DHCR24 encodes an FAD-associated, NADPH-dependent sterol reductase that reduces side-chain delta-24 double bonds during cholesterol biosynthesis, including conversion of desmosterol to cholesterol. It associates strongly with the endoplasmic reticulum membrane, with a Golgi pool also observed in human cells; its precise membrane topology remains incompletely resolved. Sterol synthesis supports membrane organization and influences protein partitioning and amyloid precursor protein processing. A separable p53-binding mechanism contributes to oncogenic and oxidative stress responses in experimental cell systems. Biallelic loss of function causes desmosterolosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: Refine broad cytoplasm to the established ER membrane. Reason: Cytoplasm includes intracellular structures, so ER membrane association does not contradict this term. Human H4 fractionation and tagged-protein localization support ER, and later membrane assays support strong ER association without settling all transmembrane boundaries. The historical PAINT cytoplasm row is absent from the reused current leaf file, which instead carries membrane from PTN000085798; preserve that historical source and refine its spatial scope. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000085798 SOURCE STALE OR MISSING Human Q15392 descends from this node. The current IBD/leaf pair carries membrane rather than the historical cytoplasm assertion. Target experimental evidence in the donor list is legitimate; the refinement rests on actual target localization. Proposed replacements: endoplasmic reticulum membrane |
| GO:0008202 steroid metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Specify cholesterol biosynthesis within inherited steroid metabolism. Reason: The actual PTHR10801 tree places human DHCR24 beneath PTN000085798, whose steroid-metabolism IBD has plant, mouse, rat and human descendant evidence. This broad ancestral function is credible; human desmosterol-to-cholesterol conversion specifies the target contribution as cholesterol biosynthesis. A short donor list or the target among descendants is not an evidential defect. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000085798 SUPPORTS TRANSFER The target is within the asserted clade; target chemistry supports a more specific human process. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0000246 Delta24(24-1) sterol reductase activity | IBA GO_REF:0000033 | MODIFY | Summary: Distinguish delta-24 sterol reduction from the different delta-24(28) activity. Reason: The current definition of GO:0000246 specifies EC 1.3.1.71 and ergosterol delta-24(28) chemistry. Human 516-residue DHCR24 expressed in yeast homogenates instead converts desmosterol to cholesterol with NADPH, consistent with GO:0050614/EC 1.3.1.72. The historical PTN000085799 node contains the target; the current assertion is at ancestral PTN000085798. This is reaction-term scope, not paralog exclusion or rejection of target-derived PAINT evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000085799 SUPPORTS SOURCE BUT NOT TARGET The target is a descendant, but the particular reaction in the term definition is not the reaction demonstrated by the target experiment. The current node placement has also changed. Proposed replacements: Delta24-sterol reductase activity Supporting Evidence: |
| GO:0050614 Delta24-sterol reductase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Retain the specific delta-24 sterol reductase activity. Reason: EC 1.3.1.72 maps to GO:0050614 and agrees with human DHCR24-dependent desmosterol conversion, NADPH dependence and FAD enhancement. This is the catalytic unit; GO:0000246 is not a synonymous reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: EC:1.3.1.72 SUPPORTS TRANSFER The actual EC mapping agrees with the experimentally supported human reaction. Supporting Evidence: |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the experimentally supported Golgi-associated pool. Reason: The UniProt location transfer agrees with original human H4 experiments: endogenous fractionation detects DHCR24 in Golgi and ER fractions, while tagged-protein imaging emphasizes ER. A less abundant Golgi pool is not excluded by the primary ER location; this evidence does not establish a separate Golgi catalytic unit. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0134 SUPPORTS TRANSFER The UniProt location transfer is corroborated by original human Golgi fractionation. Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain ER membrane localization. Reason: The mapped UniProt ER-membrane location is supported by human H4 ER localization and later membrane fractionation, protease-protection and solubilization experiments. N-terminal truncations can remain ER-associated; this location does not require a settled single-pass model or an exclusively ER distribution. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER The location mapping is supported by original ER and membrane experiments. Supporting Evidence: PMID:27919032 a cytoplasmic C-terminus and a non-accessible N-terminus |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: Specify cholesterol synthesis within lipid metabolism. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported lipid metabolism term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-KW:KW-0443 SUPPORTS TRANSFER The imported mapping is biologically compatible; direct human chemistry supports the more specific reaction or biosynthetic process. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0006694 steroid biosynthetic process | IEA GO_REF:0000043 | MODIFY | Summary: Specify cholesterol synthesis within steroid biosynthesis. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported steroid biosynthesis term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-KW:KW-0752 SUPPORTS TRANSFER The imported mapping is biologically compatible; direct human chemistry supports the more specific reaction or biosynthetic process. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0006695 cholesterol biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Retain cholesterol biosynthesis. Reason: The combined keyword, pathway and mouse-orthology routes agree with direct human enzymatic evidence. Human DHCR24 cDNA restores NADPH-dependent desmosterol conversion in yeast homogenates, identifying a catalytic cholesterol-synthesis step rather than only a downstream cholesterol phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER Combined keyword/pathway/mouse routes agree with direct human catalytic participation. ensembl:ENSMUSP00000038063 SUPPORTS TRANSFER Combined keyword/pathway/mouse routes agree with direct human catalytic participation. UniProtKB-KW:KW-0152 SUPPORTS TRANSFER Combined keyword/pathway/mouse routes agree with direct human catalytic participation. UniPathway:UPA00063 SUPPORTS TRANSFER Combined keyword/pathway/mouse routes agree with direct human catalytic participation. Supporting Evidence: |
| GO:0008202 steroid metabolic process | IEA GO_REF:0000120 | MODIFY | Summary: Specify cholesterol synthesis within steroid metabolism. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported steroid metabolism term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. ARBA00027309 has a matching FunFam 3.30.465.10:FF:000032 branch on the official human record; its broad steroid-metabolism conclusion is biologically sound. The additional rat transfer is not needed to establish the human chemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00027309 SUPPORTS TRANSFER The actual ARBA FunFam branch matches the target; the rat source and keywords are compatible, but human cholesterol synthesis is more specific. UniProtKB:Q5BQE6 SUPPORTS TRANSFER The actual ARBA FunFam branch matches the target; the rat source and keywords are compatible, but human cholesterol synthesis is more specific. ensembl:ENSRNOP00000009402 SUPPORTS TRANSFER The actual ARBA FunFam branch matches the target; the rat source and keywords are compatible, but human cholesterol synthesis is more specific. UniProtKB-KW:KW-0753 SUPPORTS TRANSFER The actual ARBA FunFam branch matches the target; the rat source and keywords are compatible, but human cholesterol synthesis is more specific. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0008203 cholesterol metabolic process | IEA GO_REF:0000120 | MODIFY | Summary: Specify cholesterol synthesis within cholesterol metabolism. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported cholesterol metabolism term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. Mouse experimental evidence also supports cholesterol-dependent membrane phenotypes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER Mouse cholesterol-dependent membrane evidence agrees with target chemistry; the biosynthetic contribution is the more specific term. ensembl:ENSMUSP00000038063 SUPPORTS TRANSFER Mouse cholesterol-dependent membrane evidence agrees with target chemistry; the biosynthetic contribution is the more specific term. UniProtKB-KW:KW-0153 SUPPORTS TRANSFER Mouse cholesterol-dependent membrane evidence agrees with target chemistry; the biosynthetic contribution is the more specific term. Proposed replacements: cholesterol biosynthetic process |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000043 | MODIFY | Summary: Specify cholesterol synthesis within sterol biosynthesis. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported sterol biosynthesis term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-KW:KW-0756 SUPPORTS TRANSFER The imported mapping is biologically compatible; direct human chemistry supports the more specific reaction or biosynthetic process. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000043 | MODIFY | Summary: Specify the established sterol reductase reaction. Reason: The oxidoreductase keyword is correct but too broad: human DHCR24 catalyzes NADPH-dependent reduction of a sterol side-chain delta-24 double bond. GO:0050614 identifies the supported activity without treating every oxidoreductase in the FAD-binding family as functionally equivalent. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-KW:KW-0560 SUPPORTS TRANSFER The imported mapping is biologically compatible; direct human chemistry supports the more specific reaction or biosynthetic process. Proposed replacements: Delta24-sterol reductase activity Supporting Evidence: |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain FAD-cofactor binding associated with the reductase unit. Reason: Target InterPro matches IPR006094 (residues 111–203) and IPR036318 (32–233) carry the flavin-binding mapping. Human DHCR24-dependent conversion in yeast homogenates is enhanced by added FAD. Together these support the cofactor role; the family description does not establish covalent FAD attachment or all family-member reactions in DHCR24. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006094 SUPPORTS TRANSFER Actual target domain/superfamily matches map to this cofactor term and are corroborated by FAD enhancement. InterPro:IPR036318 SUPPORTS TRANSFER Actual target domain/superfamily matches map to this cofactor term and are corroborated by FAD enhancement. Supporting Evidence: |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain the mapped FAD-binding function. Reason: IPR016166 is present on human DHCR24 at residues 58–234 and maps to this oxidized-FAD binding term. The FAD-enhanced sterol conversion provides target functional corroboration. This belongs to the same catalytic unit as the broader flavin-binding annotation, not an additional enzyme core. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR016166 SUPPORTS TRANSFER Actual target PCMH-type domain match maps to FAD binding, corroborated by the target reaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Summary: Retain the crosslink-supported association with PGRMC1. Reason: The curated IntAct record EBI-20911008/IM-26653-2289 identifies human Q15392 and O00264 in the Triton-soluble fraction of crosslinked U2OS nuclei; the original paper explicitly discusses ER remaining with the preparation. Sequence checks match the canonical 516-residue DHCR24 and PGRMC1 proteins. This is physical-association evidence, not purified binary binding or nuclear localization. PGRMC1 is a heme-handling and membrane-complex protein; those facts do not establish a specific protein-folding-chaperone or nuclear-receptor binding class for this pair. Retain the supported broad association as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Retain the OpenCell PGRMC1–DHCR24 association. Reason: The author interaction table lists PGRMC1 as bait and DHCR24 as prey in endogenous-tagging AP-MS from HEK293T cells. The prey protein group contains Q15392, Q15392-2 and A0A0A0MTI1, so this record does not resolve the natural isoform. The study uses biological triplicates and digitonin extraction; the association need not be stoichiometric or direct to remain supported. No narrower partner-class molecular function is established by PGRMC1 heme handling alone. Supporting Evidence: |
| GO:0006695 cholesterol biosynthetic process | TAS Reactome:R-HSA-191273 | ACCEPT | Summary: Retain the curated cholesterol-synthesis pathway role. Reason: Reactome cholesterol biosynthesis contains DHCR24-catalyzed sterol reductions. The molecular contribution is independently demonstrated by human desmosterol conversion, so this is enzyme participation in the process and not mere necessity or substrate status. |
| GO:0033489 cholesterol biosynthetic process via desmosterol | TAS Reactome:R-HSA-6807047 | MODIFY | Summary: Retain the source assertion while replacing the obsolete pathway-specific term. Reason: The imported GO identifier is obsolete; the chemistry remains cholesterol biosynthesis. DHCR24 reduces the side-chain delta-24 double bond in sterol intermediates and can connect the named pathway variants. Preserve the original GOA term and reference, and retain the previously approved replacement GO:0006695 without creating a duplicate NEW assertion. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: Reactome:R-HSA-6807047 |
| GO:0033490 cholesterol biosynthetic process via lathosterol | TAS Reactome:R-HSA-6807062 | MODIFY | Summary: Retain the source assertion while replacing the obsolete pathway-specific term. Reason: The imported GO identifier is obsolete; the chemistry remains cholesterol biosynthesis. DHCR24 reduces the side-chain delta-24 double bond in sterol intermediates and can connect the named pathway variants. Preserve the original GOA term and reference, and retain the previously approved replacement GO:0006695 without creating a duplicate NEW assertion. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: Reactome:R-HSA-6807062 |
| GO:0007265 Ras protein signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain a context-dependent role in the Ras-triggered stress response. Reason: The rat transfer is grounded in PMID15577914, whose genetic screen and human-cell follow-up place Seladin-1 in responses to oncogenic Ras. The supplement separates stress/p53-response phenotypes from the sterol-active-site mutants. Retain the existing process context as non-core; this does not assign Ras GTPase, exchange-factor or direct receptor-signaling activity to DHCR24. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5BQE6 SUPPORTS TRANSFER The rat experimental source and human follow-up support a context-dependent Ras-triggered stress response. ensembl:ENSRNOP00000009402 SUPPORTS TRANSFER The rat experimental source and human follow-up support a context-dependent Ras-triggered stress response. Supporting Evidence: |
| GO:0008104 intracellular protein localization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain cholesterol-dependent effects on protein localization. Reason: Mouse loss-of-function and human DHCR24 overexpression in PMID16407971 alter flotillin/PrPc partitioning in detergent-resistant membrane fractions. The human construct is a full-length Q15392 ORF with a C-terminal HA tag. PMID16513830 additionally reports altered insulin-receptor/caveolin partitioning in cholesterol-depleted mouse cells, but that paper was available only as an abstract. The observed localization contribution is non-core and sterol-mediated, not evidence of an autonomous protein-transport activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER Mouse and parallel human original experiments support sterol-dependent protein partitioning. ensembl:ENSMUSP00000038063 SUPPORTS TRANSFER Mouse and parallel human original experiments support sterol-dependent protein partitioning. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the stress-dependent antiproliferative contribution. Reason: The experimental grounding of the rat transfer is the Seladin-1 oncogenic/oxidative-stress study, including human-cell tests and p53-binding/response separation-of-function mutants in its genuine supplement. This supports a context-dependent growth-arrest contribution. It does not imply that DHCR24 suppresses proliferation in every cell or that its sterol reductase activity is intrinsically antiproliferative. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5BQE6 SUPPORTS TRANSFER The donor study and human stress tests support a conditional antiproliferative contribution. ensembl:ENSRNOP00000009402 SUPPORTS TRANSFER The donor study and human stress tests support a conditional antiproliferative contribution. Supporting Evidence: |
| GO:0009725 response to hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: Hormone-response transfer requires unresolved assay interpretation. Reason: The rat source PMID17210742 abstract reports ACTH-induced expression and altered cellular distribution, with pharmacological observations in adrenal cells. The original full text was not recovered. Expression responsiveness alone does not resolve whether human DHCR24 performs a response step, and the precise perturbation controls and orthology-transfer scope remain uncertain. Preserve the imported assertion without the prior categorical removal. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q5BQE6 UNRESOLVED The current donor record traces the hormone term to IEP in PMID17210742; actual original controls and human functional transfer are unresolved. Supporting Evidence: |
| GO:0009888 tissue development | IEA GO_REF:0000107 | UNDECIDED | Summary: Broad tissue-development transfer remains unresolved. Reason: The mouse donor record traces this term to PMID14684813. The genuine cached record has a title but no abstract, and the original was not recovered. Human sterol chemistry is established, but it cannot substitute for reading the developmental evidence or distinguish process participation from secondary developmental consequences. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8VCH6 UNRESOLVED The source experimental assertion is identified, but the actual developmental study is unavailable. Supporting Evidence: |
| GO:0016125 sterol metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Specify cholesterol synthesis within sterol metabolism. Reason: DHCR24 itself reduces sterol intermediates in cholesterol biosynthesis, including the directly tested desmosterol-to-cholesterol step. The imported sterol metabolism term is broader than this established contribution and should be refined to GO:0006695, even though that specific annotation is already present. The mouse transfer is independently supported at the human target by the biochemical conversion assay. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER Mouse source chemistry is compatible and direct human evidence establishes the narrower biosynthetic contribution. ensembl:ENSMUSP00000038063 SUPPORTS TRANSFER Mouse source chemistry is compatible and direct human evidence establishes the narrower biosynthetic contribution. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0030539 male genitalia development | IEA GO_REF:0000107 | UNDECIDED | Summary: Male-genitalia-development transfer remains unresolved. Reason: The mouse donor record traces this developmental assertion to PMID14684813. That source is currently title-only in the cache and the original was not recovered. A cholesterol-biosynthetic defect can affect development, but neither that plausibility nor absence of an independent human assay justifies categorical removal or confident transfer of the specific process. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8VCH6 UNRESOLVED The actual source phenotype and its allocation to this specific developmental process could not be checked. Supporting Evidence: |
| GO:0031639 plasminogen activation | IEA GO_REF:0000107 | MODIFY | Summary: Specify positive regulation of plasminogen activation. Reason: The actual source study PMID16407971 compares mouse brain membranes and human DHCR24-overexpressing SH-SY5Y cells, measuring membrane plasminogen recruitment and plasmin activity with a chromogenic substrate. DHCR24-dependent cholesterol enrichment promotes the membrane environment supporting activation; DHCR24 is not shown to proteolyze plasminogen. GO:0010756 captures the positive regulatory role demonstrated by these membrane assays. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8VCH6 SUPPORTS SOURCE BUT NOT TARGET The mouse source and parallel human construct experiments support regulation through membrane sterol composition, rather than assigning the activating proteolytic step to DHCR24. Proposed replacements: positive regulation of plasminogen activation Supporting Evidence: PMID:16407971 Plasmin enzymatic activity was assayed using the chromogenic substrate S-2251 |
| GO:0042987 amyloid precursor protein catabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Specify negative regulation of APP catabolism. Reason: In PMID16407971, DHCR24 loss changes BACE1 membrane partitioning and increases amyloidogenic APP cleavage, whereas human DHCR24 overexpression has the opposite effect. The study measures cleavage products and APP/BACE1 partitioning; it does not establish DHCR24 as an APP protease. GO:1902992 specifies the demonstrated reduction of APP catabolic processing in that cellular context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8VCH6 SUPPORTS SOURCE BUT NOT TARGET Direct inspection of the original mouse and human experiments supports a negative regulatory role, not the APP-cleaving reaction. Proposed replacements: negative regulation of amyloid precursor protein catabolic process Supporting Evidence: PMID:16407971 BACE1 was displaced from light fractions 4–6 to APP-containing heavy fractions |
| GO:0043588 skin development | IEA GO_REF:0000107 | UNDECIDED | Summary: The skin-development transfer needs the unavailable original. Reason: The mouse experimental grounding PMID16410790 explicitly reports epidermal cholesterol loss, desmosterol accumulation and a defective epidermal barrier in Dhcr24-null mice. The full original was not recovered, so detailed developmental assays are not independently reconstructed. The phenotype is biologically compatible with the conserved sterol-synthesis requirement, but the original developmental allocation and controls cannot be checked. Leave the transfer undecided; no separate skin-specific enzymatic activity or direct morphogenetic mechanism is assigned. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8VCH6 UNRESOLVED The actual abstract supports a skin/barrier phenotype, but the original process allocation and controls remain unavailable. Supporting Evidence: |
| GO:0061024 membrane organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the demonstrated contribution to membrane organization. Reason: PMID16407971 directly tests cholesterol-dependent detergent-resistant membrane composition, lipid order and protein partitioning in mouse tissue and human DHCR24-overexpressing cells. Cholesterol depletion and desmosterol-addition controls distinguish the effects of sterol composition. This is a supported organizational contribution through lipid synthesis, not an independent membrane-shaping or scaffold activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER Mouse and parallel human originals directly examine membrane composition and organization. ensembl:ENSMUSP00000038063 SUPPORTS TRANSFER Mouse and parallel human originals directly examine membrane composition and organization. Supporting Evidence: |
| GO:0050614 Delta24-sterol reductase activity | EXP PMID:11519011 Mutations in the 3beta-hydroxysterol Delta24-reductase gene ... | ACCEPT | Summary: Retain experimentally established delta-24 sterol reductase activity. Reason: PMID11519011 expresses sequence-verified human 516-residue DHCR24 in yeast and assays cell homogenates by GC-MS. Desmosterol-to-cholesterol conversion depends on NADPH and is enhanced by FAD. This is functional recombinant-expression evidence, not a purified-protein assay or evidence for every natural splice product. Supporting Evidence: |
| GO:0050614 Delta24-sterol reductase activity | TAS Reactome:R-HSA-9755937 | ACCEPT | Summary: Retain the specific catalytic activity in the lanosterol reaction. Reason: The Reactome reaction resolves through CatalystActivity 196404 to human Q15392/physical entity 196414 and GO:0050614. It describes reduction of lanosterol to 24,25-dihydrolanosterol at the ER membrane. This curated substrate context is distinguished from the desmosterol substrate directly tested in PMID11519011. |
| GO:0000246 Delta24(24-1) sterol reductase activity | IMP PMID:11519011 Mutations in the 3beta-hydroxysterol Delta24-reductase gene ... | MODIFY | Summary: Use the reaction-specific delta-24 sterol reductase term. Reason: The original human expression assay in PMID11519011 demonstrates desmosterol reduction, whereas the present GO:0000246 definition identifies the chemically distinct EC 1.3.1.71 delta-24(28) reaction. Preserve this experimental source row and refine its term to GO:0050614/EC 1.3.1.72; the paper is not rejected or reassigned to another gene. Proposed replacements: Delta24-sterol reductase activity Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:11007892 The human DIMINUTO/DWARF1 homolog seladin-1 confers resistan... | ACCEPT | Summary: Retain ER membrane association. Reason: The original human H4 study combines tagged-protein microscopy with endogenous fractionation and detects ER association. Later truncation/protease-protection work confirms strong membrane attachment but leaves exact membrane-spanning architecture unresolved. These experiments support this location without requiring a particular topology or denying other context-dependent pools. |
| GO:0006695 cholesterol biosynthetic process | IMP PMID:11519011 Mutations in the 3beta-hydroxysterol Delta24-reductase gene ... | ACCEPT | Summary: Retain the direct catalytic contribution to cholesterol biosynthesis. Reason: The human DHCR24 expression and mutant assays demonstrate the desmosterol-to-cholesterol step. The biochemical evidence establishes enzyme participation independently of the associated developmental disease phenotype. Supporting Evidence: |
| GO:0033489 cholesterol biosynthetic process via desmosterol | IMP PMID:11519011 Mutations in the 3beta-hydroxysterol Delta24-reductase gene ... | MODIFY | Summary: Retain the source assertion while replacing the obsolete pathway-specific term. Reason: The imported GO identifier is obsolete; the chemistry remains cholesterol biosynthesis. DHCR24 reduces the side-chain delta-24 double bond in sterol intermediates and can connect the named pathway variants. Preserve the original GOA term and reference, and retain the previously approved replacement GO:0006695 without creating a duplicate NEW assertion. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25637936 The terminal enzymes of cholesterol synthesis, DHCR24 and DH... | MODIFY | Summary: Specify binding to the sterol reductase enzyme DHCR7. Reason: The original study uses tagged human DHCR24 and human DHCR7 in CHO cells and confirms their association by reciprocal co-immunoprecipitation, including a more stringent RIPA experiment. DHCR7 is an established enzyme, supporting GO:0019899. Cellular 7-dehydrocholesterol conversion changes with DHCR24 activity, but the authors leave altered DHCR7 protein abundance, pathway flux and allostery unresolved; no direct allosteric activation or second catalytic core is inferred. Proposed replacements: enzyme binding Supporting Evidence: PMID:25637936 7-dehydrocholesterol reductase (DHCR7) coimmunoprecipitate |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-196417 | ACCEPT | Summary: Retain the ER membrane site of the curated sterol reaction. Reason: The desmosterol reaction resolves through DHCR24 catalyst 196404 to physical entity 196414, whose compartment is GO:0005789 and reference product is Q15392. Independent original localization supports the compartment. Reactome retains a 23–516 coordinate model; this is not used to assert physiological signal-peptide cleavage or a distinct natural product. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-6807064 | ACCEPT | Summary: Retain the ER membrane site of the curated sterol reaction. Reason: The zymosterol reaction resolves through DHCR24 catalyst 196404 to physical entity 196414, whose compartment is GO:0005789 and reference product is Q15392. Independent original localization supports the compartment. Reactome retains a 23–516 coordinate model; this is not used to assert physiological signal-peptide cleavage or a distinct natural product. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9755937 | ACCEPT | Summary: Retain the ER membrane site of the curated sterol reaction. Reason: The lanosterol reaction resolves through DHCR24 catalyst 196404 to physical entity 196414, whose compartment is GO:0005789 and reference product is Q15392. Independent original localization supports the compartment. Reactome retains a 23–516 coordinate model; this is not used to assert physiological signal-peptide cleavage or a distinct natural product. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Refine established membrane association to the supported ER membrane. Reason: Membrane association is established for DHCR24 by independent human H4 localization and later membrane-fractionation, truncation and protease-protection experiments. GO:0005789 specifies the supported ER-membrane location within this broad membrane claim. The original HDA study used YTS NK-like cells; its target peptide assignment and exact fraction remain unavailable. This refinement uses the independent localization evidence and does not claim that the HDA experiment itself resolved ER or settled membrane topology. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:27919032 both truncations were found primarily in the membrane fraction |
| GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor | IDA PMID:11519011 Mutations in the 3beta-hydroxysterol Delta24-reductase gene ... | MODIFY | Summary: Specify the demonstrated NADPH-dependent sterol reductase reaction. Reason: The IDA experiment measures the desmosterol-to-cholesterol reaction in human-DHCR24-expressing yeast homogenates. GO:0016628 is a broad oxidoreductase class; GO:0050614 captures the supported substrate/reaction specificity without changing the original experimental source. Proposed replacements: Delta24-sterol reductase activity Supporting Evidence: |
| GO:0006695 cholesterol biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the conserved cholesterol-biosynthesis role. Reason: The mouse donor experimental record supports cholesterol synthesis, including sterol replacement in the Dhcr24-null model discussed in PMID16321981. The human role is independently demonstrated by the direct desmosterol conversion assay, so acceptance does not depend on treating a donor paper title or donor count as proof. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8VCH6 SUPPORTS TRANSFER The conserved pathway transfer is independently supported by the human biochemical assay. |
| GO:0019899 enzyme binding | IPI PMID:15577914 Regulation of cellular response to oncogenic and oxidative s... | MODIFY | Summary: Specify binding to the ubiquitin protein ligase MDM2. Reason: The genuine PMID15577914 supplement describes human MDM2 and DHCR24 constructs, purified-protein p53 competition/ubiquitination assays, and human U2OS association tests comparing wild-type DHCR24 with the L210Q/F211S binding-defective mutant. MDM2 is an E3 ubiquitin protein ligase, making GO:0031625 more informative than enzyme binding. The term describes the partner class and does not give DHCR24 ubiquitin-ligase activity. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0043588 skin development | ISS GO_REF:0000024 | UNDECIDED | Summary: The skin-development transfer needs the unavailable original. Reason: The mouse experimental grounding PMID16410790 explicitly reports epidermal cholesterol loss, desmosterol accumulation and a defective epidermal barrier in Dhcr24-null mice. The full original was not recovered, so detailed developmental assays are not independently reconstructed. The phenotype is biologically compatible with the conserved sterol-synthesis requirement, but the original developmental allocation and controls cannot be checked. Leave the transfer undecided; no separate skin-specific enzymatic activity or direct morphogenetic mechanism is assigned. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8VCH6 UNRESOLVED The actual abstract supports a skin/barrier phenotype, but the original process allocation and controls remain unavailable. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:15577914 Regulation of cellular response to oncogenic and oxidative s... | KEEP AS NON CORE | Summary: Retain the reported stress-associated nuclear context with its limits. Reason: The original supplement to PMID15577914 describes immunostaining and cytoplasmic/nuclear fractionation of human WI38 cells with and without H2O2, including antibody and GAPDH controls. The main article remains abstract-only and the original figure pixels were not inspected. Preserve the curated IDA localization as a context-dependent non-core observation; later strong ER association raises a topology/trafficking question but does not by itself disprove this stress-specific observation. |
| GO:0005783 endoplasmic reticulum | IDA PMID:11007892 The human DIMINUTO/DWARF1 homolog seladin-1 confers resistan... | MODIFY | Summary: Specify the ER membrane within the observed ER location. Reason: The original human H4 microscopy and endogenous organelle fractionation establish ER association. The subsequent membrane extraction and protease-protection experiments support an ER-membrane protein. Refine the broad ER compartment to GO:0005789 without asserting an exclusive location or a settled single-pass topology. Proposed replacements: endoplasmic reticulum membrane |
| GO:0009888 tissue development | IMP PMID:12457401 Desmosterolosis presenting with multiple congenital anomalie... | UNDECIDED | Summary: The developmental process allocation cannot be settled from the clinical abstract. Reason: PMID12457401 reports a child with desmosterolosis, biochemical DHCR24 deficiency and multiple congenital anomalies. Its full original was not recovered. These observations establish a disease-associated developmental requirement, but the available text does not resolve which tissue-development step DHCR24 performs or how the curator allocated that process. Preserve the source and leave the existing IMP assertion undecided rather than rejecting it from incomplete evidence. Supporting Evidence: |
| GO:0042605 peptide antigen binding | IPI PMID:15577914 Regulation of cellular response to oncogenic and oxidative s... | MODIFY | Summary: Specify the directly studied p53-binding interaction. Reason: The current peptide-antigen-binding definition concerns binding an antigenic peptide; it is not restricted exclusively to MHC proteins. Here the actual study concerns human p53 protein, and the genuine supplement specifies recombinant p53/MDM2/DHCR24 competition assays and p53-association separation-of-function mutants. GO:0002039 directly names the demonstrated partner class and supports the distinct stress-context p53-binding unit; no antigen-presentation function is inferred. Proposed replacements: p53 binding Supporting Evidence: |
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Download this section (compressed HTML)Q: How does the 475-residue Q15392-2 product differ in sterol reduction, membrane association and p53 interaction from the tested 516-residue product?
Q: Which DHCR24 regions span or anchor in the ER membrane, and how do they relate to the reported stress-dependent nuclear pool?
Q: Does DHCR24 alter DHCR7 protein stability, sterol flux or allosteric activity in the endogenous enzyme complex?
Experiment: Compare sequence-verified natural DHCR24 products at matched expression, measuring sterol conversion, membrane topology and stress-dependent p53 association.
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Download this section (compressed HTML)📊 View Pathway Visualization Interactive pathway diagram with detailed annotations