AGK

acylglycerol kinase

Basic information

Region (hg38): 7:141551277-141655244

Previous symbols: [ "MULK" ]

Links

ENSG00000006530 ∙ NCBI:55750 ∙ OMIM:610345 ∙ HGNC:21869 ∙ Uniprot:Q53H12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Sengers syndrome (Definitive), mode of inheritance: AR
• Sengers syndrome (Supportive), mode of inheritance: AR
• total early-onset cataract (Supportive), mode of inheritance: AD
• Sengers syndrome (Strong), mode of inheritance: AR
• cataract 38 (Limited), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sengers syndrome	AR	Biochemical; Cardiovascular	Individuals can have cardiomyopathy, and early diagnosis may benefit medical management; Avoidance of factors that may precipitate lactic acidosis may be beneficial	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	1168700; 3789054; 3560758; 3337009; 15168109; 16736096; 22415731; 22277967; 22284826; 23266196

ClinVar

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

• not provided (88 variants)
• Sengers syndrome (80 variants)
• Sengers syndrome;Cataract 38 (77 variants)
• Cataract 38;Sengers syndrome (74 variants)
• Cataract 38 (61 variants)
• Inborn genetic diseases (25 variants)
• not specified (18 variants)
• Developmental cataract (7 variants)
• AGK-Related Disorders (3 variants)
• Trichohepatoenteric syndrome 1 (1 variants)
• Autosomal recessive AGK-related phenotype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGK 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	29		31
missense			72	5		77
nonsense	8					8
start loss	1					1
frameshift	3	3				6
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	6	4	1		1	12
splice region	1		5	13	4	23
non coding			29	50	20	99
Total	18	8	105	84	21

Highest pathogenic variant AF is 0.0000460

Variants in AGK

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

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

Position	Type	Phenotype	Significance	ClinVar
7-141551287-G-A		Sengers syndrome • Developmental cataract	Uncertain significance (Jun 14, 2016)
7-141551310-G-A		Sengers syndrome • Developmental cataract	Uncertain significance (Jun 14, 2016)
7-141551349-G-A		Developmental cataract • Sengers syndrome	Conflicting classifications of pathogenicity (May 01, 2023)
7-141551361-G-C		Developmental cataract • Sengers syndrome	Uncertain significance (Jun 14, 2016)
7-141551374-G-C		Sengers syndrome • Developmental cataract	Uncertain significance (Jun 14, 2016)
7-141551412-A-AG		not specified	Likely benign (Oct 03, 2017)
7-141551413-G-A		Cataract 38 • Sengers syndrome	Uncertain significance (Jan 13, 2018)
7-141551416-G-A		not specified	Likely benign (Aug 14, 2017)
7-141551465-C-G			Benign (Dec 21, 2021)
7-141555184-A-G			Benign (Jun 14, 2018)
7-141555450-T-C		Cataract 38 • Sengers syndrome	Conflicting classifications of pathogenicity (Oct 19, 2018)
7-141555458-C-G		AGK-related disorder	Likely benign (Mar 19, 2021)
7-141555469-G-C		Sengers syndrome	Pathogenic (Oct 21, 2014)
7-141555483-A-G		Sengers syndrome;Cataract 38 • Sengers syndrome • Cataract 38	Benign/Likely benign (Jan 25, 2024)
7-141555486-C-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
7-141555487-G-A		not specified	Likely benign (Feb 05, 2016)
7-141555491-C-A			Uncertain significance (Aug 26, 2022)
7-141555491-C-T		Sengers syndrome;Cataract 38	Pathogenic (Nov 19, 2023)
7-141555492-G-A		Sengers syndrome;Cataract 38 • Sengers syndrome • Cataract 38 • AGK-related disorder	Benign/Likely benign (Dec 15, 2023)
7-141555492-G-C		Sengers syndrome;Cataract 38	Uncertain significance (Mar 15, 2022)
7-141555495-A-G		Sengers syndrome;Cataract 38 • AGK-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 29, 2022)
7-141555499-C-A			Uncertain significance (Jan 23, 2017)
7-141555508-A-G		Sengers syndrome;Cataract 38	Uncertain significance (Sep 03, 2023)
7-141555521-C-T		Sengers syndrome • Cataract 38 • Cataract 38;Sengers syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 15, 2022)
7-141555529-G-C		Sengers syndrome;Cataract 38	Likely benign (Jul 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGK	protein_coding	protein_coding	ENST00000355413	15	104056

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.00e-9	0.964	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.755	196	228	0.859	0.0000115	2749
Missense in Polyphen		45	56.286	0.79948		679
Synonymous	0.672	79	87.0	0.908	0.00000499	811
Loss of Function	2.08	18	30.4	0.592	0.00000175	316

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000754	0.000735
Ashkenazi Jewish	0.00	0.00
East Asian	0.000378	0.000326
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000277	0.000273
Middle Eastern	0.000378	0.000326
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15939762). Does not phosphorylate sphingosine (PubMed:15939762). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (PubMed:28712724, PubMed:28712726). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (PubMed:28712724, PubMed:28712726). In the TIM22 complex, required for the import of a subset of metabolite carriers into mitochondria, such as ANT1/SLC25A4 and SLC25A24, while it is not required for the import of TIMM23 (PubMed:28712724). Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth (PubMed:15939762). {ECO:0000269|PubMed:15939762, ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726}.
• Disease: DISEASE: Mitochondrial DNA depletion syndrome 10 (MTDPS10) [MIM:212350]: An autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy. {ECO:0000269|PubMed:22277967, ECO:0000269|PubMed:22284826, ECO:0000269|PubMed:23266196, ECO:0000269|PubMed:25208612, ECO:0000269|PubMed:28712726}. Note=The disease is caused by mutations affecting the gene represented in this entry. The TIM22 complex and import of proteins into mitochondrion are affected in patients suffering of MTDPS10 (PubMed:28712726). {ECO:0000269|PubMed:28712726}.; DISEASE: Cataract 38 (CTRCT38) [MIM:614691]: An opacification of the crystalline lens of the eye becoming evident at birth. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:22415731}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerolipid metabolism - Homo sapiens (human);Disease;Metabolism of lipids;Metabolism;Glycerophospholipid metabolism;Glycerophospholipid biosynthesis;Phospholipid metabolism;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.892
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.15

Haploinsufficiency Scores

• pHI: 0.180
• hipred: N
• hipred_score: 0.331
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.878

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agk

Gene ontology

• Biological process: protein insertion into mitochondrial inner membrane;glycerophospholipid biosynthetic process;ceramide biosynthetic process;lipid phosphorylation
• Cellular component: mitochondrion;mitochondrial outer membrane;mitochondrial inner membrane;mitochondrial intermembrane space;cytosol;integral component of mitochondrial inner membrane;TIM22 mitochondrial import inner membrane insertion complex;intracellular membrane-bounded organelle
• Molecular function: ceramide kinase activity;NAD+ kinase activity;diacylglycerol kinase activity;ATP binding;acylglycerol kinase activity