Osteogenesis imperfecta type 16

Summary

Osteogenesis imperfecta type 16 (MONDO:0014544) is a disease caused by CREB3L1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CREB3L1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 16
Mondo ID	MONDO:0014544
OMIM	616229
DOID	DOID:0110345
UMLS	C4015610
MedGen	864047
GARD	0016072
Is cancer (heuristic)	no

Also known as: OI16 · osteogenesis imperfecta, type XVI

Data availability: 27 ClinVar variants · 2 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 16

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, osteogenesis imperfecta type 6, short stature-optic atrophy-Pelger-Huët anomaly syndrome, osteogenesis imperfecta type 14, osteogenesis imperfecta type 15, 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

27 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 pathogenic, 5 likely pathogenic, 4 likely benign, 3 benign/likely benign, 2 conflicting classifications of pathogenicity, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1687286	NM_052854.4(CREB3L1):c.1186G>T (p.Glu396Ter)	CREB3L1	Pathogenic	criteria provided, single submitter
4796547	NM_052854.4(CREB3L1):c.1267C>T (p.Arg423Ter)	CREB3L1	Pathogenic	criteria provided, single submitter
559483	NM_052854.4(CREB3L1):c.928AAG[2] (p.Lys312del)	CREB3L1	Pathogenic	criteria provided, single submitter
559484	NM_052854.4(CREB3L1):c.1284C>A (p.Tyr428Ter)	CREB3L1	Pathogenic	no assertion criteria provided
982569	NM_052854.4(CREB3L1):c.911C>T (p.Ala304Val)	CREB3L1	Pathogenic	no assertion criteria provided
3359262	NM_052854.4(CREB3L1):c.1259-7_1267del	CREB3L1	Likely pathogenic	criteria provided, single submitter
3895517	NM_052854.4(CREB3L1):c.595+2T>A	CREB3L1	Likely pathogenic	criteria provided, single submitter
4081293	NM_052854.4(CREB3L1):c.89del (p.Phe30fs)	CREB3L1	Likely pathogenic	criteria provided, single submitter
4279085	NM_052854.4(CREB3L1):c.1042C>T (p.Gln348Ter)	CREB3L1	Likely pathogenic	criteria provided, single submitter
930601	NM_052854.4(CREB3L1):c.774del (p.Pro259fs)	CREB3L1	Likely pathogenic	criteria provided, single submitter
2385280	NM_052854.4(CREB3L1):c.635A>G (p.His212Arg)	CREB3L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
710354	NM_052854.4(CREB3L1):c.599A>T (p.Asp200Val)	CREB3L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357684	NM_052854.4(CREB3L1):c.277G>A (p.Asp93Asn)	CREB3L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1423517	NM_052854.4(CREB3L1):c.284C>T (p.Ala95Val)	CREB3L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2376329	NM_052854.4(CREB3L1):c.667C>T (p.Arg223Cys)	CREB3L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440540	NM_052854.4(CREB3L1):c.627del (p.Ser210fs)	CREB3L1	Uncertain significance	criteria provided, single submitter
3599611	NM_052854.4(CREB3L1):c.1384C>T (p.Arg462Trp)	CREB3L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
432652	NM_052854.4(CREB3L1):c.488C>G (p.Pro163Arg)	CREB3L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1206040	NM_052854.4(CREB3L1):c.454G>A (p.Ala152Thr)	CREB3L1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1541243	NM_052854.4(CREB3L1):c.450G>A (p.Ala150=)	CREB3L1	Likely benign	criteria provided, multiple submitters, no conflicts
1637938	NM_052854.4(CREB3L1):c.1259-13A>G	CREB3L1	Likely benign	criteria provided, multiple submitters, no conflicts
1908157	NM_052854.4(CREB3L1):c.1259-14C>T	CREB3L1	Likely benign	criteria provided, multiple submitters, no conflicts
2920975	NM_052854.4(CREB3L1):c.132G>A (p.Thr44=)	CREB3L1	Likely benign	criteria provided, single submitter
402564	NM_052854.3(CREB3L1):c.1525dup	CREB3L1	Benign	criteria provided, multiple submitters, no conflicts
730131	NM_052854.4(CREB3L1):c.1117G>A (p.Gly373Arg)	CREB3L1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
744442	NM_052854.4(CREB3L1):c.1325T>G (p.Leu442Arg)	CREB3L1	Benign	criteria provided, multiple submitters, no conflicts
768444	NM_052854.4(CREB3L1):c.1523+6del	CREB3L1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CREB3L1	Strong	Autosomal recessive	osteogenesis imperfecta type 16	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CREB3L1	Orphanet:216812	Osteogenesis imperfecta type 3
CREB3L1	Orphanet:79105	Myxofibrosarcoma

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
CREB3L1	HGNC:18856	ENSG00000157613	Q96BA8	Cyclic AMP-responsive element-binding protein 3-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CREB3L1	Cyclic AMP-responsive element-binding protein 3-like protein 1	Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-binding and transcription activation domains…

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)
CREB3L1	Other/Unknown	no		bZIP, bZIP_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
ileal mucosa	1
nasal cavity epithelium	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CREB3L1	231	ubiquitous	marker	nasal cavity epithelium, stromal cell of endometrium, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CREB3L1	2,147

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CREB3L1	Q96BA8	55.66

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
CREB3 factors activate genes	1	1268.9×	8e-04	CREB3L1

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
extracellular matrix constituent secretion	1	8426.0×	0.002	CREB3L1
negative regulation of sprouting angiogenesis	1	1296.3×	0.004	CREB3L1
negative regulation of fibroblast growth factor receptor signaling pathway	1	1053.2×	0.004	CREB3L1
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	842.6×	0.004	CREB3L1
positive regulation of collagen biosynthetic process	1	648.1×	0.004	CREB3L1
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.005	CREB3L1
endoplasmic reticulum unfolded protein response	1	295.6×	0.006	CREB3L1
response to endoplasmic reticulum stress	1	166.8×	0.010	CREB3L1
osteoblast differentiation	1	121.2×	0.012	CREB3L1
negative regulation of gene expression	1	69.1×	0.019	CREB3L1
negative regulation of DNA-templated transcription	1	31.6×	0.037	CREB3L1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.073	CREB3L1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	CREB3L1

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
CREB3L1	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	CREB3L1

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)
CREB3L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.