GNPAT

glyceronephosphate O-acyltransferase

Basic information

Region (hg38): 1:231241207-231277973

Links

ENSG00000116906 ∙ NCBI:8443 ∙ OMIM:602744 ∙ HGNC:4416 ∙ Uniprot:O15228 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rhizomelic chondrodysplasia punctata type 2 (Definitive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 2 (Strong), mode of inheritance: AR
• glyceronephosphate O-acyltransferase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rhizomelic chondrodysplasia punctata, type 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	1405476; 8466247; 7530787; 7541833; 9536089; 20583171; 21990100

ClinVar

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

• not_provided (427 variants)
• Rhizomelic_chondrodysplasia_punctata_type_2 (102 variants)
• Inborn_genetic_diseases (63 variants)
• not_specified (14 variants)
• Rhizomelic_chondrodysplasia_punctata (4 variants)
• GNPAT-related_disorder (4 variants)
• Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNPAT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014236.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	146	2	154
missense	1	2	122	9	2	136
nonsense	4	12				16
start loss						0
frameshift	14	18	1			33
splice donor/acceptor (+/-2bp)	2	10				12
Total	21	42	129	155	4

Highest pathogenic variant AF is 0.0000102615

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNPAT	protein_coding	protein_coding	ENST00000366647	16	36767

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.304	0.696	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.674	316	352	0.899	0.0000187	4484
Missense in Polyphen		89	111.73	0.79656		1425
Synonymous	-0.0637	125	124	1.01	0.00000634	1282
Loss of Function	4.19	8	34.6	0.231	0.00000181	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: 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 mental retardation with spasticity. {ECO:0000269|PubMed:11152660, ECO:0000269|PubMed:21990100, ECO:0000269|PubMed:9536089}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);Plasmalogen Synthesis;Triacylglyceride Synthesis;Metabolism of lipids;Metabolism of proteins;Metabolism;Peroxisomal protein import;Glycerophospholipid metabolism;Glycerophospholipid biosynthesis;Phospholipid metabolism;Plasmalogen biosynthesis;Synthesis of PA (Consensus)

Recessive Scores

• pRec: 0.265

Intolerance Scores

• loftool: 0.328
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.11

Haploinsufficiency Scores

• pHI: 0.521
• hipred: N
• hipred_score: 0.426
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnpat
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; pigmentation phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: protein targeting to peroxisome;fatty acid metabolic process;phosphatidic acid biosynthetic process;synapse assembly;response to nutrient;ether lipid biosynthetic process;phospholipid biosynthetic process;cerebellum morphogenesis;paranodal junction assembly;response to drug;response to starvation;membrane organization;response to fatty acid
• Cellular component: peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol;membrane;mitochondrial membrane
• Molecular function: signaling receptor binding;glycerone-phosphate O-acyltransferase activity;palmitoyl-CoA hydrolase activity