KMO

kynurenine 3-monooxygenase

Basic information

Region (hg38): 1:241532133-241595642

Links

ENSG00000117009 ∙ NCBI:8564 ∙ OMIM:603538 ∙ HGNC:6381 ∙ Uniprot:O15229 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pellagra (No Known Disease Relationship), mode of inheritance: AR

ClinVar

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

• Inborn genetic diseases (9 variants)
• not provided (5 variants)

Variants pathogenicity by type

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

Variants in KMO

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

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

Position	Type	Phenotype	Significance	ClinVar
1-241532458-T-C		not specified	Uncertain significance (Dec 16, 2023)
1-241532484-A-G		not specified	Uncertain significance (Sep 01, 2021)
1-241548893-G-C		not specified	Uncertain significance (Mar 07, 2024)
1-241560748-C-G		not specified	Uncertain significance (Aug 16, 2022)
1-241562297-TACATGGAGTTGACTATTCC-T			Uncertain significance (Feb 08, 2023)
1-241562315-C-T			Benign (Jun 01, 2018)
1-241564987-T-C		not specified	Uncertain significance (Dec 31, 2023)
1-241565006-A-G		not specified	Uncertain significance (Dec 20, 2023)
1-241566504-C-T		KMO-related disorder	Likely benign (Nov 09, 2022)
1-241566515-T-C		not specified	Uncertain significance (Jan 19, 2024)
1-241566588-C-T			Likely benign (Jun 01, 2018)
1-241566589-G-A			Benign (Aug 28, 2018)
1-241568552-G-A		not specified	Uncertain significance (Aug 08, 2023)
1-241568588-G-C		not specified	Uncertain significance (Jan 24, 2024)
1-241568622-C-T		not specified	Uncertain significance (Apr 22, 2022)
1-241568656-T-A			Benign (Aug 28, 2018)
1-241588826-T-C		not specified	Uncertain significance (Sep 25, 2023)
1-241590214-C-G		not specified	Uncertain significance (Oct 13, 2021)
1-241590241-A-G		not specified	Uncertain significance (Dec 19, 2022)
1-241591963-A-G		not specified	Uncertain significance (Nov 18, 2022)
1-241592013-C-T		not specified	Uncertain significance (Jun 29, 2023)
1-241592023-A-G		not specified	Uncertain significance (Jan 26, 2022)
1-241592082-C-T		not specified	Likely benign (Feb 16, 2023)
1-241594687-C-T			Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KMO	protein_coding	protein_coding	ENST00000366559	15	63511

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000478	0.999	125671	0	67	125738	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	180	263	0.683	0.0000129	3218
Missense in Polyphen		55	92.729	0.59313		1131
Synonymous	-1.40	107	90.1	1.19	0.00000465	880
Loss of Function	2.79	12	27.9	0.431	0.00000142	334

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00171	0.00169
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.0000546	0.0000544
South Asian	0.000426	0.000425
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn) (PubMed:29429898, PubMed:23575632, PubMed:26752518, PubMed:28604669, PubMed:29208702). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract (Probable). {ECO:0000269|PubMed:23575632, ECO:0000269|PubMed:26752518, ECO:0000269|PubMed:28604669, ECO:0000269|PubMed:29208702, ECO:0000269|PubMed:29429898, ECO:0000305|PubMed:12402501}.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Tryptophan Metabolism;Selenium Micronutrient Network;NAD Biosynthesis II (from tryptophan);Tryptophan catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde;Metabolism;L-kynurenine degradation;Tryptophan metabolism;NAD <i>de novo</i> biosynthesis;Tryptophan degradation;superpathway of tryptophan utilization;tryptophan degradation (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.708
• rvis_EVS: 0.66
• rvis_percentile_EVS: 84.55

Haploinsufficiency Scores

• pHI: 0.0692
• hipred: N
• hipred_score: 0.475
• ghis: 0.402

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kmo
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: kmo
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: tryptophan catabolic process;aging;response to salt stress;NAD metabolic process;quinolinate biosynthetic process;kynurenic acid biosynthetic process;'de novo' NAD biosynthetic process from tryptophan;anthranilate metabolic process;oxidation-reduction process;kynurenine metabolic process;cellular response to lipopolysaccharide;cellular response to interleukin-1;L-kynurenine metabolic process;positive regulation of neuron death;positive regulation of glutamate secretion, neurotransmission
• Cellular component: extracellular space;mitochondrion;mitochondrial outer membrane;cytosol;integral component of membrane
• Molecular function: kynurenine 3-monooxygenase activity;NAD(P)H oxidase activity;flavin adenine dinucleotide binding;FAD binding