AGPS

alkylglycerone phosphate synthase

Basic information

Region (hg38): 2:177392746-177567024

Links

ENSG00000018510 ∙ NCBI:8540 ∙ OMIM:603051 ∙ HGNC:327 ∙ Uniprot:O00116 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rhizomelic chondrodysplasia punctata type 3 (Definitive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 3 (Strong), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 3 (Moderate), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 3 (Definitive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 3 (Definitive), mode of inheritance: Mitochondrial
• alkylglycerone-phosphate synthase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rhizomelic chondrodysplasia punctata, type 3	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; Musculoskeletal; Neurologic	7807941; 9553082; 21990100

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGPS 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			2	244	4	250
missense		2	66	1		69
nonsense		6	1			7
start loss						0
frameshift		7				7
inframe indel			3			3
splice donor/acceptor (+/-2bp)		5	3		1	9
splice region			5	54	6	65
non coding			128	158	62	348
Total	0	20	203	403	67

Variants in AGPS

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

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

Position	Type	Phenotype	Significance	ClinVar
2-177392776-A-G		Rhizomelic chondrodysplasia punctata type 3	Uncertain significance (Jan 13, 2018)
2-177392783-GGTA-G			Uncertain significance (Oct 18, 2016)
2-177392794-C-A			Uncertain significance (Aug 31, 2021)
2-177392795-G-A		AGPS-related disorder	Likely benign (Aug 06, 2023)
2-177392795-G-T			Likely benign (May 02, 2021)
2-177392796-G-A			Uncertain significance (Feb 15, 2017)
2-177392798-G-A			Likely benign (Aug 30, 2022)
2-177392799-G-T		Inborn genetic diseases	Uncertain significance (Apr 29, 2021)
2-177392803-C-T		Rhizomelic chondrodysplasia punctata type 3 • Rhizomelic chondrodysplasia punctata	Uncertain significance (Jan 12, 2018)
2-177392804-G-C			Likely benign (Oct 05, 2022)
2-177392809-C-T		not specified	Conflicting classifications of pathogenicity (Mar 31, 2022)
2-177392815-G-C			Uncertain significance (Jul 12, 2022)
2-177392816-T-A			Likely benign (Sep 28, 2019)
2-177392819-G-C			Likely benign (Dec 25, 2021)
2-177392822-T-A			Likely benign (Nov 14, 2022)
2-177392823-G-C			Uncertain significance (Mar 31, 2021)
2-177392824-G-A		Rhizomelic chondrodysplasia punctata type 3 • not specified	Benign/Likely benign (Jan 21, 2024)
2-177392825-C-T			Likely benign (Jun 08, 2022)
2-177392826-T-C			Likely benign (May 01, 2023)
2-177392829-G-T		Rhizomelic chondrodysplasia punctata	Uncertain significance (Sep 03, 2020)
2-177392834-G-A			Likely benign (Aug 06, 2023)
2-177392834-G-C			Likely benign (Sep 20, 2019)
2-177392835-G-GGCGCGA		not specified	Uncertain significance (Jun 28, 2022)
2-177392837-C-A			Likely benign (Nov 14, 2023)
2-177392837-C-T			Likely benign (Oct 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGPS	protein_coding	protein_coding	ENST00000264167	20	151193

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000249	125723	0	5	125728	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	186	358	0.520	0.0000172	4284
Missense in Polyphen		19	104.83	0.18125		1194
Synonymous	0.149	124	126	0.983	0.00000614	1245
Loss of Function	5.75	1	40.5	0.0247	0.00000200	487

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000331	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the exchange of an acyl for a long-chain alkyl group and the formation of the ether bond in the biosynthesis of ether phospholipids. {ECO:0000250}.
• Disease: DISEASE: Rhizomelic chondrodysplasia punctata 3 (RCDP3) [MIM:600121]: 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:9553082}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ether lipid metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);Plasmalogen Synthesis;Triacylglyceride Synthesis;Metabolism of lipids;Metabolism of proteins;Metabolism;Peroxisomal protein import;Glycerophospholipid metabolism;TYSND1 cleaves peroxisomal proteins;Plasmalogen biosynthesis (Consensus)

Recessive Scores

• pRec: 0.197

Intolerance Scores

• loftool: 0.124
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.515
• hipred: Y
• hipred_score: 0.707
• ghis: 0.659

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agps
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; vision/eye 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); reproductive system phenotype

Gene ontology

• Biological process: protein targeting to peroxisome;lipid biosynthetic process;ether lipid biosynthetic process;oxidation-reduction process
• Cellular component: nucleolus;mitochondrion;peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol;membrane
• Molecular function: protein binding;alkylglycerone-phosphate synthase activity;oxidoreductase activity;FAD binding