MATR3

matrin 3, the group of Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 5:139293673-139331677

Previous symbols: [ "MPD2" ]

Links

ENSG00000015479 ∙ NCBI:9782 ∙ OMIM:164015 ∙ HGNC:6912 ∙ Uniprot:P43243 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis type 21 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis type 21 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• distal myopathy with vocal cord weakness (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis type 21 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 21 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 21	AD	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	Audiologic/Otolaryngologic; Musculoskeletal	9837826; 19344878; 24686783; 25154462

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MATR3 gene.

• Amyotrophic lateral sclerosis type 21 (387 variants)
• not provided (52 variants)
• Inborn genetic diseases (14 variants)
• MATR3-related condition (7 variants)
• Distal myopathy (5 variants)
• not specified (3 variants)
• Amyotrophic lateral sclerosis (2 variants)
• MATR3-Related Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MATR3 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	86	5	95
missense	1		156	4	1	162
nonsense						0
start loss						0
frameshift			1			1
inframe indel			8			8
splice donor/acceptor (+/-2bp)			1			1
splice region			9	16	3	28
non coding			35	47	46	128
Total	1	0	205	137	52

Variants in MATR3

This is a list of pathogenic ClinVar variants found in the MATR3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-139294029-G-T		MATR3-related disorder	Uncertain significance (Mar 15, 2023)
5-139294274-T-G			Benign (Jul 03, 2018)
5-139307044-ATAC-A			Likely benign (Nov 21, 2019)
5-139307139-G-GT			Likely benign (Mar 25, 2020)
5-139307277-G-A		Amyotrophic lateral sclerosis type 21	Uncertain significance (Jan 13, 2018)
5-139307292-T-C		Amyotrophic lateral sclerosis type 21	Uncertain significance (Jan 12, 2018)
5-139307308-A-AT		Distal myopathy	Benign (Oct 09, 2019)
5-139307360-G-A		Amyotrophic lateral sclerosis type 21	Likely benign (Apr 27, 2017)
5-139307373-T-A		not specified • Amyotrophic lateral sclerosis type 21	Benign (Aug 10, 2019)
5-139307374-T-A			Likely benign (Mar 29, 2021)
5-139307399-CAA-C		not specified	Uncertain significance (Jun 23, 2023)
5-139307411-C-G		Amyotrophic lateral sclerosis type 21	Uncertain significance (Jan 12, 2018)
5-139307430-C-T		Amyotrophic lateral sclerosis type 21	Likely benign (Apr 10, 2023)
5-139307433-G-A		Amyotrophic lateral sclerosis type 21	Likely benign (Oct 22, 2023)
5-139307471-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2023)
5-139307478-G-C		Amyotrophic lateral sclerosis type 21	Likely benign (Jul 24, 2023)
5-139307483-C-T		Amyotrophic lateral sclerosis type 21	Uncertain significance (Mar 26, 2023)
5-139307484-G-A		Amyotrophic lateral sclerosis type 21	Benign/Likely benign (Jan 12, 2024)
5-139307491-A-G		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
5-139307496-C-G		Amyotrophic lateral sclerosis type 21	Likely benign (Feb 22, 2023)
5-139307500-C-T		Amyotrophic lateral sclerosis type 21	Uncertain significance (Nov 27, 2023)
5-139307501-T-TTGC		Amyotrophic lateral sclerosis type 21	Uncertain significance (Aug 30, 2022)
5-139307505-T-C		Amyotrophic lateral sclerosis type 21	Likely benign (Jan 03, 2023)
5-139307508-T-G		Amyotrophic lateral sclerosis type 21	Likely benign (Jul 23, 2022)
5-139307517-G-A		Amyotrophic lateral sclerosis type 21	Likely benign (Nov 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MATR3	protein_coding	protein_coding	ENST00000394805	14	57920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000144	125674	0	2	125676	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.73	289	452	0.639	0.0000230	5613
Missense in Polyphen		100	235.26	0.42505		3004
Synonymous	0.0141	159	159	0.999	0.00000845	1568
Loss of Function	5.68	0	37.5	0.00	0.00000183	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728}.
• Disease: DISEASE: Amyotrophic lateral sclerosis 21 (ALS21) [MIM:606070]: A neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia. {ECO:0000269|PubMed:19344878, ECO:0000269|PubMed:24686783, ECO:0000269|PubMed:25771394, ECO:0000269|PubMed:26199109}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;antisense pathway (Consensus)

Intolerance Scores

• loftool: 0.217
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.726
• hipred: Y
• hipred_score: 0.686
• ghis: 0.718

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Matr3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); cellular phenotype

Gene ontology

• Biological process: activation of innate immune response;posttranscriptional regulation of gene expression;innate immune response
• Cellular component: nuclear inner membrane;membrane;nuclear matrix
• Molecular function: RNA binding;structural molecule activity;protein binding;zinc ion binding;miRNA binding;identical protein binding