PTDSS1

Summary

PTDSS1 (phosphatidylserine synthase 1, HGNC:9587) is a protein-coding gene on chromosome 8q22.1, encoding Phosphatidylserine synthase 1 (P48651). Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine. It is a selective cancer dependency (DepMap: 25.8% of cell lines).

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.

Source: NCBI Gene 9791 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lenz-Majewski hyperostotic dwarfism (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 294 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 101
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 25.8% of screened cell lines
• MANE Select transcript: NM_014754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9587
Approved symbol	PTDSS1
Name	phosphatidylserine synthase 1
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0024, PSSA, PSS1
Ensembl gene	ENSG00000156471
Ensembl biotype	protein_coding
OMIM	612792
Entrez	9791

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000337004, ENST00000517309, ENST00000517557, ENST00000517982, ENST00000518776, ENST00000522072, ENST00000894612

RefSeq mRNA: 2 — MANE Select: NM_014754 NM_001290225, NM_014754

CCDS: CCDS6271

Canonical transcript exons

ENST00000517309 — 13 exons

Exon	Start	End
ENSE00002119773	96333457	96336995
ENSE00002133736	96261902	96262219
ENSE00003470037	96304040	96304181
ENSE00003494640	96330213	96330281
ENSE00003510244	96306444	96306556
ENSE00003539429	96284109	96284153
ENSE00003571578	96273299	96273390
ENSE00003595783	96320246	96320345
ENSE00003602090	96309557	96309622
ENSE00003635356	96299694	96299845
ENSE00003637814	96331026	96331095
ENSE00003656331	96287022	96287146
ENSE00003685139	96295098	96295256

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.0221 / max 557.6702, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89832	80.7087	1824
89833	1.8570	1129
89831	1.2209	702
205262	0.1936	70
89834	0.0419	10

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.80	gold quality
left ventricle myocardium	UBERON:0006566	98.60	gold quality
heart right ventricle	UBERON:0002080	98.15	gold quality
secondary oocyte	CL:0000655	97.84	gold quality
cardiac ventricle	UBERON:0002082	97.53	gold quality
myocardium	UBERON:0002349	97.53	gold quality
heart left ventricle	UBERON:0002084	97.51	gold quality
oocyte	CL:0000023	96.95	gold quality
stromal cell of endometrium	CL:0002255	96.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.87	gold quality
apex of heart	UBERON:0002098	96.83	gold quality
heart	UBERON:0000948	96.76	gold quality
cardiac atrium	UBERON:0002081	96.66	gold quality
right atrium auricular region	UBERON:0006631	96.60	gold quality
leukocyte	CL:0000738	96.44	gold quality
gingival epithelium	UBERON:0001949	96.39	gold quality
monocyte	CL:0000576	96.38	gold quality
mononuclear cell	CL:0000842	96.38	gold quality
lymph node	UBERON:0000029	96.15	gold quality
middle temporal gyrus	UBERON:0002771	96.07	gold quality
bone marrow	UBERON:0002371	96.02	gold quality
granulocyte	CL:0000094	95.97	gold quality
thymus	UBERON:0002370	95.94	gold quality
vena cava	UBERON:0004087	95.94	gold quality
gingiva	UBERON:0001828	95.84	gold quality
smooth muscle tissue	UBERON:0001135	95.41	gold quality
vermiform appendix	UBERON:0001154	95.39	gold quality
metanephric glomerulus	UBERON:0004736	95.37	gold quality
renal glomerulus	UBERON:0000074	95.33	gold quality
islet of Langerhans	UBERON:0000006	95.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

55 targeting PTDSS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-5582-5P	99.27	71.42	1879

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Purification and characterization of human phosphatidylserine synthases 1 and 2. (PMID:19014349)
• Gain-of-function missense mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. (PMID:24241535)
• RYR2, PTDSS1 and AREG are autism susceptibility genes that are implicated in a Lebanese population-based study of copy number variations in this disease. (PMID:26742492)
• PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism. (PMID:27044099)
• we report here three patients with LMS and heterozygous mutations in PTDSS1. We describe an adult phenotype and two novel PTDSS1 mutations. We suggest that LMS should be considered in the differential diagnosis of a newborn with CL. (PMID:29341480)
• used transpose-mediated transgenesis to attempt to stably express wild-type and mutant forms of human PTDSS1 ubiquitously or specifically in chondrocytes, osteoblasts or osteoclasts in zebrafish (PMID:31231513)
• Topology of phosphatidylserine synthase 1 in the endoplasmic reticulum membrane. (PMID:34516042)
• Disease-related PSS1 mutant impedes the formation and function of osteoclasts. (PMID:37714410)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptdss1a	ENSDARG00000012588
danio_rerio	ptdss1b	ENSDARG00000102114
mus_musculus	Ptdss1	ENSMUSG00000021518
rattus_norvegicus	Ptdss1	ENSRNOG00000052289
drosophila_melanogaster	Pss	FBGN0287585

Paralogs (1): PTDSS2 (ENSG00000174915)

Protein

Protein identifiers

Phosphatidylserine synthase 1 — P48651 (reviewed: P48651)

Alternative names: Serine-exchange enzyme I

All UniProt accessions (2): P48651, J3KNR6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine. Catalyzes mainly the conversion of phosphatidylcholine. Also converts, in vitro and to a lesser extent, phosphatidylethanolamine.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Requires calcium ions. Inhibited by exogenous phosphatidylserine.

Pathway. Phospholipid metabolism; phosphatidylserine biosynthesis.

Similarity. Belongs to the phosphatidyl serine synthase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P48651-1	1	yes
P48651-2	2
P48651-3	3

RefSeq proteins (2): NP_001277154, NP_055569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004277	PSS	Family

Pfam: PF03034

Enzyme classification (BRENDA):

• EC 2.7.8.29 — L-serine-phosphatidylethanolamine phosphatidyltransferase (BRENDA: 6 organisms, 11 substrates, 7 inhibitors, 1 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-SERINE	0.12	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + L-serine = a 1,2-diacyl-sn-glycero-3-phospho-L-serine + ethanolamine (RHEA:27606)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + L-serine = a 1,2-diacyl-sn-glycero-3-phospho-L-serine + choline (RHEA:45088)

UniProt features (59 total): helix 17, topological domain 10, transmembrane region 9, modified residue 5, turn 5, sequence variant 4, splice variant 3, strand 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9B4E	ELECTRON MICROSCOPY	2.7
9B4G	ELECTRON MICROSCOPY	2.87
9KQJ	ELECTRON MICROSCOPY	2.95
9KQI	ELECTRON MICROSCOPY	3.02
9KQF	ELECTRON MICROSCOPY	3.25
9B4F	ELECTRON MICROSCOPY	3.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48651-F1	81.33	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 2, 417, 425, 442, 454

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483101	Synthesis of PS

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): phosphatidylserine biosynthetic process (GO:0006659), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (3): transferase activity (GO:0016740), L-serine-phosphatidylethanolamine phosphatidyltransferase activity (GO:0106245), L-serine-phosphatidylcholine phosphatidyltransferase activity (GO:0106258)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphotransferase activity, for other substituted phosphate groups	2
phosphatidylserine metabolic process	1
modified amino acid biosynthetic process	1
glycerophospholipid biosynthetic process	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTDSS1	PISD	Q9UG56	792
PTDSS1	PEMT	Q9UBM1	603
PTDSS1	CEPT1	Q9Y6K0	513
PTDSS1	PCYT2	Q99447	506
PTDSS1	PCYT1A	P49585	495
PTDSS1	CMPK1	P30085	493
PTDSS1	CHPT1	Q8WUD6	487
PTDSS1	GPALPP1	Q8IXQ4	473
PTDSS1	PACS2	Q86VP3	466
PTDSS1	OSBPL9	Q96SU4	460
PTDSS1	CDIPT	O14735	449
PTDSS1	CLIC3	O95833	449
PTDSS1	CHKA	P35790	434
PTDSS1	IFRD2	Q12894	421
PTDSS1	ACSL4	O60488	416

IntAct

56 interactions, top by confidence:

A	B	Type	Score
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
PTDSS1	TSHR	psi-mi:“MI:0915”(physical association)	0.370
PTDSS1	CREB3	psi-mi:“MI:0915”(physical association)	0.370
PLK4	SYNPO2	psi-mi:“MI:0914”(association)	0.350
Atp2a2	ESYT2	psi-mi:“MI:0914”(association)	0.350
Dctn1	DERL1	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
Ktn1	ESYT2	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
ERBB2	SURF4	psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	AP3D1	psi-mi:“MI:0914”(association)	0.350
PTPN6	RPL35A	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
PIM1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SRPK1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SRPK2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350

BioGRID (252): PTDSS1 (Affinity Capture-MS), PTDSS1 (Proximity Label-MS), PTDSS1 (Proximity Label-MS), PTDSS1 (Two-hybrid), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), PTDSS1 (Affinity Capture-MS), STOM (Affinity Capture-MS), PTDSS1 (Affinity Capture-RNA), PTDSS1 (Affinity Capture-RNA), PTDSS1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNC1, A2VE61, A7XZ53, B1H3H9, D3ZEH5, F4HXY7, O35052, O95674, P48651, P98191, Q00576, Q01685, Q0JR55, Q0VCK9, Q28CY9, Q28H54, Q2KHY9, Q5EA65, Q5N8Q3, Q5R7B1, Q5U239, Q5ZKD1, Q5ZKJ0, Q5ZM65, Q6AXM5, Q6DD44, Q6DED0, Q6I628, Q7ZYQ3, Q803C9, Q8BGS7, Q8BXA5, Q8CIF6, Q8NBJ9, Q91XU8, Q91ZQ0, Q92903, Q96KA5, Q99KU0, Q99L43

Diamond homologs: B1H3H9, B2GV22, E1BYA3, E7EY42, F4HXY7, O08888, P48651, Q00576, Q08D11, Q0JR55, Q2KHY9, Q5N8Q3, Q5PQL5, Q5ZM65, Q6I628, Q803C9, Q99LH2, Q9BVG9, Q9VPD3, Q9Z1X2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

294 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	105
Likely benign	93
Benign	42

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
3777039	NM_014754.3(PTDSS1):c.806C>T (p.Pro269Leu)	Pathogenic
4745317	NM_014754.3(PTDSS1):c.283C>G (p.Arg95Gly)	Pathogenic
97034	NM_014754.3(PTDSS1):c.1058A>G (p.Gln353Arg)	Pathogenic
97035	NM_014754.3(PTDSS1):c.805C>T (p.Pro269Ser)	Pathogenic
97036	NM_014754.3(PTDSS1):c.794T>C (p.Leu265Pro)	Pathogenic
1027889	NM_014754.3(PTDSS1):c.848C>T (p.Ser283Phe)	Likely pathogenic
383736	NM_014754.3(PTDSS1):c.421A>G (p.Thr141Ala)	Likely pathogenic

SpliceAI

1863 predictions. Top by Δscore:

Variant	Effect	Δscore
8:96273293:TTTCA:T	acceptor_loss	1.0000
8:96273295:TCAG:T	acceptor_loss	1.0000
8:96273296:CAG:C	acceptor_loss	1.0000
8:96273297:A:AG	acceptor_gain	1.0000
8:96273297:A:C	acceptor_loss	1.0000
8:96273297:AG:A	acceptor_gain	1.0000
8:96273297:AGG:A	acceptor_gain	1.0000
8:96273298:G:GG	acceptor_gain	1.0000
8:96273298:GG:G	acceptor_gain	1.0000
8:96273298:GGG:G	acceptor_gain	1.0000
8:96273298:GGGA:G	acceptor_gain	1.0000
8:96273298:GGGAT:G	acceptor_gain	1.0000
8:96273387:AATGG:A	donor_loss	1.0000
8:96273388:ATGGT:A	donor_loss	1.0000
8:96273389:TGG:T	donor_loss	1.0000
8:96273391:G:GG	donor_gain	1.0000
8:96273392:T:TC	donor_loss	1.0000
8:96284151:TTGGT:T	donor_loss	1.0000
8:96284152:TGGT:T	donor_loss	1.0000
8:96284154:G:A	donor_loss	1.0000
8:96284156:GAGT:G	donor_loss	1.0000
8:96287020:A:AG	acceptor_gain	1.0000
8:96287021:G:GG	acceptor_gain	1.0000
8:96287132:G:T	donor_gain	1.0000
8:96295087:A:AG	acceptor_gain	1.0000
8:96295088:T:G	acceptor_gain	1.0000
8:96295092:A:AG	acceptor_gain	1.0000
8:96295093:A:AG	acceptor_gain	1.0000
8:96295093:AATAG:A	acceptor_gain	1.0000
8:96295094:ATAG:A	acceptor_gain	1.0000

AlphaMissense

3163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:96273369:A:C	S84R	1.000
8:96273371:T:A	S84R	1.000
8:96273371:T:G	S84R	1.000
8:96284138:T:A	W101R	1.000
8:96284138:T:C	W101R	1.000
8:96295182:T:A	W176R	1.000
8:96295182:T:C	W176R	1.000
8:96295233:A:C	S193R	1.000
8:96295235:T:A	S193R	1.000
8:96295235:T:G	S193R	1.000
8:96299736:T:A	W215R	1.000
8:96299736:T:C	W215R	1.000
8:96299755:A:C	D221A	1.000
8:96306462:T:C	F305L	1.000
8:96306464:C:A	F305L	1.000
8:96306464:C:G	F305L	1.000
8:96273390:G:C	G91R	0.999
8:96284109:G:A	G91D	0.999
8:96284114:T:C	F93L	0.999
8:96284115:T:C	F93S	0.999
8:96284116:C:A	F93L	0.999
8:96284116:C:G	F93L	0.999
8:96284120:C:G	R95G	0.999
8:96284123:C:T	P96S	0.999
8:96284124:C:A	P96H	0.999
8:96284126:C:G	H97D	0.999
8:96284127:A:G	H97R	0.999
8:96284140:G:C	W101C	0.999
8:96284140:G:T	W101C	0.999
8:96284153:G:A	G106R	0.999

dbSNP variants (sampled 300 via entrez): RS1000031698 (8:96285895 T>TA), RS1000046920 (8:96273089 C>G,T), RS1000069151 (8:96335565 G>C), RS1000079102 (8:96272641 T>C,G), RS1000116875 (8:96320759 A>C), RS1000148571 (8:96316924 G>A,T), RS1000235770 (8:96299926 A>C), RS1000246737 (8:96329626 T>C), RS1000257681 (8:96337014 A>C), RS1000288070 (8:96300387 T>A), RS1000291831 (8:96260716 A>C), RS1000301337 (8:96296749 A>G), RS1000318751 (8:96279673 G>T), RS1000407665 (8:96261047 TAAAG>T), RS1000463246 (8:96292499 C>A,G)

Disease associations

OMIM: gene MIM:612792 | disease phenotypes: MIM:151050

GenCC curated gene-disease

Disease	Classification	Inheritance
Lenz-Majewski hyperostotic dwarfism	Definitive	Autosomal dominant

Mondo (2): Lenz-Majewski hyperostotic dwarfism (MONDO:0007892), microcephaly (MONDO:0001149)

Orphanet (1): Lenz-Majewski hyperostotic dysplasia (Orphanet:2658)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000036	Abnormal penis morphology
HP:0000039	Epispadias
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000135	Hypogonadism
HP:0000154	Wide mouth
HP:0000164	Abnormality of the dentition
HP:0000171	Microglossia
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000270	Delayed cranial suture closure
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000452	Choanal stenosis
HP:0000453	Choanal atresia
HP:0000614	Abnormal nasolacrimal system morphology
HP:0000682	Abnormal dental enamel morphology
HP:0000885	Broad ribs

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_26	Obesity-related traits	5.000000e-06
GCST004691_8	Huntington’s disease progression	3.000000e-06
GCST010549_1	Peripheral arterial disease x type 2 diabetes interaction	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0008336	disease progression measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537115	Lenz Majewski hyperostotic dwarfism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465290 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

99 potent at pChembl≥5 of 99 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL5413526
7.27	IC50	54	nM	CHEMBL5399303
7.22	IC50	60	nM	CHEMBL5410458
7.14	IC50	73	nM	CHEMBL5422228
7.09	Kd	80.52	nM	CHEMBL5653589
7.07	ED50	84.54	nM	CHEMBL5653589
7.04	IC50	92	nM	CHEMBL5402465
7.01	IC50	98	nM	CHEMBL5415049
7.00	IC50	100	nM	CHEMBL5438925
7.00	IC50	100	nM	CHEMBL5420148
6.96	IC50	110	nM	CHEMBL5418974
6.92	IC50	120	nM	CHEMBL5400683
6.92	IC50	120	nM	CHEMBL5411892
6.92	IC50	120	nM	CHEMBL5407874
6.92	IC50	120	nM	CHEMBL5421014
6.89	IC50	130	nM	CHEMBL5425260
6.89	IC50	130	nM	CHEMBL5422282
6.89	IC50	130	nM	CHEMBL5415916
6.85	IC50	140	nM	CHEMBL5428926
6.85	IC50	140	nM	CHEMBL5408562
6.85	IC50	140	nM	CHEMBL5398843
6.85	IC50	140	nM	CHEMBL5411035
6.85	IC50	140	nM	CHEMBL5415508
6.82	IC50	150	nM	CHEMBL5429708
6.82	IC50	150	nM	CHEMBL5397090
6.82	IC50	150	nM	CHEMBL5398412
6.80	IC50	160	nM	CHEMBL5426513
6.80	IC50	160	nM	CHEMBL5422254
6.77	IC50	170	nM	CHEMBL5411302
6.77	IC50	170	nM	CHEMBL5439463
6.77	IC50	170	nM	CHEMBL5410235
6.77	IC50	170	nM	CHEMBL5398791
6.75	IC50	180	nM	CHEMBL5437469
6.75	IC50	180	nM	CHEMBL5405342
6.75	IC50	180	nM	CHEMBL5408029
6.75	IC50	180	nM	CHEMBL5422061
6.75	IC50	180	nM	CHEMBL5416880
6.75	IC50	180	nM	CHEMBL5394161
6.72	IC50	190	nM	CHEMBL5397515
6.72	IC50	190	nM	CHEMBL5424317
6.70	IC50	200	nM	CHEMBL5415979
6.70	IC50	200	nM	CHEMBL5303480
6.70	IC50	200	nM	CHEMBL5432794
6.68	IC50	210	nM	CHEMBL5397308
6.64	IC50	230	nM	CHEMBL5423868
6.62	IC50	240	nM	CHEMBL5409665
6.62	IC50	240	nM	CHEMBL5401071
6.62	IC50	240	nM	CHEMBL5406702
6.60	IC50	250	nM	CHEMBL5418646
6.60	IC50	250	nM	CHEMBL5423038

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149144: Binding affinity to human PTDSS1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0805	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149144: Binding affinity to human PTDSS1 incubated for 45 mins by Kinobead based pull down assay	kd	6.3278	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
sodium arsenite	increases expression, increases abundance	2
FR900359	affects phosphorylation	1
coumarin	decreases phosphorylation	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Dust	decreases expression	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5393552	Binding	Inhibition of C-terminal HA-tagged and N-terminal FLAG-tagged PTDSS1 (unknown origin) expressed in baculovirus-infected Sf9 insect cell membranes using L-[14C(U)]-serine as substrate incubated for 20 mins and measured by scintillation count	Pyrrolopyrazole derivative

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3F8	Abcam HEK293T PTDSS1 KO	Transformed cell line	Female
CVCL_E0M5	Ubigene HeLa PTDSS1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

17 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.