GRXCR1

glutaredoxin and cysteine rich domain containing 1, the group of Glutaredoxin domain containing|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 4:42892713-43030658

Previous symbols: [ "DFNB25" ]

Links

ENSG00000215203 ∙ NCBI:389207 ∙ OMIM:613283 ∙ HGNC:31673 ∙ Uniprot:A8MXD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 25 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 25 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 25 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 25	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	20137778

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRXCR1 gene.

• not provided (3 variants)
• Autosomal recessive nonsyndromic hearing loss 25 (2 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRXCR1 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			1	18		19
missense		1	53	3	2	59
nonsense	2	3				5
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	3	1	5
non coding	1		5	16	6	28
Total	5	4	60	37	8

Highest pathogenic variant AF is 0.0000329

Variants in GRXCR1

This is a list of pathogenic ClinVar variants found in the GRXCR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-42893015-A-G			Likely benign (Jan 06, 2019)
4-42893076-C-T			Likely benign (Dec 23, 2018)
4-42893123-G-A			Likely benign (Jan 06, 2019)
4-42893277-G-A			Uncertain significance (Aug 15, 2022)
4-42893291-G-A		not specified • Autosomal recessive nonsyndromic hearing loss 25	Benign (Jan 31, 2024)
4-42893306-C-T			Uncertain significance (Jun 19, 2023)
4-42893315-C-T		Autosomal recessive nonsyndromic hearing loss 25 • Inborn genetic diseases	Uncertain significance (Jun 13, 2022)
4-42893324-A-G		not specified	Uncertain significance (Jul 09, 2019)
4-42893326-C-T			Likely benign (Aug 07, 2023)
4-42893340-G-A			Likely benign (Nov 09, 2020)
4-42893341-T-C		not specified	Likely benign (Dec 31, 2015)
4-42893345-C-T		Autosomal recessive nonsyndromic hearing loss 25	Pathogenic/Likely pathogenic (Jul 15, 2021)
4-42893371-T-C			Likely benign (Nov 14, 2022)
4-42893372-G-A		Inborn genetic diseases	Uncertain significance (Apr 10, 2023)
4-42893379-C-T			Uncertain significance (Jul 18, 2022)
4-42893381-T-C		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
4-42893383-A-T			Uncertain significance (May 01, 2017)
4-42893406-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 25	Benign (Jan 31, 2024)
4-42893418-G-A		not specified	Uncertain significance (Aug 13, 2014)
4-42893421-T-C		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
4-42893422-A-G			Uncertain significance (Jun 13, 2023)
4-42893434-TG-T		GRXCR1-related disorder	Likely pathogenic (Jun 03, 2024)
4-42893436-A-G			Uncertain significance (Oct 03, 2022)
4-42893440-C-A			Likely benign (Jul 19, 2022)
4-42893455-T-C			Likely benign (Oct 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRXCR1	protein_coding	protein_coding	ENST00000399770	4	137392

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.94e-11	0.0270	124749	0	41	124790	0.000164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.478	174	157	1.11	0.00000969	1895
Missense in Polyphen		81	74.502	1.0872		888
Synonymous	-0.487	65	60.2	1.08	0.00000353	570
Loss of Function	-0.433	15	13.3	1.13	0.00000102	143

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000500	0.000500
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000223	0.000223
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000223	0.000223
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in actin filament architecture in developing stereocilia of sensory cells. {ECO:0000250}.

Intolerance Scores

• loftool: 0.695
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.73

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.350

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0837

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grxcr1
• Phenotype: cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear 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)

Gene ontology

• Biological process: sensory perception of sound;negative regulation of phosphatase activity;electron transport chain;cell redox homeostasis;vestibular receptor cell development;inner ear receptor cell development;inner ear receptor cell stereocilium organization
• Cellular component: microvillus;stereocilium;kinocilium
• Molecular function: molecular_function;electron transfer activity;protein disulfide oxidoreductase activity