ANG

angiogenin, the group of Ribonuclease A family|Endoribonucleases

Basic information

Region (hg38): 14:20684177-20698971

Links

ENSG00000214274 ∙ NCBI:283 ∙ OMIM:105850 ∙ HGNC:483 ∙ Uniprot:P03950 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis type 9 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 9 (Definitive), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis type 9 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 9 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 9	AD	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	Neurologic	15557516; 16501576; 17886298; 18087731; 18852347; 19153377; 20577002

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANG 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				13		13
missense		1	34	3	1	39
nonsense						0
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			7	4	12	23
Total	0	1	44	20	13

Variants in ANG

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

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

Position	Type	Phenotype	Significance	ClinVar
14-20684183-C-A		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684198-G-C		Amyotrophic lateral sclerosis type 9	Benign (Jan 12, 2018)
14-20684235-G-A		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684243-C-T		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684247-T-C		Amyotrophic lateral sclerosis type 9	Benign (Jan 12, 2018)
14-20684253-G-A		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684354-C-T		Amyotrophic lateral sclerosis type 9	Benign (Jan 12, 2018)
14-20684376-G-T		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684394-C-G		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684396-C-T		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684445-C-A		Amyotrophic lateral sclerosis type 9	Benign (Jan 12, 2018)
14-20684540-A-C		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684609-A-G		Amyotrophic lateral sclerosis type 9	Uncertain significance (Apr 27, 2017)
14-20684662-G-C		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684736-T-C		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684769-A-C		Amyotrophic lateral sclerosis type 9	Likely benign (Jan 12, 2018)
14-20693222-A-G			Benign (Jul 03, 2018)
14-20693226-T-G			Benign (Aug 11, 2018)
14-20693325-G-C			Benign (Aug 17, 2018)
14-20693471-G-A			Likely benign (May 26, 2019)
14-20693543-G-A		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20693555-G-T		ANG-related disorder	Likely benign (Jun 27, 2022)
14-20693567-G-A		Amyotrophic lateral sclerosis type 9 • Amyotrophic lateral sclerosis type 10 • ANG-related disorder	Conflicting classifications of pathogenicity (Jan 11, 2024)
14-20693600-C-T		Inborn genetic diseases	Likely benign (Mar 14, 2024)
14-20693600-C-CGTGCTG			Uncertain significance (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANG	protein_coding	protein_coding	ENST00000336811	1	14795

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.287	0.501	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0777	83	85.0	0.976	0.00000536	952
Missense in Polyphen		22	26.47	0.83113		322
Synonymous	0.324	32	34.4	0.930	0.00000207	306
Loss of Function	0.239	0	0.0668	0.00	2.76e-9	3

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo. {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:1400510, ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:21855800}.
• Disease: DISEASE: Amyotrophic lateral sclerosis 9 (ALS9) [MIM:611895]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:15557516, ECO:0000269|PubMed:16501576, ECO:0000269|PubMed:17703939, ECO:0000269|PubMed:17886298, ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:18087731, ECO:0000269|PubMed:22292843, ECO:0000269|PubMed:25372031}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication (Consensus)

Intolerance Scores

• rvis_EVS: 0.24
• rvis_percentile_EVS: 68.98

Haploinsufficiency Scores

• pHI: 0.190
• hipred: N
• hipred_score: 0.146
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• 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	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ang

Gene ontology

• Biological process: angiogenesis;ovarian follicle development;oocyte maturation;response to hypoxia;placenta development;positive regulation of endothelial cell proliferation;diacylglycerol biosynthetic process;cell communication;activation of phospholipase C activity;rRNA transcription;response to hormone;cell migration;negative regulation of translation;actin filament polymerization;activation of protein kinase B activity;activation of phospholipase A2 activity;adherens junction organization;positive regulation of phosphorylation;homeostatic process;negative regulation of smooth muscle cell proliferation;positive regulation of protein secretion;RNA phosphodiester bond hydrolysis
• Cellular component: extracellular region;basement membrane;extracellular space;nucleus;nucleolus;growth cone;cytoplasmic vesicle;angiogenin-PRI complex;neuronal cell body
• Molecular function: DNA binding;actin binding;endonuclease activity;ribonuclease activity;signaling receptor binding;copper ion binding;protein binding;heparin binding;rRNA binding;peptide binding;protein homodimerization activity