CCDC134

Summary

CCDC134 (coiled-coil domain containing 134, HGNC:26185) is a protein-coding gene on chromosome 22q13.2, encoding Coiled-coil domain-containing protein 134 (Q9H6E4). 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 a microenvironment for HSP90B1 folding.

Enables protein-macromolecule adaptor activity. Involved in positive regulation of signal transduction; regulation of ossification; and regulation of protein glycosylation. Located in cytosol and intracellular membrane-bounded organelle. Is active in endoplasmic reticulum lumen. Implicated in osteogenesis imperfecta.

Source: NCBI Gene 79879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 50 total — 2 pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_024821

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26185
Approved symbol	CCDC134
Name	coiled-coil domain containing 134
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22349
Ensembl gene	ENSG00000100147
Ensembl biotype	protein_coding
OMIM	618788
Entrez	79879

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000255784, ENST00000402061, ENST00000905562, ENST00000964378

RefSeq mRNA: 3 — MANE Select: NM_024821 NM_001304797, NM_001382346, NM_024821

CCDS: CCDS33654, CCDS77680

Canonical transcript exons

ENST00000255784 — 7 exons

Exon	Start	End
ENSE00000656152	41809879	41810000
ENSE00000656159	41810207	41810291
ENSE00000880492	41813751	41813822
ENSE00000911298	41808875	41808993
ENSE00000911301	41813264	41813445
ENSE00001175669	41800679	41800766
ENSE00001202041	41825698	41832164

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 87.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1089 / max 141.7155, expressed in 1783 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192507	8.1842	1662
192506	4.9247	1654

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	87.75	gold quality
right adrenal gland	UBERON:0001233	82.45	gold quality
adrenal gland	UBERON:0002369	82.27	gold quality
right adrenal gland cortex	UBERON:0035827	82.09	gold quality
corpus epididymis	UBERON:0004359	81.84	gold quality
left adrenal gland	UBERON:0001234	81.67	gold quality
left adrenal gland cortex	UBERON:0035825	81.67	gold quality
adrenal cortex	UBERON:0001235	81.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.71	gold quality
buccal mucosa cell	CL:0002336	78.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.81	gold quality
bone marrow cell	CL:0002092	77.41	gold quality
ventricular zone	UBERON:0003053	76.95	gold quality
granulocyte	CL:0000094	76.76	gold quality
stromal cell of endometrium	CL:0002255	75.24	gold quality
leukocyte	CL:0000738	75.21	gold quality
monocyte	CL:0000576	75.08	gold quality
cerebellar cortex	UBERON:0002129	75.03	gold quality
mononuclear cell	CL:0000842	75.02	gold quality
cerebellar hemisphere	UBERON:0002245	74.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.32	gold quality
bone marrow	UBERON:0002371	74.30	gold quality
cerebellum	UBERON:0002037	74.23	gold quality
ganglionic eminence	UBERON:0004023	74.00	gold quality
tonsil	UBERON:0002372	73.86	gold quality
pigmented layer of retina	UBERON:0001782	73.02	gold quality
retina	UBERON:0000966	73.00	gold quality
sural nerve	UBERON:0015488	72.54	gold quality
islet of Langerhans	UBERON:0000006	72.22	gold quality
blood	UBERON:0000178	72.19	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	21.29
E-ANND-3	no	2.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting CCDC134, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969

Literature-anchored findings (GeneRIF, showing 8)

• These results clearly indicate that CCDC134 is a novel member of the secretory family and down-regulates the Raf-1/MEK/ERK and JNK/ SAPK pathways. (PMID:18087676)
• CCDC134 might act as a novel regulator of hADA2a, and plays roles in the PCAF complex via hADA2a to affect its acetyltransferase activity and UV-induced DNA damage repair. (PMID:22644376)
• The attenuated expression of CCDC134 promoted the activation of Erk1/2 and JNK/SAPK, but had no effect on p38 in gastric cancer. (PMID:23070808)
• CCDC134 promotes cell proliferation through the JAK3-STAT5 pathway. (PMID:25125657)
• CCDC134 may also act as a novel regulator of human alteration/deficiency in activation 2a, and be involved in the p300-CBP-associated factor complex and affect its acetyltransferase activity (PMID:29115376)
• Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta. (PMID:32181939)
• Ccdc134 deficiency impairs cerebellar development and motor coordination. (PMID:34382738)
• miRNA-1260b Promotes Breast Cancer Cell Migration and Invasion by Downregulating CCDC134. (PMID:36056852)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc134	ENSDARG00000030508
		ENSDARG00000103285
mus_musculus	Ccdc134	ENSMUSG00000068114
rattus_norvegicus	Ccdc134	ENSRNOG00000007262
caenorhabditis_elegans		WBGENE00185001

Protein

Protein identifiers

Coiled-coil domain-containing protein 134 — Q9H6E4 (reviewed: Q9H6E4)

All UniProt accessions (2): Q9H6E4, B0QY51

UniProt curated annotations — full annotation on UniProt →

Function. 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 a microenvironment for HSP90B1 folding. In the CCDC134-containing translocon, STT3A associates with the SRT pseudosubstrate motif of HSP90B1, preventing access to facultative glycosylation sites until folding is completed, preventing hyperglycosylation and subsequent degradation of HSP90B1. In extracellular secreted form, promotes proliferation and activation of CD8(+) T-cells, suggesting a cytokine-like function. May inhibit ERK and JNK signaling activity. May suppress cell migration and invasion activity, via its effects on ERK and JNK signaling. May also localize in the nucleus: enhances stability of the PCAF histone acetyltransferase (HAT) complex member TADA2A and thus promotes PCAF-mediated histone acetyltransferase activity. Has a critical role in the regulation of osteogenesis and bone development.

Subunit / interactions. Interacts with TADA2A. Associates with the PCAF complex via TADA2A binding.

Subcellular location. Endoplasmic reticulum lumen. Secreted. Cytoplasm. Nucleus.

Tissue specificity. Expressed in cervical gland, cervical squamous epithelium, endometrium, stomach, kidney distal convoluted tubule, spermatogenic cells in testis, mammary gland, liver and striated muscle (at protein level). Also detected in placenta. Highest expression in testis relative to other tissues. Detected in T cells and dendritic cells; highly expressed in activated CD8(+) T cells, and also expressed at lower levels in CD4(+) T cells.

Post-translational modifications. O-glycosylated, with additional sialic acid modifications.

Disease relevance. Osteogenesis imperfecta 22 (OI22) [MIM:619795] An autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI22 is a severe form of the disease. The disease is caused by variants affecting the gene represented in this entry. A recurrent variant in the initiation codon has been found in multiple OI22 patients. The variant results in absence of CCDC134 protein in patient fibroblasts and osteoblasts, increased ERK1/2 phosphorylation, decreased OPN and COL1A1 expression and reduced mineralization.

Similarity. Belongs to the CCDC134 family.

RefSeq proteins (3): NP_001291726, NP_001369275, NP_079097* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026321	CC134	Family

Pfam: PF15002

UniProt features (8 total): short sequence motif 2, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9N9J	ELECTRON MICROSCOPY	3.2
9YGY	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6E4-F1	83.36	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 148

Mutagenesis-validated functional residues (1):

Position	Phenotype
229	abolished retention in the endoplasmic reticulum leading to secretion.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 185 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_NEURON_PROJECTION_EXTENSION, MODULE_255, GOBP_GROWTH, MODULE_317, GOBP_CEREBELLAR_CORTEX_MORPHOGENESIS, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_MYD88_DEPENDENT_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (10): angiogenesis (GO:0001525), placenta development (GO:0001890), regulation of glycoprotein biosynthetic process (GO:0010559), ventricular system development (GO:0021591), positive regulation of Wnt signaling pathway (GO:0030177), regulation of ossification (GO:0030278), positive regulation of MyD88-dependent toll-like receptor signaling pathway (GO:0034126), embryonic hemopoiesis (GO:0035162), embryonic liver development (GO:1990402), obsolete regulation of protein glycosylation (GO:0060049)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), nucleus (GO:0005634), endoplasmic reticulum lumen (GO:0005788), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
embryonic organ development	2
intracellular membrane-bounded organelle	2
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
animal organ development	1
glycoprotein biosynthetic process	1
regulation of macromolecule biosynthetic process	1
regulation of glycoprotein metabolic process	1
brain development	1
system development	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
ossification	1
regulation of multicellular organismal process	1
MyD88-dependent toll-like receptor signaling pathway	1
positive regulation of toll-like receptor signaling pathway	1
regulation of MyD88-dependent toll-like receptor signaling pathway	1
hemopoiesis	1
protein binding	1
molecular adaptor activity	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC134	MESD	Q14696	494
CCDC134	TMEM38B	Q9NVV0	478
CCDC134	GOLM2	Q6P4E1	462
CCDC134	APBA3	O96018	453
CCDC134	EPC2	Q52LR7	445
CCDC134	SEC23A	Q15436	438
CCDC134	MCRIP1	C9JLW8	433
CCDC134	NUTM2G	Q5VZR2	433
CCDC134	CCDC34	Q96HJ3	433
CCDC134	TMED2	Q15363	429
CCDC134	TADA2A	O75478	419
CCDC134	SGMS2	Q8NHU3	418
CCDC134	SERP1	Q9Y6X1	418
CCDC134	IFITM5	A6NNB3	415
CCDC134	TENT5A	Q96IP4	406

IntAct

136 interactions, top by confidence:

A	B	Type	Score
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
CCDC134	TADA2A	psi-mi:“MI:0915”(physical association)	0.600
CCDC134	TADA2A	psi-mi:“MI:0403”(colocalization)	0.600
PGRMC1	CCDC134	psi-mi:“MI:0915”(physical association)	0.560
PTPRN	CCDC134	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CCDC134	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PDZK1	CCDC134	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	CCDC134	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CCDC134	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (36): CCDC134 (Affinity Capture-RNA), CCDC134 (Proximity Label-MS), CCDC134 (Affinity Capture-RNA), TADA2A (Two-hybrid), TADA2A (Affinity Capture-Western), TADA2A (Reconstituted Complex), CCDC134 (Affinity Capture-Western), CCDC134 (Affinity Capture-Western), CCDC134 (Affinity Capture-Western), CCDC134 (Affinity Capture-RNA), CCDC134 (Two-hybrid), PGRMC1 (Two-hybrid), CCDC134 (Proximity Label-MS), CCDC134 (Proximity Label-MS), CCDC134 (Proximity Label-MS)

ESM2 similar proteins: A4FV27, A7MBC7, F1N4M2, F1ND48, O14524, O14525, O43556, O70258, O70367, O73698, O75829, O76095, O77049, O77770, O88823, O88824, P15383, P17404, Q08CB3, Q14C87, Q14DG7, Q1RMB5, Q29S03, Q3UN70, Q5M862, Q5PPI4, Q5R8Q2, Q5RAP2, Q5ZJY9, Q60409, Q61137, Q6AXF6, Q6Q3F5, Q6YAT4, Q6ZQE4, Q76HP2, Q76HP3, Q8BKU8, Q8BXN9, Q8C7V8

Diamond homologs: Q28F39, Q5M862, Q8C7V8, Q9H6E4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	51.0×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	48.5×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	48.5×	2e-06
Long-term potentiation	5	42.5×	4e-06
Assembly and cell surface presentation of NMDA receptors	8	36.2×	5e-09
Neurexins and neuroligins	9	31.6×	2e-09
Protein-protein interactions at synapses	5	23.7×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	77.0×	4e-16
protein localization to synapse	6	55.4×	1e-07
receptor clustering	7	52.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.8×	5e-08
cell-cell adhesion	10	12.2×	8e-07
protein-containing complex assembly	8	11.0×	4e-05
chemical synaptic transmission	7	6.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4075918	GRCh37/hg19 22q13.2(chr22:42178402-42232146)x1	Pathogenic
634649	NM_024821.5(CCDC134):c.2T>C (p.Met1Thr)	Pathogenic

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41808990:A:G	donor_gain	1.0000
22:41809872:T:A	acceptor_gain	1.0000
22:41809877:A:AG	acceptor_gain	1.0000
22:41809878:G:GA	acceptor_gain	1.0000
22:41809878:GA:G	acceptor_gain	1.0000
22:41809958:GCA:G	donor_gain	1.0000
22:41809961:G:GG	donor_gain	1.0000
22:41809996:TTAAG:T	donor_loss	1.0000
22:41809998:AAG:A	donor_loss	1.0000
22:41809999:AG:A	donor_loss	1.0000
22:41810000:GG:G	donor_loss	1.0000
22:41810001:G:T	donor_loss	1.0000
22:41810287:GGATG:G	donor_gain	1.0000
22:41810288:GATGG:G	donor_gain	1.0000
22:41813441:GCCTG:G	donor_gain	1.0000
22:41813442:CCTGG:C	donor_loss	1.0000
22:41813443:CTGGT:C	donor_loss	1.0000
22:41813446:G:GA	donor_loss	1.0000
22:41813447:T:G	donor_loss	1.0000
22:41813747:GCA:G	acceptor_loss	1.0000
22:41813749:A:AG	acceptor_gain	1.0000
22:41813749:AG:A	acceptor_loss	1.0000
22:41813749:AGAT:A	acceptor_gain	1.0000
22:41813750:G:GA	acceptor_gain	1.0000
22:41813750:G:GT	acceptor_loss	1.0000
22:41813750:GAT:G	acceptor_gain	1.0000
22:41813750:GATG:G	acceptor_gain	1.0000
22:41813820:GAG:G	donor_gain	1.0000
22:41813821:AGGTG:A	donor_loss	1.0000
22:41813822:GGTG:G	donor_loss	1.0000

AlphaMissense

1521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41813300:G:A	G116D	0.997
22:41813380:G:C	G143R	0.997
22:41809903:G:C	R43P	0.996
22:41809984:T:C	L70P	0.995
22:41813291:C:A	A113D	0.995
22:41813299:G:C	G116R	0.995
22:41813315:G:C	R121P	0.994
22:41813394:C:G	C147W	0.994
22:41810211:T:C	L77P	0.993
22:41813312:T:C	L120P	0.993
22:41809993:T:C	L73P	0.992
22:41813392:T:C	C147R	0.992
22:41809924:T:C	L50P	0.991
22:41813393:G:A	C147Y	0.991
22:41810232:T:C	L84P	0.990
22:41813764:T:C	L169P	0.990
22:41825789:G:A	G219D	0.990
22:41809933:T:C	L53P	0.989
22:41810219:T:C	S80P	0.989
22:41813282:A:T	E110V	0.989
22:41813379:G:C	W142C	0.989
22:41813379:G:T	W142C	0.989
22:41813381:G:A	G143D	0.989
22:41825787:A:C	K218N	0.989
22:41825787:A:T	K218N	0.989
22:41810232:T:A	L84H	0.988
22:41813286:C:A	N111K	0.988
22:41813286:C:G	N111K	0.988
22:41825798:T:C	I222T	0.988
22:41825791:C:T	P220S	0.987

dbSNP variants (sampled 300 via entrez): RS1000095886 (22:41820059 G>A,T), RS1000126741 (22:41831969 C>T), RS1000177249 (22:41801113 C>T), RS1000243786 (22:41813124 G>A,T), RS1000296970 (22:41806688 T>C), RS1000398112 (22:41812832 T>A,C), RS1000435082 (22:41832264 G>A,C), RS1000499079 (22:41831719 C>A,T), RS1000625746 (22:41800714 C>G,T), RS1000740090 (22:41800578 C>T), RS1000805644 (22:41807428 G>A), RS1000826319 (22:41819713 A>G), RS1000901611 (22:41830474 TCA>T), RS1000918533 (22:41812349 G>A), RS1001019897 (22:41824074 A>G)

Disease associations

OMIM: gene MIM:618788 | disease phenotypes: MIM:619795

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta	Limited	Autosomal recessive
osteogenesis imperfecta, IIA 22	Limited	Autosomal recessive

Mondo (2): osteogenesis imperfecta, IIA 22 (MONDO:0030714), osteogenesis imperfecta (MONDO:0019019)

Orphanet (0):

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000703	Dentinogenesis imperfecta
HP:0001511	Intrauterine growth retardation
HP:0002645	Wormian bones
HP:0002753	Thin bony cortex
HP:0002757	Recurrent fractures
HP:0003100	Slender long bone
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0004363	Abnormal circulating calcium concentration
HP:0005855	Multiple prenatal fractures
HP:0005864	Pseudoarthrosis
HP:0005877	Multiple small vertebral fractures
HP:0006487	Bowing of the long bones
HP:0011461	Fetal onset
HP:0011463	Childhood onset
HP:0031429	Decreased circulating osteocalcin level
HP:0031936	Delayed ability to walk
HP:0100529	Abnormal blood phosphate concentration

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000900_3	Alzheimer’s disease biomarkers	1.000000e-06
GCST005316_268	Intelligence (MTAG)	1.000000e-08
GCST010002_83	Refractive error	2.000000e-27
GCST010132_1	Processed meat consumption	1.000000e-08
GCST010143_2	Meat-related diet	4.000000e-08
GCST90002400_511	Plateletcrit	3.000000e-12
GCST90011898_171	Alanine aminotransferase levels	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004337	intelligence
EFO:0008111	diet measurement
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

77 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00187018	Not specified	COMPLETED	Marrow Mesenchymal Cell Therapy for Osteogenesis Imperfecta: A Pilot Study
NCT00655681	Not specified	COMPLETED	Prevention of Post Operative Bone Loss in Children