TCIRG1

T cell immune regulator 1, ATPase H+ transporting V0 subunit a3, the group of V-type ATPase subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:68039024-68050895

Links

ENSG00000110719 ∙ NCBI:10312 ∙ OMIM:604592 ∙ HGNC:11647 ∙ Uniprot:Q13488 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive osteopetrosis (Definitive), mode of inheritance: AR
• autosomal recessive osteopetrosis 1 (Strong), mode of inheritance: AR
• autosomal dominant severe congenital neutropenia (Supportive), mode of inheritance: AD
• dysosteosclerosis (Supportive), mode of inheritance: AR
• autosomal recessive osteopetrosis (Supportive), mode of inheritance: AR
• autosomal recessive osteopetrosis 6 (Supportive), mode of inheritance: AR
• autosomal recessive osteopetrosis 1 (Strong), mode of inheritance: AR
• autosomal recessive osteopetrosis 1 (Definitive), mode of inheritance: AR
• dysosteosclerosis (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteopetrosis, autosomal recessive 1	AR	Hematologic; Musculoskeletal	Although the disorder may be frequently recognizable, medical treatments (eg, calcitriol, interferon gamma-1b) as well as surgical interventions may be beneficial; Early and aggressive treatment of infectious and hematologic manifestations, as well as neonatal hypocalcemia, which can result in tetanic seizures, may be beneficial; Awareness of multi-organ system complications may allow surveillance and prompt interventions; BMT/HSCT has been described	Audiologic/Otolaryngologic; Dental; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	13532685; 4170880; 6986555; 6546410; 2877234; 1320672; 8291528; 7996361; 7753137; 10888887; 10942435; 12566520; 20870624; 20424301; 21042819; 23329773; 23412864
Milder forms of disease, possibly due to heterozygous variants have been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCIRG1 gene.

• not provided (1064 variants)
• Autosomal recessive osteopetrosis 1 (359 variants)
• Inborn genetic diseases (53 variants)
• not specified (11 variants)
• Osteopetrosis (10 variants)
• TCIRG1-related condition (9 variants)
• Increased bone mineral density (3 variants)
• Neutropenia, severe congenital, 1, autosomal dominant (2 variants)
• Congenital neutropenia (1 variants)
• Abnormality of the skeletal system (1 variants)
• Chorea-acanthocytosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCIRG1 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			7	336	4	347
missense		6	312	15	5	338
nonsense	20	26	1			47
start loss			2			2
frameshift	50	45				95
inframe indel	1	2	19	1		23
splice donor/acceptor (+/-2bp)	11	38	2	1		52
splice region	2	2	16	68	1	89
non coding	1	4	10	132	16	163
Total	83	121	353	485	25

Highest pathogenic variant AF is 0.000184

Variants in TCIRG1

This is a list of pathogenic ClinVar variants found in the TCIRG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-68039071-G-A		Autosomal recessive osteopetrosis 1	Uncertain significance (Jan 13, 2018)
11-68039120-G-T		Autosomal recessive osteopetrosis 1	Pathogenic/Likely pathogenic (Aug 07, 2023)
11-68039124-G-A			Uncertain significance (Jun 09, 2021)
11-68039676-A-AC			Benign (Jan 22, 2016)
11-68041265-C-T		Autosomal recessive osteopetrosis 1	Uncertain significance (Jan 13, 2018)
11-68041277-C-A			Likely benign (Jan 12, 2021)
11-68041279-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
11-68041285-TC-T		Autosomal recessive osteopetrosis 1	Likely pathogenic (Sep 01, 2022)
11-68041287-C-T		Autosomal recessive osteopetrosis 1	Uncertain significance (Jun 26, 2022)
11-68041288-G-A		Autosomal recessive osteopetrosis 1 • TCIRG1-related disorder	Uncertain significance (Aug 21, 2023)
11-68041288-G-C			Uncertain significance (Jan 16, 2022)
11-68041292-C-T		Autosomal recessive osteopetrosis 1 • TCIRG1-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
11-68041295-G-A			Likely benign (Feb 25, 2021)
11-68041298-G-A			Likely benign (Feb 21, 2020)
11-68041299-G-T			Uncertain significance (Jul 12, 2022)
11-68041305-C-T			Likely benign (Sep 04, 2023)
11-68041307-G-A			Likely benign (Jan 10, 2020)
11-68041307-G-C			Likely benign (Apr 28, 2022)
11-68041308-G-A			Uncertain significance (Jan 11, 2022)
11-68041311-C-T			Pathogenic (Sep 23, 2022)
11-68041313-G-A			Likely benign (Feb 24, 2023)
11-68041316-C-T			Likely benign (May 01, 2023)
11-68041321-T-C			Uncertain significance (Jul 18, 2022)
11-68041325-C-T			Likely benign (Jul 20, 2020)
11-68041326-A-G			Uncertain significance (Aug 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCIRG1	protein_coding	protein_coding	ENST00000265686	19	11880

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.40e-13	0.958	125630	0	116	125746	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.627	489	530	0.923	0.0000379	5307
Missense in Polyphen		189	223.42	0.84596		2400
Synonymous	-0.468	247	238	1.04	0.0000177	1752
Loss of Function	2.26	27	43.0	0.628	0.00000242	409

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000658	0.000656
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000382	0.000381
Finnish	0.000452	0.000416
European (Non-Finnish)	0.000581	0.000572
Middle Eastern	0.000382	0.000381
South Asian	0.000462	0.000457
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the proton channel of V-ATPases (By similarity). Seems to be directly involved in T-cell activation. {ECO:0000250}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Phagosome - Homo sapiens (human);Lysosome - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Collecting duct acid secretion - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);TYROBP Causal Network;Neutrophil degranulation;Signal Transduction;Transferrin endocytosis and recycling;Ion channel transport;Insulin receptor recycling;Signaling by Insulin receptor;ROS, RNS production in phagocytes;Purine metabolism;Innate Immune System;Immune System;Transport of small molecules;Iron uptake and transport;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.386

Intolerance Scores

• loftool: 0.0490
• rvis_EVS: -1.12
• rvis_percentile_EVS: 6.58

Haploinsufficiency Scores

• pHI: 0.224
• hipred: N
• hipred_score: 0.498
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.396

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tcirg1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; craniofacial 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: cellular defense response;vacuolar acidification;protein catabolic process in the vacuole;positive regulation of cell population proliferation;insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;macroautophagy;transferrin transport;ion transmembrane transport;neutrophil degranulation;proton transmembrane transport
• Cellular component: vacuolar proton-transporting V-type ATPase, V0 domain;lysosomal membrane;plasma membrane;integral component of plasma membrane;endosome membrane;apical plasma membrane;vacuolar proton-transporting V-type ATPase complex;phagocytic vesicle membrane;ficolin-1-rich granule membrane
• Molecular function: transporter activity;proton-transporting ATPase activity, rotational mechanism;ATPase binding