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.

• ACTH-independent macronodular adrenal hyperplasia 2 (3 variants)
• ARMC5-related disorder (2 variants)
• not provided (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.

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				48	12	60
missense		1	69	13	4	87
nonsense	3		1			4
start loss						0
frameshift	3	3	1			7
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	2		3
Total	6	4	72	64	16

Highest pathogenic variant AF is 0.0000197

Variants in ARMC5

This is a list of pathogenic ClinVar variants found in the ARMC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-31459322-A-C		ARMC5-related disorder	Likely benign (Feb 01, 2022)
16-31459325-A-C		ARMC5-related disorder	Likely benign (Mar 21, 2019)
16-31459340-G-A		ARMC5-related disorder	Uncertain significance (Sep 26, 2022)
16-31459541-C-T		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
16-31459565-T-A		not specified	Benign (-)
16-31459581-C-T			Likely benign (Nov 17, 2017)
16-31459582-G-A		ARMC5-related disorder	Uncertain significance (Jan 18, 2023)
16-31459587-G-A			Benign (Apr 24, 2018)
16-31459589-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
16-31459594-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2023)
16-31459613-A-G		Inborn genetic diseases	Likely benign (Feb 14, 2023)
16-31459621-C-T		Inborn genetic diseases • ARMC5-related disorder	Uncertain significance (Apr 13, 2023)
16-31459632-C-G		Inborn genetic diseases • ARMC5-related disorder	Uncertain significance (Aug 13, 2021)
16-31459633-G-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
16-31459645-A-G		ARMC5-related disorder	Benign (Dec 31, 2019)
16-31459688-C-T		ARMC5-related disorder • Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
16-31459688-CG-C		ACTH-independent macronodular adrenal hyperplasia 2	Pathogenic (Nov 28, 2013)
16-31459690-G-C		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
16-31459697-T-TC		ACTH-independent macronodular adrenal hyperplasia 2	Pathogenic (Sep 01, 2021)
16-31459698-C-T		ARMC5-related disorder	Benign (Dec 31, 2019)
16-31459701-G-A		ARMC5-related disorder	Likely benign (Jul 04, 2018)
16-31459717-G-A		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
16-31459726-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
16-31459761-A-G		ARMC5-related disorder	Likely benign (Dec 17, 2021)
16-31459763-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)

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