| VPS37 paralog | Key domains / motifs | Unique features distinguishing each paralog | Known interacting partners in ESCRT-I complex | Specific cellular functions with strongest evidence | Disease associations / translational relevance |
|---|---|---|---|---|---|
| **VPS37A** | Conserved **Mod(r)** domain shared across VPS37 family; distinctive **N-terminal ubiquitin E2 variant-like (UEVL) region** required for autophagosome closure but dispensable for core ESCRT-I assembly and EGFR endosomal sorting (pqac-00000010, pqac-00000016) | Best-characterized VPS37 paralog; uniquely directs ESCRT recruitment to phagophores through its N-terminus; forms a specialized autophagy-relevant ESCRT-I module not shared by all paralogs (pqac-00000010, pqac-00000016) | Core ESCRT-I partners **TSG101** and **VPS28**; can assemble with **UBAP1** in an endosome/autophagy-adapted ESCRT-I complex; recruits downstream **CHMP2A** and VPS4-dependent closure machinery during autophagy (pqac-00000010, pqac-00000016, pqac-00000017) | Endosomal sorting as an ESCRT-I core subunit; especially important in **autophagosome/phagophore closure** by directing ESCRT machinery to LC3-positive phagophores; contributes to broader reverse-topology membrane scission pathways (pqac-00000000, pqac-00000010, pqac-00000016, pqac-00000009) | Frequently lost/downregulated in solid tumors; associated with hepatocellular carcinoma history and worse survival when deleted; depletion linked to **hyperglycemia/insulin resistance** in review literature; reduced with VPS37B in colorectal cancer cohorts (pqac-00000010, pqac-00000011, pqac-00000013) |
| **VPS37B** | Conserved **Mod(r)** domain; contains **two PxLPxR motifs** noted in comparison with VPS37C/D; has a proline-rich region architecture distinct from some other paralogs (pqac-00000015, pqac-00000018) | Strong evidence for selective paralog-specific interactions; binds **SH3YL1** in EGFR degradative sorting; preferentially associates with **CDIP1** and **ALG-2** relative to VPS37D in apoptosis-linked ESCRT-I assemblies; incorporated into cytokinesis-related ESCRT-I modules with **UMAD1** (pqac-00000015, pqac-00000018, pqac-00000007) | Core partners **TSG101** and **VPS28**; can associate with **MVB12-like proteins**; selective interaction with **UMAD1** in cytokinesis-specific ESCRT-I; indirect/functional coupling with **SH3YL1**, **ALG-2**, and **CDIP1** (pqac-00000007, pqac-00000015, pqac-00000018, pqac-00000017) | Endosomal **EGFR sorting and degradation**; contributes to cytokinetic abscission through specialized ESCRT-I assemblies; participates in canonical ESCRT-I membrane remodeling and cargo-sorting pathways (pqac-00000007, pqac-00000015, pqac-00000009) | Expression is reduced in **advanced colorectal cancer**; reduced mRNA/protein documented in patient cohorts; loss contributes to ESCRT-I destabilization and stress/inflammatory transcriptional responses when VPS37 paralogs are depleted (pqac-00000002, pqac-00000013, pqac-00000011) |
| **VPS37C** | Conserved **Mod(r)** domain; no VPS37A-like autophagy UEVL extension described in the cited evidence (pqac-00000005, pqac-00000011) | Selectively participates in **cytokinesis-specific ESCRT-I assemblies** via **UMAD1**; preferentially associates with **CDIP1/ALG-2** similarly to VPS37B; appears functionally nonredundant with other VPS37 paralogs in stress-response studies (pqac-00000007, pqac-00000018, pqac-00000002) | Core partners **TSG101** and **VPS28**; selective association with **UMAD1**; functional linkage to **ALG-2** and **CDIP1** in specialized ESCRT-I complexes (pqac-00000007, pqac-00000018) | Supports **cytokinetic abscission** in UMAD1-containing ESCRT-I assemblies; participates in canonical ESCRT-I roles in membrane remodeling and cargo sorting; contributes to ESCRT-I integrity in paralog depletion studies (pqac-00000007, pqac-00000002, pqac-00000009) | No strong paralog-specific human disease assignment in the cited papers, but depletion potentiates ESCRT-I destabilization and cellular stress programs; therefore relevant to cancer/stress biology of ESCRT dysfunction (pqac-00000002, pqac-00000011) |
| **VPS37D / WBSCR24** | Conserved **Mod(r)** domain; UniProt-aligned VPS37 family member; literature indicates proline-rich-region diversity across VPS37 paralogs, but no VPS37A-like autophagy UEVL specialization has been established in the cited studies (pqac-00000005, pqac-00000018) | Least functionally characterized of the four human paralogs in primary mechanistic literature; confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs and likely contributes structural diversity to ESCRT-I assemblies; does **not** show the same highlighted SH3YL1 or CDIP1 preference reported for VPS37B/C (pqac-00000005, pqac-00000018, pqac-00000011) | Core ESCRT-I partners inferred and supported at family level: **TSG101**, **VPS28**, and one MVB12-like subunit (**MVB12A/B, UBAP1, UBA1L, or UMAD1**) in heterotetrameric ESCRT-I complexes; mammalian ESCRT-I can contain any one of VPS37A-D (pqac-00000017, pqac-00000007, pqac-00000011) | Best-supported function is as a **core structural ESCRT-I subunit** in pathways requiring reverse-topology membrane scission: endosomal cargo sorting/MVB biogenesis, coupling to ESCRT-II/III, and likely participation in broader ESCRT-dependent processes such as cytokinesis, membrane repair, and nuclear-envelope-related dynamics at the family level; however, direct VPS37D-specific mechanistic evidence remains limited (pqac-00000001, pqac-00000005, pqac-00000009, pqac-00000011) | Emerging biomarker relevance: a 2025 pan-cancer/breast-cancer analysis identified **VPS37D** as associated with breast cancer initiation/progression, prognosis, and immune microenvironment features; older CRC transcriptomics found **negligible VPS37D expression** in colorectal tissue relative to other paralogs, underscoring tissue-specific biology (pqac-00000003, pqac-00000013) |


*Table: This table compares VPS37A-D, emphasizing what is known specifically for human VPS37D versus better-studied paralogs. It summarizes domain architecture, ESCRT-I interactions, pathway roles, and disease links from the cited 2020-2025 literature.*