GNPAT

Summary

GNPAT (glyceronephosphate O-acyltransferase, HGNC:4416) is a protein-coding gene on chromosome 1q42.2, encoding Dihydroxyacetone phosphate acyltransferase (O15228). Dihydroxyacetonephosphate acyltransferase catalyzing the first step in the biosynthesis of plasmalogens, a subset of phospholipids that differ from other glycerolipids by having an alkyl chain attached through a vinyl ether linkage at the sn-1 position of the glycerol backbone,….

This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8443 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glyceronephosphate O-acyltransferase deficiency (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 584 total — 25 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_014236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4416
Approved symbol	GNPAT
Name	glyceronephosphate O-acyltransferase
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Aliases	DHAPAT, DAPAT, DAP-AT
Ensembl gene	ENSG00000116906
Ensembl biotype	protein_coding
OMIM	602744
Entrez	8443

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000366647, ENST00000416000, ENST00000436239, ENST00000469332, ENST00000492459, ENST00000644483, ENST00000851681, ENST00000851682, ENST00000851683, ENST00000851684, ENST00000851685, ENST00000851686, ENST00000851687, ENST00000851688, ENST00000851689, ENST00000851690, ENST00000851691, ENST00000851692, ENST00000926539, ENST00000926540, ENST00000926541, ENST00000926542, ENST00000958394, ENST00000958395, ENST00000958396, ENST00000958397, ENST00000958398, ENST00000958399

RefSeq mRNA: 2 — MANE Select: NM_014236 NM_001316350, NM_014236

CCDS: CCDS1592

Canonical transcript exons

ENST00000366647 — 16 exons

Exon	Start	End
ENSE00000921376	231250961	231251143
ENSE00000921377	231260507	231260683
ENSE00000921378	231262723	231262852
ENSE00000921379	231265293	231265420
ENSE00000921380	231265712	231265787
ENSE00001704348	231277499	231277973
ENSE00001818342	231241212	231241456
ENSE00002212025	231275221	231275320
ENSE00002230017	231270758	231271000
ENSE00002263397	231272312	231272391
ENSE00002264620	231267680	231267903
ENSE00002280603	231273922	231274062
ENSE00002286223	231266014	231266165
ENSE00003524717	231266277	231266407
ENSE00003588572	231275405	231275498
ENSE00003620220	231276135	231276196

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6767 / max 380.6183, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9046	39.3853	1823
9048	1.9681	1097
9047	0.3233	141

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	97.56	gold quality
biceps brachii	UBERON:0001507	97.53	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.29	gold quality
deltoid	UBERON:0001476	97.14	gold quality
triceps brachii	UBERON:0001509	97.09	gold quality
vastus lateralis	UBERON:0001379	96.93	gold quality
gastrocnemius	UBERON:0001388	96.68	gold quality
diaphragm	UBERON:0001103	96.50	gold quality
muscle of leg	UBERON:0001383	96.43	gold quality
muscle organ	UBERON:0001630	96.39	gold quality
sperm	CL:0000019	96.34	gold quality
skeletal muscle tissue	UBERON:0001134	96.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.21	gold quality
left ventricle myocardium	UBERON:0006566	96.11	gold quality
quadriceps femoris	UBERON:0001377	96.07	gold quality
male germ cell	CL:0000015	95.82	gold quality
heart right ventricle	UBERON:0002080	95.82	gold quality
muscle tissue	UBERON:0002385	95.77	gold quality
upper leg skin	UBERON:0004262	95.77	gold quality
tongue squamous epithelium	UBERON:0006919	95.75	gold quality
tibialis anterior	UBERON:0001385	95.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.49	gold quality
myocardium	UBERON:0002349	95.20	gold quality
ganglionic eminence	UBERON:0004023	94.93	gold quality
body of pancreas	UBERON:0001150	94.78	gold quality
parotid gland	UBERON:0001831	94.76	gold quality
choroid plexus epithelium	UBERON:0003911	94.74	gold quality
ventricular zone	UBERON:0003053	94.39	gold quality
cardiac ventricle	UBERON:0002082	94.31	gold quality
endothelial cell	CL:0000115	94.30	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting GNPAT, 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-8485	100.00	77.57	4731
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-541-3P	96.07	66.11	1271

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• peroxisomal DHAPAT is essential for the biosynthesis of plasmalogens in animal cells (PMID:15687349)
• Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia. (PMID:16997000)
• Novel mutations in GNPAT cause rhizomelic chondrodysplasia punctata (RCDP) type 2. (PMID:21990100)
• ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucoseceramide glucosyltransferase (UGCG). (PMID:23933200)
• The variant of the GNPAT gene showed the most significant association with severe iron overload. (PMID:25605615)
• C282Y homozygotes referred for HFE testing commonly have a GNPAT variant. This GNPAT variant does not appear be a co-modifying gene affecting expression of HFE related hemochromatosis in this population. The GNPAT variant does not predict the severity of iron overload. (PMID:27740525)
• Here, we report the characterization of the recombinant human DHAP acyl-transferase, which performs the first step in alkyl-DHAP synthesis. (PMID:27836547)
• GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption. (PMID:27936396)
• Reduction of GNPAT activated NF-kappaB in glial cell lines and microglia in cortex. (PMID:28292831)
• GNPAT rs11558492 is not a major modifier of iron status and is not associated with liver fibrosis in HFE-related Hemochromatosis patients. (PMID:28425416)
• GNPAT and USP30-mediated stabilization of DRP1 play a critical role in the development of hepatocellular carcinoma (PMID:30143522)
• Stabilization of FASN by ACAT1-mediated GNPAT acetylation promotes lipid metabolism and hepatocarcinogenesis. (PMID:31974474)
• Increased frequency of GNPAT p.D519G in compound HFE p.C282Y/p.H63D heterozygotes with elevated serum ferritin levels. (PMID:32652459)
• Genetic adaptation of skin pigmentation in highland Tibetans. (PMID:36161951)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnpat	ENSDARG00000074401
danio_rerio	gnpat2	ENSDARG00000078770
mus_musculus	Gnpat	ENSMUSG00000031985
rattus_norvegicus	Gnpat	ENSRNOG00000019205
drosophila_melanogaster	Gnpat	FBGN0040212
caenorhabditis_elegans		WBGENE00012911

Paralogs (2): GPAM (ENSG00000119927), GPAT2 (ENSG00000186281)

Protein

Protein identifiers

Dihydroxyacetone phosphate acyltransferase — O15228 (reviewed: O15228)

Alternative names: Acyl-CoA:dihydroxyacetonephosphateacyltransferase, Glycerone-phosphate O-acyltransferase

All UniProt accessions (4): A0A2R8YH69, O15228, Q5TBH6, Q5TBH8

UniProt curated annotations — full annotation on UniProt →

Function. Dihydroxyacetonephosphate acyltransferase catalyzing the first step in the biosynthesis of plasmalogens, a subset of phospholipids that differ from other glycerolipids by having an alkyl chain attached through a vinyl ether linkage at the sn-1 position of the glycerol backbone, and which unique physical properties have an impact on various aspects of cell signaling and membrane biology.

Subunit / interactions. Part of a heterotrimeric complex composed of GNPAT, AGPS and a modified form of GNPAT.

Subcellular location. Peroxisome membrane.

Disease relevance. Rhizomelic chondrodysplasia punctata 2 (RCDP2) [MIM:222765] A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe intellectual disability with spasticity. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.

Pathway. Membrane lipid metabolism; glycerophospholipid metabolism.

Similarity. Belongs to the GPAT/DAPAT family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15228-1	1	yes
O15228-2	2

RefSeq proteins (2): NP_001303279, NP_055051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002123	Plipid/glycerol_acylTrfase	Domain
IPR022284	GPAT/DHAPAT	Family
IPR028353	DHAPAT	Family
IPR041728	GPAT/DHAPAT_LPLAT	Domain
IPR045520	GPAT/DHAPAT_C	Domain

Pfam: PF01553, PF19277

Enzyme classification (BRENDA):

• EC 2.3.1.42 — glycerone-phosphate O-acyltransferase (BRENDA: 14 organisms, 103 substrates, 61 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DIHYDROXYACETONE PHOSPHATE	0.02–0.79	5
PALMITOYL-COA	0.04–0.065	2

Catalyzed reactions (Rhea), 2 shown:

• dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone 3-phosphate + CoA (RHEA:17657)
• dihydroxyacetone phosphate + hexadecanoyl-CoA = 1-hexadecanoylglycerone 3-phosphate + CoA (RHEA:40715)

UniProt features (14 total): sequence variant 5, modified residue 3, short sequence motif 2, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15228-F1	88.96	0.75

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 (3): 12, 17, 643

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-75896	Plasmalogen biosynthesis
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 295 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_METENCEPHALON_DEVELOPMENT, MORF_MSH3, GOBP_SYNAPSE_ASSEMBLY, GGGNRMNNYCAT_UNKNOWN, XU_GH1_AUTOCRINE_TARGETS_UP, MORF_BRCA1, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_ESR1, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (9): phosphatidic acid biosynthetic process (GO:0006654), synapse assembly (GO:0007416), ether lipid biosynthetic process (GO:0008611), cerebellum morphogenesis (GO:0021587), paranodal junction assembly (GO:0030913), membrane organization (GO:0061024), lipid metabolic process (GO:0006629), glycerophospholipid metabolic process (GO:0006650), myelination (GO:0042552)

GO Molecular Function (5): glycerone-phosphate O-acyltransferase activity (GO:0016287), catalytic activity (GO:0003824), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (7): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), cell junction (GO:0030054), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Wax and plasmalogen biosynthesis	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
peroxisome	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
nervous system development	1
cell junction assembly	1
synapse organization	1
lipid biosynthetic process	1
ether lipid metabolic process	1
glycerol ether biosynthetic process	1
anatomical structure morphogenesis	1
cerebellum development	1
hindbrain morphogenesis	1
cell-cell junction assembly	1
cellular component assembly involved in morphogenesis	1
myelin assembly	1
cellular component organization	1
primary metabolic process	1
phospholipid metabolic process	1
glycerolipid metabolic process	1
axon ensheathment	1
O-acetyltransferase activity	1
molecular_function	1
catalytic activity	1
transferase activity	1
microbody	1
microbody membrane	1
microbody lumen	1
cytoplasm	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNPAT	AGPS	O00116	979
GNPAT	ACAA1	P09110	879
GNPAT	PEX7	O00628	840
GNPAT	FAR1	Q8WVX9	832
GNPAT	FLOT1	O75955	786
GNPAT	HSD17B4	P51659	780
GNPAT	CNTNAP1	P78357	776
GNPAT	NSDHL	Q15738	761
GNPAT	ACOX1	Q15067	713
GNPAT	PEX2	P28328	693
GNPAT	FAR2	Q96K12	691
GNPAT	EHHADH	Q08426	683
GNPAT	PHYH	O14832	658
GNPAT	PEX26	Q7Z412	655
GNPAT	CNTN1	Q12860	649

IntAct

93 interactions, top by confidence:

A	B	Type	Score
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
FAM131B	AURKA	psi-mi:“MI:0914”(association)	0.530
ZNF544	GNPAT	psi-mi:“MI:0914”(association)	0.530
DCAF11	GNPAT	psi-mi:“MI:0914”(association)	0.530
ODAD4	GNPAT	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
BSG	BTAF1	psi-mi:“MI:0914”(association)	0.530
GNPAT	GPR3	psi-mi:“MI:0915”(physical association)	0.370
HSPB1	GNPAT	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ORF27	GNPAT	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
PROSER2	VWA8	psi-mi:“MI:0914”(association)	0.350
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
LYPD3	CLASP2	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
C1QTNF2	GNPAT	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Two-hybrid), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GNPAT (Affinity Capture-MS)

ESM2 similar proteins: A0A1J6KGJ9, A0A314KSQ4, A2RU49, A4IF87, A5PJU6, B4G0F3, B8BKI7, B9SQI7, C6JS30, E0CSI1, E0CTF3, G1SPE9, O08848, O15228, O22190, O23732, O43929, O82333, O88708, P11172, P31531, P37821, P42700, P46416, Q05B63, Q10D00, Q28DB5, Q2R483, Q2YDI2, Q3T067, Q3U1V6, Q4U3P8, Q5R514, Q5R6Z7, Q5R962, Q6GM82, Q6I581, Q6YJI5, Q7TNK6, Q7Z4G4

Diamond homologs: A1JRU2, A1KLH6, A4IF87, A5U5H8, A6VQ68, A8GKB6, B2HNJ0, B8ZRA3, C1AEU7, G1SPE9, O15228, P65735, P98192, P9WI58, P9WI59, P9WI60, P9WI61, Q7TYH5, Q9ES71, Q9X7B0, A0L2D7, A1AIL8, A1RE94, A1SBC6, A4W5F4, A4XWX9, A4YC03, A5W867, A6TGV0, A6V1B5, A7ZUR3, A8A7E1, A8H9R9, A9MGP8, A9N1L4, B0KS79, B0TNU4, B0U229, B1IUL1, B1JBS6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	8	20.7×	1e-06
SLC transporter disorders	5	15.2×	2e-03
R-HSA-425366	5	13.5×	3e-03
Disorders of transmembrane transporters	5	10.4×	7e-03
SLC-mediated transmembrane transport	8	7.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	36
Uncertain significance	162
Likely benign	284
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073464	NM_014236.4(GNPAT):c.1583_1586del (p.Leu528fs)	Pathogenic
1252036	NM_014236.4(GNPAT):c.569-3T>G	Pathogenic
1427016	NM_014236.4(GNPAT):c.407del (p.Lys136fs)	Pathogenic
2675939	NM_014236.4(GNPAT):c.487C>T (p.Arg163Ter)	Pathogenic
2703571	NM_014236.4(GNPAT):c.1795C>T (p.Gln599Ter)	Pathogenic
2704212	NM_014236.4(GNPAT):c.410dup (p.Cys138fs)	Pathogenic
2734108	NM_014236.4(GNPAT):c.1428del (p.Met477fs)	Pathogenic
2746333	NM_014236.4(GNPAT):c.924+1G>T	Pathogenic
2760073	NM_014236.4(GNPAT):c.397del (p.Ile133fs)	Pathogenic
2802253	NM_014236.4(GNPAT):c.1230_1231dup (p.Trp411fs)	Pathogenic
2819004	NM_014236.4(GNPAT):c.822dup (p.Thr275fs)	Pathogenic
2826633	NM_014236.4(GNPAT):c.1763del (p.Leu587_Leu588insTer)	Pathogenic
2829713	NM_014236.4(GNPAT):c.593del (p.Gly198fs)	Pathogenic
2832105	NM_014236.4(GNPAT):c.1857T>A (p.Cys619Ter)	Pathogenic
2853724	NM_014236.4(GNPAT):c.1220_1233del (p.Glu407fs)	Pathogenic
3010116	NM_014236.4(GNPAT):c.604C>T (p.Arg202Ter)	Pathogenic
35467	NM_014236.4(GNPAT):c.1429_1430del (p.Met477fs)	Pathogenic
35468	NM_014236.4(GNPAT):c.1937+5G>A	Pathogenic
4278055	NM_014236.4(GNPAT):c.1602+1G>A	Pathogenic
4700104	NM_014236.4(GNPAT):c.647_659dup (p.Trp220Ter)	Pathogenic
4736393	NM_014236.4(GNPAT):c.1285A>T (p.Lys429Ter)	Pathogenic
6841	NM_014236.4(GNPAT):c.632G>A (p.Arg211His)	Pathogenic
6843	NM_014236.4(GNPAT):c.849_850dup (p.Tyr284fs)	Pathogenic
6844	NM_014236.4(GNPAT):c.780del (p.Asn261fs)	Pathogenic
6845	NM_014236.4(GNPAT):c.1575del (p.Phe525fs)	Pathogenic
1067093	NM_014236.4(GNPAT):c.773-2A>G	Likely pathogenic
1324493	NM_014236.4(GNPAT):c.298C>T (p.Arg100Ter)	Likely pathogenic
1349149	NM_014236.4(GNPAT):c.1522+2T>G	Likely pathogenic
1898893	NM_014236.4(GNPAT):c.1603-1G>C	Likely pathogenic
2675927	NM_014236.4(GNPAT):c.1058dup (p.Tyr353Ter)	Likely pathogenic

SpliceAI

2796 predictions. Top by Δscore:

Variant	Effect	Δscore
1:231250959:A:AG	acceptor_gain	1.0000
1:231250960:G:GG	acceptor_gain	1.0000
1:231260505:A:AG	acceptor_gain	1.0000
1:231260505:A:C	acceptor_loss	1.0000
1:231260506:G:A	acceptor_loss	1.0000
1:231260506:G:GT	acceptor_gain	1.0000
1:231260506:GC:G	acceptor_gain	1.0000
1:231260506:GCTT:G	acceptor_gain	1.0000
1:231260506:GCTTT:G	acceptor_gain	1.0000
1:231260680:GAAA:G	donor_gain	1.0000
1:231260684:G:GG	donor_gain	1.0000
1:231262720:A:AG	acceptor_gain	1.0000
1:231262721:A:G	acceptor_gain	1.0000
1:231265291:A:AG	acceptor_gain	1.0000
1:231265292:G:GG	acceptor_gain	1.0000
1:231265367:G:GA	donor_gain	1.0000
1:231266052:G:GT	donor_gain	1.0000
1:231266163:ACT:A	donor_gain	1.0000
1:231266164:CT:C	donor_gain	1.0000
1:231266166:GTAC:G	donor_gain	1.0000
1:231266265:T:TA	acceptor_gain	1.0000
1:231266375:GA:G	donor_gain	1.0000
1:231266401:TTCCA:T	donor_gain	1.0000
1:231267841:TGGAA:T	donor_gain	1.0000
1:231267865:GCT:G	donor_gain	1.0000
1:231270756:A:AG	acceptor_gain	1.0000
1:231270757:G:GG	acceptor_gain	1.0000
1:231270865:G:GT	donor_gain	1.0000
1:231270963:AGC:A	donor_gain	1.0000
1:231270997:A:T	donor_gain	1.0000

AlphaMissense

4496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:231262768:C:G	H162D	0.999
1:231262786:T:C	F168L	0.999
1:231262788:C:A	F168L	0.999
1:231262788:C:G	F168L	0.999
1:231262754:T:A	V157D	0.998
1:231262774:A:C	S164R	0.998
1:231262776:T:A	S164R	0.998
1:231262776:T:G	S164R	0.998
1:231262841:C:A	A186E	0.998
1:231266074:T:A	V278D	0.998
1:231262772:G:C	R163P	0.997
1:231262784:A:T	D167V	0.997
1:231265736:T:C	F241L	0.997
1:231265738:C:A	F241L	0.997
1:231265738:C:G	F241L	0.997
1:231266082:A:C	S281R	0.997
1:231266084:T:A	S281R	0.997
1:231266084:T:G	S281R	0.997
1:231262751:T:A	V156D	0.996
1:231262760:T:C	L159P	0.996
1:231262763:C:A	P160H	0.996
1:231262763:C:G	P160R	0.996
1:231262770:T:A	H162Q	0.996
1:231262770:T:G	H162Q	0.996
1:231262783:G:C	D167H	0.996
1:231262784:A:C	D167A	0.996
1:231266014:G:A	G258D	0.996
1:231262724:T:C	L147P	0.995
1:231262768:C:A	H162N	0.995
1:231262784:A:G	D167G	0.995

dbSNP variants (sampled 300 via entrez): RS1000046295 (1:231256847 A>T), RS1000078803 (1:231256645 C>T), RS1000133362 (1:231245803 C>T), RS1000162775 (1:231240337 A>C), RS1000322185 (1:231258740 C>G), RS1000342956 (1:231277364 C>T), RS1000361746 (1:231265522 C>T), RS1000445582 (1:231270369 T>C,G), RS1000585775 (1:231252437 G>C), RS1000605104 (1:231271887 T>C,G), RS1000619601 (1:231239895 C>T), RS1000683549 (1:231277012 A>G), RS1000704028 (1:231245896 G>C), RS1000715365 (1:231264031 C>A), RS1000833282 (1:231272068 C>G)

Disease associations

OMIM: gene MIM:602744 | disease phenotypes: MIM:215100, MIM:222765

GenCC curated gene-disease

Disease	Classification	Inheritance
glyceronephosphate O-acyltransferase deficiency	Definitive	Autosomal recessive
rhizomelic chondrodysplasia punctata type 2	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glyceronephosphate O-acyltransferase deficiency	Definitive	AR

Mondo (4): rhizomelic chondrodysplasia punctata (MONDO:0015776), rhizomelic chondrodysplasia punctata type 2 (MONDO:0009112), prostate cancer (MONDO:0008315), glyceronephosphate O-acyltransferase deficiency (MONDO:0100273)

Orphanet (3): Rhizomelic chondrodysplasia punctata (Orphanet:177), Rhizomelic chondrodysplasia punctata type 2 (Orphanet:309796), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000176	Submucous cleft hard palate
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000518	Cataract
HP:0000609	Optic nerve hypoplasia
HP:0000938	Osteopenia
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001636	Tetralogy of Fallot
HP:0002644	Abnormal pelvic girdle bone morphology
HP:0002650	Scoliosis
HP:0002832	Calcific stippling
HP:0003273	Hip contracture
HP:0003301	Irregular vertebral endplates
HP:0003417	Coronal cleft vertebrae
HP:0003498	Disproportionate short stature
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0005280	Depressed nasal bridge
HP:0005792	Short humerus

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018902	Chondrodysplasia Punctata, Rhizomelic	C05.116.099.708.195.200; C16.320.565.663.265; C18.452.648.663.265
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537607	Rhizomelic chondrodysplasia punctata, type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4494 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.66	Ki	22	nM	CHEMBL177210
6.77	Ki	169	nM	CHEMBL176303
6.30	IC50	500	nM	CHEMBL177210
6.25	Ki	556	nM	CHEMBL172381
6.10	IC50	800	nM	CHEMBL176303

PubChem BioAssay actives

5 with measured affinity, of 75 total; 3 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
(2S)-2-(3-carboxypropanoylamino)-6-hydrazinylheptanedioic acid	56757: Compound was tested for binding affinity against N-Succinyl Diaminopimelic Acid Aminotransferase from Escherichia coli	ki	0.0220	uM
(2S)-2-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-6-hydrazinylheptanedioic acid	56757: Compound was tested for binding affinity against N-Succinyl Diaminopimelic Acid Aminotransferase from Escherichia coli	ki	0.1690	uM
(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-6-hydrazinylheptanedioic acid	56757: Compound was tested for binding affinity against N-Succinyl Diaminopimelic Acid Aminotransferase from Escherichia coli	ki	0.5560	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
2,2-dithiobis(4,6-dichlorophenol)	affects response to substance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Hydralazine	affects cotreatment, increases expression	1
Hydrocortisone	increases expression, decreases reaction	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Thiram	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1
Mifepristone	decreases reaction, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

14 unique, capped per target: 8 functional, 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL665110	Binding	Compound was tested for 50% inhibition of N-Succinyl Diaminopimelic Acid Aminotransferase (DAP-AT) from Escherichia coli	Peptide inhibitors of N-succinyl diaminopimelic acid aminotransferase (DAP-AT): a novel class of antimicrobial compounds. — Bioorg Med Chem Lett
CHEMBL665116	Functional	Inhibition zone when tested against DAP-AT from Escherichia coli in L-agar at concentration 0.3 ug	Peptide inhibitors of N-succinyl diaminopimelic acid aminotransferase (DAP-AT): a novel class of antimicrobial compounds. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1T4	Abcam HeLa GNPAT KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer