Osteogenesis imperfecta, type 18

disease

On this page

Also known as OI18

Summary

Osteogenesis imperfecta, type 18 (MONDO:0044329) is a disease caused by TENT5A (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: TENT5A (GenCC Strong)
Cohort genes: 1
ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta, type 18
Mondo ID	MONDO:0044329
OMIM	617952
DOID	DOID:0111848
UMLS	C4693736
MedGen	1635201
GARD	0025898
Is cancer (heuristic)	no

Also known as: OI18

Data availability: 9 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 18

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

9 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
523121	NM_017633.3(TENT5A):c.612_613dup (p.Ser205fs)	TENT5A	Pathogenic	no assertion criteria provided
523122	NM_017633.3(TENT5A):c.380A>G (p.His127Arg)	TENT5A	Pathogenic	no assertion criteria provided
523123	NM_017633.3(TENT5A):c.692A>G (p.Asp231Gly)	TENT5A	Pathogenic	no assertion criteria provided
1029627	NM_017633.3(TENT5A):c.790G>T (p.Val264Phe)	TENT5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1683688	NM_017633.3(TENT5A):c.749dup (p.Met251fs)	TENT5A	Uncertain significance	criteria provided, single submitter
2412817	NM_017633.3(TENT5A):c.204G>T (p.Trp68Cys)	TENT5A	Uncertain significance	criteria provided, single submitter
3805683	NM_017633.3(TENT5A):c.1033G>A (p.Val345Met)	TENT5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4087748	NM_017633.3(TENT5A):c.1060dup (p.Tyr354fs)	TENT5A	Uncertain significance	criteria provided, single submitter
769684	NM_017633.3(TENT5A):c.72CGGCGACTTCGGCGG[5] (p.26DFGGG[5])	TENT5A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
TENT5A	Strong	Autosomal recessive	osteogenesis imperfecta, type 18	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TENT5A	Orphanet:216812	Osteogenesis imperfecta type 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
TENT5A	HGNC:18345	ENSG00000112773	Q96IP4	Terminal nucleotidyltransferase 5A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TENT5A	Terminal nucleotidyltransferase 5A	Cytoplasmic non-canonical poly(A) RNA polymerase that catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group and participates in the cytoplasmic polyadenylation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TENT5A	Enzyme (other)	yes	2.7.7.19	TET5

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
parotid gland	1
pericardium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TENT5A	270	ubiquitous	marker	parotid gland, tibia, pericardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TENT5A	991

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TENT5A	Q96IP4	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
regulation of ossification	1	1203.7×	0.004	TENT5A
positive regulation of bone mineralization	1	391.9×	0.005	TENT5A
mRNA stabilization	1	366.4×	0.005	TENT5A
positive regulation of osteoblast differentiation	1	224.7×	0.005	TENT5A
response to bacterium	1	193.7×	0.005	TENT5A

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
TENT5A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TENT5A	2.7.7.19	polynucleotide adenylyltransferase

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	1	TENT5A
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
TENT5A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TENT5A