GPLD1

Summary

GPLD1 (glycosylphosphatidylinositol specific phospholipase D1, HGNC:4459) is a protein-coding gene on chromosome 6p22.3, encoding Phosphatidylinositol-glycan-specific phospholipase D (P80108). Hydrolyzes the inositol phosphate linkage of glycosylphosphatidylinositol (GPI)-anchored membrane proteins, thereby releasing them from the cell surface.

Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane.

Source: NCBI Gene 2822 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 159 total
• MANE Select transcript: NM_001503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4459
Approved symbol	GPLD1
Name	glycosylphosphatidylinositol specific phospholipase D1
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112293
Ensembl biotype	protein_coding
OMIM	602515
Entrez	2822

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000230036, ENST00000378243, ENST00000474784, ENST00000475417, ENST00000486892, ENST00000492917, ENST00000891935, ENST00000891936, ENST00000891937, ENST00000891938, ENST00000891939

RefSeq mRNA: 1 — MANE Select: NM_001503 NM_001503

CCDS: CCDS4553

Canonical transcript exons

ENST00000230036 — 25 exons

Exon	Start	End
ENSE00000692438	24460279	24460399
ENSE00000692441	24462730	24462795
ENSE00000692443	24466680	24466819
ENSE00000848207	24433363	24433389
ENSE00000848208	24436576	24436736
ENSE00000848213	24445546	24445639
ENSE00000848215	24445726	24445831
ENSE00000848216	24446838	24446979
ENSE00000848219	24447877	24448033
ENSE00000848221	24448134	24448208
ENSE00000848222	24449789	24449899
ENSE00000848224	24454015	24454201
ENSE00000973633	24456498	24456637
ENSE00000973634	24437113	24437289
ENSE00001175210	24489415	24489578
ENSE00001309727	24425832	24429118
ENSE00003468716	24467167	24467274
ENSE00003494193	24433187	24433237
ENSE00003507177	24479881	24479959
ENSE00003509994	24466912	24466939
ENSE00003539135	24473619	24473667
ENSE00003544832	24476181	24476278
ENSE00003595826	24486075	24486130
ENSE00003607650	24472582	24472636
ENSE00003675444	24475121	24475231

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 94.01.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5023 / max 99.2695, expressed in 542 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72182	0.6138	302
72181	0.5895	308
72177	0.1338	10
72180	0.0764	43
72179	0.0413	8
72176	0.0318	9
72178	0.0157	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.01	gold quality
penis	UBERON:0000989	88.50	gold quality
liver	UBERON:0002107	88.30	gold quality
buccal mucosa cell	CL:0002336	87.81	gold quality
oocyte	CL:0000023	87.23	gold quality
right lobe of liver	UBERON:0001114	86.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.40	gold quality
cerebellar cortex	UBERON:0002129	83.35	gold quality
cerebellar hemisphere	UBERON:0002245	83.29	gold quality
upper leg skin	UBERON:0004262	83.03	gold quality
cerebellum	UBERON:0002037	82.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.07	gold quality
blood vessel layer	UBERON:0004797	79.90	gold quality
descending thoracic aorta	UBERON:0002345	77.69	gold quality
cerebellar vermis	UBERON:0004720	77.54	gold quality
primary visual cortex	UBERON:0002436	76.91	gold quality
thoracic aorta	UBERON:0001515	75.92	gold quality
ascending aorta	UBERON:0001496	75.74	gold quality
cortical plate	UBERON:0005343	75.51	gold quality
skin of abdomen	UBERON:0001416	75.34	gold quality
skin of leg	UBERON:0001511	75.14	gold quality
mammalian vulva	UBERON:0000997	74.86	gold quality
zone of skin	UBERON:0000014	74.68	gold quality
endothelial cell	CL:0000115	74.26	silver quality
Brodmann (1909) area 23	UBERON:0013554	73.15	gold quality
occipital lobe	UBERON:0002021	73.03	gold quality
nipple	UBERON:0002030	72.97	gold quality
aorta	UBERON:0000947	72.72	gold quality
right frontal lobe	UBERON:0002810	72.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

134 targeting GPLD1, 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-1193	100.00	65.93	529
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244
HSA-LET-7A-2-3P	99.87	70.53	1921

Literature-anchored findings (GeneRIF, showing 30)

• In human ovarian cancer cell lines, GPI-PLD mRNA expression correlated with GPI-PLD enzyme activity and with the shedding of the GPI-anchored tumor and prognostic markers, urokinase receptor and CA125, from the cell surface. (PMID:12090469)
• increased serum glycosylphosphatidylinositol-specific phospholipase D is associated with insulin resistance in a cohort with a wide range of insulin sensitivity (PMID:14767861)
• identified as component of human trypanosome lytic factor 1 (TLF1) (PMID:15500911)
• PLD activation is a novel finding for the D(3) receptor, and is the first example of an effector system where D(3) signals without G(i)/G(o) protein intermediates. (PMID:15500962)
• CTLA-4 may be stored in a specialized compartment in regulatory T cells that can be triggered rapidly for deployment to the plasma membrane in a phospholipase D- and ADP ribosylation factor-1-dependent manner (PMID:15814706)
• Data describe the role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses. (PMID:16831865)
• GPI-PLD probably had no contribution to hematopoietic stem cell homing, which may due to its low or no expression in cord blood, bone marrow and mobilized peripheral blood CD34(+) cells. (PMID:17467053)
• Data indicate that a critical component of Ras signaling is the activation of PLD. (PMID:17949898)
• We show that human PLD1b and PLD2a contain functional caspase 3 cleavage sites and identify the critical aspartate residues within PLD1b that affect its activation by phorbol esters. (PMID:18298948)
• The serum GPI-PLD activities, the protein and mRNA levels of GPI-PLD in hepatocellular carcinoma patients were decreased by 40%, 60% and 56%, respectively. (PMID:19135435)
• The mRNA expression and activity of GPI-PLD in de novo and refractory or relapsed acute myeloid leukemia patients are obviously higher than those in normal controls. (PMID:20137110)
• The role of phospholipase D in the transport of VAT1 to plasma membranes and in phosphatidic acid metabolism in neutrophils is reported. (PMID:20858461)
• This study revealed the novel mechanism of bleomycin-induced redox-sensitive activation of phospholipase D leading to the generation of phosphaticid acid. (PMID:21131602)
• genetic variation of GPLD1 appears to associate with circulating glycosylphosphatidylinositol-specific phospholipase D levels (PMID:22260953)
• This study indicated that PLD participates in the same signaling pathway in this breast cancer cell line. (PMID:22481092)
• PLD1 and PLD2 mutants inhibit very-low-density lipoprotein-induced aldosterone production in HAC15 cells. (PMID:24956203)
• Functional regulation of phospholipase D expression in cancer and inflammation. (PMID:24990948)
• Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin (mTOR). (PMID:24990952)
• At the cellular level, PLD and its reaction product, phosphatidate, interact with a large number of protein partners that are directly related to the actin cytoskeleton and cell migration. (PMID:24990954)
• AMPK suppresses PLD activity, and PLD suppresses AMPK via mTOR. (PMID:25632961)
• suggest that the down-regulation of GPI-PLD protein may be involved in prion propagation in the brains of prion diseases (PMID:25867459)
• our findings showed that ANRIL is an lncRNA responsible in anti-tumorigenesis caused by PLD inhibition and combined incorporation of ANRIL into PLD inhibition-induced anti-tumorigenic signaling network (PMID:25964559)
• An observed increase in PLD activity was mediated through boosting the binding of PLD with dynamin which in turn facilitated fibronectin-induced cell spreading. (PMID:26341143)
• Low aggressive MCF-7 breast cancer cells have low endogenous PLD enzymatic activity and cell invasion, concomitant with high expression of miR-203, -887, and -3619 and miR-182 and miR-182. (PMID:26567912)
• c-Myc influences GPI-AP signaling transcriptionally and posttranslational and represses GPI-AP anti-proliferative signaling in tumors (PMID:27232633)
• Study discovered novel and independent associations of prediabetes and related traits with MASP1, and some evidence for associations with THBS1, GPLD1 and ApoA-IV, suggesting a role for these proteins in the pathophysiology of type 2 diabetes. (PMID:27344311)
• computational study suggests that although curcumin to some extent binds with Tp receptor, yet the inhibition of Arf6GDP to Arf6GTP conversion appeared to be an important mechanism by which curcumin inhibits U46619-induced increase in PLD activity in PASMCs. (PMID:28780751)
• Serum GPI-PLD in the NAFLD (+) group was significantly higher than in the NAFLD (-) group in men with metabolic syndrome. (PMID:30457913)
• RalA, PLD and mTORC1 Are Required for Kinase-Independent Pathways in DGKbeta-Induced Neurite Outgrowth. (PMID:34944458)
• The role of GPLD1 in chronic diseases. (PMID:37393554)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gpld1	ENSMUSG00000021340
rattus_norvegicus	Gpld1	ENSRNOG00000017702

Protein

Protein identifiers

Phosphatidylinositol-glycan-specific phospholipase D — P80108 (reviewed: P80108)

Alternative names: Glycoprotein phospholipase D, Glycosyl-phosphatidylinositol-specific phospholipase D

All UniProt accessions (1): P80108

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the inositol phosphate linkage of glycosylphosphatidylinositol (GPI)-anchored membrane proteins, thereby releasing them from the cell surface. Cleaves on the inositol side of the anchor, leaving the phosphate group attached to the membrane. This release of GPI-anchored proteins can modulate diverse biological processes, including the activation of signaling pathways.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Similarity. Belongs to the GPLD1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P80108-1	1	yes
P80108-2	2

RefSeq proteins (1): NP_001494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001028	Gprt_PLipase_D	Family
IPR013517	FG-GAP	Repeat
IPR013519	Int_alpha_beta-p	Repeat
IPR028994	Integrin_alpha_N	Homologous_superfamily
IPR029002	PLPC/GPLD1	Domain

Pfam: PF00882, PF01839

Enzyme classification (BRENDA):

• EC 3.1.4.50 — glycosylphosphatidylinositol phospholipase D (BRENDA: 8 organisms, 41 substrates, 31 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
PHOSPHATIDYLINOSITOL-GLYCAN-ANCHOR OF MEMBRANE F	0.0001	1

Catalyzed reactions (Rhea), 1 shown:

• [protein]-C-terminal carboxyl phosphoethanolamide-(1-radyl-2-octadecanoyl)-GPI(deacylinositol-H7) + H2O = [protein]-C-terminal carboxyl phosphoethanolamide-glycosylinositol (deacylinositol-H7) + 1-radyl-2-octadecanoyl-sn-glycero-3-phosphate + H(+) (RHEA:86263)

UniProt features (30 total): glycosylation site 10, sequence variant 8, repeat 7, splice variant 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80108-F1	87.63	0.73

Functional residue map

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

Glycosylation sites (10): 271, 292, 307, 321, 501, 568, 591, 604, 659, 94

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 304 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MORF_FLT1, GOBP_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, MODULE_64, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (28): ossification (GO:0001503), cell migration involved in sprouting angiogenesis (GO:0002042), chondrocyte differentiation (GO:0002062), complement receptor mediated signaling pathway (GO:0002430), negative regulation of cell population proliferation (GO:0008285), insulin receptor signaling pathway (GO:0008286), protein secretion (GO:0009306), response to glucose (GO:0009749), positive regulation of endothelial cell migration (GO:0010595), positive regulation of alkaline phosphatase activity (GO:0010694), positive regulation of triglyceride biosynthetic process (GO:0010867), negative regulation of triglyceride catabolic process (GO:0010897), positive regulation of glucose metabolic process (GO:0010907), positive regulation of high-density lipoprotein particle clearance (GO:0010983), cellular response to insulin stimulus (GO:0032869), hematopoietic stem cell migration (GO:0035701), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), positive regulation of apoptotic process (GO:0043065), phosphatidylcholine metabolic process (GO:0046470), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), transepithelial transport (GO:0070633), cellular response to cholesterol (GO:0071397), cellular response to triglyceride (GO:0071401), cellular response to xenobiotic stimulus (GO:0071466), cellular response to pH (GO:0071467), hematopoietic stem cell migration to bone marrow (GO:0097241), regulation of cellular response to insulin stimulus (GO:1900076), lipid metabolic process (GO:0006629)

GO Molecular Function (4): GPI anchor phospholipase D activity (GO:0004621), D-type glycerophospholipase activity (GO:0004630), sodium channel regulator activity (GO:0017080), hydrolase activity (GO:0016787)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), extracellular matrix (GO:0031012), intracellular membrane-bounded organelle (GO:0043231), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular anatomical structure	2
multicellular organismal process	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
cell differentiation	1
cartilage development	1
immune response-activating cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
response to hexose	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
alkaline phosphatase activity	1
positive regulation of phosphatase activity	1
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
positive regulation of lipid biosynthetic process	1
positive regulation of triglyceride metabolic process	1
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
negative regulation of lipid catabolic process	1
negative regulation of triglyceride metabolic process	1
glucose metabolic process	1
regulation of glucose metabolic process	1
positive regulation of carbohydrate metabolic process	1
positive regulation of small molecule metabolic process	1
regulation of high-density lipoprotein particle clearance	1
positive regulation of lipoprotein particle clearance	1
high-density lipoprotein particle clearance	1
response to insulin	1
cellular response to peptide hormone stimulus	1

Protein interactions and networks

STRING

914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPLD1	PLD2	O14939	842
GPLD1	PLD1	Q13393	841
GPLD1	PLPP3	O14495	761
GPLD1	PLPP2	O43688	761
GPLD1	PLPP1	O14494	745
GPLD1	ALPL	P05186	640
GPLD1	APOA2	P02652	582
GPLD1	APOL1	O14791	524
GPLD1	ALDH5A1	P51649	512
GPLD1	APOF	Q13790	511
GPLD1	SPHK1	Q9NYA1	505
GPLD1	FCER1A	P12319	497
GPLD1	CRTAC1	Q9NQ79	467
GPLD1	ITIH3	Q06033	462
GPLD1	ITIH1	P19827	456

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): HIF1A (Affinity Capture-Western), GPLD1 (Affinity Capture-Western), GPLD1 (Affinity Capture-Western), GPLD1 (Affinity Capture-MS), APOA4 (Affinity Capture-Western), APOA1 (Affinity Capture-Western), APOA1 (Reconstituted Complex), APOA4 (Reconstituted Complex), GPLD1 (Affinity Capture-MS), GPLD1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A0JPF9, A1A4L5, A4IF69, G3GXG9, O43933, O70362, P19686, P57075, P80108, P80109, Q02108, Q0V9N0, Q14703, Q28CZ7, Q2TBM9, Q3B7N1, Q3U213, Q3U3W5, Q3UY23, Q4ZHS0, Q5BL07, Q5XFW6, Q5ZI67, Q5ZKL5, Q6NRS1, Q6P2P2, Q6ZPR6, Q80Y20, Q86WJ1, Q8BGG7, Q8BWR4, Q8BZW8, Q8C042, Q8L735, Q8LEV3, Q8NBF2, Q8R2H5, Q8TF42, Q8VZ10

Diamond homologs: A2ARA8, O70362, P06756, P08514, P08648, P11688, P12080, P26008, P26009, P34446, P43406, P53708, P53711, P80108, P80109, P80746, Q06274, Q27977, Q61739, Q86AV9, Q8R2H5, Q9QUM0, F1MMS9, P05555, P17852, P23229, P26006, P26007, Q13683, Q61738, Q62470, Q63258, O75578, P20701, P38570, Q00651, Q13797, Q24247, Q60677, Q91687

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3186 predictions. Top by Δscore:

Variant	Effect	Δscore
6:24429119:C:CC	acceptor_gain	1.0000
6:24436572:TTACC:T	donor_loss	1.0000
6:24436573:TACC:T	donor_loss	1.0000
6:24436574:A:AC	donor_gain	1.0000
6:24436574:AC:A	donor_gain	1.0000
6:24436575:C:CC	donor_gain	1.0000
6:24436575:CC:C	donor_gain	1.0000
6:24436575:CCT:C	donor_gain	1.0000
6:24436575:CCTT:C	donor_gain	1.0000
6:24436575:CCTTT:C	donor_gain	1.0000
6:24436732:TTCAT:T	acceptor_gain	1.0000
6:24436733:TCAT:T	acceptor_gain	1.0000
6:24436734:CAT:C	acceptor_gain	1.0000
6:24436734:CATC:C	acceptor_gain	1.0000
6:24436735:AT:A	acceptor_gain	1.0000
6:24436736:TC:T	acceptor_loss	1.0000
6:24436737:C:CA	acceptor_loss	1.0000
6:24436737:C:CC	acceptor_gain	1.0000
6:24436744:C:CT	acceptor_gain	1.0000
6:24436745:A:T	acceptor_gain	1.0000
6:24436746:A:AC	acceptor_gain	1.0000
6:24436746:A:C	acceptor_gain	1.0000
6:24437110:TACCT:T	donor_loss	1.0000
6:24437111:ACC:A	donor_loss	1.0000
6:24445539:GACCT:G	donor_loss	1.0000
6:24445540:ACCT:A	donor_loss	1.0000
6:24445541:CCTAC:C	donor_loss	1.0000
6:24445542:CTA:C	donor_loss	1.0000
6:24445543:TA:T	donor_loss	1.0000
6:24445544:ACCG:A	donor_loss	1.0000

AlphaMissense

5496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:24476223:G:C	S96R	0.995
6:24476223:G:T	S96R	0.995
6:24476225:T:G	S96R	0.995
6:24467254:A:G	L189P	0.993
6:24475168:A:G	W132R	0.991
6:24475168:A:T	W132R	0.991
6:24472583:A:G	W182R	0.990
6:24472583:A:T	W182R	0.990
6:24472620:G:C	S169R	0.989
6:24472620:G:T	S169R	0.989
6:24472622:T:G	S169R	0.989
6:24475166:C:A	W132C	0.988
6:24475166:C:G	W132C	0.988
6:24467192:A:G	C210R	0.987
6:24467190:A:C	C210W	0.986
6:24475140:A:G	F141S	0.986
6:24475208:G:C	F118L	0.986
6:24475208:G:T	F118L	0.986
6:24475210:A:G	F118L	0.986
6:24433221:C:T	G801E	0.985
6:24475180:C:G	A128P	0.985
6:24479889:C:G	C75S	0.985
6:24479890:A:T	C75S	0.985
6:24433222:C:A	G801W	0.984
6:24449832:G:T	A468D	0.983
6:24448208:C:G	G483R	0.981
6:24449883:C:T	G451D	0.981
6:24467274:C:A	W182C	0.981
6:24467274:C:G	W182C	0.981
6:24475200:C:T	G121E	0.981

dbSNP variants (sampled 300 via entrez): RS1000063174 (6:24492376 C>G,T), RS1000072673 (6:24442192 A>G), RS1000088723 (6:24451940 G>A,C), RS1000221633 (6:24488579 A>T), RS1000271913 (6:24431015 A>G), RS1000303966 (6:24478606 G>C), RS1000314887 (6:24436477 T>C), RS1000370319 (6:24494925 TCCCCGCGAC>T), RS1000375469 (6:24457831 C>G,T), RS1000435859 (6:24453012 C>CA), RS1000445173 (6:24441188 T>A), RS1000481622 (6:24494187 T>C), RS1000637074 (6:24490611 G>T), RS1000684240 (6:24492262 T>C), RS1000818669 (6:24492428 C>A,G)

Disease associations

OMIM: gene MIM:602515 | disease phenotypes: MIM:271980

GenCC curated gene-disease

Mondo (1): succinic semialdehyde dehydrogenase deficiency (MONDO:0010083)

Orphanet (1): Succinic semialdehyde dehydrogenase deficiency (Orphanet:22)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000248_6	Liver enzyme levels	1.000000e-11
GCST000583_14	Hematological and biochemical traits	2.000000e-11
GCST001276_12	Liver enzyme levels (alkaline phosphatase)	6.000000e-26
GCST006016_31	Serum alkaline phosphatase levels	6.000000e-84
GCST009652_44	Serum alkaline phosphatase levels	3.000000e-43
GCST009652_45	Serum alkaline phosphatase levels	2.000000e-29
GCST009652_46	Serum alkaline phosphatase levels	9.000000e-17
GCST009652_47	Serum alkaline phosphatase levels	1.000000e-13
GCST009652_48	Serum alkaline phosphatase levels	4.000000e-11
GCST009652_9	Serum alkaline phosphatase levels	2.000000e-111
GCST011353_41	Serum alkaline phosphatase levels	2.000000e-107
GCST90011900_141	Serum alkaline phosphatase levels	2.000000e-248

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004761	uric acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535803	succinic semialdehyde dehydrogenase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
Aflatoxin B1	decreases expression, increases methylation	3
Nickel	decreases expression	2
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	increases methylation	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
Resveratrol	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Carbamazepine	affects expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Diclofenac	affects expression	1
Ellagic Acid	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00246870	Not specified	COMPLETED	PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
NCT03758521	Not specified	RECRUITING	Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency