GRXCR2

glutaredoxin and cysteine rich domain containing 2, the group of Glutaredoxin domain containing

Basic information

Region (hg38): 5:145858521-145937126

Links

ENSG00000204928 ∙ NCBI:643226 ∙ OMIM:615762 ∙ HGNC:33862 ∙ Uniprot:A6NFK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 101 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 101 (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 101	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	24619944

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRXCR2 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRXCR2 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	11	1	13
missense			31	2	4	37
nonsense	2					2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				3	8	11
Total	2	0	34	16	13

Highest pathogenic variant AF is 0.0000197

Variants in GRXCR2

This is a list of pathogenic ClinVar variants found in the GRXCR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-145859441-A-G			Benign (Jun 19, 2021)
5-145859556-G-C			Benign (Nov 12, 2018)
5-145859720-C-G			Benign (Jul 11, 2019)
5-145859730-G-A		GRXCR2-related disorder	Likely benign (May 23, 2019)
5-145859730-GGGCTATTGATTGCAAATCTGGCAA-G			Uncertain significance (Apr 17, 2021)
5-145859738-G-T		not specified	Uncertain significance (Feb 06, 2023)
5-145859765-C-CA		Autosomal recessive nonsyndromic hearing loss 101	Pathogenic (May 01, 2014)
5-145859770-T-A			Uncertain significance (Jan 02, 2022)
5-145859798-GA-G			Uncertain significance (Apr 25, 2022)
5-145859800-T-C		not specified	Uncertain significance (Nov 24, 2024)
5-145859801-A-G			Uncertain significance (Mar 18, 2022)
5-145859804-A-G			Uncertain significance (May 20, 2022)
5-145859808-C-CTTT			Uncertain significance (Nov 08, 2022)
5-145859813-A-G		not specified	Uncertain significance (Oct 29, 2024)
5-145859817-G-C		not specified	Uncertain significance (Apr 04, 2024)
5-145859843-C-T		not specified	Uncertain significance (Feb 22, 2023)
5-145859844-G-A			Uncertain significance (May 25, 2017)
5-145859854-G-A		not specified	Uncertain significance (Oct 13, 2021)
5-145859871-C-G			Likely benign (Jul 31, 2023)
5-145859900-C-T		Autosomal recessive nonsyndromic hearing loss 101 • not specified	Uncertain significance (Aug 17, 2023)
5-145859901-G-A		GRXCR2-related disorder	Benign (Dec 28, 2023)
5-145859925-A-G			Likely benign (Dec 17, 2023)
5-145866186-A-T			Benign (Nov 12, 2018)
5-145866399-C-G			Benign (May 12, 2021)
5-145866490-C-T			Likely benign (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRXCR2	protein_coding	protein_coding	ENST00000377976	3	13236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.01e-7	0.186	125708	0	38	125746	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.853	167	139	1.20	0.00000751	1641
Missense in Polyphen		64	57.379	1.1154		663
Synonymous	-0.866	63	54.8	1.15	0.00000304	458
Loss of Function	0.134	11	11.5	0.957	8.00e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000233	0.000233
Ashkenazi Jewish	0.000111	0.0000992
East Asian	0.000166	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000169	0.000167
Middle Eastern	0.000166	0.000163
South Asian	0.000235	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Could play a role in maintaining cochlear stereocilia bundles that are involved in sound detection. {ECO:0000269|PubMed:24619944}.
• Disease: DISEASE: Deafness, autosomal recessive, 101 (DFNB101) [MIM:615837]: A form of non-syndromic deafness characterized by bilateral, moderate to severe hearing loss. Vestibular function is unaffected. {ECO:0000269|PubMed:24619944}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.600
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.53

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.196

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.106

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grxcr2
• Phenotype: hearing/vestibular/ear phenotype

Gene ontology

• Biological process: sensory perception of sound
• Cellular component: microvillus;stereocilium