Osteogenesis imperfecta type 5

Summary

Osteogenesis imperfecta type 5 (MONDO:0012591) is a disease caused by IFITM5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: IFITM5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		47	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 5
Mondo ID	MONDO:0012591
MeSH	C567042
OMIM	610967
Orphanet	216828
DOID	DOID:0110344
ICD-11	1718903422
UMLS	C2931093
MedGen	419332
GARD	0008699
Is cancer (heuristic)	no

Also known as: IFITM5 osteogenesis imperfecta · OI type 5 · OI type V · OI with calcification in interosseous membranes · OI5 · osteogenesis imperfecta caused by mutation in IFITM5 · osteogenesis imperfecta, type V · type V OI

Data availability: 10 ClinVar variants · 4 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 5

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 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

10 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
183677	NM_001025295.3(IFITM5):c.119C>T (p.Ser40Leu)	IFITM5	Pathogenic	criteria provided, multiple submitters, no conflicts
37143	NM_001025295.3(IFITM5):c.-14C>T	IFITM5	Pathogenic	criteria provided, multiple submitters, no conflicts
689498	NM_001025295.3(IFITM5):c.119C>G (p.Ser40Trp)	IFITM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
290777	NM_001025295.3(IFITM5):c.100C>T (p.Arg34Ter)	IFITM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
506680	NM_001025295.3(IFITM5):c.278C>T (p.Thr93Met)	IFITM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
743647	NM_001025295.3(IFITM5):c.190C>T (p.Arg64Ter)	IFITM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333457	NM_001025295.3(IFITM5):c.143A>G (p.Asn48Ser)	IFITM5	Uncertain significance	criteria provided, multiple submitters, no conflicts
193131	NM_001025295.3(IFITM5):c.80G>C (p.Gly27Ala)	IFITM5	Benign	criteria provided, multiple submitters, no conflicts
193132	NM_001025295.3(IFITM5):c.120G>T (p.Ser40=)	IFITM5	Benign	criteria provided, multiple submitters, no conflicts
768407	NM_001025295.3(IFITM5):c.91C>A (p.Pro31Thr)	IFITM5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
IFITM5	Definitive	Autosomal dominant	osteogenesis imperfecta type 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFITM5	Orphanet:216828	Osteogenesis imperfecta type 5

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
IFITM5	HGNC:16644	ENSG00000206013	A6NNB3	Interferon-induced transmembrane protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFITM5	Interferon-induced transmembrane protein 5	Required for normal bone mineralization.

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)
IFITM5	Other/Unknown	no		CD225/Dispanin_fam, IFITM_antiviral_protein

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
blood	1
body of pancreas	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFITM5	83	tissue_specific	marker	body of pancreas, granulocyte, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFITM5	835

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFITM5	A6NNB3	65.49

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
response to tacrolimus	1	8426.0×	7e-04	IFITM5
response to rapamycin	1	4213.0×	7e-04	IFITM5
regulation of bone mineralization	1	732.7×	0.002	IFITM5
bone morphogenesis	1	601.9×	0.002	IFITM5
bone mineralization	1	271.8×	0.004	IFITM5
in utero embryonic development	1	72.0×	0.014	IFITM5

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
IFITM5	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	IFITM5

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)
IFITM5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.