osteogenesis imperfecta, IIA 22

Summary

osteogenesis imperfecta, IIA 22 (MONDO:0030714) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta, IIA 22
Mondo ID	MONDO:0030714
OMIM	619795
UMLS	C5676943
MedGen	1801631
GARD	0025621
Is cancer (heuristic)	no

Also known as: OI22 · osteogenesis imperfecta, IIA 22

Data availability: 3 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, IIA 22

Related subtypes (9): brittle bone disorder, osteogenesis imperfecta type 13, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, high bone mass osteogenesis imperfecta, osteogenesis imperfecta, type 21, osteogenesis imperfecta, type 20, COL1A2-related osteogenesis imperfecta, osteogenesis imperfecta and a reduction of bone mineral density., osteogenesis imperfecta, type 23

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
634649	NM_024821.5(CCDC134):c.2T>C (p.Met1Thr)	CCDC134	Pathogenic	criteria provided, single submitter
3065715	NM_024821.5(CCDC134):c.676C>T (p.Gln226Ter)	CCDC134	Uncertain significance	criteria provided, single submitter
3588100	NM_024821.5(CCDC134):c.362G>A (p.Arg121His)	CCDC134	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
CCDC134	Limited	Autosomal recessive	osteogenesis imperfecta	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
CCDC134	HGNC:26185	ENSG00000100147	Q9H6E4	Coiled-coil domain-containing protein 134	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC134	Coiled-coil domain-containing protein 134	Molecular adapter required to prevent protein hyperglycosylation of HSP90B1: during translation, associates with nascent HSP90B1 and the STT3A catalytic component of the OST-A complex and tethers them to a specialized translocon that forms…

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)
CCDC134	Other/Unknown	no		CC134

Expression context

Cohort genes with no expression data: 0.

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
adrenal gland	1
adrenal tissue	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC134	201	ubiquitous	yes	adrenal tissue, right adrenal gland, adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCDC134	744

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCDC134	Q9H6E4	2

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
positive regulation of MyD88-dependent toll-like receptor signaling pathway	1	16852.0×	5e-04	CCDC134
embryonic liver development	1	8426.0×	5e-04	CCDC134
regulation of glycoprotein biosynthetic process	1	4213.0×	7e-04	CCDC134
regulation of ossification	1	1203.7×	0.002	CCDC134
embryonic hemopoiesis	1	991.3×	0.002	CCDC134
ventricular system development	1	842.6×	0.002	CCDC134
placenta development	1	443.5×	0.003	CCDC134
positive regulation of Wnt signaling pathway	1	383.0×	0.003	CCDC134
angiogenesis	1	62.4×	0.016	CCDC134

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
CCDC134	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	CCDC134

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)
CCDC134	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.