RINT1

RAD50 interactor 1, the group of NRZ tethering complex

Basic information

Region (hg38): 7:105532169-105567677

Links

ENSG00000135249 ∙ NCBI:60561 ∙ OMIM:610089 ∙ HGNC:21876 ∙ Uniprot:Q6NUQ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile liver failure syndrome 2 (Supportive), mode of inheritance: AR
• infantile liver failure syndrome 3 (Limited), mode of inheritance: AR
• breast cancer (Disputed Evidence), mode of inheritance: AD
• infantile liver failure syndrome 3 (Strong), mode of inheritance: AR
• familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
• hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Infantile liver failure syndrome 3	AR	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	Gastrointestinal; Musculoskeletal	31204009
Liver transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RINT1 gene.

• not provided (20 variants)
• RINT1-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RINT1 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			9	317	6	332
missense			723	11	4	738
nonsense	6		13			19
start loss						0
frameshift	14		15			29
inframe indel			10			10
splice donor/acceptor (+/-2bp)	1	12	6			19
splice region			36	28	4	68
non coding			9	64	5	78
Total	21	12	785	392	15

Highest pathogenic variant AF is 0.0000131

Variants in RINT1

This is a list of pathogenic ClinVar variants found in the RINT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-105532312-C-T		not specified	Uncertain significance (Aug 10, 2023)
7-105532314-A-C		not specified	Uncertain significance (May 02, 2023)
7-105532320-T-C		not specified	Uncertain significance (Dec 26, 2022)
7-105532321-A-C		not specified	Likely benign (Oct 08, 2022)
7-105532323-C-T		not specified	Uncertain significance (Dec 18, 2022)
7-105532327-C-T		not specified	Likely benign (Oct 21, 2023)
7-105532328-G-A		not specified	Uncertain significance (Oct 13, 2023)
7-105532330-C-A		not specified	Likely benign (Mar 19, 2022)
7-105532332-A-C		not specified	Uncertain significance (Jun 26, 2022)
7-105532332-A-G		not specified	Uncertain significance (Mar 19, 2024)
7-105532334-A-T		not specified	Uncertain significance (Feb 11, 2021)
7-105532336-C-T		not specified	Likely benign (Aug 31, 2022)
7-105532337-G-A		not specified	Uncertain significance (Dec 23, 2022)
7-105532339-C-A		not specified	Likely benign (Jun 17, 2023)
7-105532339-C-T		not specified	Likely benign (Jan 22, 2020)
7-105532341-C-T		not specified	Uncertain significance (Dec 03, 2022)
7-105532342-C-G		not specified	Likely benign (Sep 03, 2022)
7-105532344-C-A		Infantile liver failure syndrome 3 • not specified	Conflicting classifications of pathogenicity (Mar 29, 2024)
7-105532344-C-T		not specified	Uncertain significance (Jan 26, 2024)
7-105532348-T-C		not specified	Likely benign (May 30, 2022)
7-105532352-G-T		not specified	Uncertain significance (Sep 28, 2022)
7-105532353-C-T		not specified	Uncertain significance (Aug 17, 2023)
7-105532354-C-A		not specified	Likely benign (Jan 12, 2023)
7-105532356-C-T		not specified	Conflicting classifications of pathogenicity (Nov 17, 2023)
7-105532357-G-A		not specified	Uncertain significance (Jun 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RINT1	protein_coding	protein_coding	ENST00000257700	15	35593

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.29e-13	0.986	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.825	363	410	0.885	0.0000204	5203
Missense in Polyphen		81	110.69	0.73174		1499
Synonymous	-0.485	158	150	1.05	0.00000786	1479
Loss of Function	2.49	27	45.1	0.599	0.00000250	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000776	0.000760
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000514	0.000510
Middle Eastern	0.000544	0.000544
South Asian	0.000330	0.000327
Other	0.000511	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. May play a role in cell cycle checkpoint control (PubMed:11096100). Essential for telomere length control (PubMed:16600870). {ECO:0000269|PubMed:11096100, ECO:0000269|PubMed:16600870, ECO:0000305}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.836
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.15

Haploinsufficiency Scores

• pHI: 0.217
• hipred: Y
• hipred_score: 0.637
• ghis: 0.590

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rint1
• Phenotype: embryo phenotype; 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); neoplasm; 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;Golgi organization;cell cycle;protein transport;regulation of ER to Golgi vesicle-mediated transport;regulation of signal transduction involved in mitotic G2 DNA damage checkpoint
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;Dsl1/NZR complex
• Molecular function: protein binding