TCOF1

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

Basic information

Region (hg38): 5:150357628-150400308

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 (466 variants)
• not provided (299 variants)
• Inborn genetic diseases (58 variants)
• not specified (40 variants)
• TCOF1-related condition (11 variants)
• Treacher Collins syndrome (6 variants)
• Treacher Collins Syndrome, Dominant (4 variants)
• Hearing impairment (2 variants)
• Treacher Collins syndrome;Crouzon syndrome (1 variants)
• Microcephaly (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	82	26	112
missense	1	2	185	53	19	260
nonsense	23	9				32
start loss	1					1
frameshift	76	23				99
inframe indel			18	1	3	22
splice donor/acceptor (+/-2bp)	7	2	4			13
splice region	1	1	10	10	4	26
non coding			4	57	32	93
Total	108	36	215	193	80

Highest pathogenic variant AF is 0.0000131

Variants in TCOF1

This is a list of pathogenic ClinVar variants found in the TCOF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-150357658-T-G			Benign (Oct 16, 2018)
5-150357688-G-A		Treacher Collins syndrome 1	Likely benign (-)
5-150357728-C-T		Treacher Collins Syndrome, Dominant	Uncertain significance (Jun 14, 2016)
5-150357747-A-T		Treacher Collins syndrome 1	Pathogenic (Dec 12, 2022)
5-150357771-G-T		Treacher Collins syndrome 1	Pathogenic (Jul 16, 2019)
5-150357779-TC-T			Likely pathogenic (May 02, 2023)
5-150357787-T-G		Treacher Collins syndrome 1	Uncertain significance (Feb 23, 2023)
5-150357788-C-G		Treacher Collins syndrome 1	Uncertain significance (Oct 23, 2019)
5-150357796-A-G		Treacher Collins syndrome 1	Pathogenic/Likely pathogenic (Sep 27, 2018)
5-150357799-T-C			Uncertain significance (Oct 05, 2022)
5-150357822-G-A			Uncertain significance (Dec 24, 2019)
5-150357824-G-A			Likely benign (May 01, 2022)
5-150357831-G-C		Treacher Collins syndrome 1	Uncertain significance (Feb 02, 2022)
5-150357835-T-G		Treacher Collins syndrome 1	Likely pathogenic (Oct 04, 2019)
5-150357848-CG-TAAGCTGCACCAC		TCOF1-related disorder	Likely pathogenic (Feb 25, 2023)
5-150357854-G-A		Treacher Collins syndrome 1	Uncertain significance (Sep 20, 2023)
5-150357855-G-A		TCOF1-related disorder	Likely pathogenic (Feb 16, 2024)
5-150357865-G-T		Treacher Collins syndrome 1	Likely benign (Apr 20, 2022)
5-150357905-AGCGGCCC-A		Treacher Collins syndrome 1	Likely benign (-)
5-150361128-T-C		Treacher Collins syndrome 1	Likely benign (-)
5-150361143-T-C		Treacher Collins syndrome 1	Benign (Jan 15, 2024)
5-150361148-C-G		Treacher Collins syndrome 1	Uncertain significance (Oct 05, 2023)
5-150361152-GC-G		Treacher Collins syndrome 1	Likely pathogenic (Oct 23, 2021)
5-150361154-AG-A		Treacher Collins syndrome 1	Pathogenic (Dec 23, 2020)
5-150361164-C-A		Treacher Collins syndrome 1	Uncertain significance (Aug 26, 2021)

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