GPD1

Summary

GPD1 (glycerol-3-phosphate dehydrogenase 1, HGNC:4455) is a protein-coding gene on chromosome 12q13.12, encoding Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic (P21695). Has glycerol-3-phosphate dehydrogenase activity.

This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carbohydrate and lipid metabolism by catalyzing the reversible conversion of dihydroxyacetone phosphate (DHAP) and reduced nicotine adenine dinucleotide (NADH) to glycerol-3-phosphate (G3P) and NAD+. The encoded cytosolic protein and mitochondrial glycerol-3-phosphate dehydrogenase also form a glycerol phosphate shuttle that facilitates the transfer of reducing equivalents from the cytosol to mitochondria. Mutations in this gene are a cause of transient infantile hypertriglyceridemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 2819 — RefSeq curated summary.

At a glance

• Gene–disease (curated): transient infantile hypertriglyceridemia and hepatosteatosis (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 173 total — 10 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 12
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_005276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4455
Approved symbol	GPD1
Name	glycerol-3-phosphate dehydrogenase 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167588
Ensembl biotype	protein_coding
OMIM	138420
Entrez	2819

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000301149, ENST00000547190, ENST00000547964, ENST00000548152, ENST00000548814, ENST00000550172, ENST00000551939, ENST00000872073, ENST00000872074, ENST00000872075, ENST00000872076, ENST00000872077, ENST00000872078, ENST00000942601, ENST00000942602, ENST00000942603, ENST00000942604

RefSeq mRNA: 2 — MANE Select: NM_005276 NM_001257199, NM_005276

CCDS: CCDS58229, CCDS8799

Canonical transcript exons

ENST00000301149 — 8 exons

Exon	Start	End
ENSE00001194116	50108024	50108130
ENSE00001239159	50109423	50111313
ENSE00001728210	50107567	50107800
ENSE00003511179	50105548	50105688
ENSE00003534304	50106288	50106426
ENSE00003550740	50106805	50106917
ENSE00003607132	50104574	50104751
ENSE00003633962	50104008	50104091

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 98.42.

FANTOM5 (CAGE): breadth broad, TPM avg 22.0004 / max 2791.0607, expressed in 375 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125413	20.0539	322
125414	0.9442	159
125412	0.9398	213
125411	0.0625	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	98.42	gold quality
adipose tissue	UBERON:0001013	98.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.20	gold quality
gastrocnemius	UBERON:0001388	97.73	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.12	gold quality
omental fat pad	UBERON:0010414	97.00	gold quality
peritoneum	UBERON:0002358	96.91	gold quality
triceps brachii	UBERON:0001509	96.82	gold quality
muscle of leg	UBERON:0001383	96.79	gold quality
connective tissue	UBERON:0002384	96.70	gold quality
muscle organ	UBERON:0001630	96.41	gold quality
vastus lateralis	UBERON:0001379	96.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.26	gold quality
right lobe of liver	UBERON:0001114	95.83	gold quality
quadriceps femoris	UBERON:0001377	95.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.32	gold quality
gluteal muscle	UBERON:0002000	95.18	gold quality
skeletal muscle tissue	UBERON:0001134	95.10	gold quality
biceps brachii	UBERON:0001507	94.51	gold quality
spinal cord	UBERON:0002240	94.47	gold quality
adult mammalian kidney	UBERON:0000082	93.58	gold quality
diaphragm	UBERON:0001103	93.23	silver quality
liver	UBERON:0002107	92.09	gold quality
nephron tubule	UBERON:0001231	91.35	gold quality
jejunal mucosa	UBERON:0000399	90.95	gold quality
duodenum	UBERON:0002114	90.88	gold quality
muscle tissue	UBERON:0002385	90.87	gold quality
thoracic mammary gland	UBERON:0005200	90.01	gold quality
mammary gland	UBERON:0001911	89.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	175.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, PPARA, TP53

miRNA regulators (miRDB)

102 targeting GPD1, 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-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 20)

• Identification and function of mutations in FAD-binding domain of mitochonrial glycerophosphate dehydrogenase in caucasians with type 2 diabetes mellitus. (PMID:11822825)
• GPD1 has a role in increased triacylglycerol production in adipose tissue of obese humans (PMID:14674682)
• The apoenzyme structure of GPD1 has been determined; an electrophilic catalytic mechanism by the epsilon-NH3+ group of Lys204 is proposed on the basis of structural analyses. (PMID:16460752)
• GpD1 is a weight-loss-responsive gene in skeletal muscle. Its observed transcriptional modulation may decrease triglyceride synthesis, with weight loss. (PMID:16849634)
• The activities of glycerol phosphate dehydrogenase were decreased by 73% in pancreatic islets of patients with type 2 diabetes. (PMID:19296078)
• the discovery overexpression of GPD1 and RRBP1 proteins and lack of expression for HNRNPH1 and SERPINB6 proteins which are new candidate biomarkers of colon cancer. (PMID:19425502)
• The expression levels of the GPD1 gene did not differ between patients with OSA and their matched controls. The results were not affected by the clinical and biochemical measurements, the sleep parameters or the severity of nocturnal hypoxemia. (PMID:20404019)
• Mutation analysis revealed a homozygous splicing mutation, c.361-1G>C, which resulted in an aberrantly spliced mRNA in the ten affected individuals. (PMID:22226083)
• massive hepatomegaly, fatty liver and severe hypertriglyceridemia carrying a compound heterozygous mutation in GPD1 (PMID:24549054)
• The R269A mutation of GPDH1 results in a 110-fold increase in K(m) (2.8 kcal/mol effect) and a 41,000-fold decrease in k(cat) (6.3 kcal/mol effect), which corresponds to a 9.1 kcal/mol destabilization of the transition state. (PMID:25884759)
• To recognize this entity by considering GPD1 mutations in appropriate clinical settings. (PMID:27368975)
• Although these data indicate that a lack of GPD1 inhibits gluconeogenesis from glycerol, chronic GPD1 deficiency may induce an adaptation that enhances gluconeogenesis from glycogenic amino acids (PMID:27733253)
• These results support the conclusion that the rate acceleration for Glycerol-3-Phosphate Dehydrogenase-catalyzed reactions is due to the stabilization of the transition state for hydride transfer by interactions with the protein catalyst. (PMID:29927590)
• Bioinformatics analyses performed with differentially regulated proteins highlighted the changes occurring in triacylglyceride (TAG) metabolism, and directed our attention to TAG metabolism-associated proteins, namely glycerol-3-phosphate dehydrogenase 1 (GPD1) and monoacylglycerol lipase (MAGL). (PMID:31467232)
• The Organization of Active Site Side Chains of Glycerol-3-phosphate Dehydrogenase Promotes Efficient Enzyme Catalysis and Rescue of Variant Enzymes. (PMID:32250105)
• [Transient infantile hypertriglyceridemia caused by GPD1 deficiency: report of two cases and literature review]. (PMID:33120465)
• A HIF1alpha-GPD1 feedforward loop inhibits the progression of renal clear cell carcinoma via mitochondrial function and lipid metabolism. (PMID:34098990)
• Decreased serum levels of glycerol-3- phosphate dehydrogenase 1 and monoacylglycerol lipase act as diagnostic biomarkers for breast cancer. (PMID:34657876)
• Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression. (PMID:36632231)
• Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases. (PMID:38689091)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpd1b	ENSDARG00000043180
danio_rerio	gpd1a	ENSDARG00000043701
mus_musculus	Gpd1	ENSMUSG00000023019
rattus_norvegicus	Gpd1	ENSRNOG00000056457
drosophila_melanogaster	Gpdh1	FBGN0001128
drosophila_melanogaster	Gpdh2	FBGN0034825
drosophila_melanogaster	Gpdh3	FBGN0263048
caenorhabditis_elegans	gpdh-1	WBGENE00009824
caenorhabditis_elegans		WBGENE00010778

Paralogs (1): GPD1L (ENSG00000152642)

Protein

Protein identifiers

Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic — P21695 (reviewed: P21695)

All UniProt accessions (3): A0A024R138, P21695, F8VSE8

UniProt curated annotations — full annotation on UniProt →

Function. Has glycerol-3-phosphate dehydrogenase activity.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in liver (at protein level).

Disease relevance. Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480] An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by zinc ions and sulfate.

Similarity. Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P21695-1	1	yes
P21695-2	2

RefSeq proteins (2): NP_001244128, NP_005267* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006109	G3P_DH_NAD-dep_C	Domain
IPR006168	G3P_DH_NAD-dep	Family
IPR008927	6-PGluconate_DH-like_C_sf	Homologous_superfamily
IPR011128	G3P_DH_NAD-dep_N	Domain
IPR013328	6PGD_dom2	Homologous_superfamily
IPR017751	G3P_DH_NAD-dep_euk	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF01210, PF07479

Enzyme classification (BRENDA):

• EC 1.1.1.8 — glycerol-3-phosphate dehydrogenase (NAD+) (BRENDA: 44 organisms, 55 substrates, 122 inhibitors, 158 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0044–316	40
NADH	0.001–32.4	28
DIHYDROXYACETONE PHOSPHATE	0.012–25	24
SN-GLYCEROL 3-PHOSPHATE	0.41–469	24
GLYCERONE PHOSPHATE	0.052–137	11
DL-GLYCEROL-3-PHOSPHATE	0.19–1.2	4
GLYCEROL 3-PHOSPHATE	0.59–2	4
GLYCEROL-3-PHOSPHATE	0.468–34	4
NADPH	0.0589–0.0726	4
ALPHA-GLYCEROPHOSPHATE	0.11–3.39	3
L-GLYCEROL-3-PHOSPHATE	2.3–3.9	2
ALPHA-GLYCEROL PHOSPHATE	0.3	1
GLYCEROL PHOSPHATE	1.6	1
SN-GLYCEROL-3-PHOSPHATE	0.143	1

Catalyzed reactions (Rhea), 1 shown:

• sn-glycerol 3-phosphate + NAD(+) = dihydroxyacetone phosphate + NADH + H(+) (RHEA:11092)

UniProt features (54 total): helix 19, strand 12, binding site 9, sequence variant 6, modified residue 3, turn 2, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6E8Y	X-RAY DIFFRACTION	1.85
6PYP	X-RAY DIFFRACTION	1.95
6E90	X-RAY DIFFRACTION	2.05
6E8Z	X-RAY DIFFRACTION	2.1
1X0V	X-RAY DIFFRACTION	2.3
1WPQ	X-RAY DIFFRACTION	2.5
1X0X	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21695-F1	96.39	0.95

Functional residue map

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

Catalytic / active sites (1): 204 (proton acceptor)

Ligand- & substrate-binding residues (9): 298; 10–15; 41; 97; 120; 153; 269–270; 269; 296

Post-translational modifications (3): 154, 289, 326

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 258 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6, SHEPARD_CRASH_AND_BURN_MUTANT_UP, AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RACCACAR_AML_Q6, TAL1ALPHAE47_01

GO Biological Process (9): glycerol-3-phosphate metabolic process (GO:0006072), gluconeogenesis (GO:0006094), glycerol-3-phosphate shuttle (GO:0006127), positive regulation of glycolytic process (GO:0045821), glycerol-3-phosphate catabolic process (GO:0046168), cellular response to cAMP (GO:0071320), cellular response to tumor necrosis factor (GO:0071356), carbohydrate metabolic process (GO:0005975), obsolete NADH oxidation (GO:0006116)

GO Molecular Function (7): protein homodimerization activity (GO:0042803), glycerol-3-phosphate dehydrogenase [NAD(P)+] activity (GO:0047952), NAD binding (GO:0051287), glycerol-3-phosphate dehydrogenase (NAD+) activity (GO:0141152), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

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
cellular anatomical structure	2
alditol phosphate metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
glycerol-3-phosphate dehydrogenase (quinone) activity	1
NAD+ metabolic process	1
glycerol-3-phosphate dehydrogenase (NAD+) activity	1
glycolytic process	1
regulation of glycolytic process	1
positive regulation of purine nucleotide catabolic process	1
positive regulation of carbohydrate metabolic process	1
positive regulation of ATP metabolic process	1
glycerol-3-phosphate metabolic process	1
organophosphate catabolic process	1
carbohydrate derivative catabolic process	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
primary metabolic process	1
identical protein binding	1
protein dimerization activity	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
adenyl nucleotide binding	1
glycerol-3-phosphate dehydrogenase [NAD(P)+] activity	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPD1	GPD2	P43304	980
GPD1	PLB1	Q6P1J6	749
GPD1	EPHA2	P29317	720
GPD1	LMF1	Q96S06	624
GPD1	ALDH18A1	P54886	619
GPD1	CUBN	O60494	610
GPD1	SCN5A	Q14524	594
GPD1	PC	P11498	593
GPD1	TPI1	P00938	532
GPD1	SOD1	P00441	532
GPD1	DGAT2	Q96PD7	518
GPD1	GAPDH	P00354	508
GPD1	GPIHBP1	Q8IV16	506
GPD1	GK	P32189	473
GPD1	ACACA	Q13085	471

IntAct

12 interactions, top by confidence:

A	B	Type	Score
FAM25C	GPD1	psi-mi:“MI:0915”(physical association)	0.560
GPD1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
GPD1	GK	psi-mi:“MI:0915”(physical association)	0.370
GPD1	IDH3B	psi-mi:“MI:0914”(association)	0.350
GPD1	SLC27A2	psi-mi:“MI:0914”(association)	0.350
TGDS	GPD1	psi-mi:“MI:0914”(association)	0.350
GPD1	FAM25C	psi-mi:“MI:0915”(physical association)	0.000
GPD1	POMP	psi-mi:“MI:0915”(physical association)	0.000
GPD1	PTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): GNPNAT1 (Co-fractionation), GPD1 (Co-fractionation), GPD1 (Co-fractionation), GPD1L (Affinity Capture-MS), IDH3B (Affinity Capture-MS), NMD3 (Affinity Capture-MS), GPD1 (Affinity Capture-MS), GPD1 (Affinity Capture-RNA), PTN (Two-hybrid), FAM25A (Two-hybrid), FAM25G (Two-hybrid), FAM25C (Two-hybrid), GPD1 (Two-hybrid), IDH3B (Affinity Capture-MS), GPD1L (Affinity Capture-MS)

ESM2 similar proteins: A7M6E7, A7M6E8, B3FHT4, O04226, O08371, O13750, O19069, O35077, O57656, O65361, P0AGE9, P0AGF0, P0AGF1, P11024, P13086, P13707, P21695, P32296, P36967, P40939, P45102, P53591, P53596, P53597, P56571, P68209, Q13423, Q16798, Q1RH56, Q29554, Q3ULJ0, Q4ULQ8, Q51567, Q58DR8, Q5EA88, Q5RCE0, Q61941, Q64428, Q6DQL1, Q6ZL94

Diamond homologs: A0A0F6AK91, A0KR80, A1RQ92, A2RCE5, A2RK98, A3DAM7, A4TSB8, A4Y1E6, A6WHD0, A7FCV2, A8AUM5, A9KUC1, A9R691, B0K3E2, B1JQV5, B2JYQ1, B3WCP6, B4U0Q8, B5XJM4, B8E3F7, B9DVX9, C0M6I2, L7IGD3, O35077, O57656, O67555, O97463, P07735, P08507, P0CT11, P0DB22, P0DB23, P13706, P13707, P21695, P21696, P34517, P41911, P52425, P61740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	10
Uncertain significance	67
Likely benign	55
Benign	8

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1071286	NM_005276.4(GPD1):c.544C>T (p.Gln182Ter)	Pathogenic
1687411	NM_005276.4(GPD1):c.219+1G>A	Pathogenic
29741	NM_005276.4(GPD1):c.361-1G>C	Pathogenic
3238866	NM_005276.4(GPD1):c.806G>A (p.Arg269Gln)	Pathogenic
3238867	NM_005276.4(GPD1):c.640T>C (p.Cys214Arg)	Pathogenic
3238869	NM_005276.4(GPD1):c.116G>A (p.Trp39Ter)	Pathogenic
3244385	NC_000012.11:g.(?50497834)(50497894_?)del	Pathogenic
3619818	NM_005276.4(GPD1):c.883C>T (p.Gln295Ter)	Pathogenic
419206	NM_005276.4(GPD1):c.751dup (p.Thr251fs)	Pathogenic
4293669	NM_005276.4(GPD1):c.540_541insTTTG (p.Met181fs)	Pathogenic
1184562	NM_005276.4(GPD1):c.219+1_219+3del	Likely pathogenic
3391232	NM_005276.4(GPD1):c.686G>A (p.Arg229Gln)	Likely pathogenic
3726712	NM_005276.4(GPD1):c.847-2A>C	Likely pathogenic
3779705	NM_005276.4(GPD1):c.905del (p.Thr302fs)	Likely pathogenic
3901172	NM_005276.4(GPD1):c.91C>T (p.Gln31Ter)	Likely pathogenic
4265533	NM_005276.4(GPD1):c.42G>A (p.Trp14Ter)	Likely pathogenic
4759257	NM_005276.4(GPD1):c.220-1G>A	Likely pathogenic
4774537	NM_005276.4(GPD1):c.835_846+11del	Likely pathogenic
521341	NM_005276.4(GPD1):c.866_867del (p.Lys289fs)	Likely pathogenic
804465	NM_005276.4(GPD1):c.953+1G>A	Likely pathogenic

SpliceAI

1423 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50106798:A:AG	acceptor_gain	1.0000
12:50106803:A:AG	acceptor_gain	1.0000
12:50106803:AG:A	acceptor_gain	1.0000
12:50106803:AGGCT:A	acceptor_gain	1.0000
12:50106804:G:GG	acceptor_gain	1.0000
12:50106804:GG:G	acceptor_gain	1.0000
12:50106804:GGCT:G	acceptor_gain	1.0000
12:50106804:GGCTG:G	acceptor_gain	1.0000
12:50106915:AAGG:A	donor_loss	1.0000
12:50106916:AGGTG:A	donor_loss	1.0000
12:50106917:GGTG:G	donor_loss	1.0000
12:50106918:G:GC	donor_loss	1.0000
12:50106919:T:A	donor_loss	1.0000
12:50107565:A:G	acceptor_gain	1.0000
12:50107768:A:T	donor_gain	1.0000
12:50107796:G:GT	donor_gain	1.0000
12:50107797:A:T	donor_gain	1.0000
12:50107998:A:AG	acceptor_gain	1.0000
12:50107999:T:G	acceptor_gain	1.0000
12:50108002:A:AG	acceptor_gain	1.0000
12:50108003:C:G	acceptor_gain	1.0000
12:50108006:A:AG	acceptor_gain	1.0000
12:50108006:ATCCT:A	acceptor_gain	1.0000
12:50108007:T:G	acceptor_gain	1.0000
12:50108010:T:A	acceptor_gain	1.0000
12:50108017:T:A	acceptor_gain	1.0000
12:50108020:A:AG	acceptor_gain	1.0000
12:50108021:C:G	acceptor_gain	1.0000
12:50108022:A:AG	acceptor_gain	1.0000
12:50108023:G:GG	acceptor_gain	1.0000

AlphaMissense

2297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:50105688:G:C	K120N	0.999
12:50105688:G:T	K120N	0.999
12:50106380:C:A	N151K	0.999
12:50106380:C:G	N151K	0.999
12:50106917:G:C	K204N	0.999
12:50106917:G:T	K204N	0.999
12:50104079:G:A	G10D	0.998
12:50104085:G:A	G12E	0.998
12:50104712:T:A	N60K	0.998
12:50104712:T:G	N60K	0.998
12:50106372:G:A	G149R	0.998
12:50106372:G:C	G149R	0.998
12:50106372:G:T	G149W	0.998
12:50106916:A:T	K204M	0.998
12:50107717:A:C	S255R	0.998
12:50107719:C:A	S255R	0.998
12:50107719:C:G	S255R	0.998
12:50107722:T:G	C256W	0.998
12:50107736:T:C	L261P	0.998
12:50104078:G:C	G10R	0.997
12:50104574:G:C	W14C	0.997
12:50104574:G:T	W14C	0.997
12:50104719:T:C	Y63H	0.997
12:50105552:C:A	A75D	0.997
12:50105617:T:C	F97L	0.997
12:50105619:C:A	F97L	0.997
12:50105619:C:G	F97L	0.997
12:50106385:C:A	A153D	0.997
12:50106413:T:G	C162W	0.997
12:50106915:A:G	K204E	0.997

dbSNP variants (sampled 300 via entrez): RS1001021106 (12:50111290 A>C,G), RS1001091099 (12:50110927 G>A), RS1001479399 (12:50104044 C>G,T), RS1001699546 (12:50106994 A>G), RS1002151706 (12:50107316 A>T), RS1002188938 (12:50102973 C>T), RS1002930188 (12:50107322 G>A), RS1003203604 (12:50102424 G>A), RS1003379190 (12:50108379 C>T), RS1003674023 (12:50108955 T>A,G), RS1004829442 (12:50106942 T>C), RS1005161953 (12:50108314 A>G), RS1005223707 (12:50105251 G>T), RS1005235929 (12:50108065 A>T), RS1005763384 (12:50102170 C>T)

Disease associations

OMIM: gene MIM:138420 | disease phenotypes: MIM:614480

GenCC curated gene-disease

Disease	Classification	Inheritance
transient infantile hypertriglyceridemia and hepatosteatosis	Strong	Autosomal recessive

Mondo (1): transient infantile hypertriglyceridemia and hepatosteatosis (MONDO:0013771)

Orphanet (1): Transient infantile hypertriglyceridemia and hepatosteatosis (Orphanet:300293)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001395	Hepatic fibrosis
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001744	Splenomegaly
HP:0002013	Vomiting
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0030948	Elevated gamma-glutamyltransferase level

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007293_76	Body fat distribution (arm fat ratio)	4.000000e-07
GCST007294_123	Body fat distribution (trunk fat ratio)	2.000000e-09
GCST007294_2	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007295_152	Body fat distribution (leg fat ratio)	4.000000e-13
GCST010989_42	Body size at age 10	1.000000e-11
GCST012227_650	Hip circumference adjusted for BMI	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, increases methylation	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	decreases expression	3
perfluorooctane sulfonic acid	decreases expression	2
bisphenol S	increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
OTX015	decreases expression	1
bisphenol F	increases expression	1
mivebresib	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
chlortoluron	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	increases expression	1
benzo(e)pyrene	increases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
propiconazole	increases expression, decreases expression, affects cotreatment	1
NCS 382	increases expression	1
tebuconazole	affects cotreatment, increases expression	1
cyproconazole	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
bisphenol B	increases expression	1

Clinical trials (associated diseases)

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