| Category | Key points | Evidence/citation IDs to support |
|---|---|---|
| concept/definition | Human EMC7 is the ER membrane protein complex subunit 7, a conserved EMC component; literature also uses the legacy human name **C11orf3** and notes the yeast homolog **Sop4**. EMC7 is not the catalytic insertase core itself, but part of the EMC machine that supports membrane protein biogenesis. | (pqac-00000003, pqac-00000004, pqac-00000013) |
| localization/topology | EMC7 is an **ER membrane** subunit with a **lumenal N-terminus** and **type I single-pass topology**; protease-protection experiments support a single membrane span, and cryo-EM places EMC7 in the EMC lumenal/front dynamic region with a flexible TMD. | (pqac-00000015, pqac-00000049, pqac-00000050, pqac-00000047) |
| molecular function/mechanism | At the complex level, EMC acts as a **co-/post-translational insertase** and membrane-protein biogenesis factor using a hydrophilic vestibule centered on EMC3/EMC6. EMC7 contributes a **dynamic TMD** and **cytosolic hydrophobic loops** beneath the vestibule that help transiently capture incoming substrate TMDs; an EMC7 C-terminal amphipathic element is functionally important for client biogenesis. | (pqac-00000006, pqac-00000008, pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019) |
| interaction partners | Within EMC, EMC7 associates with **EMC1** and **EMC10** in the lumenal domain and is proximal to **EMC3** in the membrane region. Beyond the complex, EMC7 binds **Rab7** and **syntaxin18/Stx18** in ER-late endosome tethering, and its TMH forms a major interface with **VDAC1** at mitochondria-ER contact sites. | (pqac-00000045, pqac-00000046, pqac-00000047, pqac-00000048, pqac-00000050) |
| substrates/clients | EMC7-specific experiments show it is required for biogenesis of the EMC client **squalene synthase (SQS)**; more broadly, EMC supports clients such as **SOAT1** and many multipass membrane proteins, but most substrate assignments are **complex-level** rather than uniquely EMC7-specific. EMC7 loss can reduce TA clients and retain multipass clients in the ER. | (pqac-00000009, pqac-00000015, pqac-00000026, pqac-00000048) |
| recent 2023-2024 developments | **2023:** EMC7 was mechanistically assigned a role in early substrate capture/selectivity and experimentally confirmed as a type I single-pass subunit. **2024:** EMC7 TMH was shown to become ordered upon **VDAC1** binding and to contribute about **one-third** of the EMC-VDAC1 interface; EMC context was expanded by the finding that EMC rectifies topology of ~**250** multipass proteins post-translationally. | (pqac-00000015, pqac-00000018, pqac-00000019, pqac-00000043, pqac-00000022) |
| human genetics/clinical | Direct disease causality for human EMC7 remains limited. A **2024 GWAS** in **520** sickle cell disease subjects identified a genome-wide significant locus **near EMC7** for HbF (**rs8182015, P=2.07×10⁻⁸**), but the paper explicitly supports cautious interpretation because proximity does not prove EMC7 causality. OpenTargets also lists disease associations for EMC7 based largely on functional-screen evidence rather than Mendelian proof. | (pqac-00000038, pqac-00000039, pqac-00000040, pqac-00000014) |
| applications | EMC7 has real-world relevance as part of a host pathway exploited in **SV40** entry, where EMC7/EMC4 tether late endosomes to the ER through Rab7 and cooperate with Stx18. At the broader EMC level, this biology matters because EMC governs biogenesis of pharmacologically important membrane proteins, including **GPCRs**, **ion channels**, and sterol-homeostasis enzymes. | (pqac-00000031, pqac-00000032, pqac-00000034, pqac-00000035, pqac-00000037, pqac-00000057, pqac-00000058) |


*Table: This table condenses the strongest functional-annotation evidence for human EMC7 (UniProt Q9NPA0), separating EMC7-specific findings from broader complex-level EMC biology. It is useful as a quick reference for function, localization, mechanism, interactions, recent studies, and biomedical relevance.*