SMOX

protein-coding

spermine oxidase

Gene summary

Polyamines are ubiquitous polycationic alkylamines which include spermine, spermidine, putrescine, and agmatine. These molecules participate in a broad range of cellular functions which include cell cycle modulation, scavenging reactive oxygen species, and the control of gene expression. These molecules also play important roles in neurotransmission through their regulation of cell-surface receptor activity, involvement in intracellular signalling pathways, and their putative roles as neurotransmitters. This gene encodes an FAD-containing enzyme that catalyzes the oxidation of spermine to spermadine and secondarily produces hydrogen peroxide. Multiple transcript variants encoding different isoenzymes have been identified for this gene, some of which have failed to demonstrate significant oxidase activity on natural polyamine substrates. The characterized isoenzymes have distinctive biochemical characteristics and substrate specificities, suggesting the existence of additional levels of complexity in polyamine catabolism. [provided by RefSeq, Jul 2012]

Previous symbols:

C20orf16

MANE transcript

NM_175839.3

Inheritance

—

ClinVar variants

U:56B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr20:4,120,980-4,187,747

External References & Databases

Ensembl (ENSG00000088826)

Transcript & Mutation Effects

hg38 • Region Span ~66.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMOX variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175839.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	3 clinvar	5
missense			54 clinvar	3 clinvar		57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	56	5	3	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175839.3	RefSeq	NP_787033.1	6	MANE Select
ENST00000305958.9	Ensembl	ENSP00000307252.4	6	MANE Select
NM_001270691.2	RefSeq	NP_001257620.1	7	Standard
NM_175840.3	RefSeq	NP_787034.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smox	Danio rerio	Structure: thrombocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

smox

Danio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arginine and proline metabolism - Homo sapiens (human)
beta-Alanine metabolism - Homo sapiens (human)
PAOs oxidise polyamines to amines
Amine Oxidase reactions
Phase I - Functionalization of compounds

Biological Process

polyamine biosynthetic process
polyamine catabolic process
spermine catabolic process
oxidation-reduction process

Molecular Function

oxidoreductase activity
polyamine oxidase activity
norspermine:oxygen oxidoreductase activity
N1-acetylspermine:oxygen oxidoreductase (N1-acetylspermidine-forming) activity
spermine:oxygen oxidoreductase (spermidine-forming) activity

Cellular Component

nucleoplasm
cytosol
nuclear membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305958
Coding exons: 6
Length: 66768
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.26	256	380	0.674	0.0000256	3605
Missense (PolyPhen)		97	165.01	0.58785		1508
Synonymous	0.463	151	158	0.953	0.0000117	1110
Loss of Function	3.42	5	22.5	0.222	0.00000113	238

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00024	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000064	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00037	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use N(1)-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal.;

Recessive Scores

pRec: 0.412

Intolerance Scores

LoFtool: 0.0276
RVIS EVS: -1.15
RVIS percentile EVS: 6.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.228

Gene Damage Prediction

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