AMBRA1

autophagy and beclin 1 regulator 1, the group of WD repeat domain containing|DDB1 and CUL4 associated factors|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:46396414-46594125

Links

ENSG00000110497 ∙ NCBI:55626 ∙ OMIM:611359 ∙ HGNC:25990 ∙ Uniprot:Q9C0C7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMBRA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMBRA1 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					3	3
missense			58	4		62
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	59	4	3

Variants in AMBRA1

This is a list of pathogenic ClinVar variants found in the AMBRA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-46397473-T-C		AMBRA1-related disorder	Uncertain significance (Jun 25, 2023)
11-46397493-C-G		not specified	Uncertain significance (Feb 23, 2023)
11-46397526-T-C		not specified	Likely benign (Sep 15, 2021)
11-46397547-G-T		not specified	Uncertain significance (Jun 29, 2023)
11-46397590-G-A		not specified	Uncertain significance (May 24, 2023)
11-46397631-G-A		not specified	Uncertain significance (Mar 15, 2024)
11-46397662-G-A		not specified	Uncertain significance (Sep 29, 2023)
11-46397709-C-T		not specified	Uncertain significance (Aug 20, 2023)
11-46397730-G-A		not specified	Uncertain significance (Oct 26, 2021)
11-46397773-A-C		not specified	Uncertain significance (Dec 01, 2022)
11-46397889-C-T		not specified	Uncertain significance (Feb 03, 2022)
11-46397907-G-A		not specified	Uncertain significance (Oct 29, 2021)
11-46397943-C-T		not specified	Uncertain significance (Nov 09, 2023)
11-46408630-C-T		not specified	Likely benign (Jan 26, 2022)
11-46410282-C-T		not specified	Uncertain significance (Feb 05, 2024)
11-46410297-C-G		not specified	Uncertain significance (May 23, 2023)
11-46410310-C-T		not specified	Uncertain significance (Apr 25, 2023)
11-46410321-G-A		AMBRA1-related disorder	Uncertain significance (Sep 05, 2023)
11-46410349-C-T		not specified	Uncertain significance (Nov 17, 2023)
11-46410357-G-A		Neural tube defect	Uncertain significance (-)
11-46418036-A-G		not specified	Uncertain significance (Sep 29, 2023)
11-46418040-C-T		not specified	Uncertain significance (Jul 13, 2022)
11-46433499-G-A		not specified	Uncertain significance (Jan 29, 2024)
11-46433530-T-C		Neural tube defect	Uncertain significance (-)
11-46433539-T-C		not specified	Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMBRA1	protein_coding	protein_coding	ENST00000314845	18	197712

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.44e-7	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	502	725	0.692	0.0000449	7798
Missense in Polyphen		209	366.55	0.57019		3788
Synonymous	1.18	254	279	0.910	0.0000161	2538
Loss of Function	6.53	3	55.5	0.0541	0.00000305	575

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000126	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000333	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates autophagy and development of the nervous system. Involved in autophagy in controlling protein turnover during neuronal development, and in regulating normal cell survival and proliferation (By similarity). {ECO:0000250}.
• Pathway: Autophagy - animal - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;Nanoparticle triggered autophagic cell death;Senescence and Autophagy in Cancer;Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.200
• rvis_EVS: -0.97
• rvis_percentile_EVS: 8.95

Haploinsufficiency Scores

• pHI: 0.369
• hipred: Y
• hipred_score: 0.819
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.889

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ambra1
• Phenotype: cellular 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); 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); embryo phenotype

Zebrafish Information Network

• Gene name: ambra1a
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: undulate

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;mitophagy;autophagy;negative regulation of cell population proliferation;cellular response to starvation;positive regulation of autophagy;negative regulation of cardiac muscle cell apoptotic process;macroautophagy;neural tube development;cell differentiation;negative regulation of neuron apoptotic process;positive regulation of phosphatidylinositol 3-kinase activity;response to mitochondrial depolarisation
• Cellular component: cytoplasm;mitochondrion;mitochondrial outer membrane;autophagosome;cytosol;axoneme;phagocytic vesicle;perinuclear region of cytoplasm
• Molecular function: protein binding;ubiquitin protein ligase binding;GTPase binding