Osteogenesis imperfecta type 7

Summary

Osteogenesis imperfecta type 7 (MONDO:0012536) is a disease caused by CRTAP (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CRTAP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 645

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 7
Mondo ID	MONDO:0012536
OMIM	610682
DOID	DOID:0110337
SNOMED CT	254111008
UMLS	C1853162
MedGen	343981
GARD	0008701
Is cancer (heuristic)	no

Also known as: CRTAP osteogenesis imperfecta · OI type 7 · OI type VII · OI7 · osteogenesis imperfecta caused by mutation in CRTAP · osteogenesis imperfecta type 7 · osteogenesis imperfecta, type VII

Data availability: 645 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 7

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 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, 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

600 retrieved; paginated sample, class counts are floors:

245 likely benign, 228 uncertain significance, 50 pathogenic, 31 benign, 24 conflicting classifications of pathogenicity, 11 pathogenic/likely pathogenic, 11 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1019549	NM_006371.5(CRTAP):c.1153-3C>G	CRTAP	Pathogenic	criteria provided, single submitter
1299365	NM_006371.5(CRTAP):c.470A>G (p.Lys157Arg)	CRTAP	Pathogenic	criteria provided, single submitter
1395362	NM_006371.5(CRTAP):c.1001del (p.Asn334fs)	CRTAP	Pathogenic	criteria provided, single submitter
1451956	NM_006371.5(CRTAP):c.172G>T (p.Glu58Ter)	CRTAP	Pathogenic	criteria provided, single submitter
1453839	NM_006371.5(CRTAP):c.731_732del (p.Leu244fs)	CRTAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459770	NC_000003.11:g.(?33155570)(33166091_?)del	CRTAP	Pathogenic	criteria provided, single submitter
1687175	NM_006371.5(CRTAP):c.404del (p.Ser135fs)	CRTAP	Pathogenic	criteria provided, multiple submitters, no conflicts
1805264	NM_006371.5(CRTAP):c.153_175dup (p.His59fs)	CRTAP	Pathogenic	criteria provided, multiple submitters, no conflicts
1925740	NM_006371.5(CRTAP):c.445A>T (p.Lys149Ter)	CRTAP	Pathogenic	criteria provided, single submitter
208570	NM_006371.5(CRTAP):c.471+2C>A	CRTAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2161328	NM_006371.5(CRTAP):c.22del (p.Ala8fs)	CRTAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217257	NM_006371.5(CRTAP):c.118G>T (p.Glu40Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2425587	NC_000003.11:g.(?33155570)(33156060_?)del	CRTAP	Pathogenic	criteria provided, single submitter
2506711	NM_006371.5(CRTAP):c.822_826delinsT (p.Lys274fs)	CRTAP	Pathogenic	criteria provided, multiple submitters, no conflicts
2715306	NM_006371.5(CRTAP):c.923-2A>G	CRTAP	Pathogenic	criteria provided, single submitter
2718077	NM_006371.5(CRTAP):c.370C>T (p.Gln124Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2725831	NM_006371.5(CRTAP):c.18_25dup (p.Ala9fs)	CRTAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2751904	NM_006371.5(CRTAP):c.997C>T (p.Gln333Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2753603	NM_006371.5(CRTAP):c.157del (p.Asp53fs)	CRTAP	Pathogenic	criteria provided, single submitter
2759682	NM_006371.5(CRTAP):c.406del (p.Arg136fs)	CRTAP	Pathogenic	criteria provided, single submitter
2822885	NM_006371.5(CRTAP):c.638del (p.Ala213fs)	CRTAP	Pathogenic	criteria provided, single submitter
2823552	NM_006371.5(CRTAP):c.535G>T (p.Glu179Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2825842	NM_006371.5(CRTAP):c.427C>T (p.Gln143Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2828362	NM_006371.5(CRTAP):c.179G>A (p.Trp60Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2853470	NM_006371.5(CRTAP):c.57C>A (p.Cys19Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2855717	NM_006371.5(CRTAP):c.409G>T (p.Glu137Ter)	CRTAP	Pathogenic	criteria provided, single submitter
2856018	NM_006371.5(CRTAP):c.887_888insACAATGATACAAGT (p.Thr296_Met297insGlnTer)	CRTAP	Pathogenic	criteria provided, single submitter
2886785	NM_006371.5(CRTAP):c.759del (p.Lys254fs)	CRTAP	Pathogenic	criteria provided, single submitter
2914570	NM_006371.5(CRTAP):c.2T>C (p.Met1Thr)	CRTAP	Pathogenic	criteria provided, single submitter
2980850	NM_006371.5(CRTAP):c.1020C>G (p.Tyr340Ter)	CRTAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 4 · 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
CRTAP	Strong	Autosomal recessive	osteogenesis imperfecta type 7	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRTAP	Orphanet:2050	Cole-Carpenter syndrome
CRTAP	Orphanet:216804	Osteogenesis imperfecta type 2
CRTAP	Orphanet:216812	Osteogenesis imperfecta type 3
CRTAP	Orphanet:216820	Osteogenesis imperfecta type 4

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRTAP	HGNC:2379	ENSG00000170275	O75718	Cartilage-associated protein	gencc,clinvar
TMPPE	HGNC:33865	ENSG00000188167	Q6ZT21	Transmembrane protein with metallophosphoesterase domain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRTAP	Cartilage-associated protein	Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRTAP	Other/Unknown	no		TPR-like_helical_dom_sf, Collagen_mod_leprecan, Leprecan_dom
TMPPE	Other/Unknown	no		Calcineurin-like_PHP, Metallo-depent_PP-like, Metallophosphoesterase

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endocervix	1
stromal cell of endometrium	1
tendon of biceps brachii	1
male germ line stem cell (sensu Vertebrata) in testis	1
monocyte	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRTAP	288	ubiquitous	marker	tendon of biceps brachii, stromal cell of endometrium, endocervix
TMPPE	132	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRTAP	951
TMPPE	674

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRTAP	O75718	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMPPE	Q6ZT21	91.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	CRTAP

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
negative regulation of post-translational protein modification	1	4213.0×	0.001	CRTAP
collagen fibril organization	1	224.7×	0.011	CRTAP
protein folding	1	103.4×	0.016	CRTAP
protein stabilization	1	66.9×	0.019	CRTAP
spermatogenesis	1	35.2×	0.028	CRTAP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
CRTAP	0	0
TMPPE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	CRTAP, TMPPE

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CRTAP	0	—
TMPPE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.