SRM
protein-codingspermidine synthase, the group of Seven-beta-strand methyltransferase motif containing
Gene summary
The polyamines putrescine, spermine, and spermidine are ubiquitous polycationic mediators of cell growth and differentiation. Spermidine synthase is one of four enzymes in the polyamine-biosynthetic pathway and carries out the final step of spermidine biosynthesis. This enzyme catalyzes the conversion of putrescine to spermidine using decarboxylated S-adenosylmethionine as the cofactor. [provided by RefSeq, Jul 2008]
- SRML1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 kbGenCC 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 SRM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003132.3. 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 | 1 | 1 | ||||
| missense | 28 | 1 | 29 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 34 | 1 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003123.2 | 8 | MANE Select | |
| Ensembl | ENSP00000366156.2 | 8 | MANE Select | |
| Ensembl | ENSP00000465687.1 | 2 | Standard | |
| Ensembl | ENSP00000467669.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| srm | Danio rerio | Structure: melanophore stripe Quality: patchy 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)
- Glutathione metabolism - Homo sapiens (human)
- Cysteine and methionine metabolism - Homo sapiens (human)
- S-Adenosylhomocysteine (SAH) Hydrolase Deficiency
Biological Process
- polyamine metabolic process
- polyamine biosynthetic process
- spermidine biosynthetic process
- cellular response to leukemia inhibitory factor
Molecular Function
- spermidine synthase activity
- protein binding
- identical protein binding
- protein homodimerization activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376957
- Coding exons
- 8
- Length
- 5441
- Individuals with no LoFs
- 125620
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125627
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.55 | 81 | 176 | 0.459 | 0.0000101 | 1958 |
| Missense (PolyPhen) | 11 | 65.46 | 0.16804 | 713 | ||
| Synonymous | -0.409 | 82 | 77.4 | 1.06 | 0.00000498 | 565 |
| Loss of Function | 2.78 | 4 | 16.0 | 0.249 | 6.84e-7 | 183 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the production of spermidine from putrescine and decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference for putrescine as substrate, and has very low activity towards 1,3-diaminopropane. Has extremely low activity towards spermidine. {ECO:0000269|PubMed:17585781}.;
Recessive Scores
- pRec
- 0.291
Intolerance Scores
- LoFtool
- 0.268
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |