GNPAT

glyceronephosphate O-acyltransferase

Basic information

Region (hg38): 1:231241206-231277973

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 (271 variants)
• Rhizomelic chondrodysplasia punctata type 2 (99 variants)
• Inborn genetic diseases (24 variants)
• not specified (17 variants)
• Rhizomelic chondrodysplasia punctata (5 variants)
• GNPAT-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	53	3	63
missense	1	1	93	4	1	100
nonsense	3	9				12
start loss						0
frameshift	9	10				19
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	5				6
splice region		1	7	13	1	22
non coding			17	62	18	97
Total	14	25	118	119	22

Highest pathogenic variant AF is 0.0000131

Variants in GNPAT

This is a list of pathogenic ClinVar variants found in the GNPAT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-231241226-A-C		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 13, 2018)
1-231241232-G-C		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 13, 2018)
1-231241234-G-A		Rhizomelic chondrodysplasia punctata type 2	Benign/Likely benign (Oct 21, 2018)
1-231241258-C-T		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 13, 2018)
1-231241295-C-T		Rhizomelic chondrodysplasia punctata type 2	Benign/Likely benign (Jun 14, 2018)
1-231241297-G-T		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 13, 2018)
1-231241325-A-G		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 12, 2018)
1-231241332-C-A		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 13, 2018)
1-231241332-C-T			not provided (-)
1-231241335-C-T		Rhizomelic chondrodysplasia punctata type 2 • not specified	Benign (Aug 10, 2021)
1-231241373-C-T		Rhizomelic chondrodysplasia punctata type 2	Uncertain significance (Jan 12, 2018)
1-231241401-A-G			Uncertain significance (Aug 07, 2021)
1-231241401-ACT-A		Rhizomelic chondrodysplasia punctata type 2	Likely pathogenic (Jul 03, 2023)
1-231241404-C-T		not specified • Rhizomelic chondrodysplasia punctata type 2	Benign (Jan 31, 2024)
1-231241408-T-C			Likely benign (Dec 02, 2022)
1-231241415-G-T			Uncertain significance (Nov 03, 2021)
1-231241420-C-G			Likely benign (Aug 28, 2023)
1-231241424-ACCAGTC-A			Uncertain significance (Jan 02, 2021)
1-231241434-G-C			Uncertain significance (Aug 14, 2021)
1-231241435-C-T		Rhizomelic chondrodysplasia punctata type 2	Conflicting classifications of pathogenicity (Jan 22, 2024)
1-231241441-C-T			Likely benign (Apr 28, 2023)
1-231241443-T-C		Rhizomelic chondrodysplasia punctata type 2	Conflicting classifications of pathogenicity (Jan 19, 2024)
1-231241444-G-A			Likely benign (Sep 21, 2023)
1-231241444-G-T			Likely benign (Dec 15, 2022)
1-231241447-C-T			Likely benign (Sep 22, 2023)

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