NXN

nucleoredoxin, the group of Nucleoredoxin family

Basic information

Region (hg38): 17:799309-979776

Links

ENSG00000167693 ∙ NCBI:64359 ∙ OMIM:612895 ∙ HGNC:18008 ∙ Uniprot:Q6DKJ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• robinow syndrome, autosomal recessive 2 (Limited), mode of inheritance: AR
• autosomal recessive Robinow syndrome (Supportive), mode of inheritance: AR
• robinow syndrome, autosomal recessive 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Robinow syndrome, autosomal recessive 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal	29276006

ClinVar

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

• not provided (145 variants)
• Inborn genetic diseases (16 variants)
• Robinow syndrome, autosomal recessive 2 (4 variants)
• not specified (1 variants)
• Distal shortening of limbs (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NXN 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				36	9	45
missense			49	1	1	51
nonsense	2	1				3
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	2	3	6
non coding				21	31	52
Total	3	1	50	58	41

Variants in NXN

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

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

Position	Type	Phenotype	Significance	ClinVar
17-800777-A-G			Benign (May 14, 2021)
17-800802-T-G			Benign (May 14, 2021)
17-800947-C-T		NXN-related disorder	Likely benign (Jun 27, 2019)
17-800958-C-T			Likely benign (Sep 10, 2023)
17-800961-C-T			Benign (Jan 29, 2024)
17-801000-C-G			Uncertain significance (Jun 13, 2022)
17-801001-T-C		not specified	Uncertain significance (Jun 24, 2022)
17-801006-G-A			Likely benign (Oct 01, 2023)
17-801020-TCTC-T		Robinow syndrome, autosomal recessive 2	Pathogenic (Aug 08, 2019)
17-801024-C-G		not specified	Uncertain significance (Jul 28, 2021)
17-801027-C-T			Likely benign (Jan 11, 2022)
17-801039-G-A		NXN-related disorder	Likely benign (Aug 17, 2023)
17-801072-G-A			Likely benign (Oct 05, 2023)
17-801083-C-A			Uncertain significance (Aug 31, 2021)
17-801095-G-C		not specified	Uncertain significance (Oct 06, 2022)
17-801102-G-A			Likely benign (Apr 04, 2022)
17-801140-G-A			Likely benign (Jun 11, 2023)
17-801240-C-A			Benign (May 14, 2021)
17-801260-G-T			Benign (May 15, 2021)
17-803622-G-C			Benign (May 14, 2021)
17-803673-C-T		NXN-related disorder	Likely benign (Jan 24, 2024)
17-803674-G-A		NXN-related disorder	Benign (Dec 17, 2023)
17-803675-C-T			Likely benign (Aug 12, 2022)
17-803675-C-CA			Likely benign (Jan 03, 2023)
17-803687-C-T		not specified	Uncertain significance (Jul 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NXN	protein_coding	protein_coding	ENST00000336868	8	180458

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00275	125728	0	4	125732	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.18	155	252	0.614	0.0000162	2779
Missense in Polyphen		41	81.159	0.50518		890
Synonymous	0.922	101	113	0.890	0.00000778	892
Loss of Function	4.12	1	21.7	0.0460	0.00000125	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000515	0.0000462
European (Non-Finnish)	0.0000186	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a redox-dependent negative regulator of the Wnt signaling pathway, possibly by preventing ubiquitination of DVL3 by the BCR(KLHL12) complex. May also function as a transcriptional regulator act as a regulator of protein phosphatase 2A (PP2A) (By similarity). {ECO:0000250}.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.0963
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.294
• hipred: Y
• hipred_score: 0.707
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nxn
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; hematopoietic system 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); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: Wnt signaling pathway;cell differentiation;negative regulation of Wnt signaling pathway;negative regulation of protein ubiquitination;cell redox homeostasis;oxidation-reduction process;cardiovascular system development;cellular oxidant detoxification
• Cellular component: nucleus;cytosol
• Molecular function: thioredoxin-disulfide reductase activity;protein-disulfide reductase activity