NNT

nicotinamide nucleotide transhydrogenase

Basic information

Region (hg38): 5:43602692-43707405

Links

ENSG00000112992 ∙ NCBI:23530 ∙ OMIM:607878 ∙ HGNC:7863 ∙ Uniprot:Q13423 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glucocorticoid deficiency 4 (Definitive), mode of inheritance: AR
• glucocorticoid deficiency 4 (Strong), mode of inheritance: AR
• familial glucocorticoid deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucocorticoid deficiency 4, with or without mineralocorticoid deficiency	AR	Cardiovascular; Endocrine	The condition can involve early-onset life-threatening sequelae of glucocorticoid deficiency as well as later effects involving mineralocorticoid deficiency and other manifestations (eg, possible thyroid and cardiac findings) and awareness may allow preventive/treatment measures (eg, with corticosteroid replacement therapy) related to adrenal insufficiency	Cardiovascular; Endocrine	22634753; 23474776; 25879317; 26070314; 27129361

ClinVar

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

• Glucocorticoid deficiency 4 (5 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NNT 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				43	7	50
missense	1	2	73	5	5	86
nonsense						0
start loss						0
frameshift	4	1				5
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			4	11	1	16
non coding			1	13	7	21
Total	6	4	74	61	19

Variants in NNT

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

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

Position	Type	Phenotype	Significance	ClinVar
5-43609170-T-C		Glucocorticoid deficiency 4	Benign (Sep 05, 2021)
5-43609207-A-G			Likely benign (Dec 13, 2023)
5-43609208-T-C			Likely benign (Apr 23, 2022)
5-43609233-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
5-43609234-G-A			Likely benign (Sep 26, 2023)
5-43609241-C-T		not specified • Glucocorticoid deficiency 4	Benign (Feb 01, 2024)
5-43609252-T-C		NNT-related disorder	Likely benign (Aug 29, 2022)
5-43609275-G-A		Glucocorticoid deficiency 4	Benign (Jan 08, 2024)
5-43609287-A-AT		Glucocorticoid deficiency 4	Pathogenic (May 12, 2023)
5-43609291-T-G		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
5-43609300-A-T			Likely benign (Jul 25, 2023)
5-43609324-G-C			Benign (Dec 08, 2023)
5-43609339-A-G		NNT-related disorder	Likely benign (Jan 22, 2024)
5-43609344-C-T		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
5-43609358-C-G			Likely benign (Nov 14, 2023)
5-43612882-T-TA		Glucocorticoid deficiency 4	Benign (Sep 05, 2021)
5-43612921-G-A			Likely benign (May 23, 2023)
5-43612944-A-G			Benign (Feb 01, 2024)
5-43612944-A-T			Uncertain significance (Dec 17, 2022)
5-43612967-C-T		Glucocorticoid deficiency 4	Pathogenic (Oct 11, 2016)
5-43613006-A-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
5-43613026-C-T			Likely benign (Aug 02, 2023)
5-43613041-G-T			Likely benign (Mar 20, 2022)
5-43613044-C-A			Likely benign (Aug 31, 2022)
5-43613063-G-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NNT	protein_coding	protein_coding	ENST00000264663	21	104714

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0273	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.08	448	591	0.759	0.0000298	6969
Missense in Polyphen		174	272.41	0.63874		3166
Synonymous	0.480	217	226	0.959	0.0000126	2302
Loss of Function	5.22	8	46.4	0.172	0.00000253	576

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000280	0.000280
Ashkenazi Jewish	0.000202	0.0000992
East Asian	0.000110	0.000109
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000720	0.0000703
Middle Eastern	0.000110	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland. {ECO:0000269|PubMed:22634753}.
• Pathway: Nicotinate and nicotinamide metabolism - Homo sapiens (human);Nicotinate and Nicotinamide Metabolism;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Vitamin B3 (nicotinate and nicotinamide) metabolism;Metabolism;NAD phosphorylation and dephosphorylation (Consensus)

Recessive Scores

• pRec: 0.0918

Intolerance Scores

• loftool: 0.0186
• rvis_EVS: -0.39
• rvis_percentile_EVS: 27.03

Haploinsufficiency Scores

• pHI: 0.372
• hipred: Y
• hipred_score: 0.592
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nnt
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of protein phosphorylation;tricarboxylic acid cycle;NADPH regeneration;positive regulation of mitochondrial membrane potential;oxygen homeostasis;response to vitamin;negative regulation of apoptotic process;cell redox homeostasis;oxidation-reduction process;reactive oxygen species metabolic process;cellular oxidant detoxification;proton transmembrane transport;positive regulation of hydrogen peroxide catabolic process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respirasome;membrane;integral component of membrane
• Molecular function: NAD(P)+ transhydrogenase (B-specific) activity;NAD(P)+ transhydrogenase activity;NADP binding;NAD binding