TMEM165 Golgi cation-homeostasis protein

Where it participates (unsigned role)

1. With serum lot 4, combining 1 micromolar manganese and 1 millimolar galactose restored fully glycosylated LAMP2 more effectively than either alone.

   Galactose and manganese coadministration → LAMP2 N-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   Manganese(II) ion (combined_ion); D-Galactose (combined_sugar); TMEM165 Golgi cation-homeostasis protein (affected_protein)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 9; use 1 mM galactose from setup and legend, rather than the subsequent prose unit typo", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 9804, "end_char": 10848, "text_sha256": "3547ececbb7198f699bd64bcd033276f18a8e3d3b7c02c4f907f25a267444bec", "text_characters": 1044}

   experimental_model

   TMEM165-knockout HEK cell cultures with different fetal bovine serum lots

   exposure

   Serum lot 4; 1 micromolar manganese, 1 millimolar galactose or both for 24 hours.

   limitations

   Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   A combined supply improved a result that responded poorly to either component alone.

   primary_references

   [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   tissue_or_cell_type

   Golgi glycosylation in HEK cells

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 866–878

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft

   ### mn-gly-gal-mn-combination With serum lot 4, combining 1 micromolar manganese and 1 millimolar galactose restored fully glycosylated LAMP2 more effectively than either alone. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A combined supply improved a result that responded poorly to either component alone. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Serum lot 4; 1 micromolar manganese, 1 millimolar galactose or both for 24 hours. cross_nutrient: Manganese(II) ion (combined_ion); D-Galactose (combined_sugar); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 9; use 1 mM galactose from setup and legend, rather than the subsequent prose unit typo", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 9804, "end_char": 10848, "text_sha256": "3547ececbb7198f699bd64bcd033276f18a8e3d3b7c02c4f907f25a267444bec", "text_characters": 1044} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   Complete structured claim and evidence

2. D-galactose improved LAMP2 N-glycosylation only partially across the tested concentrations and times; the authors attributed residual underglycosylated protein to slow turnover.

   D-Galactose → LAMP2 N-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein); UDP-galactose (related_donor)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 subset recovery", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092}

   experimental_model

   Control and TMEM165-knockout HEK293 glycosylation assays

   exposure

   Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours.

   limitations

   Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   Providing the sugar helped this readout, but some abnormal forms persisted throughout the tested conditions.

   primary_references

   [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   tissue_or_cell_type

   HEK293 cells and secretory glycoproteins

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 796–808

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft

   ### mn-gly-gal-n-linked-rescue D-galactose improved LAMP2 N-glycosylation only partially across the tested concentrations and times; the authors attributed residual underglycosylated protein to slow turnover. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the sugar helped this readout, but some abnormal forms persisted throughout the tested conditions. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours. cross_nutrient: Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein); UDP-galactose (related_donor) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 subset recovery", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   Complete structured claim and evidence

3. D-galactose partially improved the 24-hour O-glycan lectin readout but failed to rescue the three-day benzyl-GalNAc mass-spectrometry phenotype in TMEM165-knockout HEK cells.

   D-Galactose → Mucin-type O-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (effective_comparator)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; O-linked lectin and mass-spectrometry endpoints", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 19358, "end_char": 22255, "text_sha256": "e0b72a5427217107308f73e2304f47c761a25448096f516ca75c497eb8e389d5", "text_characters": 2897}

   experimental_model

   Control and TMEM165-knockout HEK293 glycosylation assays

   exposure

   Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days.

   limitations

   Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   One O-glycan test improved partly while a different test remained abnormal; galactose did not normalize this pathway.

   primary_references

   [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   tissue_or_cell_type

   HEK293 cells and secretory glycoproteins

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 810–822

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft

   ### mn-gly-gal-o-linked-limited D-galactose partially improved the 24-hour O-glycan lectin readout but failed to rescue the three-day benzyl-GalNAc mass-spectrometry phenotype in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: One O-glycan test improved partly while a different test remained abnormal; galactose did not normalize this pathway. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (effective_comparator) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; O-linked lectin and mass-spectrometry endpoints", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 19358, "end_char": 22255, "text_sha256": "e0b72a5427217107308f73e2304f47c761a25448096f516ca75c497eb8e389d5", "text_characters": 2897} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   Complete structured claim and evidence

4. At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions.

   Ferric iron → LAMP2 N-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209}

   experimental_model

   TMEM165-knockout HEK cell cultures with different fetal bovine serum lots

   exposure

   Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison.

   limitations

   Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   Iron changed this cellular readout but did not act as an equivalent manganese replacement.

   primary_references

   [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   tissue_or_cell_type

   Golgi glycosylation in HEK cells

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 852–864

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft

   ### mn-gly-iron-glycan-partial At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron changed this cellular readout but did not act as an equivalent manganese replacement. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison. cross_nutrient: Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   Complete structured claim and evidence

5. MnCl2 restored the measured N-glycosylation phenotype in TMEM165-knockout HEK cells.

   Manganese(II) chloride → LAMP2 N-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   Manganese(II) ion (supplied_ion); Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 and TGN46 electrophoretic profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092}

   experimental_model

   Control and TMEM165-knockout HEK293 glycosylation assays

   exposure

   Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours.

   limitations

   Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   Manganese improved the N-linked sugar-chain readout.

   primary_references

   [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   tissue_or_cell_type

   HEK293 cells and secretory glycoproteins

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 754–766

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft

   ### mn-gly-mn-n-linked-rescue MnCl2 restored the measured N-glycosylation phenotype in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese improved the N-linked sugar-chain readout. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours. cross_nutrient: Manganese(II) ion (supplied_ion); Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 and TGN46 electrophoretic profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   Complete structured claim and evidence

6. MnCl2 restored the measured O-linked glycosylation defects in TMEM165-knockout HEK cells.

   Manganese(II) chloride → Mucin-type O-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   Manganese(II) ion (supplied_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; lectin staining and benzyl-GalNAc mass-spectrometry profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 24441, "end_char": 25329, "text_sha256": "40d6513f6782e8f624ca1d04f64d8153282e2beed8877766a60140128e1b438d", "text_characters": 888}

   experimental_model

   Control and TMEM165-knockout HEK293 glycosylation assays

   exposure

   Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days.

   limitations

   Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   Manganese also improved a different class of sugar chains.

   primary_references

   [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   tissue_or_cell_type

   HEK293 cells and secretory glycoproteins

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 768–780

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft

   ### mn-gly-mn-o-linked-rescue MnCl2 restored the measured O-linked glycosylation defects in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese also improved a different class of sugar chains. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days. cross_nutrient: Manganese(II) ion (supplied_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; lectin staining and benzyl-GalNAc mass-spectrometry profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 24441, "end_char": 25329, "text_sha256": "40d6513f6782e8f624ca1d04f64d8153282e2beed8877766a60140128e1b438d", "text_characters": 888} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953

   Complete structured claim and evidence

7. Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences.

   Cell glycosylation response to serum-lot composition → LAMP2 N-linked glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results; serum comparisons, ion measurements and manganese rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 6062, "end_char": 7726, "text_sha256": "9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4", "text_characters": 1664}

   experimental_model

   TMEM165-knockout HEK cell cultures with different fetal bovine serum lots

   exposure

   Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations.

   limitations

   Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Homo sapiens

   plain_language

   The same genetic defect behaved differently as the surrounding nutrient mixture changed.

   primary_references

   [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   tissue_or_cell_type

   Golgi glycosylation in HEK cells

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 838–850

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft

   ### mn-gly-serum-lot-context Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same genetic defect behaved differently as the surrounding nutrient mixture changed. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results; serum comparisons, ion measurements and manganese rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 6062, "end_char": 7726, "text_sha256": "9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4", "text_characters": 1664} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

   Complete structured claim and evidence

8. Manganese supplementation restored glycosylation in the TMEM165-depleted mammalian-cell experiments.

   Mn2+ → Golgi protein glycosylation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   cross_nutrient

   TMEM165 Golgi cation-homeostasis protein (affected_protein); Golgi apparatus (affected_compartment)

   evidence_span

   {"source_cache": "artifacts/manganese-glycosylation-sources/potelle2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "start_char": 0, "end_char": 1190, "text_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "text_characters": 1190}

   experimental_model

   TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments

   exposure

   Mn2+ supplementation of depleted cells.

   limitations

   These records describe the mammalian-cell arm. The indexed abstract does not specify every line, dose or treatment duration; rescue supports a homeostasis role rather than establishing a transport stoichiometry.

   nutrient_topic

   Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

   organism

   Mammalian cell model; yeast comparison

   plain_language

   More available manganese could compensate for this Golgi-handling defect in cells.

   primary_references

   [mn-gly-potelle2016] Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. (2016). https://pubmed.ncbi.nlm.nih.gov/27008884/ DOI: 10.1093/hmg/ddw026

   tissue_or_cell_type

   Golgi glycosylation

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 740–752

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments · source_derived_draft · unverified_draft

   ### mn-gly-tmem165-mn-rescue Manganese supplementation restored glycosylation in the TMEM165-depleted mammalian-cell experiments. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: More available manganese could compensate for this Golgi-handling defect in cells. organism: Mammalian cell model; yeast comparison tissue_or_cell_type: Golgi glycosylation experimental_model: TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments limitations: These records describe the mammalian-cell arm. The indexed abstract does not specify every line, dose or treatment duration; rescue supports a homeostasis role rather than establishing a transport stoichiometry. exposure: Mn2+ supplementation of depleted cells. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Golgi apparatus (affected_compartment) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/potelle2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "start_char": 0, "end_char": 1190, "text_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "text_characters": 1190} [mn-gly-potelle2016] Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. (2016). https://pubmed.ncbi.nlm.nih.gov/27008884/ DOI: 10.1093/hmg/ddw026

   Complete structured claim and evidence