AMBRA1

protein-coding

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

Gene summary

Enables enzyme binding activity; protein phosphatase activator activity; and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including macroautophagy; positive regulation of free ubiquitin chain polymerization; and positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in cytosol. Part of Cul4-RING E3 ubiquitin ligase complex. Is active in cytoskeleton; mitochondrion; and nucleus. Biomarker of multiple system atrophy. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001387011.1

Inheritance

ClinVar variants

U:168B:14

Top phenotype

neural tube defects, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr11:46,396,414-46,594,125

External References & Databases

Ensembl (ENSG00000110497)

Transcript & Mutation Effects

hg38 • Region Span ~197.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neural tube defects, susceptibility toSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020705

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMBRA1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 144

AMBRA1-related disorderTotal: 10

not providedTotal: 8

Neural tube defectTotal: 5

Pyloric stenosisTotal: 1

Esophageal atresiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001387011.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	3 clinvar	3 clinvar	9
missense			152 clinvar	8 clinvar		160
nonsense			5 clinvar			5
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	168	11	3	182

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001387011.1	RefSeq	NP_001373940.1	17	MANE Select
ENST00000683756.1	Ensembl	ENSP00000508322.1	17	MANE Select
NM_001267782.2	RefSeq	NP_001254711.1	19	Standard
NM_001267783.2	RefSeq	NP_001254712.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ambra1a	Danio rerio	Structure: fast muscle cell Quality: undulate abnormal

Gene / Model

Organism

Observed Phenotype

ambra1a

Danio rerio

Structure: fast muscle cell

Quality: undulate

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Autophagy - animal - Homo sapiens (human)
Mitophagy - animal - Homo sapiens (human)
Phosphatidylinositol Phosphate Metabolism
Joubert syndrome
Inositol Metabolism

Biological Process

autophagosome assembly
autophagy of mitochondrion
mitophagy
autophagy
negative regulation of cell population proliferation

Molecular Function

protein binding
ubiquitin protein ligase binding
GTPase binding

Cellular Component

cytoplasm
mitochondrion
mitochondrial outer membrane
autophagosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314845
Coding exons: 18
Length: 197712
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	502	725	0.692	0.0000449	7798
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.200
RVIS EVS: -0.97
RVIS percentile EVS: 8.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.889

Gene Damage Prediction

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