TRIP11

Summary

TRIP11 (thyroid hormone receptor interactor 11, HGNC:12305) is a protein-coding gene on chromosome 14q32.12, encoding Thyroid receptor-interacting protein 11 (Q15643). Is a membrane tether required for vesicle tethering to Golgi.

This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.

Source: NCBI Gene 9321 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TRIP11-related skeletal dysplasia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 31
• Clinical variants (ClinVar): 1,068 total — 64 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 105
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_004239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12305
Approved symbol	TRIP11
Name	thyroid hormone receptor interactor 11
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	CEV14, Trip230, GMAP-210, GMAP210
Ensembl gene	ENSG00000100815
Ensembl biotype	protein_coding
OMIM	604505
Entrez	9321

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000267622, ENST00000554357, ENST00000555105, ENST00000555516, ENST00000557017, ENST00000876362, ENST00000876363, ENST00000913145, ENST00000913146, ENST00000913147, ENST00000913148, ENST00000964014, ENST00000964015

RefSeq mRNA: 2 — MANE Select: NM_004239 NM_001321851, NM_004239

CCDS: CCDS9899

Canonical transcript exons

ENST00000267622 — 21 exons

Exon	Start	End
ENSE00001004733	92011755	92011795
ENSE00001004735	92003419	92006448
ENSE00001004736	91999240	91999433
ENSE00001004740	92015696	92015861
ENSE00001004741	91974627	91974743
ENSE00001004745	91999968	92000108
ENSE00001004746	91972717	91972861
ENSE00001004747	91993809	91993912
ENSE00001004748	92007640	92007852
ENSE00001004749	92014215	92014577
ENSE00001004750	91988284	91988383
ENSE00001004751	92010986	92011072
ENSE00001004752	92017682	92017750
ENSE00001004753	91995352	91995515
ENSE00002464317	91965991	91969893
ENSE00002696026	92039547	92040059
ENSE00003475124	92025310	92025420
ENSE00003521998	91976108	91976189
ENSE00003537990	92033192	92033253
ENSE00003622524	92021556	92021831
ENSE00003638353	91975172	91975286

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3846 / max 344.4867, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144576	19.3846	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.46	gold quality
adrenal tissue	UBERON:0018303	91.48	gold quality
buccal mucosa cell	CL:0002336	91.09	gold quality
colonic epithelium	UBERON:0000397	90.66	gold quality
tendon	UBERON:0000043	89.95	gold quality
stromal cell of endometrium	CL:0002255	89.44	gold quality
islet of Langerhans	UBERON:0000006	89.36	gold quality
sural nerve	UBERON:0015488	88.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.37	gold quality
pancreas	UBERON:0001264	86.54	gold quality
body of pancreas	UBERON:0001150	86.43	gold quality
monocyte	CL:0000576	85.49	gold quality
mononuclear cell	CL:0000842	84.85	gold quality
corpus callosum	UBERON:0002336	84.84	gold quality
gastrocnemius	UBERON:0001388	84.78	gold quality
secondary oocyte	CL:0000655	84.77	gold quality
leukocyte	CL:0000738	84.54	gold quality
muscle of leg	UBERON:0001383	84.18	gold quality
tonsil	UBERON:0002372	83.66	gold quality
rectum	UBERON:0001052	83.27	gold quality
stomach	UBERON:0000945	83.05	gold quality
gall bladder	UBERON:0002110	82.97	gold quality
tibia	UBERON:0000979	82.83	gold quality
ventricular zone	UBERON:0003053	82.73	gold quality
adrenal gland	UBERON:0002369	82.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.02	gold quality
body of stomach	UBERON:0001161	81.81	gold quality
left adrenal gland	UBERON:0001234	81.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

230 targeting TRIP11, 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-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 14)

• The overexpression of this protein blocks anterograde and retrograde transport between the endoplasmic reticulum and the Golgi apparatus. (PMID:12383348)
• demonstrate that the thyroid hormone receptor/retinoblastoma-interacting protein 230 (TRIP230) interacts directly with aryl hydrocarbon receptor nuclear translocator(ARNT) and is essential for both hypoxic and TCDD-mediated transcriptional responses (PMID:15485806)
• the attachment of golgin GMAP-210 to lipid membranes (PMID:18451304)
• Localisation of GMAP-210 (TRIP11) to Golgi is the result of the combined action of two domains (N- and C-terminal) that recognize different sub-regions of the Golgi apparatus. (PMID:19715559)
• identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia (PMID:20089971)
• Rb is present in HIF1alpha-ARNT/HIF1beta transcriptional complexes associated with TRIP230 as determined by co-immuno-precipitation, GST-pull-down and ChIP assays (PMID:24919196)
• GMAP-210 has a role for membrane tethering in maintaining Golgi structure and a role for Rab2 binding in linking tethering with downstream docking and fusion events at the Golgi apparatus. (PMID:25473115)
• role for GMAP-210 in several trafficking steps at the ER-Golgi interface (PMID:25717001)
• The authors conclude that the Golgi uses GMAP-210 as a filter to select transport vesicles according to their size and bulk lipid composition. (PMID:27458799)
• Decreased expressions of TRIP11, THRA, and THRB correlated with poor survival of renal cell cancer patients. Expressions of TRIP11 and HIF-1beta correlated with tumor grades. (PMID:29022645)
• A common pathogenic mechanism in GMAP-210- and LBR-related diseases attributable to defective secretory trafficking at the Golgi apparatus. (PMID:30518689)
• Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A. (PMID:31903676)
• Description of four patients with TRIP11 variants expand the clinical spectrum of odontochondroplasia (ODCD) and demonstrate the existence of common variants. (PMID:33746040)
• Biallelic deep intronic variant c.5457+81T>A in TRIP11 causes loss of function and results in achondrogenesis 1A. (PMID:34057271)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trip11	ENSDARG00000078381
mus_musculus	Trip11	ENSMUSG00000021188
rattus_norvegicus	Trip11	ENSRNOG00000005292
drosophila_melanogaster	Gmap	FBGN0027287
caenorhabditis_elegans		WBGENE00013730

Protein

Protein identifiers

Thyroid receptor-interacting protein 11 — Q15643 (reviewed: Q15643)

Alternative names: Clonal evolution-related gene on chromosome 14 protein, Golgi-associated microtubule-binding protein 210, Trip230

All UniProt accessions (4): Q15643, G3V4R7, H0YJ97, H0YJI2

UniProt curated annotations — full annotation on UniProt →

Function. Is a membrane tether required for vesicle tethering to Golgi. Has an essential role in the maintenance of Golgi structure and function. It is required for efficient anterograde and retrograde trafficking in the early secretory pathway, functioning at both the ER-to-Golgi intermediate compartment (ERGIC) and Golgi complex. Binds the ligand binding domain of the thyroid receptor (THRB) in the presence of triiodothyronine and enhances THRB-modulated transcription.

Subunit / interactions. Interacts with the active form of RAB2A. Interacts with IFT20. Binds RB1.

Subcellular location. Golgi apparatus. cis-Golgi network membrane. Cytoplasm. Cytoskeleton. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Tissue specificity. Highly expressed in pancreas, muscle, heart, testis, peripheral blood leukocytes, and in several leukemia cell lines. Detected at intermediate levels in placenta and kidney, and at low levels in brain and lung. Isoform 1 and isoform 2 are expressed in articular chondrocytes.

Disease relevance. A chromosomal aberration involving TRIP11 may be a cause of acute myelogenous leukemia. Translocation t(5;14)(q33;q32) with PDGFRB. The fusion protein may be involved in clonal evolution of leukemia and eosinophilia. Achondrogenesis 1A (ACG1A) [MIM:200600] A form of achondrogenesis type 1, a lethal form of chondrodysplasia characterized by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. The disease is caused by variants affecting the gene represented in this entry. Odontochondrodysplasia 1 (ODCD1) [MIM:184260] An autosomal recessive disorder of skeletal and dental development characterized by mesomelic shortening of tubular bones, ligamentous laxity, scoliosis, and dentinogenesis imperfecta involving both primary and secondary dentition. Radiologic features include trident pelvis, posteriorly flattened vertebrae, and brachydactyly with cone-shaped epiphyses. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Extended rod-like protein with coiled-coil domains. The C-terminus is required for recruitment to the Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15643-1	1	yes
Q15643-2	2

RefSeq proteins (2): NP_001308780, NP_004230* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000237	GRIP_dom	Domain

UniProt features (55 total): sequence variant 25, sequence conflict 12, modified residue 5, region of interest 4, mutagenesis site 2, initiator methionine 1, chain 1, splice variant 1, domain 1, coiled-coil region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15643-F1	66.78	0.00

Functional residue map

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

Catalytic / active sites (1): 1754–1755 (breakpoint for translocation to form trip11-pdgfrb)

Post-translational modifications (5): 2, 464, 1842, 1846, 1891

Mutagenesis-validated functional residues (2):

Position	Phenotype
2–38	abolishes tethering of intra-golgi vesicles.
1113–1423	abolishes interaction with rab2a.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport
R-HSA-6811438	Intra-Golgi traffic
R-HSA-9703465	Signaling by FLT3 fusion proteins

MSigDB gene sets: 440 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_VESICLE_LOCALIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_VESICLE_TARGETING, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, CAGCTG_AP4_Q5

GO Biological Process (13): ventricular septum development (GO:0003281), chondrocyte differentiation involved in endochondral bone morphogenesis (GO:0003413), transcription by RNA polymerase II (GO:0006366), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), cartilage development (GO:0051216), inner ear receptor cell stereocilium organization (GO:0060122), protein transmembrane transport (GO:0071806), Golgi ribbon formation (GO:0090161), obsolete vesicle tethering to Golgi (GO:0099041), obsolete protein glycosylation (GO:0006486), positive regulation of DNA-templated transcription (GO:0045893), bone development (GO:0060348)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), acrosomal membrane (GO:0002080), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), cytoskeleton (GO:0005856), cilium (GO:0005929), transport vesicle (GO:0030133), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
FLT3 signaling in disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
intracellular membrane-bounded organelle	3
DNA-templated transcription	2
skeletal system development	2
animal organ development	2
Golgi apparatus	2
bounding membrane of organelle	2
endomembrane system	2
cellular anatomical structure	2
cardiac ventricle development	1
cardiac septum development	1
chondrocyte differentiation	1
endochondral bone morphogenesis	1
cartilage development involved in endochondral bone morphogenesis	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
connective tissue development	1
neuron projection development	1
inner ear receptor cell development	1
protein transport	1
transmembrane transport	1
Golgi organization	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
GTPase binding	1
binding	1
acrosomal vesicle	1
secretory granule membrane	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoplasmic vesicle	1
endoplasmic reticulum-Golgi intermediate compartment	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2657 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIP11	IFT20	Q8IY31	959
TRIP11	ARF1	P10947	916
TRIP11	SLC26A2	P50443	788
TRIP11	GOLGA5	Q8TBA6	739
TRIP11	GRIP1	Q9Y3R0	739
TRIP11	GOLGA3	Q08378	703
TRIP11	MYO18A	Q92614	701
TRIP11	GORASP1	Q9BQQ3	674
TRIP11	COL2A1	P02458	658
TRIP11	HSPG2	P98160	656
TRIP11	GOLGA2	Q08379	656
TRIP11	RABEP1	Q15276	634
TRIP11	GOLGB1	Q14789	620
TRIP11	GORASP2	Q9H8Y8	604
TRIP11	RAB30	Q15771	589

IntAct

117 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
TRIP11	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.560
ASB7	POLR3A	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
TRIP11	YWHAB	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
ASB7	TRIP11	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
EPHA6	HGS	psi-mi:“MI:0914”(association)	0.420
OR6X1	TRIP11	psi-mi:“MI:0915”(physical association)	0.400
LEKR1	TRIP11	psi-mi:“MI:0915”(physical association)	0.400
	TRIP11	psi-mi:“MI:0915”(physical association)	0.400
TRIP11	SPTAN1	psi-mi:“MI:0915”(physical association)	0.400
TRIP11	RALY	psi-mi:“MI:0915”(physical association)	0.400
S100A9	TRIP11	psi-mi:“MI:0915”(physical association)	0.370
	TRIP11	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (217): TRIP11 (Affinity Capture-MS), TRIP11 (Proximity Label-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Proximity Label-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), TRIP11 (Affinity Capture-MS), ATG16L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z8P9, A6QR54, B4KE73, E9Q7G0, F1R4Y7, O15083, O55156, O60437, O61308, Q11102, Q13439, Q15643, Q3SWS9, Q5DTN8, Q5M9N0, Q5PQ23, Q5RI56, Q5U4E6, Q5VZ66, Q5ZKK5, Q66H89, Q6DFL0, Q6PH08, Q6ZU80, Q7ZW57, Q811U3, Q8BI22, Q8BVL9, Q8CDI6, Q8CDI7, Q8CGB3, Q8HYY4, Q8IUD2, Q8K3M6, Q8WXW3, Q91VW5, Q96AA8, Q96N16

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
RAB2A	“up-regulates activity”	TRIP11	binding
TRIP11	“up-regulates activity”	THR	binding
TRIP11	up-regulates	THR	binding
RB1	down-regulates	TRIP11	binding
TRIP11	up-regulates	THRA	binding
TRIP11	up-regulates	THRB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	47.0×	6e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	41.5×	9e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	41.5×	9e-06
Activation of BH3-only proteins	5	30.6×	3e-05
RHO GTPases activate PKNs	5	19.6×	2e-04
Intrinsic Pathway for Apoptosis	5	18.1×	3e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	9	17.1×	1e-06
Negative regulation of MAPK pathway	5	16.4×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	25.0×	1e-04
protein targeting	5	18.1×	1e-03
cell surface receptor protein tyrosine kinase signaling pathway	7	12.0×	6e-04
protein autophosphorylation	7	10.1×	1e-03
positive regulation of neuron projection development	6	8.1×	8e-03
intracellular protein localization	7	7.2×	7e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	9	7.0×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — BLCA.

Clinical variants and AI predictions

ClinVar

1068 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	64
Likely pathogenic	27
Uncertain significance	476
Likely benign	291
Benign	110

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028711	NM_004239.4(TRIP11):c.2611C>T (p.Arg871Ter)	Pathogenic
1098269	NM_004239.4(TRIP11):c.5457+81T>A	Pathogenic
1251989	NM_004239.4(TRIP11):c.4459_4460del (p.Met1487fs)	Pathogenic
1251991	NM_004239.4(TRIP11):c.763C>T (p.Arg255Ter)	Pathogenic
1338763	NM_004239.4(TRIP11):c.526C>T (p.Arg176Ter)	Pathogenic
1351407	NM_004239.4(TRIP11):c.2123dup (p.Asn708fs)	Pathogenic
1390930	NM_004239.4(TRIP11):c.2123del (p.Asn708fs)	Pathogenic
1415474	NM_004239.4(TRIP11):c.2782C>T (p.Gln928Ter)	Pathogenic
1419547	NM_004239.4(TRIP11):c.774_777del (p.Ser259fs)	Pathogenic
1451176	NM_004239.4(TRIP11):c.1987dup (p.Gln663fs)	Pathogenic
1460090	NM_004239.4(TRIP11):c.922del (p.Met308fs)	Pathogenic
1702497	NM_004239.4(TRIP11):c.1735C>T (p.Gln579Ter)	Pathogenic
1711135	t(13;14)(q12.2;q32.12)	Pathogenic
1727207	NM_004239.4(TRIP11):c.581_582insA (p.Ala195fs)	Pathogenic
1804974	NM_004239.4(TRIP11):c.5269C>T (p.Arg1757Ter)	Pathogenic
1895654	NM_004239.4(TRIP11):c.2448dup (p.Ile817fs)	Pathogenic
1917995	NM_004239.4(TRIP11):c.4508_4511del (p.Met1503fs)	Pathogenic
2017964	NM_004239.4(TRIP11):c.5392C>T (p.Gln1798Ter)	Pathogenic
2096778	NM_004239.4(TRIP11):c.3641del (p.Lys1213_Leu1214insTer)	Pathogenic
2416088	NM_004239.4(TRIP11):c.877dup (p.Thr293fs)	Pathogenic
2430364	NM_004239.4(TRIP11):c.5408T>G (p.Leu1803Ter)	Pathogenic
2635180	NM_004239.4(TRIP11):c.757C>T (p.Arg253Ter)	Pathogenic
2644465	NM_004239.4(TRIP11):c.1942_1943del (p.Glu648fs)	Pathogenic
2702312	NM_004239.4(TRIP11):c.3173del (p.Thr1058fs)	Pathogenic
2766007	NM_004239.4(TRIP11):c.1622dup (p.Arg542fs)	Pathogenic
2768141	NM_004239.4(TRIP11):c.944_948del (p.Ile315fs)	Pathogenic
2768462	NM_004239.4(TRIP11):c.5519C>G (p.Ser1840Ter)	Pathogenic
2791084	NM_004239.4(TRIP11):c.3507del (p.Asp1170fs)	Pathogenic
2814011	NM_004239.4(TRIP11):c.2911dup (p.Thr971fs)	Pathogenic
2833369	NM_004239.4(TRIP11):c.3104_3105insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGAGATTAAACTTCT (p.Leu1035_Asn1036insPhePhePhePhePhePheXaaXaaXaaXaaSerThrArgLeuGlyLeuProLysCysTrpAspTyrArgArgGluProProArgProAlaGluIleLysLeuLeu)	Pathogenic

SpliceAI

3549 predictions. Top by Δscore:

Variant	Effect	Δscore
14:91972711:TTTTA:T	donor_loss	1.0000
14:91972712:TTTA:T	donor_loss	1.0000
14:91972713:TTA:T	donor_loss	1.0000
14:91972714:TA:T	donor_loss	1.0000
14:91972715:A:C	donor_loss	1.0000
14:91972716:C:CA	donor_loss	1.0000
14:91974626:CA:C	donor_gain	1.0000
14:91975093:A:AC	donor_gain	1.0000
14:91975094:C:CC	donor_gain	1.0000
14:91975285:CT:C	acceptor_gain	1.0000
14:91975287:C:CC	acceptor_gain	1.0000
14:91976106:A:AC	donor_gain	1.0000
14:91976107:C:CC	donor_gain	1.0000
14:91976119:T:A	donor_gain	1.0000
14:91976193:T:TC	acceptor_gain	1.0000
14:91976202:A:C	acceptor_gain	1.0000
14:91988280:CTA:C	donor_loss	1.0000
14:91988281:TA:T	donor_loss	1.0000
14:91988282:A:AC	donor_gain	1.0000
14:91988282:ACTT:A	donor_loss	1.0000
14:91988283:C:CT	donor_gain	1.0000
14:91988283:CT:C	donor_gain	1.0000
14:91988283:CTTT:C	donor_gain	1.0000
14:91988283:CTTTG:C	donor_gain	1.0000
14:91988382:TCC:T	acceptor_loss	1.0000
14:91988384:C:CG	acceptor_loss	1.0000
14:91988385:T:G	acceptor_loss	1.0000
14:91993804:CCTA:C	donor_loss	1.0000
14:91993805:CTA:C	donor_loss	1.0000
14:91993806:TAC:T	donor_loss	1.0000

AlphaMissense

13188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:91995381:A:G	L1676P	0.997
14:91972835:A:C	F1867L	0.995
14:91972835:A:T	F1867L	0.995
14:91972837:A:G	F1867L	0.995
14:92003636:A:G	L1447P	0.995
14:92004344:C:G	R1211P	0.993
14:92003649:C:G	A1443P	0.991
14:91972833:A:G	L1868P	0.990
14:91972836:A:G	F1867S	0.989
14:91975269:A:G	L1787P	0.989
14:92004356:A:G	L1207P	0.989
14:92004449:A:G	L1176P	0.989
14:92004167:A:G	L1270P	0.988
14:92004453:C:G	A1175P	0.988
14:92004476:C:G	R1167P	0.988
14:91995369:A:G	L1680P	0.987
14:92015716:A:G	L268P	0.987
14:91972833:A:T	L1868Q	0.985
14:92004239:A:G	L1246P	0.985
14:92004306:A:G	W1224R	0.984
14:92004306:A:T	W1224R	0.984
14:92015728:C:G	R264P	0.984
14:92015857:A:G	L221P	0.984
14:92021614:A:G	L177P	0.984
14:91999369:A:G	L1588P	0.983
14:91995390:A:G	L1673P	0.981
14:92039676:A:G	W4R	0.981
14:92039676:A:T	W4R	0.981
14:91972836:A:C	F1867C	0.979
14:91999378:C:G	R1585P	0.979

dbSNP variants (sampled 300 via entrez): RS1000008066 (14:92028797 C>G), RS1000048864 (14:92009906 G>A), RS1000172636 (14:92032463 T>C), RS1000181119 (14:92006914 T>C), RS1000187551 (14:91990741 T>C), RS1000189547 (14:91979995 G>A), RS1000228725 (14:92018800 A>C), RS1000357779 (14:91965832 T>C), RS1000397128 (14:92038783 C>T), RS1000397443 (14:91982137 A>G), RS1000443126 (14:91996861 A>C), RS1000449318 (14:92020043 T>G), RS1000475059 (14:92012993 G>A), RS1000502914 (14:92033978 T>C), RS1000517835 (14:92001369 T>C)

Disease associations

OMIM: gene MIM:604505 | disease phenotypes: MIM:200600, MIM:184260

GenCC curated gene-disease

Disease	Classification	Inheritance
TRIP11-related skeletal dysplasia	Definitive	Autosomal recessive
achondrogenesis type IA	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TRIP11-related skeletal dysplasia	Definitive	AR

Mondo (6): achondrogenesis type IA (MONDO:0008701), odontochondrodysplasia 1 (MONDO:0100325), connective tissue disorder (MONDO:0003900), myeloid neoplasm (MONDO:0005170), autism spectrum disorder (MONDO:0005258), TRIP11-related skeletal dysplasia (MONDO:1040009)

Orphanet (4): Achondrogenesis (Orphanet:932), Achondrogenesis type 1A (Orphanet:93299), Odontochondrodysplasia (Orphanet:166272), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000090	Nephronophthisis
HP:0000113	Polycystic kidney dysplasia
HP:0000256	Macrocephaly
HP:0000262	Turricephaly
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000684	Delayed eruption of teeth
HP:0000703	Dentinogenesis imperfecta
HP:0000768	Pectus carinatum
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000882	Hypoplastic scapulae
HP:0000894	Short clavicles
HP:0000904	Flaring of rib cage
HP:0000916	Broad clavicles
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000944	Abnormal metaphysis morphology
HP:0001156	Brachydactyly
HP:0001216	Delayed ossification of carpal bones
HP:0001270	Motor delay

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000175_32	Height	1.000000e-10
GCST000176_15	Height	6.000000e-10
GCST000817_169	Height	1.000000e-10
GCST002647_108	Height	5.000000e-20
GCST002702_70	Height	4.000000e-27
GCST004063_112	Waist circumference adjusted for body mass index	3.000000e-08
GCST004063_58	Waist circumference adjusted for body mass index	4.000000e-08
GCST004500_4	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	7.000000e-08
GCST004500_46	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-08
GCST004501_76	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-08
GCST004501_77	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-06
GCST004504_25	Waist circumference adjusted for BMI in non-smokers	8.000000e-06
GCST004562_44	Waist circumference adjusted for body mass index	2.000000e-08
GCST004563_130	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004564_87	Waist circumference adjusted for BMI in active individuals	1.000000e-06
GCST007429_151	Lung function (FVC)	5.000000e-09
GCST007432_153	FEV1	5.000000e-13
GCST008163_114	Height	7.000000e-06
GCST008480_10	Lung function (FEV1)	1.000000e-09
GCST008482_8	Lung function (FVC)	8.000000e-07
GCST008839_171	Height	5.000000e-64
GCST009614_3	LDL cholesterol levels x loop diuretics use interaction	4.000000e-07
GCST009616_4	HDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	3.000000e-07
GCST010002_158	Refractive error	4.000000e-24
GCST010989_65	Body size at age 10	4.000000e-09
GCST012304_1	Major depressive disorder	6.000000e-06
GCST012305_3	Major depressive disorder x sex interaction	2.000000e-06
GCST90000025_546	Appendicular lean mass	5.000000e-14
GCST90020028_1873	Hip circumference adjusted for BMI	1.000000e-13
GCST90020029_278	Waist circumference adjusted for body mass index	2.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
C536015	Achondrogenesis type 1A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
potassium perchlorate	increases expression	1
arsenite	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
corosolic acid	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzene	decreases expression	1
Caffeine	affects phosphorylation	1
Clorgyline	increases expression	1
Diazinon	increases methylation	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Nicotine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression, increases expression	1
Tetrachlorodibenzodioxin	affects response to substance	1
Thiram	increases expression	1
Cyclosporine	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7Z0	HAP1 TRIP11 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

163 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT03608059	PHASE4	COMPLETED	ATG/PTCy in Haplo-PBSCT Randomized Controlled,Multi-center
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00866918	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01366612	PHASE3	TERMINATED	Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation
NCT01371981	PHASE3	COMPLETED	Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT01817075	PHASE3	COMPLETED	Chlorhexidine Gluconate Cleansing in Preventing Central Line Associated Bloodstream Infection and Acquisition of Multi-drug Resistant Organisms in Younger Patients With Cancer or Undergoing Donor Stem Cell Transplant