TMEM231 (Q9H6L2) review notes

Deep research status

• Falcon was run with --fallback perplexity-lite (600 s; fallback not available here), then rerun with --timeout 2400; the outcome is at the bottom of this file. The review rests on cached primary literature.

Protein

• Two-pass transmembrane protein (TM 23-43, 262-282), TMEM231 family; only in ciliated organisms PMID:25869670.
• Disease: JBTS20 PMID:23012439, MKS11, OFD3.

Key findings

• Early basal body arrival PMID:22179047.
• Interdependence PMID:22179047.
• MKS complex PMID:25869670.
• Organizes the TZ PMID:25869670. The NPHP module is independent of it PMID:25869670.
• Membrane composition PMID:25869670. Not essential for ciliogenesis in MEFs PMID:25869670. Knockdown reduced cilia in Chih et al. PMID:22179047.
• Worm: TMEM-231 TZ localization needs MKS-2 and MKS-5 but not NPHP-4 PMID:25869670.

Curation decisions

• Protein binding: HuRI Y2H (KRT31, KRT40, NOTCH2NLA) REMOVE; TMEM107 REMOVE (MKS complex covers it).
• Cilium assembly: ACCEPT, with a tissue-dependence caveat.
• Smoothened signalling: KEEP_AS_NON_CORE.
• NEW: GO:1905349 ciliary transition zone assembly (IMP, PMID:25869670). The paper's own conclusion is "organizes the ciliary transition zone". Scaffold-case participation; see the reason text for the comparator/sparse-term argument.

HPA cilium atlas vs module role

• HPA (member_evidence.md): no cilium/centrosome call; HPA main location "Vesicles". Hansen et al. 2025 PMID:41005307. The atlas did not detect TMEM231 at cilia in its three cell lines. A vesicular signal is compatible with trafficking of a membrane protein (it is septin-dependent and reaches the basal body via vesicles), but it is not evidence against TZ localization: the TZ pool is small, and the literature (mouse tissues, worms) is strong.
• Module role: MKS module component, ciliary diffusion barrier, TZ assembly. Fully consistent with the literature. TMEM231 is one of the best-supported MKS members for the TZ assembly role, and core_functions follow the module.

Deep research outcome

• Falcon succeeded on the --timeout 2400 rerun (TMEM231-deep-research-falcon.md). Its synthesis (MKS/NPHP-module transition-zone organizer; non-enzymatic; ciliary gate/composition role) matches the conclusions above. No annotation decisions changed after reading it.