UBTF

upstream binding transcription factor, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 17:44205033-44221626

Links

ENSG00000108312 ∙ NCBI:7343 ∙ OMIM:600673 ∙ HGNC:12511 ∙ Uniprot:P17480 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Strong), mode of inheritance: AD
• childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Supportive), mode of inheritance: AD
• childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Definitive), mode of inheritance: AD
• childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Definitive), mode of inheritance: AD
• childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, childhood-onset, with brain atrophy	AD	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	Neurologic	28777933

ClinVar

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

• not_provided (61 variants)
• Inborn_genetic_diseases (37 variants)
• Childhood-onset_motor_and_cognitive_regression_syndrome_with_extrapyramidal_movement_disorder (18 variants)
• not_specified (17 variants)
• UBTF-related_disorder (14 variants)
• Obesity (1 variants)
• Neurodevelopmental_disorder (1 variants)
• Rare_syndromic_intellectual_disability (1 variants)
• Infantile_or_childhood_onset_neurodegenerative_disease,_global_developmental_delay,_and_intellectual_disability (1 variants)
• UBTF_E210K_Neuroregression_Syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBTF gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014233.4. 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			1	7	5	13
missense		2	81	4		87
nonsense		3	3			6
start loss						0
frameshift			5			5
splice donor/acceptor (+/-2bp)		1	3			4
Total	0	6	93	11	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBTF	protein_coding	protein_coding	ENST00000302904	20	16594

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.41e-8	125659	0	1	125660	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.75	172	458	0.376	0.0000277	5111
Missense in Polyphen		26	176.52	0.14729		1928
Synonymous	-1.42	210	185	1.13	0.0000122	1302
Loss of Function	6.55	0	49.9	0.00	0.00000258	571

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. {ECO:0000269|PubMed:28777933, ECO:0000269|PubMed:7982918}.
• Disease: DISEASE: Neurodegeneration, childhood-onset, with brain atrophy (CONDBA) [MIM:617672]: An autosomal dominant neurodegenerative disease with onset in childhood, characterized by progressive cortical atrophy, developmental delay, developmental regression, loss of motor skills and ambulation, absence of language, and intellectual disability. {ECO:0000269|PubMed:28777933}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ectoderm Differentiation;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Epigenetic regulation of gene expression;Gene expression (Transcription);RNA Polymerase I Promoter Clearance;RNA Polymerase I Promoter Opening;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;RNA Polymerase I Chain Elongation;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.00537
• rvis_EVS: -1.16
• rvis_percentile_EVS: 6.17

Haploinsufficiency Scores

• pHI: 0.820
• hipred: Y
• hipred_score: 0.825
• ghis: 0.704

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.878

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ubtf
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype

Gene ontology

• Biological process: RNA polymerase I preinitiation complex assembly;regulation of transcription by RNA polymerase I;regulation of transcription by RNA polymerase II;transcription by RNA polymerase I;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;positive regulation of transcription by RNA polymerase I;regulation of glucose mediated signaling pathway
• Cellular component: fibrillar center;nucleus;nucleoplasm;nucleolus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase I CORE element sequence-specific DNA binding;RNA polymerase I upstream control element sequence-specific DNA binding;chromatin binding;RNA binding;protein binding;scaffold protein binding