PTDSS1
protein-codingphosphatidylserine synthase 1
Gene summary
The protein encoded by this gene catalyzes the formation of phosphatidylserine from either phosphatidylcholine or phosphatidylethanolamine. Phosphatidylserine localizes to the mitochondria-associated membrane of the endoplasmic reticulum, where it serves a structural role as well as a signaling role. Defects in this gene are a cause of Lenz-Majewski hyperostotic dwarfism. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~75.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007892
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007892
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007892
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007892
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007892
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTDSS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014754.3. 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 | 51 | 2 | 55 | ||
| missense | 5 | 3 | 99 | 19 | 4 | 130 |
| nonsense | 4 | 1 | 5 | |||
| start loss | 0 | |||||
| frameshift | 6 | 6 | ||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 5 | 3 | 123 | 71 | 6 | 208 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055569.1 | 13 | MANE Select | |
| Ensembl | ENSP00000430548.1 | 13 | MANE Select | |
| RefSeq | NP_001277154.1 | 10 | Standard | |
| Ensembl | ENSP00000337331.4 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerophospholipid metabolism - Homo sapiens (human)
- Phospholipid Biosynthesis
- Kennedy pathway from Sphingolipids
- Metabolism of lipids
- Metabolism
Biological Process
- phosphatidylserine biosynthetic process
Molecular Function
- transferase activity
Cellular Component
- endoplasmic reticulum membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000517309
- Coding exons
- 13
- Length
- 75281
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 158 | 267 | 0.591 | 0.0000137 | 3159 |
| Missense (PolyPhen) | 45 | 103.12 | 0.43637 | 1266 | ||
| Synonymous | 0.470 | 92 | 97.9 | 0.940 | 0.00000553 | 857 |
| Loss of Function | 3.95 | 8 | 32.2 | 0.248 | 0.00000166 | 313 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine. In membranes, PTDSS1 catalyzes mainly the conversion of phosphatidylcholine. Also converts, in vitro and to a lesser extent, phosphatidylethanolamine.;
- Disease
- DISEASE: Lenz-Majewski hyperostotic dwarfism (LMHD) [MIM:151050]: A syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. LMHD is characterized by the combination of sclerosing bone dysplasia, intellectual disability and distinct craniofacial, dental, cutaneous and distal limb anomalies. The progressive generalized hyperostosis associated with this syndrome affects the cranium, the vertebrae and the diaphyses of tubular bones, leading to severe growth restriction. {ECO:0000269|PubMed:24241535}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.516
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.938
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |