TRIP4

thyroid hormone receptor interactor 4, the group of Zinc fingers|Activating signal cointegrator 1 complex

Basic information

Region (hg38): 15:64387748-64455303

Links

ENSG00000103671 ∙ NCBI:9325 ∙ OMIM:604501 ∙ HGNC:12310 ∙ Uniprot:Q15650 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinal muscular atrophy with congenital bone fractures 1 (Strong), mode of inheritance: AR
• prenatal-onset spinal muscular atrophy with congenital bone fractures (Strong), mode of inheritance: AR
• spinal muscular atrophy with congenital bone fractures 1 (Strong), mode of inheritance: AR
• spinal muscular atrophy with congenital bone fractures 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinal muscular atrophy with congenital bone fractures 1; Muscular dystrophy, congenital, Davignon-Chauveau type	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	26924529; 27008887

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIP4 gene.

• not_provided (215 variants)
• Inborn_genetic_diseases (76 variants)
• TRIP4-related_disorder (14 variants)
• Spinal_muscular_atrophy_with_congenital_bone_fractures_1 (13 variants)
• Congenital_muscular_dystrophy-respiratory_failure-skin_abnormalities-joint_hyperlaxity_syndrome (6 variants)
• Centronuclear_myopathy (2 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIP4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016213.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				43	4	47
missense	1		120	8		129
nonsense	10	5				15
start loss						0
frameshift	8	3	2			13
splice donor/acceptor (+/-2bp)		3	1			4
Total	19	11	123	51	4

Highest pathogenic variant AF is 0.0000489435

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIP4	protein_coding	protein_coding	ENST00000261884	13	67556

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.99e-7	1.00	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.569	275	303	0.908	0.0000154	3789
Missense in Polyphen		85	105.16	0.80829		1294
Synonymous	-0.373	114	109	1.05	0.00000535	1077
Loss of Function	3.18	17	38.2	0.445	0.00000227	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000879	0.000872
Ashkenazi Jewish	0.00	0.00
East Asian	0.00112	0.00109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.00112	0.00109
South Asian	0.000166	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. Plays a role in thyroid hormone receptor and estrogen receptor transactivation (PubMed:10454579, PubMed:25219498). Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1. Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF- kappa-B (PubMed:12077347). May play a role in the development of neuromuscular junction (PubMed:26924529). May play a role in late myogenic differentiation (By similarity). {ECO:0000250|UniProtKB:Q9QXN3, ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26924529}.
• Disease: DISEASE: Spinal muscular atrophy with congenital bone fractures 1 (SMABF1) [MIM:616866]: An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures. {ECO:0000269|PubMed:26924529}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy, congenital, Davignon-Chauveau type (MDCDC) [MIM:617066]: An autosomal recessive, severe congenital muscular dystrophy characterized by neonatal onset of muscle weakness predominantly involving axial muscles, life-threatening respiratory failure, skin abnormalities and joint hyperlaxity without contractures. Muscle biopsies show multi-minicores, caps and dystrophic lesions. {ECO:0000269|PubMed:27008887}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.214
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.04

Haploinsufficiency Scores

• pHI: 0.447
• hipred: Y
• hipred_score: 0.657
• ghis: 0.576

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trip4

Zebrafish Information Network

• Gene name: trip4
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: regulation of transcription, DNA-templated;intracellular estrogen receptor signaling pathway;regulation of myoblast differentiation;positive regulation of transcription, DNA-templated;toxin transport
• Cellular component: nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;nuclear body;neuromuscular junction;protein-containing complex;activating signal cointegrator 1 complex
• Molecular function: protease binding;transcription coactivator activity;protein binding;zinc ion binding;nuclear receptor binding;protein kinase binding;estrogen receptor binding;histone acetyltransferase binding;ubiquitin-like protein ligase binding