ACD

ACD shelterin complex subunit and telomerase recruitment factor, the group of Shelterin complex

Basic information

Region (hg38): 16:67657511-67660810

Links

ENSG00000102977 ∙ NCBI:65057 ∙ OMIM:609377 ∙ HGNC:25070 ∙ Uniprot:Q96AP0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
• hereditary isolated aplastic anemia (Supportive), mode of inheritance: AD
• dyskeratosis congenita, autosomal dominant 6 (Strong), mode of inheritance: AR
• dyskeratosis congenita, autosomal dominant 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, autosomal dominant 6; Dyskeratosis congenita, autosomal recessive 7	AD/AR	Allergy/Immunology/Infectious; Hematologic; Oncologic	Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; HSCT may be indicated due to manifestations including leukemia and bone marrow failure; Awareness of infectious risk may allow prompt diagnosis and treatment of infections	Allergy/Immunology/Infectious; Hematologic; Oncologic; Neurologic	25205116; 25233904

ClinVar

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

• Inborn genetic diseases (604 variants)
• Dyskeratosis congenita, autosomal dominant 6 (376 variants)
• not specified (85 variants)
• not provided (29 variants)
• ACD-related condition (4 variants)
• Dyskeratosis congenita, autosomal recessive 7 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACD 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				247	1	248
missense			367	13	1	381
nonsense			8			8
start loss			1			1
frameshift	1		11			12
inframe indel	2		5			7
splice donor/acceptor (+/-2bp)			6			6
splice region			11	23	2	36
non coding			44	81	5	130
Total	3	0	442	341	7

Variants in ACD

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

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

Position	Type	Phenotype	Significance	ClinVar
16-67657515-C-T			Likely benign (Nov 25, 2023)
16-67657574-A-T		not specified	Benign (Nov 12, 2023)
16-67657610-A-G		Inborn genetic diseases	Uncertain significance (Jul 01, 2023)
16-67657610-A-T		Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (Apr 19, 2022)
16-67657611-T-C		Inborn genetic diseases	Likely benign (Jun 15, 2023)
16-67657612-C-A		Dyskeratosis congenita, autosomal dominant 6 • not specified	Benign (Feb 01, 2024)
16-67657612-C-T		Inborn genetic diseases • Dyskeratosis congenita, autosomal dominant 6	Likely benign (Jan 28, 2024)
16-67657612-CG-AA		Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (Sep 23, 2020)
16-67657613-G-A		not specified • Dyskeratosis congenita, autosomal dominant 6 • Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
16-67657613-G-C		Inborn genetic diseases	Uncertain significance (Nov 22, 2021)
16-67657614-G-C		Inborn genetic diseases • Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (May 17, 2023)
16-67657614-G-T		Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (May 04, 2022)
16-67657615-AGTTG-A		Dyskeratosis congenita, autosomal dominant 6 • Inborn genetic diseases	Uncertain significance (May 27, 2023)
16-67657616-G-A		Inborn genetic diseases	Uncertain significance (Jun 05, 2022)
16-67657620-G-A		Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (Mar 28, 2022)
16-67657622-T-A		Inborn genetic diseases	Uncertain significance (Sep 04, 2023)
16-67657624-A-G		Dyskeratosis congenita, autosomal dominant 6	Likely benign (Oct 05, 2023)
16-67657626-A-C		Inborn genetic diseases	Uncertain significance (Dec 24, 2022)
16-67657627-C-T		Dyskeratosis congenita, autosomal dominant 6 • Inborn genetic diseases	Likely benign (Apr 11, 2023)
16-67657628-C-A		Inborn genetic diseases	Uncertain significance (Mar 24, 2022)
16-67657628-C-T		Inborn genetic diseases	Likely benign (Feb 03, 2023)
16-67657629-C-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
16-67657632-G-A		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
16-67657636-T-G		Inborn genetic diseases	Likely benign (Jun 18, 2021)
16-67657639-A-G		Inborn genetic diseases	Likely benign (Jan 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACD	protein_coding	protein_coding	ENST00000393919	12	3299

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.11e-12	0.159	125685	0	56	125741	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.486	345	321	1.08	0.0000162	3398
Missense in Polyphen		55	73.209	0.75128		931
Synonymous	-1.88	167	139	1.20	0.00000716	1218
Loss of Function	0.822	21	25.5	0.824	0.00000120	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000579	0.000573
Ashkenazi Jewish	0.00	0.00
East Asian	0.000384	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000266	0.000264
Middle Eastern	0.000384	0.000381
South Asian	0.0000657	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity. May play a role in organogenesis. {ECO:0000269|PubMed:15181449, ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:16880378, ECO:0000269|PubMed:17237768, ECO:0000269|PubMed:20231318, ECO:0000269|PubMed:25205116, ECO:0000269|PubMed:25233904}.
• Disease: DISEASE: Dyskeratosis congenita, autosomal dominant, 6 (DKCA6) [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25205116}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyskeratosis congenita, autosomal recessive, 7 (DKCB7) [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25233904}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.872
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.14

Haploinsufficiency Scores

• pHI: 0.162
• hipred: N
• hipred_score: 0.396
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.778

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acd
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype; neoplasm; pigmentation phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: acd
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved dorsal

Gene ontology

• Biological process: telomere maintenance;skeletal system development;urogenital system development;intracellular protein transport;telomere capping;embryonic limb morphogenesis;protection from non-homologous end joining at telomere;telomere assembly;negative regulation of telomere maintenance via telomerase;positive regulation of telomere maintenance via telomerase;segmentation;positive regulation of telomerase activity;positive regulation of single-stranded telomeric DNA binding;protein localization to chromosome, telomeric region;establishment of protein localization to telomere;mitotic telomere maintenance via semi-conservative replication;telomere-telomerase complex assembly
• Cellular component: nuclear telomere cap complex;nuclear chromosome, telomeric region;nucleoplasm;nuclear body;shelterin complex
• Molecular function: protein binding;telomeric DNA binding;protein-containing complex binding;DNA polymerase binding;protein binding involved in negative regulation of telomere maintenance via telomerase