ARMC5

armadillo repeat containing 5, the group of Armadillo repeat containing

Basic information

Region (hg38): 16:31458080-31467166

Links

ENSG00000140691 ∙ NCBI:79798 ∙ OMIM:615549 ∙ HGNC:25781 ∙ Uniprot:Q96C12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ACTH-independent macronodular adrenal hyperplasia 2 (Strong), mode of inheritance: AD
• ACTH-independent macronodular adrenal hyperplasia 2 (Definitive), mode of inheritance: AD
• ACTH-independent macronodular adrenal hyperplasia 2 (Strong), mode of inheritance: AD
• Cushing syndrome due to macronodular adrenal hyperplasia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
ACTH-independent macronodular adrenal hyperplasia 2	AD	Endocrine; Oncologic	Surveillance for neoplasms, can allow early detection and treatment, which can involve surgical excision of the neoplasm or medical management (eg, targeting aberrant receptor expression) to control cortisol production	Endocrine; Oncologic	19018784; 24283224; 24601692; 24708098; 24905064
Germline variants in this tumor suppressor gene may result in the clinical phenotype in the presence of a second, somatic variant

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARMC5 gene.

• Inborn_genetic_diseases (130 variants)
• ARMC5-related_disorder (80 variants)
• not_provided (68 variants)
• ACTH-independent_macronodular_adrenal_hyperplasia_2 (33 variants)
• not_specified (5 variants)
• Cushing_syndrome_due_to_macronodular_adrenal_hyperplasia (1 variants)
• Hereditary_cancer-predisposing_syndrome (1 variants)
• Macronodular_adrenal_hyperplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARMC5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001105247.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				47	12	59
missense	4	6	148	20	4	182
nonsense	5	3	1			9
start loss						0
frameshift	9	3	1			13
splice donor/acceptor (+/-2bp)						0
Total	18	12	150	67	16

Highest pathogenic variant AF is 0.000019708317

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARMC5	protein_coding	protein_coding	ENST00000268314	6	9087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.107	0.892	124838	0	16	124854	0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	476	593	0.803	0.0000393	5660
Missense in Polyphen		135	243.76	0.55383		2355
Synonymous	-2.21	319	273	1.17	0.0000169	2291
Loss of Function	3.54	7	26.8	0.262	0.00000149	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000254	0.000251
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000564	0.0000556
Finnish	0.0000488	0.0000464
European (Non-Finnish)	0.0000635	0.0000618
Middle Eastern	0.0000564	0.0000556
South Asian	0.0000330	0.0000327
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in fetal development, T-cell function and adrenal gland growth homeostasis (By similarity). Negatively regulates adrenal cells survival. Plays a role in steroidogenesis, modulates steroidogenic enzymes expression and cortisol production (PubMed:24283224, PubMed:28676429). {ECO:0000250|UniProtKB:Q5EBP3, ECO:0000269|PubMed:24283224, ECO:0000269|PubMed:28676429}.
• Disease: DISEASE: ACTH-independent macronodular adrenal hyperplasia 2 (AIMAH2) [MIM:615954]: A form of macronodular adrenal hyperplasia characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:24283224, ECO:0000269|PubMed:24601692, ECO:0000269|PubMed:24708098, ECO:0000269|PubMed:24905064, ECO:0000269|PubMed:25822102, ECO:0000269|PubMed:25853793, ECO:0000269|PubMed:26604299, ECO:0000269|PubMed:27094308, ECO:0000269|PubMed:28458897, ECO:0000269|PubMed:28676429}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cushing,s syndrome - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.454
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.69

Haploinsufficiency Scores

• pHI: 0.208
• hipred: N
• hipred_score: 0.471
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.443

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Armc5
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region 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); embryo phenotype

Gene ontology

• Cellular component: nucleoplasm;cytoplasm;cytosol;focal adhesion