TMEM38B

Summary

TMEM38B (transmembrane protein 38B, HGNC:25535) is a protein-coding gene on chromosome 9q31.2, encoding Trimeric intracellular cation channel type B (Q9NVV0). Intracellular monovalent cation channel required for maintenance of rapid intracellular calcium release.

This gene encodes an intracellular monovalent cation channel that functions in maintenance of intracellular calcium release. Mutations in this gene may be associated with autosomal recessive osteogenesis.

Source: NCBI Gene 55151 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 14 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 44
• Clinical variants (ClinVar): 231 total — 19 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_018112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25535
Approved symbol	TMEM38B
Name	transmembrane protein 38B
Location	9q31.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10493, bA219P18.1, D4Ertd89e, TRIC-B
Ensembl gene	ENSG00000095209
Ensembl biotype	protein_coding
OMIM	611236
Entrez	55151

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000374688, ENST00000374692, ENST00000434214, ENST00000435034, ENST00000451560, ENST00000884630, ENST00000884631, ENST00000884632, ENST00000884633, ENST00000956696

RefSeq mRNA: 1 — MANE Select: NM_018112 NM_018112

CCDS: CCDS6768

Canonical transcript exons

ENST00000374692 — 6 exons

Exon	Start	End
ENSE00000983304	105721537	105721721
ENSE00000983305	105722534	105722621
ENSE00001023568	105748073	105748190
ENSE00003619209	105694541	105694772
ENSE00003643141	105705597	105705753
ENSE00003845109	105773865	105776629

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3771 / max 182.6972, expressed in 1802 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97848	12.4994	1766
97849	6.6467	1601
97850	1.1275	571
97847	0.0533	23
97851	0.0427	15
97852	0.0076	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.39	gold quality
biceps brachii	UBERON:0001507	98.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.56	gold quality
heart right ventricle	UBERON:0002080	96.68	gold quality
male germ cell	CL:0000015	95.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.78	gold quality
tibialis anterior	UBERON:0001385	94.51	gold quality
skeletal muscle tissue	UBERON:0001134	94.34	gold quality
muscle of leg	UBERON:0001383	94.22	gold quality
gastrocnemius	UBERON:0001388	94.15	gold quality
muscle organ	UBERON:0001630	94.00	gold quality
vastus lateralis	UBERON:0001379	93.50	gold quality
quadriceps femoris	UBERON:0001377	92.58	gold quality
deltoid	UBERON:0001476	91.99	silver quality
muscle tissue	UBERON:0002385	91.96	gold quality
choroid plexus epithelium	UBERON:0003911	91.11	gold quality
adrenal tissue	UBERON:0018303	91.03	gold quality
islet of Langerhans	UBERON:0000006	90.26	gold quality
corpus epididymis	UBERON:0004359	89.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.62	gold quality
calcaneal tendon	UBERON:0003701	88.70	gold quality
diaphragm	UBERON:0001103	88.68	silver quality
popliteal artery	UBERON:0002250	88.60	gold quality
tibial artery	UBERON:0007610	88.57	gold quality
body of tongue	UBERON:0011876	88.43	gold quality
pigmented layer of retina	UBERON:0001782	88.36	gold quality
myocardium	UBERON:0002349	88.23	gold quality
cardiac ventricle	UBERON:0002082	87.73	gold quality
heart left ventricle	UBERON:0002084	87.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	7.67
E-ANND-3	yes	5.02
E-MTAB-6911	no	195.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting TMEM38B, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068

Literature-anchored findings (GeneRIF, showing 5)

• TMEM38B is a novel candidate gene for autosomal recessive Osteogenesis imperfecta (OI). Future studies are needed to explore fully the contribution of this gene to autosomal recessive Osteogenesis imperfecta (OI) in other populations. (PMID:23054245)
• A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta. (PMID:23316006)
• TMEM38B mutations could lead to a rare form of OI, with an autosomal recessive pattern of inheritance. We identified two novel mutations (c.455-7T>G in intron 3 and c.507G>A in exon 4) in TMEM38B in three Chinese children with OI. The two mutations created a new acceptor splice site (p.R151_G152insVL) and a novel downstream termination codon (p.W169X), respectively (PMID:26911354)
• Absence of TMEM38B causes osteogenesis imperfecta by dysregulation of calcium flux kinetics in the endoplasmic reticulum, impacting multiple collagen-specific chaperones and modifying enzymes. (PMID:27441836)
• Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study. (PMID:37348683)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000100549
mus_musculus	Tmem38b	ENSMUSG00000028420
rattus_norvegicus	Tmem38b	ENSRNOG00000028063
drosophila_melanogaster	CG4239	FBGN0030745
caenorhabditis_elegans		WBGENE00013255
caenorhabditis_elegans		WBGENE00013268

Paralogs (1): TMEM38A (ENSG00000072954)

Protein

Protein identifiers

Trimeric intracellular cation channel type B — Q9NVV0 (reviewed: Q9NVV0)

Alternative names: Transmembrane protein 38B

All UniProt accessions (5): Q9NVV0, A0A0A0MRS4, H7C3B3, H7C4C1, X6RGH1

UniProt curated annotations — full annotation on UniProt →

Function. Intracellular monovalent cation channel required for maintenance of rapid intracellular calcium release. Acts as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores. Activated by increased cytosolic Ca(2+) levels.

Subunit / interactions. Homotrimer; conformation seems to be controled by binding to diacylglycerol (DAG).

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Osteogenesis imperfecta 14 (OI14) [MIM:615066] 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. OI14 is characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is activated by increased cytosolic Ca(2+) levels and blocked by luminal high Ca(2+) levels.

Similarity. Belongs to the TMEM38 family.

RefSeq proteins (1): NP_060582* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007866	TRIC_channel	Family

Pfam: PF05197

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (25 total): topological domain 8, transmembrane region 7, sequence variant 3, binding site 2, sequence conflict 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVV0-F1	80.17	0.54

Functional residue map

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

Ligand- & substrate-binding residues (2): 118; 122

Post-translational modifications (1): 262

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 323 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_LUNG_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_REGULATION_OF_THE_RELEASE_OF_SEQUESTERED_CALCIUM_ION, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (20): endoplasmic reticulum organization (GO:0007029), phospholipid biosynthetic process (GO:0008654), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0014808), bone mineralization (GO:0030282), lung alveolus development (GO:0048286), regulation of release of sequestered calcium ion into cytosol (GO:0051279), establishment of localization in cell (GO:0051649), bone development (GO:0060348), lung epithelial cell differentiation (GO:0060487), secretion by lung epithelial cell involved in lung growth (GO:0061033), extracellular matrix constituent secretion (GO:0070278), cellular response to caffeine (GO:0071313), ossification (GO:0001503), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), release of sequestered calcium ion into cytosol (GO:0051209), potassium ion transmembrane transport (GO:0071805), release of sequestered calcium ion into cytosol by endoplasmic reticulum (GO:1903514)

GO Molecular Function (3): potassium channel activity (GO:0005267), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), nuclear membrane (GO:0031965), sarcoplasmic reticulum membrane (GO:0033017), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
release of sequestered calcium ion into cytosol	2
secretion by cell	2
intracellular membrane-bounded organelle	2
organelle membrane	2
organelle organization	1
endomembrane system organization	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
sarcoplasmic reticulum calcium ion transport	1
release of sequestered calcium ion into cytosol by endoplasmic reticulum	1
ossification	1
biomineral tissue development	1
lung development	1
anatomical structure development	1
regulation of calcium ion transmembrane transport	1
establishment of localization	1
cellular localization	1
skeletal system development	1
animal organ development	1
epithelial cell differentiation	1
lung epithelium development	1
lung cell differentiation	1
lung growth	1
extracellular matrix organization	1
response to caffeine	1
cellular response to alkaloid	1
cellular response to purine-containing compound	1
multicellular organismal process	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation channel activity	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM38B	CRTAP	O75718	833
TMEM38B	FKBP10	Q96AY3	828
TMEM38B	P3H1	Q32P28	796
TMEM38B	IFITM5	A6NNB3	776
TMEM38B	SEC24D	O94855	751
TMEM38B	CREB3L1	Q96BA8	734
TMEM38B	PLOD2	O00469	728
TMEM38B	MBTPS2	O43462	718
TMEM38B	SERPINF1	P36955	706
TMEM38B	PPIB	P23284	696
TMEM38B	SERPINH1	P29043	694
TMEM38B	PLS3	P13797	678
TMEM38B	BMP1	P13497	670
TMEM38B	WNT1	P04628	597
TMEM38B	SP7	Q8TDD2	592

IntAct

60 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
AQP1	TMEM38B	psi-mi:“MI:0915”(physical association)	0.560
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ABHD5	ZPR1	psi-mi:“MI:0914”(association)	0.530
LRRTM2	GPC3	psi-mi:“MI:0914”(association)	0.530
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
TMEM38B	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.350
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
ABHD5	KDM4A	psi-mi:“MI:0914”(association)	0.350
LRRTM2	PTPRD	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
COPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPE	ESYT2	psi-mi:“MI:0914”(association)	0.350
FAM241A	PGRMC1	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
POLR1D	BDP1	psi-mi:“MI:0914”(association)	0.350
NCLN	PGRMC1	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
LRCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LRRC25	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): TMEM38B (Affinity Capture-MS), TMEM38B (Proximity Label-MS), TMEM38B (Proximity Label-MS), TMEM38B (Affinity Capture-MS), TMEM38B (Affinity Capture-MS), TMEM38B (Affinity Capture-MS), TMEM38B (Affinity Capture-MS), TMEM38B (Affinity Capture-RNA), TMEM38B (Affinity Capture-MS), TMEM38B (Proximity Label-MS), TMEM38B (Proximity Label-MS), AQP1 (Two-hybrid), TMEM38B (Proximity Label-MS), TMEM38B (Proximity Label-MS), TMEM38B (Proximity Label-MS)

ESM2 similar proteins: A2AF53, A4FV75, A5A6S6, A6ZIQ8, B8AT51, D3ZEH5, O60337, Q08DE2, Q0JAW2, Q0VC58, Q15005, Q28250, Q2TBU2, Q2V4F9, Q3TMP8, Q4R512, Q4R5B4, Q58DA4, Q5JZQ8, Q5M8Y1, Q5R8H8, Q5R9W1, Q5RAY6, Q5REE3, Q5RF53, Q5XIK2, Q5ZK43, Q6GLK9, Q6P2T0, Q6P8F8, Q6ZQ89, Q7SYC7, Q7ZY07, Q80YV4, Q8CIF6, Q8NBJ9, Q8NFB2, Q8R3R5, Q8TCT6, Q8VIJ8

Diamond homologs: A4FV75, A5A6S6, A6ZIQ8, Q0VC58, Q28FA9, Q3KQE5, Q3TMP8, Q5ZK43, Q68FV1, Q6GN30, Q6P2T0, Q6P8F8, Q7ZVP8, Q7ZY07, Q9DAV9, Q9H6F2, Q9NA73, Q9NA75, Q9NVV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	7
Uncertain significance	90
Likely benign	74
Benign	19

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1323694	NM_018112.3(TMEM38B):c.507G>A (p.Trp169Ter)	Pathogenic
1424337	NC_000009.11:g.(?108483798)(108484922_?)del	Pathogenic
1527539	GRCh37/hg19 9q31.1-33.3(chr9:104604851-126253089)	Pathogenic
155632	GRCh38/hg38 9q31.2(chr9:105721899-105741297)x0	Pathogenic
1723336	NC_000009.11:g.(?108456805)(108468035_108483817)del	Pathogenic
2426437	NC_000009.11:g.(?108456942)(108536361_?)del	Pathogenic
2426438	NC_000009.11:g.(?108467858)(108536361_?)del	Pathogenic
2698038	NM_018112.3(TMEM38B):c.408T>G (p.Tyr136Ter)	Pathogenic
2784416	NM_018112.3(TMEM38B):c.331C>T (p.Gln111Ter)	Pathogenic
2988606	NM_018112.3(TMEM38B):c.15G>A (p.Trp5Ter)	Pathogenic
3063086	GRCh37/hg19 9q31.2(chr9:108443820-108476067)x1	Pathogenic
3245359	NC_000009.11:g.(?108467858)(108468054_?)del	Pathogenic
3245360	NC_000009.11:g.(?108456942)(108468054_?)del	Pathogenic
3381053	NM_018112.3:c.454+279_543-5092delinsATTAAGGTATA	Pathogenic
39494	NM_018112.3(TMEM38B):c.454+279_543-5092delinsAATTAAGGTATA	Pathogenic
4715203	NM_018112.3(TMEM38B):c.14G>A (p.Trp5Ter)	Pathogenic
688394	GRCh37/hg19 9q31.2(chr9:108444651-108476067)x1	Pathogenic
688413	GRCh37/hg19 9q31.2(chr9:108444651-108476067)x1	Pathogenic
872679	GRCh37/hg19 9q31.2(chr9:108484815-108484902)x0	Pathogenic
2445843	NC_000009.11:g.(108484903_108510353)(108538893?)del	Likely pathogenic
2501234	NM_018112.3(TMEM38B):c.532A>T (p.Lys178Ter)	Likely pathogenic
2869687	NM_018112.3(TMEM38B):c.542+2T>G	Likely pathogenic
3064997	NM_018112.3(TMEM38B):c.455-64_542+7del	Likely pathogenic
3596219	NM_018112.3(TMEM38B):c.63del (p.Phe21fs)	Likely pathogenic
3596220	NM_018112.3(TMEM38B):c.286dup (p.Cys96fs)	Likely pathogenic
3596221	NM_018112.3(TMEM38B):c.451C>T (p.Arg151Ter)	Likely pathogenic

SpliceAI

1593 predictions. Top by Δscore:

Variant	Effect	Δscore
9:105694768:GCCGG:G	donor_gain	1.0000
9:105694771:GG:G	donor_gain	1.0000
9:105694772:GG:G	donor_gain	1.0000
9:105705595:A:AG	acceptor_gain	1.0000
9:105705596:G:GA	acceptor_gain	1.0000
9:105705596:GGA:G	acceptor_gain	1.0000
9:105705750:TCTGG:T	donor_loss	1.0000
9:105705751:CTGG:C	donor_loss	1.0000
9:105705752:TGGTA:T	donor_loss	1.0000
9:105705754:G:GA	donor_loss	1.0000
9:105705754:G:GG	donor_gain	1.0000
9:105705755:T:TC	donor_loss	1.0000
9:105720806:G:GG	donor_gain	1.0000
9:105721622:G:GT	donor_gain	1.0000
9:105721646:G:GG	donor_gain	1.0000
9:105722354:G:T	donor_gain	1.0000
9:105722622:G:GG	donor_gain	1.0000
9:105694769:CCGGG:C	donor_loss	0.9900
9:105694770:CGGGT:C	donor_loss	0.9900
9:105694772:GGT:G	donor_loss	0.9900
9:105694773:G:GG	donor_gain	0.9900
9:105694773:G:T	donor_loss	0.9900
9:105694774:TGAG:T	donor_loss	0.9900
9:105694775:GA:G	donor_loss	0.9900
9:105694776:AGTG:A	donor_loss	0.9900
9:105696156:G:GT	donor_gain	0.9900
9:105705587:A:AG	acceptor_gain	0.9900
9:105705588:C:G	acceptor_gain	0.9900
9:105705590:A:AG	acceptor_gain	0.9900
9:105705594:CAGG:C	acceptor_gain	0.9900

AlphaMissense

1893 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:105705635:T:A	W51R	0.994
9:105705635:T:C	W51R	0.994
9:105705659:T:C	F59L	0.991
9:105705661:T:A	F59L	0.991
9:105705661:T:G	F59L	0.991
9:105705752:T:A	W90R	0.991
9:105705752:T:C	W90R	0.991
9:105721712:T:A	W149R	0.991
9:105721712:T:C	W149R	0.991
9:105705632:A:C	S50R	0.985
9:105705634:C:A	S50R	0.985
9:105705634:C:G	S50R	0.985
9:105705658:T:G	C58W	0.985
9:105694712:T:C	F18L	0.984
9:105694714:T:A	F18L	0.984
9:105694714:T:G	F18L	0.984
9:105721644:T:A	I126K	0.984
9:105694731:C:A	A24E	0.982
9:105748095:G:A	G189R	0.980
9:105748095:G:C	G189R	0.980
9:105721710:G:A	G148E	0.978
9:105705741:C:A	A86E	0.977
9:105705656:T:C	C58R	0.976
9:105721547:T:C	F94L	0.975
9:105721549:T:A	F94L	0.975
9:105721549:T:G	F94L	0.975
9:105721621:G:C	K118N	0.975
9:105721621:G:T	K118N	0.975
9:105721644:T:G	I126R	0.975
9:105721665:C:A	A133D	0.975

dbSNP variants (sampled 300 via entrez): RS1000006331 (9:105742314 G>C), RS1000013241 (9:105767191 T>G), RS1000035636 (9:105702952 T>C), RS1000115891 (9:105731513 G>A), RS1000118642 (9:105774603 G>A,T), RS1000145829 (9:105754225 A>G), RS1000150995 (9:105738909 G>A), RS1000201236 (9:105758854 A>G), RS1000238612 (9:105775008 A>T), RS1000289610 (9:105717541 C>A), RS1000368336 (9:105729294 C>T), RS1000382198 (9:105763683 A>G), RS1000389298 (9:105733775 CTTA>C), RS1000465654 (9:105749180 A>C,G), RS1000494332 (9:105727225 C>T)

Disease associations

OMIM: gene MIM:611236 | disease phenotypes: MIM:615066, MIM:166200

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 14	Strong	Autosomal recessive
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (3): osteogenesis imperfecta type 14 (MONDO:0014029), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 4 (MONDO:0008148)

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

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000592	Blue sclerae
HP:0000703	Dentinogenesis imperfecta
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002659	Increased susceptibility to fractures
HP:0002753	Thin bony cortex
HP:0002757	Recurrent fractures
HP:0002980	Femoral bowing
HP:0003100	Slender long bone
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004322	Short stature
HP:0004363	Abnormal circulating calcium concentration
HP:0011463	Childhood onset
HP:0030674	Antenatal onset
HP:0031425	Elevated circulating beta-CTX concentration

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000189_15	Protein quantitative trait loci	8.000000e-07
GCST000404_1	Menarche (age at onset)	2.000000e-09
GCST000880_17	Menarche (age at onset)	2.000000e-33
GCST001524_14	Visceral adipose tissue/subcutaneous adipose tissue ratio	4.000000e-06
GCST001876_14	Pubertal anthropometrics	2.000000e-06
GCST002541_73	Menarche (age at onset)	2.000000e-08
GCST002541_74	Menarche (age at onset)	6.000000e-66
GCST002541_75	Menarche (age at onset)	4.000000e-41
GCST003061_4	Cutaneous malignant melanoma	7.000000e-11
GCST003075_13	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003075_136	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST003993_20	Menarche (age at onset)	2.000000e-34
GCST003994_12	Age at voice drop	2.000000e-10
GCST004142_1	Melanoma	7.000000e-11
GCST004500_135	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-11
GCST004501_74	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-11
GCST004501_75	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	7.000000e-11
GCST004504_108	Waist circumference adjusted for BMI in non-smokers	2.000000e-11
GCST004504_24	Waist circumference adjusted for BMI in non-smokers	2.000000e-10
GCST004562_109	Waist circumference adjusted for body mass index	1.000000e-07
GCST004562_141	Waist circumference adjusted for body mass index	2.000000e-07
GCST004562_232	Waist circumference adjusted for body mass index	3.000000e-08
GCST004562_36	Waist circumference adjusted for body mass index	1.000000e-07
GCST004562_56	Waist circumference adjusted for body mass index	2.000000e-08
GCST004563_118	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004563_122	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	5.000000e-07
GCST004563_14	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-08
GCST004563_195	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004563_95	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004564_82	Waist circumference adjusted for BMI in active individuals	5.000000e-09

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004703	age at menarche
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0001382	puberty
EFO:0007710	cognitive decline measurement
EFO:0007888	age at voice drop
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0004340	body mass index
EFO:0004713	FEV/FVC ratio
EFO:0003924	hair color
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007828	daytime rest measurement

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
bisphenol A	decreases reaction, increases abundance, decreases expression, increases expression	4
Estradiol	increases expression, affects expression	3
Tobacco Smoke Pollution	increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
GSK-J4	increases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Diazinon	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TS95	HAP1 TMEM38B (-) 1	Cancer cell line	Male
CVCL_XU51	HAP1 TMEM38B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

78 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)
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