TMEM216 (Q9P0N5) review notes

Deep research status

• Falcon was run with --fallback perplexity-lite (600 s default; fallback not available here), then rerun with --timeout 2400. The first 2400 s attempt exited with code 137 (killed), so it was retried; the outcome is at the bottom of this file. The review rests on cached primary literature.

Protein

• Small (148 aa) tetraspan membrane protein (Transmemb_17 / IPR019184). Worm ortholog MKS-2.
• Disease: JBTS2 PMID:20036350, MKS2, OFD VI, RP98.

Location

• Ciliary base PMID:22282472; PMID:20512146.
• Vesicles/Golgi PMID:22282472.
• Mouse TZ/basal body PMID:21725307.
• MKS components between axoneme and membrane PMID:28401750.

Complex

• PMID:21725307. Possibly peripheral PMID:21725307.
• With meckelin PMID:20512146.
• Worm: core, mutually dependent MKS proteins PMID:26982032.

Function

• Ciliogenesis PMID:20512146; PMID:22282472.
• Dvl1/RhoA, possible non-canonical Wnt co-receptor with meckelin PMID:20512146. Speculative; not annotated.

Curation decisions

• Cytosol (Reactome TAS, x3): REMOVE. It is a multi-pass membrane protein.
• Protein binding (TMEM107): REMOVE (uninformative; MKS complex covers it).
• Positive regulation of cilium assembly (IEA/ISS): MODIFY to cilium assembly. The evidence is a requirement, not modulation.
• Photoreceptor morphogenesis/maintenance, positive regulation of Smo signalling (ISS/IEA): KEEP_AS_NON_CORE.
• No NEW TZ-assembly annotation. Unlike TCTN2/TMEM231, there is no direct mammalian data showing TMEM216 loss removes other TZ components or TZ structure, so I did not add GO:1905349. The worm MKS-2 mutual-dependence data support protein localization to TZ.

HPA cilium atlas vs module role

• HPA (member_evidence.md): no cilium/centrosome call; "not in HPA" (no HPA v25 subcellular data). The Hansen et al. 2025 cilium atlas PMID:41005307 therefore gives no evidence either way. A small tetraspan protein may lack a validated antibody.
• Module role: MKS module component (diffusion barrier; TZ assembly). Literature supports MKS module membership and TZ/ciliary-base localization. Direct evidence that TMEM216 itself builds the TZ is weaker than for TMEM231/TCTN2. core_functions therefore list MKS complex, TZ location, protein localization to TZ and cilium assembly, but not TZ assembly itself. This is a mild divergence from the module, which assigns TZ assembly to the whole MKS complex. Holding it at the complex level is fine.

Deep research outcome

• Falcon succeeded on the --timeout 2400 rerun (TMEM216-deep-research-falcon.md; TMEM216 needed a second 2400 s attempt after the first was killed with exit 137). Its synthesis matches the conclusions above (non-enzymatic transition-zone organizer/adaptor). No annotation decisions changed after reading it.