ACD (ACD, Shelterin Complex Subunit)
Telomere maintenance and protection gene
Gene Information Card
| Symbol | ACD |
|---|---|
| Full Name | ACD, Shelterin Complex Subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 65057 ncbi.nlm.nih.gov/gene/65057 |
| Ensembl ID | ENSG00000102977 |
| UniProt ID | Q96AP0 |
| OMIM ID | 609377 |
| HGNC ID | 25070 |
| Aliases | PTOP, TINT1, TPP1, PIP1 |
Description
The ACD gene encodes TPP1, a component of the shelterin complex that protects telomeres from being recognized as DNA damage and regulates telomerase access. TPP1 interacts with POT1 and TIN2 to facilitate telomere end protection and length homeostasis. Mutations in ACD are associated with telomere biology disorders including dyskeratosis congenita and pulmonary fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dyskeratosis congenita, autosomal dominant 6 | Loss-of-function mutations impair telomere maintenance, leading to premature telomere shortening and stem cell failure. | ClinVar, OMIM |
| Pulmonary fibrosis, idiopathic | Heterozygous missense variants disrupt shelterin complex stability, accelerating telomere attrition in lung epithelium. | ClinVar, OMIM |
| Bone marrow failure syndrome | Biallelic or dominant-negative mutations cause severe telomere dysfunction and hematopoietic defects. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.7 | Medium |
| Lung | 6.2 | Low |
| Skin | 5.1 | Low |
| Blood | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.5 | Cervical carcinoma |
| K562 | 7.2 | Leukemia |
| A549 | 6.8 | Lung carcinoma |
| HEK293 | 5.9 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.139C>T (p.Arg47Trp) | Missense | Rare | Dominant-negative; disrupts POT1 binding, telomere elongation defect |
| c.511G>A (p.Gly171Arg) | Missense | Rare | Loss of function; impairs TIN2 interaction, telomere uncapping |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; no protein production |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, or start-loss variants that reduce TPP1 protein levels or disrupt shelterin complex assembly.
Gain of Function (GOF)
Not reported for ACD; gain-of-function mechanisms are not established.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg47Trp) that retain partial function but interfere with wild-type TPP1, causing telomere dysfunction.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (GO:0005515) | • GO:0007004 (GO:0007004) |
| • GO:0000783 (GO:0000783) | • GO:0042162 (GO:0042162) |
| • GO:0005634 (GO:0005634) |
Pathways
• Telomere maintenance (shelterin complex) - Reactome R-HSA-171306
• Telomere C-strand synthesis - Reactome R-HSA-174411
Protein Summary
TPP1 (encoded by ACD) is a 544-amino acid protein that forms the shelterin complex together with TRF1, TRF2, POT1, TIN2, and RAP1. It bridges POT1 to TIN2, enabling telomere end protection and regulating telomerase recruitment. The protein contains an OB-fold domain for DNA binding and a TEL-patch motif essential for telomerase processivity. Post-translational phosphorylation modulates its interaction with telomerase.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACD Knockout HEK293 Cell Line | EDJ-KQ12159 | Human | 65057 | Details Get a Quote |
| ACD Knockout A-549 Cell Line | EDJ-KQ40853 | Human | 65057 | Details Get a Quote |
| ACD Knockout HCT 116 Cell Line | EDJ-KQ40854 | Human | 65057 | Details Get a Quote |
| ACD Knockout HeLa Cell Line | EDJ-KQ40855 | Human | 65057 | Details Get a Quote |
