TICRR

TOPBP1 interacting checkpoint and replication regulator

Basic information

Region (hg38): 15:89575468-89631056

Previous symbols: [ "C15orf42" ]

Links

ENSG00000140534 ∙ NCBI:90381 ∙ OMIM:613298 ∙ HGNC:28704 ∙ Uniprot:Q7Z2Z1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Acrocallosal syndrome (276 variants)
• Inborn genetic diseases (119 variants)
• not provided (84 variants)
• not specified (20 variants)
• Hydrolethalus syndrome 2 (6 variants)
• Multiple epiphyseal dysplasia, Al-Gazali type (4 variants)
• Intellectual disability (1 variants)
• Familial aplasia of the vermis (1 variants)
• Acrocallosal syndrome;Hydrolethalus syndrome 2;Multiple epiphyseal dysplasia, Al-Gazali type (1 variants)
• Scoliosis, isolated, susceptibility to, 1 (1 variants)
• Acrocallosal syndrome;Multiple epiphyseal dysplasia, Al-Gazali type;Hydrolethalus syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TICRR 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				3	2	5
missense			85	7	3	95
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding	8	5	152	112	16	293
Total	8	5	237	122	21

Highest pathogenic variant AF is 0.0000197

Variants in TICRR

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

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

Position	Type	Phenotype	Significance	ClinVar
15-89575638-G-C		not specified	Uncertain significance (Aug 04, 2021)
15-89575702-G-A		not specified	Uncertain significance (Jun 09, 2022)
15-89575830-G-A		not specified	Uncertain significance (Jul 14, 2022)
15-89575861-G-A		not specified	Uncertain significance (Jul 10, 2023)
15-89575875-G-A		not specified	Uncertain significance (Mar 16, 2022)
15-89575981-G-A		not specified	Uncertain significance (Oct 03, 2023)
15-89576014-C-A		not specified	Uncertain significance (Jan 24, 2024)
15-89576028-G-C		not specified	Uncertain significance (Mar 07, 2024)
15-89576139-C-T		not specified	Uncertain significance (Apr 25, 2022)
15-89576217-G-A		not specified	Uncertain significance (Feb 26, 2024)
15-89576224-C-T		not specified	Uncertain significance (Apr 27, 2022)
15-89582692-G-A		not specified	Uncertain significance (Apr 28, 2022)
15-89582740-C-G		not specified	Uncertain significance (Sep 20, 2023)
15-89582839-C-G		not specified	Uncertain significance (Nov 01, 2022)
15-89582852-C-A		not specified	Uncertain significance (Mar 16, 2022)
15-89582863-A-G		not specified	Uncertain significance (Nov 09, 2022)
15-89582893-T-G		not specified	Uncertain significance (Feb 12, 2024)
15-89582925-G-A			Likely benign (Jan 01, 2023)
15-89582933-G-A			Benign (Mar 29, 2018)
15-89582935-A-G		not specified	Uncertain significance (Mar 07, 2024)
15-89584309-T-G		not specified	Uncertain significance (Feb 06, 2024)
15-89584315-G-A		not specified	Uncertain significance (May 03, 2023)
15-89584319-C-A		not specified	Uncertain significance (Oct 12, 2021)
15-89584398-G-C		not specified	Uncertain significance (Oct 29, 2021)
15-89584466-C-T		not specified	Uncertain significance (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TICRR	protein_coding	protein_coding	ENST00000268138	22	55575

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.21e-14	1.00	125598	0	150	125748	0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.45	1150	1.02e+3	1.13	0.0000529	12306
Missense in Polyphen		257	262.69	0.97835		3331
Synonymous	-1.59	445	404	1.10	0.0000219	3938
Loss of Function	4.51	36	79.4	0.454	0.00000445	941

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00118
Ashkenazi Jewish	0.00	0.00
East Asian	0.000443	0.000435
Finnish	0.00160	0.00129
European (Non-Finnish)	0.000568	0.000545
Middle Eastern	0.000443	0.000435
South Asian	0.000372	0.000359
Other	0.00136	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre- initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}.

Intolerance Scores

• rvis_EVS: 1.27
• rvis_percentile_EVS: 93.64

Haploinsufficiency Scores

• pHI: 0.662
• hipred: N
• hipred_score: 0.233
• ghis: 0.568

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ticrr
• 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)

Zebrafish Information Network

• Gene name: ticrr
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved dorsal

Gene ontology

• Biological process: formation of translation preinitiation complex;DNA replication;DNA repair;mitotic cell cycle checkpoint;response to ionizing radiation;regulation of DNA-dependent DNA replication initiation;mitotic DNA replication checkpoint
• Cellular component: nucleus;nucleoplasm
• Molecular function: chromatin binding;protein binding