TENT5A

Summary

TENT5A (terminal nucleotidyltransferase 5A, HGNC:18345) is a protein-coding gene on chromosome 6q14.1, encoding Terminal nucleotidyltransferase 5A (Q96IP4). 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.

Enables poly(A) RNA polymerase activity. Predicted to be involved in mRNA stabilization; positive regulation of bone mineralization; and positive regulation of osteoblast differentiation. Predicted to act upstream of or within response to bacterium. Predicted to be located in cytoplasm. Implicated in lung non-small cell carcinoma; osteoarthritis; and osteogenesis imperfecta type 18.

Source: NCBI Gene 55603 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta, type 18 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 56
• Clinical variants (ClinVar): 193 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_017633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18345
Approved symbol	TENT5A
Name	terminal nucleotidyltransferase 5A
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20037
Ensembl gene	ENSG00000112773
Ensembl biotype	protein_coding
OMIM	611357
Entrez	55603

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000320172, ENST00000369754, ENST00000369756, ENST00000412306, ENST00000423467, ENST00000874672, ENST00000874673, ENST00000874674, ENST00000959717

RefSeq mRNA: 1 — MANE Select: NM_017633 NM_017633

CCDS: CCDS34489

Canonical transcript exons

ENST00000320172 — 3 exons

Exon	Start	End
ENSE00001513666	81745730	81750471
ENSE00001953986	81752431	81752681
ENSE00003591823	81751590	81752178

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1535 / max 1267.6571, expressed in 1638 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74530	27.2275	1631
74528	0.8446	442
74533	0.0448	16
74532	0.0365	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.52	gold quality
tibia	UBERON:0000979	98.45	gold quality
pericardium	UBERON:0002407	98.41	gold quality
trachea	UBERON:0003126	98.16	gold quality
nipple	UBERON:0002030	98.13	gold quality
trabecular bone tissue	UBERON:0002483	98.09	gold quality
heart right ventricle	UBERON:0002080	98.00	gold quality
skin of hip	UBERON:0001554	97.58	gold quality
vena cava	UBERON:0004087	97.50	gold quality
cartilage tissue	UBERON:0002418	97.49	gold quality
seminal vesicle	UBERON:0000998	96.97	gold quality
pylorus	UBERON:0001166	96.80	gold quality
synovial joint	UBERON:0002217	96.72	gold quality
saphenous vein	UBERON:0007318	96.63	gold quality
upper leg skin	UBERON:0004262	95.90	gold quality
bone marrow	UBERON:0002371	95.74	gold quality
jejunal mucosa	UBERON:0000399	95.72	gold quality
placenta	UBERON:0001987	95.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.57	gold quality
periodontal ligament	UBERON:0008266	95.18	gold quality
amniotic fluid	UBERON:0000173	94.84	gold quality
colonic mucosa	UBERON:0000317	94.78	gold quality
calcaneal tendon	UBERON:0003701	94.76	gold quality
layer of synovial tissue	UBERON:0007616	94.66	gold quality
mucosa of urinary bladder	UBERON:0001259	94.63	gold quality
corpus epididymis	UBERON:0004359	94.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.41	gold quality
myocardium	UBERON:0002349	94.36	gold quality
urethra	UBERON:0000057	94.23	gold quality
dorsal root ganglion	UBERON:0000044	94.20	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	33.04
E-MTAB-9067	yes	22.99
E-MTAB-9801	yes	3.59
E-MTAB-7052	no	910.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

283 targeting TENT5A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-LET-7A-3P	100.00	74.03	3932

Literature-anchored findings (GeneRIF, showing 12)

• a candidate of human retinal disease on chromosome 6 (PMID:12054608)
• A novel VNTR polymorphism in C6orf37 exists in Chinese population and is not associated with colorectal cancer risk (PMID:16545789)
• Genetic analysis of FAM46A in Spanish families with autosomal recessive retinitis pigmentosa: characterization of novel VNTRs is reported. (PMID:17803723)
• VNTR in the coding region of the FAM46A gene, FAM46A rs11040 SNP and BAG6 rs3117582 SNP are associated with susceptibility to tuberculosis (PMID:24625963)
• Susceptibility to large-joint osteoarthritis (hip and knee) is associated with BAG6 rs3117582 SNP and the VNTR polymorphism in the second exon of the FAM46A gene on chromosome 6. (PMID:25231575)
• Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects (PMID:25884493)
• This exploratory genome-wide association studies confirmed APOE and identified the novel loci: rs72907046 near FAM46A (P = 1 x 10(-9) OR = 3.2 [2.1-4.9]). (PMID:26993346)
• By functional analysis based on a set of 1129 proteins from 494 obese subjects study identified and validated FAM46A as a trans regulator for leptin. (PMID:29234017)
• We conclude that FAM46A mutations are responsible for a severe form of osteogenesis imperfecta (OI) with congenital bowing of the lower limbs and suggest screening this gene in unexplained OI forms. (PMID:29358272)
• FAM46A expression is elevated in glioblastoma and predicts poor prognosis of patients. (PMID:33370626)
• Tent5a modulates muscle fiber formation in adolescent idiopathic scoliosis via maintenance of myogenin expression. (PMID:35137485)
• A Genetic Variant of FAM46A is Associated With the Development of Adolescent Idiopathic Scoliosis in the Chinese Population. (PMID:37141460)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	tent5ab	ENSDARG00000054641
danio_rerio	tent5aa	ENSDARG00000116442
mus_musculus	Tent5a	ENSMUSG00000032265
rattus_norvegicus	Tent5a	ENSRNOG00000010240
drosophila_melanogaster	CG46385	FBGN0286778
caenorhabditis_elegans	tent-5	WBGENE00004131
caenorhabditis_elegans		WBGENE00011957
caenorhabditis_elegans		WBGENE00016596
caenorhabditis_elegans		WBGENE00017841
caenorhabditis_elegans		WBGENE00044662
caenorhabditis_elegans		WBGENE00219325

Paralogs (3): TENT5B (ENSG00000158246), TENT5D (ENSG00000174016), TENT5C (ENSG00000183508)

Protein

Protein identifiers

Terminal nucleotidyltransferase 5A — Q96IP4 (reviewed: Q96IP4)

Alternative names: HBV X-transactivated gene 11 protein, HBV XAg-transactivated protein 11

All UniProt accessions (4): Q96IP4, H0Y5Y3, H0Y6D7, Q5TF85

UniProt curated annotations — full annotation on UniProt →

Function. 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. Polyadenylates mRNA encoding extracellular matrix constituents and other genes crucial for bone mineralization and during osteoblast mineralization, mainly focuses on ER-targeted mRNAs.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed, with preferential expression observed in the retina compared to other ocular tissues. Also expressed in osteoblasts.

Disease relevance. Osteogenesis imperfecta 18 (OI18) [MIM:617952] 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. OI18 is a severe form characterized by congenital bowing of the lower limb, wormian bones, blue sclerae, vertebral collapses and multiple fractures in the first years of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TENT family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IP4-1	1	yes
Q96IP4-2	2

RefSeq proteins (1): NP_060103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012937	TET5	Family

Pfam: PF07984

Enzyme classification (BRENDA):

• EC 2.7.7.19 — polynucleotide adenylyltransferase (BRENDA: 35 organisms, 181 substrates, 125 inhibitors, 114 Km, 53 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.028–2.191	54
RNA (A)15	0.51–24.99	23
CTP	0.1036–4.7	7
(A)N	0.0468–0.711	5
OLIGO(A)14	0.0005–0.037	5
(A)15	0.0009–0.0053	3
GTP	0.055–0.062	2
OLIGO(A)18	0.0468–0.0642	2
OLIGO(A)N	0.01–0.3	2
2-AMINOPURINE RIBOSIDE TRIPHOSPHATE	0.0197	1
DATP	0.06	1
OLIGO(A)12	0.0004	1
OLIGO(A)17C	0.0263	1
OLIGOADENYLATE	0.2	1
POLY(A)N	0.0036	1

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + ATP = RNA(n)-3’-adenine ribonucleotide + diphosphate (RHEA:11332)

UniProt features (41 total): helix 15, strand 11, sequence variant 5, repeat 4, mutagenesis site 2, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8EXF	X-RAY DIFFRACTION	3.22
8EXE	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IP4-F1	80.67	0.62

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
139	does not elongate poly(a) tail; when associated with n-141.
141	does not elongate poly(a) tail; when associated with n-139.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 481 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_OSTEOBLAST_DIFFERENTIATION, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, AP1_Q4_01, CATTTCA_MIR203, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_BONE_MINERALIZATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (5): response to bacterium (GO:0009617), regulation of ossification (GO:0030278), positive regulation of bone mineralization (GO:0030501), positive regulation of osteoblast differentiation (GO:0045669), mRNA stabilization (GO:0048255)

GO Molecular Function (5): RNA binding (GO:0003723), poly(A) RNA polymerase activity (GO:1990817), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to other organism	1
ossification	1
regulation of multicellular organismal process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
nucleic acid binding	1
adenylyltransferase activity	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENT5A	ELOVL4	Q9GZR5	921
TENT5A	BCCIP	Q9P287	602
TENT5A	MTO1	Q9Y2Z2	574
TENT5A	TMEM38B	Q9NVV0	573
TENT5A	ZFYVE9	O95405	520
TENT5A	IFITM5	A6NNB3	511
TENT5A	CRTAP	O75718	507
TENT5A	ATOSB	Q7L5A3	507
TENT5A	TRIP6	Q15654	497
TENT5A	TRAFD1	O14545	497
TENT5A	YWHAZ	P29213	492
TENT5A	MESD	Q14696	479
TENT5A	TMEM248	Q9NWD8	479
TENT5A	SEC24D	O94855	477
TENT5A	FKBP10	Q96AY3	476

IntAct

20 interactions, top by confidence:

A	B	Type	Score
ATXN1	TENT5A	psi-mi:“MI:0915”(physical association)	0.740
TENT5A	SH2D2A	psi-mi:“MI:0915”(physical association)	0.570
TENT5A	SYK	psi-mi:“MI:0915”(physical association)	0.570
SYK	TENT5A	psi-mi:“MI:0915”(physical association)	0.570
SH2D2A	TENT5A	psi-mi:“MI:0915”(physical association)	0.570
TNS2	TENT5A	psi-mi:“MI:0915”(physical association)	0.370
TENT5A	RIN3	psi-mi:“MI:0915”(physical association)	0.370
TENT5A	CD93	psi-mi:“MI:0915”(physical association)	0.370
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TENT5A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
TENT5A	ATXN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (107): FAM46A (Two-hybrid), FAM46A (Two-hybrid), FAM46A (Two-hybrid), FAM46A (Two-hybrid), SH2D2A (Affinity Capture-Luminescence), SYK (Affinity Capture-Luminescence), ATP5I (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), GGCX (Affinity Capture-MS), JAK1 (Affinity Capture-MS), NFX1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), CBX4 (Affinity Capture-MS), TRIP12 (Affinity Capture-MS), ZNF273 (Affinity Capture-MS)

ESM2 similar proteins: A2VE39, A4IID4, A4QP78, A9X1A0, B0BNK8, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, D2HRF1, D3Z5S8, F7E7M3, F8VPU6, O00763, O02019, O02810, O08561, O35099, P31266, Q06330, Q08BW6, Q29RH2, Q2M146, Q3SZ41, Q4R8X4, Q5R981, Q5RFK6, Q5RHQ8, Q5SSF7, Q5U4W6, Q5VWP2, Q5XIV0, Q5ZJT0, Q5ZL95, Q6GN16, Q6PCM2, Q7Z5Y7, Q7ZUP1, Q8BKC8

Diamond homologs: B0BNK8, D3Z5S8, F7E7M3, Q29RH2, Q4R8X4, Q5SSF7, Q5VWP2, Q5XIV0, Q5ZL95, Q7ZUP1, Q8C152, Q8NEK8, Q96A09, Q96IP4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	84
Likely benign	81
Benign	15

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
523121	NM_017633.3(TENT5A):c.612_613dup (p.Ser205fs)	Pathogenic
523122	NM_017633.3(TENT5A):c.380A>G (p.His127Arg)	Pathogenic
523123	NM_017633.3(TENT5A):c.692A>G (p.Asp231Gly)	Pathogenic
691346	NM_017633.3(TENT5A):c.65C>G (p.Pro22Arg)	Likely pathogenic

SpliceAI

664 predictions. Top by Δscore:

Variant	Effect	Δscore
6:81751584:TGTTA:T	donor_loss	1.0000
6:81751585:GTTAC:G	donor_loss	1.0000
6:81751586:TTACC:T	donor_loss	1.0000
6:81751587:TACC:T	donor_loss	1.0000
6:81751589:C:CT	donor_loss	1.0000
6:81750469:TTCC:T	acceptor_loss	0.9900
6:81750470:TCC:T	acceptor_loss	0.9900
6:81750471:CCT:C	acceptor_loss	0.9900
6:81750472:C:T	acceptor_loss	0.9900
6:81750473:T:A	acceptor_loss	0.9900
6:81752174:CAGTC:C	acceptor_gain	0.9900
6:81752177:TCC:T	acceptor_loss	0.9900
6:81752179:C:A	acceptor_loss	0.9900
6:81752179:C:CC	acceptor_gain	0.9900
6:81752180:T:C	acceptor_loss	0.9900
6:81752495:T:TA	donor_gain	0.9900
6:81752573:C:CA	donor_gain	0.9900
6:81752589:T:TA	donor_gain	0.9900
6:81750164:T:TA	donor_gain	0.9800
6:81751588:A:AC	donor_gain	0.9800
6:81751589:C:CC	donor_gain	0.9800
6:81752176:GTC:G	acceptor_gain	0.9800
6:81752177:TC:T	acceptor_gain	0.9800
6:81752178:CC:C	acceptor_gain	0.9800
6:81752384:T:C	donor_gain	0.9800
6:81752600:TGC:T	donor_gain	0.9800
6:81752602:C:CT	donor_gain	0.9800
6:81752603:C:CT	donor_gain	0.9800
6:81750468:CTTC:C	acceptor_gain	0.9700
6:81752395:T:C	donor_gain	0.9700

AlphaMissense

2930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:81749885:A:G	L380P	1.000
6:81749902:T:A	R374S	1.000
6:81749902:T:G	R374S	1.000
6:81749906:T:A	E373V	1.000
6:81749914:C:A	M370I	1.000
6:81749914:C:G	M370I	1.000
6:81749914:C:T	M370I	1.000
6:81749915:A:G	M370T	1.000
6:81749918:A:G	L369P	1.000
6:81749918:A:T	L369Q	1.000
6:81749920:G:C	C368W	1.000
6:81749921:C:G	C368S	1.000
6:81749921:C:T	C368Y	1.000
6:81749922:A:G	C368R	1.000
6:81749922:A:T	C368S	1.000
6:81749927:G:A	T366I	1.000
6:81749951:A:G	L358P	1.000
6:81749951:A:T	L358H	1.000
6:81749960:A:G	L355P	1.000
6:81749960:A:T	L355H	1.000
6:81749995:G:C	H343Q	1.000
6:81749995:G:T	H343Q	1.000
6:81749997:G:C	H343D	1.000
6:81750017:A:G	L336P	1.000
6:81750046:G:C	F326L	1.000
6:81750046:G:T	F326L	1.000
6:81750047:A:G	F326S	1.000
6:81750048:A:G	F326L	1.000
6:81750048:A:T	F326I	1.000
6:81750050:T:A	D325V	1.000

dbSNP variants (sampled 300 via entrez): RS1000090701 (6:81746497 G>C), RS1001210075 (6:81752299 G>A,T), RS1001353149 (6:81745701 A>G,T), RS1001769585 (6:81753797 G>A,C), RS1001829436 (6:81752490 A>G), RS1001933510 (6:81748598 T>C), RS1002764340 (6:81752857 G>A,T), RS1003769840 (6:81751310 A>T), RS1003867946 (6:81747331 GAA>G), RS1003880987 (6:81748862 G>A), RS1004315259 (6:81748622 C>T), RS1004753037 (6:81752884 G>A,C), RS1004886519 (6:81747053 G>A), RS1004917730 (6:81746782 C>T), RS1005118052 (6:81752954 ATC>A)

Disease associations

OMIM: gene MIM:611357 | disease phenotypes: MIM:617952

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta, type 18	Strong	Autosomal recessive
osteogenesis imperfecta	Supportive	Autosomal dominant

Mondo (4): osteogenesis imperfecta, type 18 (MONDO:0044329), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), osteogenesis imperfecta (MONDO:0019019)

Orphanet (0):

HPO phenotypes

20 total (22 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000431	Wide nasal bridge
HP:0000527	Long eyelashes
HP:0000592	Blue sclerae
HP:0000750	Delayed speech and language development
HP:0000883	Thin ribs
HP:0001270	Motor delay
HP:0001382	Joint hypermobility
HP:0001537	Umbilical hernia
HP:0002645	Wormian bones
HP:0002753	Thin bony cortex
HP:0002757	Recurrent fractures
HP:0002953	Vertebral compression fracture
HP:0002980	Femoral bowing
HP:0004586	Biconcave vertebral bodies
HP:0006487	Bowing of the long bones
HP:0040160	Generalized osteoporosis
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000817_149	Height	2.000000e-13
GCST001683_4	Breast cancer	3.000000e-07
GCST001806_7	Corneal structure	1.000000e-12
GCST001956_77	Height	1.000000e-10
GCST002143_2	Blood pressure	6.000000e-07
GCST002647_56	Height	3.000000e-27
GCST002804_3	Antibody level in response to infection	2.000000e-07
GCST003452_18	Posterior cortical atrophy and Alzheimer’s disease	1.000000e-09
GCST003771_12	Loneliness	4.000000e-06
GCST003772_9	Loneliness (linear analysis)	8.000000e-06
GCST003979_6	Excessive daytime sleepiness	2.000000e-07
GCST004608_30	Granulocyte percentage of myeloid white cells	4.000000e-26
GCST004609_72	Monocyte percentage of white cells	2.000000e-24
GCST004618_67	White blood cell count (basophil)	8.000000e-09
GCST004625_87	Monocyte count	2.000000e-13
GCST004633_62	Neutrophil percentage of white cells	3.000000e-09
GCST005170_29	Intraocular pressure	9.000000e-18
GCST005667_10	Central corneal thickness	6.000000e-15
GCST005667_23	Central corneal thickness	3.000000e-06
GCST006628_51	Systolic blood pressure	1.000000e-11
GCST006979_297	Heel bone mineral density	3.000000e-10
GCST006979_298	Heel bone mineral density	3.000000e-09
GCST008163_378	Height	2.000000e-06
GCST008163_387	Height	2.000000e-06
GCST008163_602	Height	8.000000e-06
GCST008317_11	Central corneal thickness	2.000000e-06
GCST008789_8	Adolescent idiopathic scoliosis	3.000000e-09
GCST008839_205	Height	6.000000e-27
GCST008839_252	Height	2.000000e-09
GCST009414_11	Central corneal thickness	3.000000e-08

EFO canonical traits (25, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0006336	diastolic blood pressure
EFO:0007034	seropositivity measurement
EFO:0007039	human herpesvirus 8 seropositivity
EFO:0007865	loneliness measurement
EFO:0007875	excessive daytime sleepiness measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0004747	protein measurement
EFO:0010731	response to low calorie diet
EFO:0010576	liver fibrosis measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	7
Benzo(a)pyrene	increases methylation, increases expression	6
trichostatin A	affects cotreatment, decreases expression, affects expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Cisplatin	decreases expression, increases expression, affects response to substance	3
Tretinoin	decreases expression, increases expression	3
Aflatoxin B1	decreases methylation, increases expression, affects expression	3
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression, affects methylation	2
Formaldehyde	increases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Zinc	increases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
Particulate Matter	affects expression, affects methylation, increases abundance, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
zinc chromate	increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
chloropicrin	increases expression	1
entinostat	decreases 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

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1HY	Abcam A-549 TENT5A KO 2	Cancer cell line	Male
CVCL_B2QG	Abcam A-549 TENT5A KO 1	Cancer cell line	Male
CVCL_D8C5	Ubigene A-549 TENT5A KO	Cancer cell line	Male

Clinical trials (associated diseases)

136 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
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
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
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
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)
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
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