Osteogenesis imperfecta type 14

Summary

Osteogenesis imperfecta type 14 (MONDO:0014029) is a disease caused by TMEM38B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TMEM38B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 14
Mondo ID	MONDO:0014029
OMIM	615066
DOID	DOID:0110343
UMLS	C3554428
MedGen	767342
GARD	0015901
Is cancer (heuristic)	no

Also known as: OI14 · osteogenesis imperfecta caused by mutation in TMEM38B · osteogenesis imperfecta, type XIV · TMEM38B osteogenesis imperfecta

Data availability: 14 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 14

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 7, 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 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

14 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 2 pathogenic, 2 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323694	NM_018112.3(TMEM38B):c.507G>A (p.Trp169Ter)	TMEM38B	Pathogenic	criteria provided, multiple submitters, no conflicts
39494	NM_018112.3(TMEM38B):c.454+279_543-5092delinsAATTAAGGTATA	TMEM38B	Pathogenic	no assertion criteria provided
3064997	NM_018112.3(TMEM38B):c.455-64_542+7del	TMEM38B	Likely pathogenic	criteria provided, single submitter
3596219	NM_018112.3(TMEM38B):c.63del (p.Phe21fs)	TMEM38B	Likely pathogenic	criteria provided, single submitter
3596220	NM_018112.3(TMEM38B):c.286dup (p.Cys96fs)	TMEM38B	Likely pathogenic	criteria provided, single submitter
3596221	NM_018112.3(TMEM38B):c.451C>T (p.Arg151Ter)	TMEM38B	Likely pathogenic	criteria provided, single submitter
1029513	NM_018112.3(TMEM38B):c.543-10T>G	TMEM38B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299480	NM_018112.3(TMEM38B):c.662T>C (p.Ile221Thr)	TMEM38B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
708103	NM_018112.3(TMEM38B):c.799G>A (p.Val267Ile)	TMEM38B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4685880	NM_018112.3(TMEM38B):c.79C>G (p.Leu27Val)	TMEM38B	Uncertain significance	criteria provided, single submitter
931131	NM_018112.3(TMEM38B):c.661-8del	TMEM38B	Uncertain significance	criteria provided, single submitter
1202024	NM_018112.3(TMEM38B):c.750G>A (p.Pro250=)	TMEM38B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1540962	NM_018112.3(TMEM38B):c.875A>G (p.Ter292=)	TMEM38B	Likely benign	criteria provided, multiple submitters, no conflicts
713913	NM_018112.3(TMEM38B):c.113-7A>G	TMEM38B	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
TMEM38B	Strong	Autosomal recessive	osteogenesis imperfecta type 14	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TMEM38B	Orphanet:216820	Osteogenesis imperfecta type 4

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
TMEM38B	HGNC:25535	ENSG00000095209	Q9NVV0	Trimeric intracellular cation channel type B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TMEM38B	Trimeric intracellular cation channel type B	Intracellular monovalent cation channel required for maintenance of rapid intracellular calcium release.

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)
TMEM38B	Other/Unknown	no		TRIC_channel

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
biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMEM38B	264	ubiquitous	marker	sperm, biceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TMEM38B	839

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM38B	Q9NVV0	80.17

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
extracellular matrix constituent secretion	1	8426.0×	0.001	TMEM38B
secretion by lung epithelial cell involved in lung growth	1	5617.3×	0.001	TMEM38B
lung epithelial cell differentiation	1	1872.4×	0.002	TMEM38B
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	1685.2×	0.002	TMEM38B
cellular response to caffeine	1	1532.0×	0.002	TMEM38B
regulation of release of sequestered calcium ion into cytosol	1	936.2×	0.002	TMEM38B
phospholipid biosynthetic process	1	674.1×	0.002	TMEM38B
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.002	TMEM38B
endoplasmic reticulum organization	1	421.3×	0.003	TMEM38B
lung alveolus development	1	351.1×	0.004	TMEM38B
bone development	1	276.3×	0.004	TMEM38B
bone mineralization	1	271.8×	0.004	TMEM38B
establishment of localization in cell	1	160.5×	0.006	TMEM38B

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
TMEM38B	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	TMEM38B

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)
TMEM38B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.