TCOF1

treacle ribosome biogenesis factor 1, the group of Ribosomal biogenesis factors

Basic information

Region (hg38): 5:150357629-150400308

Links

ENSG00000070814

∙ NCBI:6949 ∙ OMIM:606847 ∙ HGNC:11654 ∙ Uniprot:Q13428 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Treacher Collins syndrome 1 (Definitive), mode of inheritance: AD
Treacher Collins syndrome 1 (Strong), mode of inheritance: AD
Treacher-Collins syndrome (Supportive), mode of inheritance: AD
Treacher-Collins syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Treacher Collins syndrome 1	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Ophthalmologic	8563749; 8875242; 8894686; 9042910; 9096354; 11013442; 14598341; 15150774; 15214011; 15340364; 19050407; 19067896; 19572402; 20301704; 22317976; 22729243; 25790162

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCOF1 gene.

Treacher_Collins_syndrome_1 (654 variants)
not_provided (340 variants)
Inborn_genetic_diseases (209 variants)
TCOF1-related_disorder (94 variants)
not_specified (37 variants)
Treacher_Collins_syndrome (9 variants)
Hearing_impairment (2 variants)
Treacher_Collins_Syndrome,_Dominant (2 variants)
Cleft_lip/palate (1 variants)
Ehlers-Danlos_syndrome (1 variants)
Microcephaly (1 variants)
Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCOF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001371623.1. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	136 clinvar	21 clinvar	162
missense	3 clinvar	9 clinvar	351 clinvar	105 clinvar	12 clinvar	480
nonsense	31 clinvar	11 clinvar				42
start loss	3					3
frameshift	100 clinvar	39 clinvar	2 clinvar			141
splice donor/acceptor (+/-2bp)	11 clinvar	6 clinvar	4 clinvar			21
Total	148	65	362	241	33

Highest pathogenic variant AF is 0.00000657082

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCOF1	protein_coding	protein_coding	ENST00000504761	26	42670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.954	0.0459	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.339	773	800	0.966	0.0000438	9467
Missense in Polyphen		196	226.22	0.86643		3025
Synonymous	-1.24	365	336	1.09	0.0000213	3123
Loss of Function	5.92	12	62.6	0.192	0.00000302	843

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000215	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000169	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000982	0.0000980
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.;
Disease: DISEASE: Treacher Collins syndrome 1 (TCS1) [MIM:154500]: A form of Treacher Collins syndrome, a disorder of craniofacial development. Treacher Collins syndrome is characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. {ECO:0000269|PubMed:9042910}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human) (Consensus)

Recessive Scores

pRec: 0.195

Intolerance Scores

loftool: 0.456
rvis_EVS: 0.47
rvis_percentile_EVS: 78.7

Haploinsufficiency Scores

pHI: 0.117
hipred: Y
hipred_score: 0.658
ghis: 0.500

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.575

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tcof1
Phenotype: vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype; respiratory system 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process: skeletal system development;regulation of translation;neural crest formation;neural crest cell development
Cellular component: fibrillar center;nucleus;nucleolus;cytosol
Molecular function: RNA polymerase I core binding;RNA binding;transporter activity;protein binding;protein heterodimerization activity;scaffold protein binding