SLC10A7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000139 Golgi membrane	EXP PMID:29878199 Integrating glycomics and genomics uncovers SLC10A7 as essen...	ACCEPT	Summary: Ashikov et al. examined the localization of the human protein directly and found it in the Golgi, explicitly contrasting this with the fungal orthologs. The Golgi is also the compartment that the functional data point to, since loss of SLC10A7 produces a post-Golgi glycoprotein transport defect. Reason: This is the best-supported and physiologically meaningful localization for SLC10A7. It is the only compartment assigned on the basis of a question about where the human protein sits (rather than incidentally during an over-expression transport assay), and it coheres with the secretory-pathway phenotype of SLC10A7 deficiency - reduced heparan sulfate, abnormal N-glycans and failure of post-Golgi glycoprotein delivery - all processes that are executed in the Golgi [PMID:30082715, PMID:29878199]. UniProt records Golgi apparatus membrane with ECO:0000269 from this paper. Supporting Evidence: PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi. PMID:29878199 Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane.
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: Automatic mapping of UniProt's Golgi-apparatus-membrane subcellular location (SL-0134) to GO:0000139. The underlying UniProt statement carries ECO:0000269 from PMID:29878199, the same experimental observation accepted above. Reason: The mapping is correct and the source statement is experimentally grounded. This row is redundant with the EXP row from PMID:29878199, which is not a defect - duplicate term assertions from different evidence routes are expected and acceptable. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0134 · Golgi apparatus membrane SUPPORTS TRANSFER UniProt's Golgi apparatus membrane location for Q0GE19 is annotated ECO:0000269\|PubMed:29878199, so the SL-to-GO mapping rests on experimental evidence. Supporting Evidence: PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: An IntAct record of a single interactor, Q7Z388 (DPY19L4, a probable C-mannosyltransferase), detected in the BioPlex 2.0 proteome-scale affinity purification-mass spectrometry survey. The annotation asserts only that SLC10A7 binds some protein. Reason: GO:0005515 conveys no functional information - it names no activity, no specificity and no biological role, and cannot be used in any inference about SLC10A7. The cited paper is a genome-scale AP-MS screen that does not discuss SLC10A7 at all (the cached full text does not mention the gene) and therefore supports no more informative molecular function, so MODIFY is not available. Removal does not assert that the SLC10A7-DPY19L4 co-purification is false; the interaction is recorded four times in IntAct and is worth following up, especially given that DPY19L4 is a putative glycosyltransferase and SLC10A7 deficiency perturbs glycosylation. Per the reviewing standards, generic protein binding is removed as uninformative rather than marked as an over-annotation. Supporting Evidence: PMID:28514442 Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: The same single interactor (Q7Z388, DPY19L4) re-detected in BioPlex 3.0, a proteome-scale AP-MS network built from affinity purification of 10,128 human proteins in 293T cells. Reason: Identical reasoning to the PMID:28514442 row. The screen is high-throughput and hypothesis-free, the cached full text never mentions SLC10A7, and the annotation leaves the molecular function of SLC10A7 entirely unspecified. No specific molecular function can be inferred from a co-purification alone, so there is no replacement term to propose. Supporting Evidence: PMID:33961781 The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins.
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	REMOVE	Summary: The same single interactor (Q7Z388, DPY19L4) recorded a third time, now from the RESOLUTE SLC superfamily interactome, which mapped the protein-protein interactions of 396 solute carriers by AP-MS from HEK293 cells. Reason: Identical reasoning to the two BioPlex rows. This study is the most relevant of the three to SLC10A7 (SLC10A7 was within its bait set of 396 SLCs) and its interactor list is a genuinely useful resource, but an AP-MS interaction still supports no informative molecular function, and the cached full text makes no gene-specific statement about SLC10A7. The recurrence of DPY19L4 across three independent screens strengthens the case that the interaction is real, which is an argument for investigating it, not for retaining an uninformative GO:0005515 row. Supporting Evidence: PMID:40355756 We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics.
GO:0005783 endoplasmic reticulum	IDA PMID:17628207 Molecular and phylogenetic characterization of a novel putat...	UNDECIDED	Summary: An ER localization attributed to Godoy et al. 2007. UniProt likewise records Endoplasmic reticulum membrane with ECO:0000269\|PubMed:17628207. The cached publication is abstract-only, and the abstract reports only that SLC10A7 was detected in the plasma membrane; the ER observation must lie in figures of the full text that I could not read. Reason: The evidence cannot be adjudicated from what is available here, and the reviewing rules require UNDECIDED rather than a decision in that situation. Both UniProt and GOA curators read Godoy's full text and assigned ER with experimental evidence, so this is not to be overruled from an abstract. Biologically an early-secretory-pathway pool is plausible for a polytopic Golgi membrane protein, and GAG assembly on which SLC10A7 is required begins at the ER exit [PMID:30082715]. What cannot be judged without the figures is whether the ER signal reflects the endogenous steady-state distribution or incomplete export of an over-expressed tagged construct in HEK293 cells, which is the same caveat that applies to this paper's plasma-membrane claim. Resolution needs Godoy's full text or an endogenous-tag localization study. Supporting Evidence: PMID:17628207 When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:17628207 Molecular and phylogenetic characterization of a novel putat...	UNDECIDED	Summary: The membrane-level counterpart of the GO:0005783 row, from the same abstract-only paper. UniProt states Endoplasmic reticulum membrane; Multi-pass membrane protein with ECO:0000269\|PubMed:17628207. Reason: Same situation as GO:0005783 above - the supporting observation is in a full text that is not available in this environment, and the abstract mentions only the plasma membrane. The term is the appropriate specificity for a multi-pass membrane protein if the ER localization holds, so there is nothing to modify; the open question is whether it holds for the endogenous protein. UNDECIDED rather than REMOVE, since an experimental curator-assigned localization must not be overturned on an abstract. Supporting Evidence: PMID:17628207 By immunofluorescence analysis of dual hemagglutinin (HA)- and FLAG-labeled SLC10A7 proteins in HEK293 cells, we established a topology of 10 transmembrane domains with an intracellular cis orientation of the N-terminal and C-terminal ends.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	UNDECIDED	Summary: Automatic mapping of UniProt's Endoplasmic reticulum membrane subcellular location (SL-0097) to GO:0005789. The mapping step is sound; the uncertainty is inherited entirely from the source statement, which traces to PubMed:17628207. Reason: The SL-to-GO mapping is mechanically correct, so there is no propagation error as such. But this row adds no evidence beyond the UniProt statement it mirrors, and that statement rests on the same unreadable full text as the two rows above. Deciding this row therefore means deciding those, so it is marked UNDECIDED for consistency rather than accepted as if it were independent support. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB-SubCell:SL-0097 · Endoplasmic reticulum membrane UNRESOLVED UniProt's ER membrane location for Q0GE19 is annotated ECO:0000269\|PubMed:17628207, whose full text is not available here; the abstract reports only plasma membrane, so the underlying observation could not be checked.
GO:0005794 Golgi apparatus	IDA PMID:29878199 Integrating glycomics and genomics uncovers SLC10A7 as essen...	ACCEPT	Summary: The organelle-level counterpart of the GO:0000139 Golgi membrane annotation, from the same direct observation of the human protein by Ashikov et al. Reason: Correct and well supported. GO:0005794 is a parent of the Golgi membrane assignment rather than new information, but duplicate and less specific assertions from a different evidence route are acceptable, and the organelle-level term is the one that matches what the paper states in words. Supporting Evidence: PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi.
GO:0005886 plasma membrane	EXP PMID:30082715 SLC10A7 mutations cause a skeletal dysplasia with amelogenes...	MARK AS OVER ANNOTATED	Summary: Dubail et al. transfected c-myc-tagged wild-type SLC10A7 into HEK293F cells and reported punctate anti-myc staining which they read as consistent with a cell membrane localization, citing Godoy et al. for the plasma-membrane assignment. The experiment's purpose was to compare expression levels of wild-type and patient-mutant constructs, not to establish the compartment. Reason: The observation is real but it is an over-annotation of the physiological site of the endogenous protein. Three features limit it - the protein was over-expressed from a plasmid in a heterologous cell line; no plasma-membrane co-marker was used, and the staining is described as uniform punctate, which is as compatible with a Golgi or vesicular pool as with the surface; and the paper's own wording is hedged, confirmed by reference to the earlier study rather than by an independent surface assay. Against this, the only study that asked where the human protein sits found the Golgi and framed it as a difference from the fungal orthologs [PMID:29878199], and every functional consequence of SLC10A7 loss is a secretory-pathway phenotype. MARK_AS_OVER_ANNOTATED rather than REMOVE - over-expressed tagged SLC10A7 plainly does reach the surface, and the annotation is not fabricated - it simply should not be read as the compartment where SLC10A7 acts. Supporting Evidence: PMID:30082715 C-myc immunolabelling demonstrated a uniform punctate staining following transfection with wild-type SLC10A7, consistent with a cell membrane localization. PMID:30082715 SLC10A7, previously named C4orf1317, is a 340-amino acid 10-transmembrane-domain protein localized at the plasma membrane (confirmed by the immunocytofluorescence assay performed in this study). PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi.
GO:0005886 plasma membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: A PAINT inference placing is_active_in plasma membrane at ancestral node PANTHER:PTN000428041. The descendant evidences behind the node are dominated by non-vertebrate members - Saccharomyces RCH1 (SGD:S000004637), the Candida ortholog (CGD:CAL0000187136) and the Escherichia coli putative symporter YfeH (UniProtKB:P39836) - together with rat Slc10a7 and human SLC10A7's own annotation. Reason: The node placement is defensible for the family as a whole; what does not transfer is the compartment, for the specific human member. Ashikov et al. report the human protein in the Golgi and present this as a contrast with yeast, which identifies the fungal members as the plasma-membrane ones and the human member as having diverged in localization [PMID:29878199]. That is target-specific evidence against the inherited compartment, which is the relevant way to argue with an IBA. The human entry's own appearance in the WITH/FROM column is expected and not circular - it marks that experimental grounding exists on the target - but that grounding is the same over-expression-based IDA assessed in the rows above, so it does not rescue the compartment claim. Not REMOVE - the protein is a polytopic membrane protein, a surface pool is observed on over-expression, and a plasma-membrane role in calcium entry regulation (the yeast Rch1p model) remains a live hypothesis. Marked as over-annotated, with the Golgi rows carrying the physiological localization. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000428041 SUPPORTS SOURCE BUT NOT TARGET Ancestral node carrying the is_active_in plasma membrane assertion; sound for the family, but the human descendant has a published Golgi localization contrasted explicitly with yeast. SGD:S000004637 · RCH1 SUPPORTS SOURCE BUT NOT TARGET Budding yeast Rch1p, regulator of calcium homeostasis 1; the calcium-regulatory function transfers to human SLC10A7, the fungal compartment does not. CGD:CAL0000187136 SUPPORTS SOURCE BUT NOT TARGET Candida ortholog CaRch1p, the second fungal calcium regulator behind this node; same compartment caveat as the Saccharomyces donor. UniProtKB:P39836 · yfeH SOURCE WEAK OR INFERRED Escherichia coli putative symporter YfeH; a bacterial member whose cell membrane assignment cannot speak to the organellar membranes of a human cell. RGD:1564388 UNRESOLVED Rat Slc10a7; the rodent ortholog's localization evidence was not traced here. UniProtKB:Q0GE19 · SLC10A7 SUPPORTS TRANSFER The target's own experimental annotation, expected among the descendant evidences behind the IBD; it is the over-expression-based IDA from PMID:17628207, so it carries the same caveat rather than independent weight. Supporting Evidence: PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi.
GO:0005886 plasma membrane	IDA PMID:17628207 Molecular and phylogenetic characterization of a novel putat...	MARK AS OVER ANNOTATED	Summary: The original plasma-membrane observation - HA- and FLAG-tagged SLC10A7 expressed in Xenopus oocytes and HEK293 cells was detected at the plasma membrane, in the course of transport assays that returned no activity for bile acids or steroid sulfates. Reason: This is the root of the plasma-membrane claim and the same over-expression caveat applies - a tagged construct expressed heterologously in oocytes and HEK293 cells, assayed because the authors were testing for surface transport activity. The surface pool was real enough to support uptake assays, so the annotation is not wrong as an observation - which is why this is not REMOVE, and why the full text (unavailable here) cannot be second-guessed on whether the protein was at the surface. What it does not establish is that the plasma membrane is where endogenous SLC10A7 resides and acts - the later direct examination of the human protein found the Golgi [PMID:29878199], and the transport assays at the surface were negative, which is itself consistent with the physiological site being intracellular. Supporting Evidence: PMID:17628207 When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates. PMID:29878199 In contrast to yeast, human SLC10A7 localized to the Golgi.
GO:0005886 plasma membrane	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Automatic mapping of UniProt's Cell membrane subcellular location (SL-0039) to GO:0005886. The UniProt statement cites ECO:0000269 from both PubMed:17628207 and PubMed:30082715, i.e. the two over-expression experiments assessed above. Reason: The SL-to-GO mapping is correct, so the defect is not in the propagation step but in the strength of what is being propagated - both source observations are heterologous over-expression of tagged constructs, neither used a surface marker or surface-specific assay, and the one study that interrogated the endogenous human protein's compartment reported Golgi [PMID:29878199]. Marked as over-annotated for the same reason as its sources rather than removed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH SOURCE EVIDENCE WEAK Sources checked: UniProtKB-SubCell:SL-0039 · Cell membrane SOURCE WEAK OR INFERRED UniProt's Cell membrane location for Q0GE19 cites PubMed:17628207 and PubMed:30082715; both are over-expressed tagged-construct immunofluorescence, and the endogenous protein has been reported in the Golgi. Supporting Evidence: PMID:17628207 When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates.
GO:0006874 intracellular calcium ion homeostasis	IMP PMID:30082715 SLC10A7 mutations cause a skeletal dysplasia with amelogenes...	ACCEPT	Summary: Fibroblasts from SLC10A7-deficient patients showed significantly increased Ca2+ influx relative to controls after addition of extracellular CaCl2, so loss of the protein raises calcium entry and the wild-type protein acts as a negative regulator of it. The experiment was prompted by, and agrees with, the characterization of the yeast and Candida orthologs Rch1p and CaRch1p as negative regulators of cytosolic calcium homeostasis. Reason: This is the one mechanistic function of SLC10A7 that is both measured directly in human cells and conserved across the family's deep homologs, and it is the natural function for a solute carrier. The evidence is a loss-of-function readout in patient cells, which establishes that SLC10A7 is required for normal calcium handling; in this case that is also a statement about the protein's own activity rather than a downstream phenotype, because a transporter regulating ion flux is doing the work itself - there is no intervening enzyme to which the step belongs. Accepted as a core function. A more specific directional term (negative regulation of calcium import) was considered and not proposed - the readout is whole-cell influx in a patient line, the transported species is unidentified, and whether the protein acts at the plasma membrane or within the Golgi is unresolved. Supporting Evidence: PMID:30082715 After addition of extracellular CaCl2, SLC10A7-deficient patient fibroblasts showed a significantly increased Ca2+ influx compared with control fibroblasts PMID:30082715 two studies performed with SLC10A7 homologues in yeast, CaRch1p and Rch1p, suggest a possible role as a negative regulator of cytosolic calcium homoeostasis15,16.
GO:0030210 heparin proteoglycan biosynthetic process	IEA GO_REF:0000107	MODIFY	Summary: Ensembl Compara transfer from mouse Slc10a7 (Q5PT53), whose own annotation comes from the same study, PMID:30082715, in which Slc10a7 knockout mouse cartilage showed reduced heparan sulfate. The orthology is one-to-one and uncontroversial; the problem is the term. Reason: The transfer itself is sound - mouse and human SLC10A7 are orthologs and the mouse evidence is a knockout cartilage measurement from the same paper - but it carries over a mis-scoped term. What was measured in both species is heparan sulfate, not heparin - heparin is the hypersulfated mast-cell glycosaminoglycan, and GO:0030210 is defined specifically as the formation of heparin proteoglycans, which this study never assayed. GO:0015012 heparan sulfate proteoglycan biosynthetic process is the term the evidence supports in both organisms. The replacement should be read as a permissive upstream contribution rather than a catalytic role (see the IMP row below for that argument), and consequently as non-core. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q5PT53 · Slc10a7 SUPPORTS TRANSFER Mouse ortholog; its GO:0030210 annotation rests on reduced heparan sulfate in Slc10a7 knockout cartilage in PMID:30082715, so the orthology transfer is sound and only the term's specificity is wrong - the same correction applies to the mouse record. ensembl:ENSMUSP00000034111 SUPPORTS TRANSFER Ensembl protein identifier for the same mouse ortholog; no independent evidence beyond the Q5PT53 annotation. Proposed replacements: heparan sulfate proteoglycan biosynthetic process Supporting Evidence: PMID:30082715 Furthermore, we identify decreased heparan sulfate levels in Slc10a7-/- mouse cartilage and patient fibroblasts.
GO:0030210 heparin proteoglycan biosynthetic process	IMP PMID:30082715 SLC10A7 mutations cause a skeletal dysplasia with amelogenes...	MODIFY	Summary: Dubail et al. found the proportion of heparan sulfate reduced about two-fold in SLC10A7-deficient patient fibroblasts and about 2.5-fold in Slc10a7 knockout mouse cartilage, with total glycosaminoglycan unchanged and with chain length and sulfation pattern normal, so the deficit is in the number of heparan sulfate chains. The authors attribute the defect to deregulated calcium homeostasis rather than to a direct action of SLC10A7 on the glycosaminoglycan. Reason: Two separate problems, one of which is decisive for the term and one of which is a caveat on how to read it. First, specificity: heparin was never assayed. Heparin is the hypersulfated glycosaminoglycan of mast-cell serglycin and GO:0030210 is defined as formation of heparin proteoglycans; what the study measured was heparan sulfate, so GO:0015012 heparan sulfate proteoglycan biosynthetic process is the correct term. Second, the participation question: SLC10A7 catalyses no step of chain initiation, elongation, epimerization or sulfation, and the authors' own mechanism is indirect, placing calcium deregulation upstream of the glycosaminoglycan defect. The knockout and patient data establish necessity, which is not the same as participation. The comparator check is genuinely mixed and is why this is MODIFY rather than REMOVE. TMEM165, a Golgi calcium/manganese transporter whose loss causes a congenital disorder of glycosylation, carries only transport and calcium-homeostasis terms (GO:0032472, GO:0032468, GO:0071421) and no glycan-biosynthesis term; SLC35D1, the Golgi UDP-sugar transporter mutated in Schneckenbecken dysplasia, likewise carries only transport terms. But SLC35B2, the Golgi PAPS transporter, does carry GO:0050650 chondroitin sulfate proteoglycan biosynthetic process by IMP - a transporter that delivers the donor substrate into the lumen is accepted as a participant. Since SLC10A7's substrate is unknown, it cannot be placed in either camp: it may be a TMEM165-style ion transporter acting only permissively, or an SLC35B2-style donor transporter that genuinely supplies a biosynthetic step. Keeping the biosynthetic process term at the correct specificity, while recording the role as upstream and non-core, is the honest reading; the ambiguity is raised explicitly in suggested_questions. Proposed replacements: heparan sulfate proteoglycan biosynthetic process Supporting Evidence: PMID:30082715 the proportion of heparan sulfate (HS) was significantly reduced by ~2-fold in SLC10A7-deficient patient fibroblasts compared with control fibroblasts and by about 2.5-fold in Slc10a7−/− mouse cartilage compared with wild-type mouse cartilage PMID:30082715 indicating that HS decrease in Slc10a7−/− is mostly related to the number of HS chains, rather than to their sulfation and length. PMID:30082715 This deregulation of Ca2+ homoeostasis due to SLC10A7 deficiency is most likely responsible for defects in GAG synthesis and glycosylation.
GO:0060348 bone development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from mouse Slc10a7 (Q5PT53), annotated from the knockout mouse phenotype in PMID:30082715 - shortened long bones, growth-plate disorganization and strongly reduced Safranin O staining of sulfated glycosaminoglycan in cartilage. Reason: The orthology transfer is correct and the mouse evidence is strong, so the term is kept. It is marked non-core for the same reason as the human IMP row below - the skeletal phenotype is the tissue-level consequence of a general extracellular-matrix glycosaminoglycan defect in a widely expressed protein, not the molecular function SLC10A7 evolved to perform. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5PT53 · Slc10a7 SUPPORTS TRANSFER Mouse ortholog with a knockout skeletal phenotype in PMID:30082715 that recapitulates the human disorder; transfer to human is well founded. ensembl:ENSMUSP00000034111 SUPPORTS TRANSFER Ensembl protein identifier for the same mouse ortholog; no independent evidence beyond the Q5PT53 annotation. Supporting Evidence: PMID:30082715 We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype.
GO:0060348 bone development	IMP PMID:30082715 SLC10A7 mutations cause a skeletal dysplasia with amelogenes...	KEEP AS NON CORE	Summary: Biallelic SLC10A7 variants cause skeletal dysplasia with multiple dislocations, short stature, scoliosis and reduced bone mineral density; the Slc10a7 knockout mouse shows shortened long bones and growth-plate disorganization, and zebrafish morphants show strongly reduced bone mineralization. SLC10A7 is therefore required for normal bone development in three species. Reason: The requirement is beyond dispute, so the term is kept rather than removed - but it records a developmental consequence of losing the protein, not work that the protein performs in skeletogenesis. SLC10A7 is widely expressed, with highest levels in liver, and its molecular lesion is general: fewer heparan sulfate chains, mislocalized glycoproteins, abnormal plasma N-glycans and deregulated calcium. Bone and tooth enamel are simply the tissues where a generalized extracellular-matrix glycosaminoglycan deficit becomes clinically visible, which is the classic pleiotropic-developmental pattern the KEEP_AS_NON_CORE action exists for. The entities that perform the steps of bone development are the chondrocytes' and osteoblasts' differentiation programmes and matrix-mineralization machinery; SLC10A7 supplies an upstream cell-biological prerequisite in the secretory pathway. Keeping the term preserves the disease-relevant link for users querying skeletal genes; marking it non-core keeps it out of the gene's core function synthesis. Supporting Evidence: PMID:30082715 We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. PMID:30082715 There was a strong reduction of Safranin O staining, a marker of sulfated GAG chains, in Slc10a7−/− mice compared with wild-type mice, which was associated with disorganization of the growth plate PMID:29878199 Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization.

Core Functions

Golgi-membrane solute carrier of the bile acid:sodium symporter fold that acts as a negative regulator of cellular calcium entry, a function conserved from its fungal orthologs Rch1p and CaRch1p. Loss of the protein increases Ca2+ influx into human cells. The transported species is unidentified - SLC10A7 transports neither bile acids nor steroid sulfates, and no other substrate has been tested, so the activity is asserted only at the level of transmembrane transporter activity rather than as a specific ion or solute transport. Through this activity SLC10A7 maintains the lumenal conditions the secretory pathway needs, which is why its loss reduces the number of heparan sulfate chains, perturbs N-glycosylation and blocks post-Golgi delivery of glycoproteins.

Molecular Function:

transmembrane transporter activity

Directly Involved In:

intracellular calcium ion homeostasis

Cellular Locations:

Golgi membrane

Supporting Evidence:

PMID:30082715
After addition of extracellular CaCl2, SLC10A7-deficient patient fibroblasts showed a significantly increased Ca2+ influx compared with control fibroblasts
PMID:30082715
two studies performed with SLC10A7 homologues in yeast, CaRch1p and Rch1p, suggest a possible role as a negative regulator of cytosolic calcium homoeostasis15,16.
PMID:29878199
In contrast to yeast, human SLC10A7 localized to the Golgi.
PMID:17628207
When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates.
file:human/SLC10A7/SLC10A7-bioinformatics/RESULTS.md
The SLC10 fold is still recognisable (TM-score 0.766 against the experimental NTCP chain), but the ion-binding chemistry is not.
file:human/SLC10A7/SLC10A7-hypotheses/structure-translocation-pathway/openscientist.md
SLC10A7 is best described as a **transporter scaffold with an unknown, non-NTCP substrate**

References

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Suggested Experiments

Experiment: Purify recombinant human SLC10A7 and reconstitute it into proteoliposomes, then screen candidate substrates by radiotracer and fluorescence-based uptake - Ca2+, Mn2+, sulfate, PAPS, UDP-sugars and the nucleotide monophosphate antiport products - under lumenal and cytosolic pH and ion conditions matching the Golgi. Include the patient missense variants p.Leu74Pro and p.Gly130Arg as loss-of-function controls.

Hypothesis: SLC10A7 transports an ion or small solute across the Golgi membrane, and the identity of that solute explains both the calcium and the glycosaminoglycan phenotypes.

Type: in vitro transport assay

Experiment: Knock in a small epitope or fluorescent tag at the endogenous SLC10A7 locus in a cell type with a measurable phenotype (patient-matched fibroblasts or chondrocyte-like cells) and localize the protein by confocal imaging against Golgi, ER and plasma-membrane markers, with surface biotinylation and protease-protection assays to quantify any genuine surface fraction. Compare side by side with the same construct over-expressed from a plasmid.

Hypothesis: Endogenous SLC10A7 is a Golgi protein, and the reported plasma-membrane pool is a consequence of over-expression.

Type: endogenous tagging and localization

Experiment: Measure Golgi lumenal Ca2+ and Mn2+ directly in SLC10A7-deficient and control cells with targeted genetically encoded sensors, then test whether restoring lumenal cation levels (manganese supplementation, as used for TMEM165 deficiency, or expression of an orthogonal Golgi cation transporter) rescues heparan sulfate chain number and the N-glycan profile. Rescue would place SLC10A7 upstream of the biosynthetic machinery rather than within it.

Hypothesis: The glycosaminoglycan defect is downstream of a calcium or divalent-cation imbalance in the Golgi lumen rather than of a missing biosynthetic donor.

Type: organelle ion imaging with rescue

Experiment: Validate the interaction at endogenous levels by reciprocal co-immunoprecipitation and proximity labelling in an unmodified cell line, test whether the two proteins co-localize, and ask whether DPY19L4 loss phenocopies any part of the SLC10A7 glycosylation or heparan sulfate phenotype.

Hypothesis: SLC10A7 and DPY19L4 act together in the secretory pathway.

Type: interaction validation

Deep Research

OpenScientist

(SLC10A7-hypotheses/structure-translocation-pathway/openscientist.md)

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📚 Additional Documentation

Notes

(SLC10A7-notes.md)

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Bioinformatics Results

(RESULTS.md)

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Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

OpenScientist

📚 Additional Documentation

Notes

Bioinformatics Results

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