NAXD

NAD(P)HX dehydratase

Basic information

Region (hg38): 13:110615544-110639996

Previous symbols: [ "CARKD" ]

Links

ENSG00000213995 ∙ NCBI:55739 ∙ OMIM:615910 ∙ HGNC:25576 ∙ Uniprot:Q8IW45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• NAD(P)HX dehydratase deficiency (Moderate), mode of inheritance: AD
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2	AR	Allergy/Immunology/Infectious	In addition to severe neurologic features, individuals have been described with skin lesions consistent with epidermal necrosis and pancytopenia, and awareness may allow care related to immune and infectious complications	Allergy/Immunology/Infectious; Hematologic; Neurologic	30576410

ClinVar

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

• not provided (121 variants)
• NAD(P)HX dehydratase deficiency (15 variants)
• Inborn genetic diseases (14 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAXD 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			6	14	7	27
missense			39	4	2	45
nonsense	1	1				2
start loss						0
frameshift	1		1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region		1	2	4	1	8
non coding			13	21	10	44
Total	2	3	60	39	19

Highest pathogenic variant AF is 0.0000394

Variants in NAXD

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

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

Position	Type	Phenotype	Significance	ClinVar
13-110615636-C-T		Inborn genetic diseases	Uncertain significance (Jan 01, 2024)
13-110615644-CG-C		NAD(P)HX dehydratase deficiency	Pathogenic (Sep 17, 2020)
13-110615647-G-A		NAD(P)HX dehydratase deficiency	Uncertain significance (Nov 26, 2019)
13-110615686-C-T			Likely benign (Sep 01, 2022)
13-110615713-C-T		NAXD-related disorder	Benign (Jan 22, 2024)
13-110615716-G-C		NAXD-related disorder	Benign/Likely benign (Dec 18, 2023)
13-110615740-C-T			Likely benign (Mar 08, 2023)
13-110615741-G-A			Uncertain significance (Jul 18, 2022)
13-110615746-C-T			Likely benign (Dec 27, 2022)
13-110615748-C-G			Uncertain significance (Jul 15, 2022)
13-110615761-G-A			Likely benign (Nov 29, 2022)
13-110615771-G-A			Uncertain significance (May 27, 2022)
13-110615772-C-T			Uncertain significance (Sep 13, 2022)
13-110615792-G-C			Likely benign (Aug 22, 2022)
13-110615794-C-T			Benign (Oct 08, 2022)
13-110622219-TAGAA-T		NAD(P)HX dehydratase deficiency • NAXD-related disorder	Pathogenic (Feb 13, 2024)
13-110622229-G-A		NAXD-related disorder	Benign/Likely benign (Mar 01, 2024)
13-110622234-C-T			Uncertain significance (Oct 03, 2023)
13-110622235-G-T			Likely benign (Aug 10, 2023)
13-110622238-A-G		NAXD-related disorder	Likely benign (Dec 28, 2022)
13-110622239-C-A			Uncertain significance (Sep 24, 2021)
13-110622239-C-T		Inborn genetic diseases	Uncertain significance (Feb 13, 2021)
13-110622240-G-C		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
13-110622240-G-T		Inborn genetic diseases	Uncertain significance (Sep 30, 2021)
13-110622269-AAT-A		NAD(P)HX dehydratase deficiency	Pathogenic (Aug 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAXD	protein_coding	protein_coding	ENST00000309957	10	24460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00700	0.978	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.895	203	242	0.838	0.0000150	2449
Missense in Polyphen		50	79.679	0.62752		837
Synonymous	-1.21	117	101	1.15	0.00000661	846
Loss of Function	2.12	6	14.8	0.405	6.27e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000479	0.000477
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000204	0.000202
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. {ECO:0000255|HAMAP-Rule:MF_03157}.
• Pathway: Metabolism;Nicotinamide salvaging;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;NADH repair (Consensus)

Recessive Scores

• pRec: 0.0852

Intolerance Scores

• rvis_EVS: 0.76
• rvis_percentile_EVS: 86.75

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.169
• ghis: 0.519

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Naxd

Gene ontology

• Biological process: biological_process;NAD biosynthesis via nicotinamide riboside salvage pathway
• Cellular component: cellular_component;mitochondrial matrix
• Molecular function: molecular_function;protein binding;ATP binding;ATP-dependent NAD(P)H-hydrate dehydratase activity;ADP-dependent NAD(P)H-hydrate dehydratase activity