TINF2

TERF1 interacting nuclear factor 2, the group of Shelterin complex

Basic information

Region (hg38): 14:24238286-24242663

Links

ENSG00000092330 ∙ NCBI:26277 ∙ OMIM:604319 ∙ HGNC:11824 ∙ Uniprot:Q9BSI4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Revesz syndrome (Definitive), mode of inheritance: AD
• Revesz syndrome (Strong), mode of inheritance: AD
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• Revesz syndrome (Supportive), mode of inheritance: AD
• Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
• dyskeratosis congenita, autosomal dominant 3 (Strong), mode of inheritance: AD
• pulmonary fibrosis (Moderate), mode of inheritance: AD
• thyroid gland papillary carcinoma (Limited), mode of inheritance: AD
• dyskeratosis congenita, autosomal dominant 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, autosomal dominant 3; Revesz syndrome	AD	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary	Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal; Awareness of infectious risk may allow prompt diagnosis and treatment of infections	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Pulmonary	1404302; 18252230; 18669893; 20301779; 21199492

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TINF2 gene.

• Dyskeratosis congenita (6 variants)
• Dyskeratosis congenita, autosomal dominant 3 (4 variants)
• Dyskeratosis congenita, autosomal dominant 1 (4 variants)
• not provided (3 variants)
• Revesz syndrome (1 variants)
• Dyskeratosis congenita, autosomal dominant 3;Revesz syndrome;Dyskeratosis congenita, autosomal dominant 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TINF2 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			2	88	1	91
missense	4	6	205	6	2	223
nonsense	1	2	4			7
start loss						0
frameshift	2	1	19			22
inframe indel			4			4
splice donor/acceptor (+/-2bp)			1			1
splice region			5	5	1	11
non coding			22	50	10	82
Total	7	9	257	144	13

Variants in TINF2

This is a list of pathogenic ClinVar variants found in the TINF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-24238360-C-T			Uncertain significance (-)
14-24238396-C-T		not specified	Uncertain significance (Jun 18, 2021)
14-24238402-A-C		not specified	Uncertain significance (May 18, 2023)
14-24238600-G-A		not specified	Uncertain significance (Mar 19, 2024)
14-24238635-G-C		not specified	Uncertain significance (Apr 22, 2024)
14-24238704-A-G		not specified	Uncertain significance (Dec 21, 2023)
14-24238720-G-A		not specified	Uncertain significance (Jan 17, 2023)
14-24238735-G-A		not specified	Uncertain significance (Dec 03, 2021)
14-24239706-A-G		Dyskeratosis congenita, autosomal dominant 3 • Revesz syndrome	Benign (Jan 13, 2018)
14-24239744-C-T		Dyskeratosis congenita, autosomal dominant 3 • Revesz syndrome	Uncertain significance (Jan 13, 2018)
14-24239764-G-A		Revesz syndrome • Dyskeratosis congenita, autosomal dominant 3	Benign/Likely benign (Jan 12, 2018)
14-24239800-C-T		TINF2-related disorder	Likely benign (May 02, 2019)
14-24239804-G-A		Dyskeratosis congenita	Uncertain significance (Oct 05, 2022)
14-24239810-G-A		Dyskeratosis congenita	Uncertain significance (Jun 17, 2022)
14-24239813-CTG-C		Revesz syndrome	Uncertain significance (-)
14-24239816-T-A		Dyskeratosis congenita • TINF2-related disorder	Uncertain significance (Nov 01, 2018)
14-24239820-T-C		Dyskeratosis congenita	Uncertain significance (Nov 24, 2021)
14-24239821-A-G		Dyskeratosis congenita	Likely benign (Feb 13, 2020)
14-24239822-C-T		Dyskeratosis congenita	Uncertain significance (Oct 28, 2019)
14-24239824-G-A		Dyskeratosis congenita	Likely benign (Oct 25, 2023)
14-24239840-G-A		Dyskeratosis congenita	Uncertain significance (Aug 28, 2022)
14-24239841-G-C		Dyskeratosis congenita	Uncertain significance (Nov 12, 2023)
14-24239844-T-C		Dyskeratosis congenita	Uncertain significance (Jul 19, 2022)
14-24239846-G-A		Dyskeratosis congenita • Revesz syndrome • Dyskeratosis congenita, autosomal dominant 3	Conflicting classifications of pathogenicity (Nov 03, 2023)
14-24239846-G-C		Dyskeratosis congenita	Uncertain significance (Sep 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TINF2	protein_coding	protein_coding	ENST00000267415	9	3032

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00127	0.997	124785	0	10	124795	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.725	203	234	0.867	0.0000117	2870
Missense in Polyphen		12	15.012	0.79936		173
Synonymous	-1.71	117	95.7	1.22	0.00000487	954
Loss of Function	2.76	9	23.4	0.385	0.00000130	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000441
Middle Eastern	0.000167	0.000167
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:16880378}.
• Disease: DISEASE: Dyskeratosis congenita, autosomal dominant, 3 (DKCA3) [MIM:613990]: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:18252230}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyskeratosis congenita, autosomal dominant, 5 (DKCA5) [MIM:268130]: A disease characterized by bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, oral leukoplakia, bilateral exudative retinopathy, cerebellar hypoplasia, and growth retardation. {ECO:0000269|PubMed:18252230}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.146
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.45

Haploinsufficiency Scores

• pHI: 0.114
• hipred: Y
• hipred_score: 0.542
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tinf2
• Phenotype: cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); reproductive system 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; hematopoietic system phenotype

Gene ontology

• Biological process: negative regulation of protein ADP-ribosylation;telomere capping;telomere assembly;negative regulation of telomere maintenance via telomerase;negative regulation of epithelial cell proliferation;protein localization to chromosome, telomeric region;regulation of telomere maintenance via telomere lengthening
• Cellular component: chromosome, telomeric region;nuclear telomere cap complex;nuclear chromosome, telomeric region;nucleoplasm;perinucleolar chromocenter;nuclear matrix;nuclear body;shelterin complex
• Molecular function: DNA binding;protein binding;telomeric DNA binding