NXN

nucleoredoxin, the group of Nucleoredoxin family

Basic information

Region (hg38): 17:799310-979776

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 (Moderate), mode of inheritance: AR
• robinow syndrome, autosomal recessive 2 (Strong), mode of inheritance: AR
• autosomal recessive Robinow syndrome (Supportive), 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 (178 variants)
• not_specified (56 variants)
• NXN-related_disorder (15 variants)
• Robinow_syndrome,_autosomal_recessive_2 (6 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. These statistics are base on transcript: NM_000022463.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	62	8	71
missense			86	3	1	90
nonsense	3	1				4
start loss						0
frameshift	2		1			3
splice donor/acceptor (+/-2bp)						0
Total	5	1	88	65	9

Highest pathogenic variant AF is 0.000006661604

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
		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

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

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