogenic	criteria provided, single submitter
684390	NM_002615.7(SERPINF1):c.651G>A (p.Trp217Ter)	SERPINF1	Pathogenic	criteria provided, single submitter
870121	NM_002615.7(SERPINF1):c.808G>T (p.Gly270Ter)	SERPINF1	Pathogenic	criteria provided, multiple submitters, no conflicts
1685437	NM_002615.7(SERPINF1):c.998-2A>G	SERPINF1	Likely pathogenic	criteria provided, single submitter
1687527	NM_002615.7(SERPINF1):c.1091G>A (p.Trp364Ter)	SERPINF1	Likely pathogenic	criteria provided, single submitter
1687552	NM_002615.7(SERPINF1):c.1092G>A (p.Trp364Ter)	SERPINF1	Likely pathogenic	criteria provided, single submitter
1709930	NM_002615.7(SERPINF1):c.1075del (p.Arg359fs)	SERPINF1	Likely pathogenic	criteria provided, single submitter
3064103	NM_002615.7(SERPINF1):c.4C>T (p.Gln2Ter)	SERPINF1	Likely pathogenic	criteria provided, single submitter
3362585	NM_002615.7(SERPINF1):c.1118_1119del (p.Pro373fs)	SERPINF1	Likely pathogenic	criteria provided, single submitter
3581691	NM_002615.7(SERPINF1):c.283+2T>G	SERPINF1	Likely 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
SERPINF1	Strong	Autosomal recessive	osteogenesis imperfecta type 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPINF1	Orphanet:216812	Osteogenesis imperfecta type 3
SERPINF1	Orphanet:216820	Osteogenesis imperfecta type 4

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
SERPINF1	HGNC:8824	ENSG00000132386	P36955	Pigment epithelium-derived factor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINF1	Pigment epithelium-derived factor	Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells.

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)
SERPINF1	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
endocervix	1
pericardium	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINF1	280	ubiquitous	marker	pigmented layer of retina, pericardium, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINF1	1,809

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SERPINF1	P36955	3

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
cellular response to cobalt ion	1	5617.3×	0.002	SERPINF1
negative regulation of epithelial cell proliferation involved in prostate gland development	1	2808.7×	0.002	SERPINF1
ovulation cycle	1	2407.4×	0.002	SERPINF1
epithelial cell proliferation involved in prostate gland development	1	2106.5×	0.002	SERPINF1
short-term memory	1	1296.3×	0.002	SERPINF1
response to acidic pH	1	1296.3×	0.002	SERPINF1
response to arsenic-containing substance	1	1203.7×	0.002	SERPINF1
response to peptide	1	1123.5×	0.002	SERPINF1
negative regulation of endothelial cell migration	1	766.0×	0.003	SERPINF1
positive regulation of neurogenesis	1	581.1×	0.003	SERPINF1
cellular response to dexamethasone stimulus	1	581.1×	0.003	SERPINF1
cellular response to glucose stimulus	1	267.5×	0.005	SERPINF1
retina development in camera-type eye	1	255.3×	0.005	SERPINF1
cellular response to retinoic acid	1	234.1×	0.005	SERPINF1
negative regulation of angiogenesis	1	168.5×	0.007	SERPINF1
kidney development	1	140.4×	0.008	SERPINF1
positive regulation of neuron projection development	1	137.0×	0.008	SERPINF1
negative regulation of gene expression	1	69.1×	0.014	SERPINF1

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
SERPINF1	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
SERPINF1	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	SERPINF1

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)
SERPINF1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.