CRTAP

Summary

CRTAP (cartilage associated protein, HGNC:2379) is a protein-coding gene on chromosome 3p22.3, encoding Cartilage-associated protein (O75718). Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues.

The protein encoded by this gene is similar to the chicken and mouse CRTAP genes. The encoded protein is a scaffolding protein that may influence the activity of at least one member of the cytohesin/ARNO family in response to specific cellular stimuli. Defects in this gene are associated with osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility and low bone mass.

Source: NCBI Gene 10491 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 7 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 699 total — 43 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2379
Approved symbol	CRTAP
Name	cartilage associated protein
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	CASP, LEPREL3, P3H5
Ensembl gene	ENSG00000170275
Ensembl biotype	protein_coding
OMIM	605497
Entrez	10491

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000320954, ENST00000449224, ENST00000485310, ENST00000858647, ENST00000858648, ENST00000946647, ENST00000946648, ENST00000946649, ENST00000946650

RefSeq mRNA: 4 — MANE Select: NM_006371 NM_001393363, NM_001393364, NM_001393365, NM_006371

CCDS: CCDS2657, CCDS93231

Canonical transcript exons

ENST00000320954 — 7 exons

Exon	Start	End
ENSE00001141566	33134182	33134265
ENSE00001141573	33132555	33132700
ENSE00001222541	33114014	33114548
ENSE00003529302	33129939	33130067
ENSE00003660981	33124408	33124579
ENSE00003687107	33120344	33120493
ENSE00003697569	33142395	33147773

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 105.2361 / max 490.7828, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35938	60.7155	1815
35936	24.5174	1815
35937	20.0033	1780

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.59	gold quality
stromal cell of endometrium	CL:0002255	99.29	gold quality
endocervix	UBERON:0000458	99.22	gold quality
descending thoracic aorta	UBERON:0002345	99.19	gold quality
right coronary artery	UBERON:0001625	99.13	gold quality
tendon	UBERON:0000043	99.08	gold quality
thoracic aorta	UBERON:0001515	99.05	gold quality
ascending aorta	UBERON:0001496	99.04	gold quality
body of uterus	UBERON:0009853	98.97	gold quality
aorta	UBERON:0000947	98.95	gold quality
gall bladder	UBERON:0002110	98.93	gold quality
popliteal artery	UBERON:0002250	98.91	gold quality
tibial artery	UBERON:0007610	98.91	gold quality
left uterine tube	UBERON:0001303	98.89	gold quality
mucosa of stomach	UBERON:0001199	98.88	gold quality
left coronary artery	UBERON:0001626	98.87	gold quality
calcaneal tendon	UBERON:0003701	98.84	gold quality
coronary artery	UBERON:0001621	98.80	gold quality
omental fat pad	UBERON:0010414	98.73	gold quality
ectocervix	UBERON:0012249	98.72	gold quality
peritoneum	UBERON:0002358	98.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.68	gold quality
left ovary	UBERON:0002119	98.67	gold quality
right ovary	UBERON:0002118	98.57	gold quality
monocyte	CL:0000576	98.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.27	gold quality
adipose tissue	UBERON:0001013	98.23	gold quality
tibia	UBERON:0000979	98.15	gold quality
connective tissue	UBERON:0002384	98.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	11.28
E-CURD-112	no	3.02
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• complexes with prolyl 3-hydroxylase 1 (P3H1) to decrease prolyl 3 hydroxylation; dysregulation of prolyl 3 hydroxylation is a mechanism for connective tissue disease (PMID:17055431)
• Screening of 78 subjects diagnosed with osteogenesis imperfecta type II or III, identified three probands with mutations in CRTAP and 16 with mutations in LEPRE1. (PMID:18566967)
• Mutations in CRTAP and LEPRE1 are found in 3 patients with type II osteogenesis imperfecta. (PMID:18996919)
• CRTAP mutations not described earlier were identified in 10 individuals who had a clinical diagnosis of lethal and severe osteogenesis imperfecta. (PMID:19550437)
• SNP rs7623768 and the haplotype G-C of rs4076086-rs7623768 in CRTAP were associated with femoral neck bone mineral density (p = 0.009 and p = 0.003, respectively). (PMID:19727905)
• CRTAP and P3H1 are mutually stabilized in the collagen prolyl 3-hydroxylation complex in endoplasmic reticulum. (PMID:19846465)
• Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta. (PMID:19862557)
• CRTAP deficiency results in higher bone mineral content of the bone matrix in osteogenesis imperfecta type VII. (PMID:19895918)
• Importantly, human mutations in the CRTAP gene have been associated with recessive forms of OI. (PMID:20425614)
• An additional function of the rough endoplasmic reticulum protein complex prolyl 3-hydroxylase 1.cartilage-associated protein.cyclophilin B: the CXXXC motif reveals disulfide isomerase activity in vitro. (PMID:24043621)
• This study enhances our knowledge about the mutational pattern of the LEPRE1, CRTAP, and PPIB genes. LEPRE1 should be the first gene analyzed in mutation detection studies in patients with recessive OI. (PMID:26634552)
• To the best of our knowledge, our study is the first to exclude potential correlations between heterozygous variants in CRTAP and milder skeletal impairments in a large number of patients (PMID:27901313)
• Osteogenesis imperfecta caused by COL1A1, CRTAP and LEPRE1 mutations. Report of 2cases.", trans “Osteogenesis imperfecta causada por mutacion en los genes COL1A1, CRTAP y LEPRE1. Estudio de 2casos. (PMID:30389107)
• Novel BMP1, CRTAP, and SERPINF1 variants causing autosomal recessive osteogenesis imperfecta. (PMID:35703132)
• Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants. (PMID:38214665)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crtap	ENSDARG00000018010
mus_musculus	Crtap	ENSMUSG00000032431
rattus_norvegicus	Crtap	ENSRNOG00000009878
caenorhabditis_elegans		WBGENE00013531

Paralogs (1): P3H4 (ENSG00000141696)

Protein

Protein identifiers

Cartilage-associated protein — O75718 (reviewed: O75718)

All UniProt accessions (2): O75718, C9JP16

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Found in articular chondrocytes. Expressed in a variety of tissues.

Disease relevance. Osteogenesis imperfecta 7 (OI7) [MIM:610682] A 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. OI7 is an autosomal recessive, severe form. Multiple fractures are present at birth and patients have short stature, short humeri and femora, coxa vara, and white sclera. Dentinogenesis imperfecta is absent. Death can occur in the perinatal period due to secondary respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the leprecan family.

RefSeq proteins (4): NP_001380292, NP_001380293, NP_001380294, NP_006362* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR052284	Collagen_mod_leprecan	Family
IPR056585	Leprecan_dom	Domain

Pfam: PF23557

UniProt features (36 total): helix 21, sequence variant 5, strand 4, turn 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8K0M	ELECTRON MICROSCOPY	3.17
8K17	ELECTRON MICROSCOPY	3.18
8K0F	ELECTRON MICROSCOPY	3.37
8K0I	ELECTRON MICROSCOPY	3.62
8K0E	ELECTRON MICROSCOPY	3.65
8KC9	ELECTRON MICROSCOPY	3.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75718-F1	88.81	0.77

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 (2): 87, 363

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes

MSigDB gene sets: 356 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, ATACCTC_MIR202, MEF2_02, GOBP_MALE_GAMETE_GENERATION, PATIL_LIVER_CANCER, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_STABILIZATION, chr3p22, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_FOLDING, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, IGLESIAS_E2F_TARGETS_UP

GO Biological Process (5): protein folding (GO:0006457), spermatogenesis (GO:0007283), collagen fibril organization (GO:0030199), protein stabilization (GO:0050821), negative regulation of post-translational protein modification (GO:1901874)

GO Molecular Function (2): protein binding (GO:0005515), collagen binding (GO:0005518)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), protein-containing complex (GO:0032991), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
developmental process involved in reproduction	1
male gamete generation	1
extracellular matrix organization	1
regulation of protein stability	1
negative regulation of protein modification process	1
post-translational protein modification	1
regulation of post-translational protein modification	1
binding	1
protein-containing complex binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular_component	1
cellular anatomical structure	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRTAP	PPIB	P23284	999
CRTAP	P3H1	Q32P28	977
CRTAP	COL1A2	P02464	932
CRTAP	COL1A1	P02452	925
CRTAP	FKBP10	Q96AY3	862
CRTAP	TMEM38B	Q9NVV0	833
CRTAP	SERPINH1	P29043	826
CRTAP	IFITM5	A6NNB3	783
CRTAP	PLOD2	O00469	746
CRTAP	SERPINF1	P36955	743
CRTAP	BMP1	P13497	717
CRTAP	SEC24D	O94855	701
CRTAP	CREB3L1	Q96BA8	693
CRTAP	PLOD1	Q02809	667
CRTAP	MBTPS2	O43462	652

IntAct

109 interactions, top by confidence:

A	B	Type	Score
CPSF6	NUDT21	psi-mi:“MI:0914”(association)	0.890
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
COL1A1	P4HA2	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
SF3B4	SF3B1	psi-mi:“MI:0914”(association)	0.610
HRG	PLSCR1	psi-mi:“MI:0914”(association)	0.590
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
CRTAP	P3H1	psi-mi:“MI:0915”(physical association)	0.560
INAVA	DCTN6	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
ALX3	CRTAP	psi-mi:“MI:0914”(association)	0.530
VPS37D	CRTAP	psi-mi:“MI:0914”(association)	0.530
CSTF2T	CRTAP	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
CBFA2T3	CBFA2T2	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480

BioGRID (158): CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Co-fractionation), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS), CRTAP (Affinity Capture-MS)

ESM2 similar proteins: A5A6P7, F1QCC6, G3X745, O75487, O75718, P08591, P09113, P09585, P29235, P29971, P35052, P35053, P45654, P48248, P50593, P51653, P51655, P70302, P78333, P79885, P84903, P87391, P87495, Q01282, Q01283, Q05163, Q0V9W0, Q13586, Q17QN8, Q24114, Q3V5L5, Q58CP9, Q58T08, Q5RE54, Q6UX71, Q6V9Y8, Q765H6, Q8BKV1, Q8CAL5, Q8CFZ4

Diamond homologs: O75718, Q32P28, Q3V1T4, Q4KLM6, Q64375, Q6JHU7, Q6JHU8, Q8CG71, Q8IVL5, Q8K2B0, Q90830, Q92791, Q9CYD3, Q9R1J8, Q6PK18, Q8CG70, Q8IVL6, Q5M843, Q5XGE0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
RNA Polymerase II Transcription Termination	7	18.5×	1e-05
mRNA 3’-end processing	7	16.6×	2e-05
Collagen biosynthesis and modifying enzymes	8	16.4×	7e-06
mRNA Polyadenylation	10	10.6×	7e-06
mRNA Splicing	8	10.6×	8e-05
Processing of Capped Intron-Containing Pre-mRNA	8	7.9×	5e-04
Dengue Virus-Host Interactions	11	6.0×	1e-04
mRNA Splicing - Major Pathway	8	5.3×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	8	7.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	15
Uncertain significance	296
Likely benign	257
Benign	52

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1019549	NM_006371.5(CRTAP):c.1153-3C>G	Pathogenic
1175017	NM_006371.5(CRTAP):c.21_22dup (p.Ala8fs)	Pathogenic
1299365	NM_006371.5(CRTAP):c.470A>G (p.Lys157Arg)	Pathogenic
1395362	NM_006371.5(CRTAP):c.1001del (p.Asn334fs)	Pathogenic
1451956	NM_006371.5(CRTAP):c.172G>T (p.Glu58Ter)	Pathogenic
1459770	NC_000003.11:g.(?33155570)(33166091_?)del	Pathogenic
1687175	NM_006371.5(CRTAP):c.404del (p.Ser135fs)	Pathogenic
1805264	NM_006371.5(CRTAP):c.153_175dup (p.His59fs)	Pathogenic
1925740	NM_006371.5(CRTAP):c.445A>T (p.Lys149Ter)	Pathogenic
217257	NM_006371.5(CRTAP):c.118G>T (p.Glu40Ter)	Pathogenic
2425587	NC_000003.11:g.(?33155570)(33156060_?)del	Pathogenic
2506711	NM_006371.5(CRTAP):c.822_826delinsT (p.Lys274fs)	Pathogenic
2715306	NM_006371.5(CRTAP):c.923-2A>G	Pathogenic
2718077	NM_006371.5(CRTAP):c.370C>T (p.Gln124Ter)	Pathogenic
2751904	NM_006371.5(CRTAP):c.997C>T (p.Gln333Ter)	Pathogenic
2753603	NM_006371.5(CRTAP):c.157del (p.Asp53fs)	Pathogenic
2759682	NM_006371.5(CRTAP):c.406del (p.Arg136fs)	Pathogenic
2822885	NM_006371.5(CRTAP):c.638del (p.Ala213fs)	Pathogenic
2823552	NM_006371.5(CRTAP):c.535G>T (p.Glu179Ter)	Pathogenic
2825842	NM_006371.5(CRTAP):c.427C>T (p.Gln143Ter)	Pathogenic
2828362	NM_006371.5(CRTAP):c.179G>A (p.Trp60Ter)	Pathogenic
2853470	NM_006371.5(CRTAP):c.57C>A (p.Cys19Ter)	Pathogenic
2855717	NM_006371.5(CRTAP):c.409G>T (p.Glu137Ter)	Pathogenic
2856018	NM_006371.5(CRTAP):c.887_888insACAATGATACAAGT (p.Thr296_Met297insGlnTer)	Pathogenic
2886785	NM_006371.5(CRTAP):c.759del (p.Lys254fs)	Pathogenic
2914570	NM_006371.5(CRTAP):c.2T>C (p.Met1Thr)	Pathogenic
3011269	NM_006371.5(CRTAP):c.436G>T (p.Glu146Ter)	Pathogenic
3246880	NC_000003.11:g.(?33171411)(33171579_?)del	Pathogenic
3246881	NC_000003.11:g.(?33155570)(33175777_?)del	Pathogenic
3246882	NC_000003.11:g.(?33171411)(33174212_?)del	Pathogenic

SpliceAI

1021 predictions. Top by Δscore:

Variant	Effect	Δscore
3:33120343:GGCAA:G	acceptor_gain	1.0000
3:33120491:G:GT	donor_gain	1.0000
3:33120491:GAA:G	donor_gain	1.0000
3:33120494:G:GG	donor_gain	1.0000
3:33130063:TAAGT:T	donor_gain	1.0000
3:33130064:AAGT:A	donor_gain	1.0000
3:33130066:GT:G	donor_gain	1.0000
3:33130068:G:GG	donor_gain	1.0000
3:33130068:GTAA:G	donor_loss	1.0000
3:33130069:TAAG:T	donor_loss	1.0000
3:33132547:A:AG	acceptor_gain	1.0000
3:33132548:A:G	acceptor_gain	1.0000
3:33132549:C:G	acceptor_gain	1.0000
3:33132551:CTAGT:C	acceptor_loss	1.0000
3:33132553:A:AG	acceptor_gain	1.0000
3:33132553:A:C	acceptor_loss	1.0000
3:33132553:AGT:A	acceptor_gain	1.0000
3:33132554:G:GA	acceptor_gain	1.0000
3:33132554:GT:G	acceptor_gain	1.0000
3:33132554:GTG:G	acceptor_gain	1.0000
3:33132554:GTGA:G	acceptor_gain	1.0000
3:33132554:GTGAA:G	acceptor_gain	1.0000
3:33132696:GACCT:G	donor_gain	1.0000
3:33132697:ACCT:A	donor_gain	1.0000
3:33132697:ACCTG:A	donor_loss	1.0000
3:33132698:CCT:C	donor_gain	1.0000
3:33132699:CT:C	donor_gain	1.0000
3:33132699:CTGT:C	donor_loss	1.0000
3:33132700:TG:T	donor_loss	1.0000
3:33132701:G:GG	donor_gain	1.0000

AlphaMissense

2650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:33114257:G:C	W60C	0.999
3:33114257:G:T	W60C	0.999
3:33114285:A:C	S70R	0.999
3:33114287:C:A	S70R	0.999
3:33114287:C:G	S70R	0.999
3:33114327:T:A	C84S	0.999
3:33114327:T:C	C84R	0.999
3:33114328:G:A	C84Y	0.999
3:33114328:G:C	C84S	0.999
3:33114328:G:T	C84F	0.999
3:33114329:C:G	C84W	0.999
3:33114442:G:A	C122Y	0.999
3:33114529:T:C	L151P	0.999
3:33124423:G:C	A213P	0.999
3:33132590:A:C	S320R	0.999
3:33132592:C:A	S320R	0.999
3:33132592:C:G	S320R	0.999
3:33114183:T:C	F36L	0.998
3:33114184:T:G	F36C	0.998
3:33114185:C:A	F36L	0.998
3:33114185:C:G	F36L	0.998
3:33114208:T:A	L44H	0.998
3:33114295:T:C	L73P	0.998
3:33114301:G:C	R75P	0.998
3:33114339:T:C	C88R	0.998
3:33114340:G:A	C88Y	0.998
3:33114341:C:G	C88W	0.998
3:33114441:T:A	C122S	0.998
3:33114441:T:C	C122R	0.998
3:33114442:G:C	C122S	0.998

dbSNP variants (sampled 300 via entrez): RS1000090899 (3:33125644 C>G,T), RS1000206940 (3:33141598 A>T), RS1000254785 (3:33125257 C>G), RS1000286765 (3:33127491 A>G), RS1000472009 (3:33127939 C>G,T), RS1000605659 (3:33136188 A>G), RS1000677034 (3:33134480 A>C), RS1000753624 (3:33129591 G>A,T), RS1000826071 (3:33115428 A>C,T), RS1000839608 (3:33138582 A>G), RS1000856957 (3:33122385 A>G), RS1000892185 (3:33133648 A>C,G), RS1000925010 (3:33133455 C>T), RS1000955452 (3:33133222 A>G), RS1000983682 (3:33120855 A>G)

Disease associations

OMIM: gene MIM:605497 | disease phenotypes: MIM:610682, MIM:166200

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 7	Strong	Autosomal recessive
osteogenesis imperfecta type 2	Supportive	Autosomal dominant
osteogenesis imperfecta type 3	Supportive	Autosomal dominant
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (5): osteogenesis imperfecta type 7 (MONDO:0012536), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 2 (MONDO:0008147), osteogenesis imperfecta type 3 (MONDO:0009804), osteogenesis imperfecta type 4 (MONDO:0008148)

Orphanet (1): Osteogenesis imperfecta (Orphanet:666)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000260	Wide anterior fontanel
HP:0000262	Turricephaly
HP:0000270	Delayed cranial suture closure
HP:0000311	Round face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000592	Blue sclerae
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000703	Dentinogenesis imperfecta
HP:0000767	Pectus excavatum
HP:0000772	Abnormal rib morphology
HP:0000774	Narrow chest
HP:0000938	Osteopenia
HP:0000944	Abnormal metaphysis morphology
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001334	Communicating hydrocephalus
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001608	Abnormality of the voice
HP:0001623	Breech presentation
HP:0002007	Frontal bossing

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005231_44	Major depressive disorder	2.000000e-08
GCST008916_8	Asthma	5.000000e-09
GCST009597_174	Multiple sclerosis	1.000000e-07
GCST009798_68	Asthma	3.000000e-12
GCST009959_27	Retinal detachment or retinal break	4.000000e-06
GCST010002_420	Refractive error	2.000000e-15
GCST012490_340	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010698	retinal break
EFO:0004531	urate measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C536042	Osteogenesis imperfecta, type 2A (supp.)
C536044	Osteogenesis imperfecta, type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
Tretinoin	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
calfactant	affects cotreatment, increases expression	1
fenpyroximate	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
thifluzamide	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Glyphosate	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Benztropine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

79 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
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
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)
NCT01061099	PHASE1	COMPLETED	Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta
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
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
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
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