SMS

spermine synthase, the group of Seven-beta-strand methyltransferase motif containing

Basic information

Region (hg38): X:21940709-21994837

Previous symbols: [ "SRS" ]

Links

ENSG00000102172 ∙ NCBI:6611 ∙ OMIM:300105 ∙ HGNC:11123 ∙ Uniprot:P52788 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Snyder type (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability Snyder type (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability Snyder type (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability Snyder type (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type	XL	Musculoskeletal	Individuals manifest with osteoporosis, and calcium supplementation (with ectopic calcification monitoring) and awareness of fracture risk may be beneficial	Craniofacial; Musculoskeletal; Neurologic	5823961; 14508504; 18550699; 19206178; 19277733; 21318891; 22612257; 23696453; 23805436
As with other disorders that manifest with seizures, maximal seizure control is beneficial

ClinVar

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

• not_provided (87 variants)
• Inborn_genetic_diseases (40 variants)
• Syndromic_X-linked_intellectual_disability_Snyder_type (36 variants)
• SMS-related_disorder (14 variants)
• not_specified (6 variants)
• Intellectual_disability (2 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• Smith-Magenis_syndrome (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004595.5. 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	18	6	25
missense	8	18	68	4	1	99
nonsense		1				1
start loss			1			1
frameshift	1		2			3
splice donor/acceptor (+/-2bp)		2	1			3
Total	9	21	73	22	7

Highest pathogenic variant AF is 0.0000018307541

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMS	protein_coding	protein_coding	ENST00000404933	11	67108

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0270	122687	0	1	122688	0.00000408

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.32	66	144	0.457	0.0000113	2405
Missense in Polyphen		4	36.234	0.11039		678
Synonymous	-0.289	62	59.2	1.05	0.00000519	667
Loss of Function	3.42	1	15.5	0.0643	0.00000121	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000124	0.00000897
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
• Disease: DISEASE: X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR) [MIM:309583]: Characterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive. {ECO:0000269|PubMed:14508504, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:19206178, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Cysteine and methionine metabolism - Homo sapiens (human);Spermidine and Spermine Biosynthesis;Methionine De Novo and Salvage Pathway;Amino Acid metabolism;Urea cycle and metabolism of amino groups;Metabolism of polyamines;Metabolism of amino acids and derivatives;Metabolism;Arginine Proline metabolism;spermine biosynthesis (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.0880
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.580
• hipred: Y
• hipred_score: 0.673
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sms
• Phenotype: skeleton phenotype; immune system phenotype; reproductive system phenotype; hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: sms
• Affected structure: spermine biosynthetic process
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: methionine metabolic process;polyamine metabolic process;spermine biosynthetic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: spermine synthase activity