PTDSS1

phosphatidylserine synthase 1

Basic information

Region (hg38): 8:96261902-96336995

Links

ENSG00000156471 ∙ NCBI:9791 ∙ OMIM:612792 ∙ HGNC:9587 ∙ Uniprot:P48651 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lenz-Majewski hyperostotic dwarfism (Definitive), mode of inheritance: AD
• Lenz-Majewski hyperostotic dwarfism (Strong), mode of inheritance: AD
• Lenz-Majewski hyperostotic dwarfism (Supportive), mode of inheritance: AD
• Lenz-Majewski hyperostotic dwarfism (Strong), mode of inheritance: AD
• Lenz-Majewski hyperostotic dwarfism (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lenz-Majewski hyperostotic dwarfism	AD	General	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	Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic	24241535

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTDSS1 gene.

• Lenz-Majewski hyperostosis syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTDSS1 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				31	3	34
missense	1	2	61	10	6	80
nonsense			3	1		4
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	4	4	13
non coding			1	23	28	52
Total	1	2	67	65	37

Variants in PTDSS1

This is a list of pathogenic ClinVar variants found in the PTDSS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-96262045-C-A		Inborn genetic diseases	Uncertain significance (May 26, 2024)
8-96262052-C-T			Likely benign (Oct 17, 2022)
8-96262067-C-T			Likely benign (Dec 18, 2022)
8-96262093-A-G			Uncertain significance (Apr 29, 2022)
8-96262096-T-C			Uncertain significance (Dec 24, 2022)
8-96262112-C-T			Likely benign (Jun 02, 2022)
8-96262138-C-G			Benign (Jun 13, 2022)
8-96262153-A-C			Likely benign (Aug 23, 2022)
8-96262156-G-A			Uncertain significance (Aug 17, 2023)
8-96262188-A-G			Uncertain significance (Jun 12, 2023)
8-96262190-C-G			Uncertain significance (Oct 30, 2022)
8-96262208-C-A			Uncertain significance (Oct 05, 2023)
8-96262224-G-A			Uncertain significance (Aug 09, 2022)
8-96262230-C-G			Likely benign (Apr 26, 2022)
8-96273201-G-A			Benign (Nov 12, 2018)
8-96273283-G-A			Likely benign (Dec 23, 2021)
8-96273290-T-C			Likely benign (Jan 21, 2024)
8-96273296-C-T		PTDSS1-related disorder	Uncertain significance (Aug 25, 2023)
8-96273333-G-A		Inborn genetic diseases	Likely benign (Jan 22, 2024)
8-96273350-T-C			Likely benign (Apr 06, 2021)
8-96273366-A-C		Lenz-Majewski hyperostosis syndrome	Uncertain significance (Oct 03, 2019)
8-96273367-T-C			Uncertain significance (Nov 20, 2022)
8-96273374-G-A			Likely benign (Jun 27, 2023)
8-96273388-A-G			Uncertain significance (Nov 04, 2023)
8-96273389-T-C			Benign (Jan 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTDSS1	protein_coding	protein_coding	ENST00000517309	13	75281

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.151	0.849	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.38	158	267	0.591	0.0000137	3159
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000218	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000712	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Phospholipid Biosynthesis;Kennedy pathway from Sphingolipids;Metabolism of lipids;Metabolism;phosphatidylserine biosynthesis I;Synthesis of PS;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.516
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.269
• hipred: Y
• hipred_score: 0.685
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptdss1
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: phosphatidylserine biosynthetic process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: transferase activity