SLC17A5

Summary

SLC17A5 (solute carrier family 17 member 5, HGNC:10933) is a protein-coding gene on chromosome 6q13, encoding Sialin (Q9NRA2). Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport.

This gene encodes a membrane transporter that exports free sialic acids that have been cleaved off of cell surface lipids and proteins from lysosomes. Mutations in this gene cause sialic acid storage diseases, including infantile sialic acid storage disorder and and Salla disease, an adult form.

Source: NCBI Gene 26503 — RefSeq curated summary.

At a glance

• Gene–disease (curated): free sialic acid storage disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 672 total — 51 pathogenic, 75 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_012434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10933
Approved symbol	SLC17A5
Name	solute carrier family 17 member 5
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	AST, SD, ISSD, NSD, SIALIN, SLD
Ensembl gene	ENSG00000119899
Ensembl biotype	protein_coding
OMIM	604322
Entrez	26503

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000355773, ENST00000481996, ENST00000908537, ENST00000908538, ENST00000933630, ENST00000933631, ENST00000957535, ENST00000957536

RefSeq mRNA: 9 — MANE Select: NM_012434 NM_001382629, NM_001382630, NM_001382631, NM_001382632, NM_001382633, NM_001382634, NM_001382635, NM_001382636, NM_012434

CCDS: CCDS4981

Canonical transcript exons

ENST00000355773 — 11 exons

Exon	Start	End
ENSE00000918573	73600351	73600441
ENSE00000918574	73610400	73610547
ENSE00000918581	73644407	73644603
ENSE00001452143	73593379	73595214
ENSE00001836471	73653793	73653992
ENSE00003481916	73635382	73635500
ENSE00003546010	73615315	73615447
ENSE00003553472	73641691	73641924
ENSE00003561636	73638412	73638499
ENSE00003585596	73621804	73621962
ENSE00003610019	73636621	73636707

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 95.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7648 / max 71.2178, expressed in 1726 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74386	7.7055	1723
74387	0.0593	16

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	95.20	gold quality
stromal cell of endometrium	CL:0002255	94.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.34	gold quality
colonic mucosa	UBERON:0000317	92.87	gold quality
germinal epithelium of ovary	UBERON:0001304	92.10	gold quality
ileal mucosa	UBERON:0000331	92.02	gold quality
jejunal mucosa	UBERON:0000399	91.00	gold quality
visceral pleura	UBERON:0002401	89.53	gold quality
right lobe of thyroid gland	UBERON:0001119	89.35	gold quality
islet of Langerhans	UBERON:0000006	89.34	gold quality
synovial joint	UBERON:0002217	89.34	gold quality
trachea	UBERON:0003126	89.19	gold quality
left lobe of thyroid gland	UBERON:0001120	89.17	gold quality
rectum	UBERON:0001052	88.86	gold quality
thyroid gland	UBERON:0002046	88.86	gold quality
amniotic fluid	UBERON:0000173	88.20	gold quality
duodenum	UBERON:0002114	88.09	gold quality
placenta	UBERON:0001987	87.97	gold quality
tibia	UBERON:0000979	87.90	gold quality
pericardium	UBERON:0002407	87.89	gold quality
pleura	UBERON:0000977	87.86	gold quality
palpebral conjunctiva	UBERON:0001812	87.66	gold quality
calcaneal tendon	UBERON:0003701	87.44	gold quality
parietal pleura	UBERON:0002400	87.26	gold quality
bronchial epithelial cell	CL:0002328	87.23	gold quality
lower lobe of lung	UBERON:0008949	87.22	gold quality
cauda epididymis	UBERON:0004360	87.02	gold quality
skin of hip	UBERON:0001554	86.98	gold quality
adult organism	UBERON:0007023	86.67	gold quality
seminal vesicle	UBERON:0000998	86.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	229.12
E-ANND-3	yes	6.66

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• expression, localization, and targeting of the wild-type sialin, as well as two mutant polypeptides in sialic acid storage disorders (PMID:12359136)
• In primary neuronal cultures sialin was not targeted into lysosomes but rather revealed a punctate staining along the neuronal processes and was also seen in the plasma membrane. (PMID:15006695)
• Molecular studies showed that all four affected individuals were homozygous for the same novel 983G > A mutation in exon 8 of the SLC17A5 gene, replacing glycine with glutamic acid at position 328 of the sialin protein (PMID:15172005)
• Two missense mutations and one small, in-frame deletion in sialin are associated with ISSD abolished transport, the mutation causing Salla disease (R39C) slowed down, but did not stop the transport cycle. (PMID:15510212)
• there is a direct correlation between sialin function and the disease state of sialic acid storage disorders (PMID:15516337)
• a SLC17A5 p.K136E mutation may have a role in a case of Italian severe Salla disease (PMID:16170568)
• study assessed the effect of missense mutations in the sialin gene (G328E and G409E) and found complete loss of measurable transport activity with both and impaired trafficking of the G409E protein (PMID:17933575)
• The lysosomal localization of human sialin was not or only partially affected by pathogenic missense mutations; in contrast, all pathogenic mutations abolished transport of sialic acid. (PMID:18399798)
• sialin possesses dual physiological functions and acts as a vesicular aspartate/glutamate transporter (PMID:18695252)
• Mutations in the SLC17A5 gene must be considered in two siblings with hypomyelination, even in the absence of sialuria. (PMID:19557856)
• analysis of crucial residues and substrate-induced conformational changes in SLC17 transporter sialin (PMID:20424173)
• Human SLC17A5 carrying mutations that causes both phenotypes of Salla disease and mutations that cause infantile sialic acid storage disease showed no transport activity (PMID:21781115)
• the substrate-binding site of sialin (SLC17A5) (PMID:22334707)
• These data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. (PMID:22778404)
• Elevated levels of AST are Associated with Cardiovascular disease. (PMID:27872510)
• study describes a novel pathogenic variant in SLC17A5, namely an intronic transposal insertion, in a patient with mild biochemical and clinical phenotypes. The presence of a small fraction of normal transcript may explain the mild phenotype. This case illustrates the importance of including lysosomal sialic acid storage disease in the differential diagnosis of developmental delay with postnatal onset and hypomyelination. (PMID:28187749)
• Serum alanine transaminase is predictive of fasting and postprandial insulin and glucagon concentrations in type 2 diabetes. (PMID:37673303)

Cross-species orthologs

54 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc17a5	ENSDARG00000055190
danio_rerio	slc37a4b	ENSDARG00000077180
danio_rerio	slc37a4bl	ENSDARG00000093531
mus_musculus	Slc17a5	ENSMUSG00000049624
rattus_norvegicus	Slc17a5	ENSRNOG00000090360
drosophila_melanogaster	dmGlut	FBGN0010497
drosophila_melanogaster	MFS14	FBGN0010651
drosophila_melanogaster	Picot	FBGN0024315
drosophila_melanogaster	CG9254	FBGN0028513
drosophila_melanogaster	CG6978	FBGN0029727
drosophila_melanogaster	VGlut	FBGN0031424
drosophila_melanogaster	CG7881	FBGN0033048
drosophila_melanogaster	MFS12	FBGN0033234
drosophila_melanogaster	MFS15	FBGN0034392
drosophila_melanogaster	CG15096	FBGN0034394
drosophila_melanogaster	MFS16	FBGN0034611
drosophila_melanogaster	CG12490	FBGN0034782
drosophila_melanogaster	CG9825	FBGN0034783
drosophila_melanogaster	CG9826	FBGN0034784
drosophila_melanogaster	CG3649	FBGN0034785
drosophila_melanogaster	CG2003	FBGN0039886
drosophila_melanogaster	CG30265	FBGN0050265
drosophila_melanogaster	MFS1	FBGN0050272
caenorhabditis_elegans		WBGENE00001135
caenorhabditis_elegans		WBGENE00007669
caenorhabditis_elegans		WBGENE00008000
caenorhabditis_elegans		WBGENE00008677
caenorhabditis_elegans		WBGENE00010755
caenorhabditis_elegans		WBGENE00010931
caenorhabditis_elegans		WBGENE00011185
caenorhabditis_elegans		WBGENE00011349
caenorhabditis_elegans		WBGENE00011556
caenorhabditis_elegans		WBGENE00012443
caenorhabditis_elegans		WBGENE00015271
caenorhabditis_elegans		WBGENE00015272
caenorhabditis_elegans		WBGENE00016003
caenorhabditis_elegans		WBGENE00018429
caenorhabditis_elegans		WBGENE00018918
caenorhabditis_elegans		WBGENE00018920
caenorhabditis_elegans		WBGENE00019187
caenorhabditis_elegans		WBGENE00019655
caenorhabditis_elegans		WBGENE00020583
caenorhabditis_elegans		WBGENE00020584
caenorhabditis_elegans		WBGENE00020697
caenorhabditis_elegans		WBGENE00020698
caenorhabditis_elegans		WBGENE00020699
caenorhabditis_elegans		WBGENE00020700
caenorhabditis_elegans		WBGENE00021157
caenorhabditis_elegans		WBGENE00021158
caenorhabditis_elegans		WBGENE00021219
caenorhabditis_elegans		WBGENE00021220
caenorhabditis_elegans		WBGENE00021223
caenorhabditis_elegans		WBGENE00021226
caenorhabditis_elegans		WBGENE00302978

Paralogs (12): SLC17A6 (ENSG00000091664), SLC17A9 (ENSG00000101194), SLC17A7 (ENSG00000104888), SLC17A2 (ENSG00000112337), SLC17A3 (ENSG00000124564), SLC17A1 (ENSG00000124568), SLC37A2 (ENSG00000134955), SLC37A4 (ENSG00000137700), SLC17A4 (ENSG00000146039), SLC37A3 (ENSG00000157800), SLC37A1 (ENSG00000160190), SLC17A8 (ENSG00000179520)

Protein

Protein identifiers

Sialin — Q9NRA2 (reviewed: Q9NRA2)

Alternative names: H(+)/nitrate cotransporter, H(+)/sialic acid cotransporter, Membrane glycoprotein HP59, Solute carrier family 17 member 5, Vesicular excitatory amino acid transporter

All UniProt accessions (1): Q9NRA2

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport. Electroneutral proton-coupled acidic monosaccharide symporter, with a sugar to proton stoichiometry of 1:1. Exports glucuronic acid and free sialic acid derived from sialoglycoconjugate degradation out of lysosomes, driven by outwardly directed lysosomal pH gradient. May regulate lysosome function and metabolism of sialylated conjugates that impact oligodendrocyte lineage differentiation and myelinogenesis in the central nervous system. Electrogenic proton-coupled nitrate symporter that transports nitrate ions across the basolateral membrane of salivary gland acinar cells, with nitrate to proton stoichiometry of 2:1. May contribute to nitrate clearance from serum by salivary glands, where it is further concentrated and secreted in the saliva. Uses membrane potential to drive the uptake of acidic amino acids and peptides into synaptic vesicles. Responsible for synaptic vesicular storage of L-aspartate and L-glutamate in pinealocytes as well as vesicular uptake of N-acetyl-L-aspartyl-L-glutamate neuropeptide, relevant to aspartegic-associated glutamatergic neurotransmission and activation of metabotropic receptors that inhibit subsequent transmitter release. Receptor for CM101, a polysaccharide produced by group B Streptococcus with antipathoangiogenic properties.

Subcellular location. Basolateral cell membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Lysosome membrane.

Tissue specificity. In the adult, detected in placenta, kidney and pancreas. Abundant in the endothelial cells of tumors from ovary, colon, breast and lung, but is not detected in endothelial cells from the corresponding normal tissues. Highly expressed in salivary glands and liver, with lower levels of expression in brain, spleen kidney, muscle and pancreas. Expressed in acinar cells of salivary glands (at protein level).

Disease relevance. Salla disease (SD) [MIM:604369] Sialic acid storage disease (SASD). SASDs are autosomal recessive neurodegenerative disorders characterized by hypotonia, cerebellar ataxia and intellectual disability. They are caused by a defect in the metabolism of sialic acid which results in increased urinary excretion of unconjugated sialic acid, specifically N-acetylneuraminic acid. Enlarged lysosomes are seen on electron microscopic studies. Clinical symptoms of SD present usually at age less than 1 year and progression is slow. The disease is caused by variants affecting the gene represented in this entry. Infantile sialic acid storage disorder (ISSD) [MIM:269920] Severe form of sialic acid storage disease. Affected newborns exhibit visceromegaly, coarse features and failure to thrive immediately after birth. These patients have a shortened life span, usually less than 2 years. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRA2-1	1	yes
Q9NRA2-2	2

RefSeq proteins (9): NP_001369558, NP_001369559, NP_001369560, NP_001369561, NP_001369562, NP_001369563, NP_001369564, NP_001369565, NP_036566* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050382	MFS_Na/Anion_cotransporter	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 6 shown:

• N-acetylneuraminate(in) + H(+)(in) = N-acetylneuraminate(out) + H(+)(out) (RHEA:28987)
• L-aspartate(out) = L-aspartate(in) (RHEA:66332)
• L-glutamate(out) = L-glutamate(in) (RHEA:66336)
• 2 nitrate(out) + H(+)(out) = 2 nitrate(in) + H(+)(in) (RHEA:71539)
• D-glucuronate(out) + H(+)(out) = D-glucuronate(in) + H(+)(in) (RHEA:72591)
• N-acetyl-L-aspartyl-L-glutamate(out) = N-acetyl-L-aspartyl-L-glutamate(in) (RHEA:72599)

UniProt features (78 total): helix 24, topological domain 13, transmembrane region 12, sequence variant 8, turn 5, mutagenesis site 4, glycosylation site 3, splice variant 2, strand 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8U3D	ELECTRON MICROSCOPY	2.83
8U3E	ELECTRON MICROSCOPY	3.19
9AYB	ELECTRON MICROSCOPY	3.19
8U3F	ELECTRON MICROSCOPY	3.31
8DWI	ELECTRON MICROSCOPY	3.4
8U3G	ELECTRON MICROSCOPY	3.42
8U3H	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRA2-F1	84.12	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 3

Glycosylation sites (3): 71, 77, 95

Mutagenesis-validated functional residues (4):

Position	Phenotype
22–23	targeted to plasma membrane.
22–23	targeted to plasma membrane; sialic acid uptake strongly activated at acidic ph.
198–199	localizes in vesicular structures mainly concentrated in the perinuclear region.
266–267	localizes in vesicular structures mainly concentrated in the perinuclear region.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-2160916	Hyaluronan degradation
R-HSA-4085001	Sialic acid metabolism
R-HSA-428643	Organic anion transport by SLC5/17/25 transporters
R-HSA-5619035	Defective SLC17A5 causes Salla disease (SD) and ISSD
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 263 (showing top): GOBP_CARBOHYDRATE_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, KEGG_LYSOSOME, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GTGCCTT_MIR506, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, ATCATGA_MIR433, CUI_TCF21_TARGETS_2_DN

GO Biological Process (12): monoatomic ion transport (GO:0006811), monoatomic anion transport (GO:0006820), amino acid transport (GO:0006865), response to bacterium (GO:0009617), sialic acid transport (GO:0015739), neurotransmitter loading into synaptic vesicle (GO:0098700), carbohydrate derivative transport (GO:1901264), carbohydrate transmembrane transport (GO:0034219), D-glucuronate transmembrane transport (GO:0042874), carboxylic acid transport (GO:0046942), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (7): carbohydrate:proton symporter activity (GO:0005351), glucuronate transmembrane transporter activity (GO:0015135), sialic acid transmembrane transporter activity (GO:0015136), sialic acid:proton symporter activity (GO:0015538), D-glucuronate transmembrane transporter activity (GO:0042880), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (11): lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), synaptic vesicle membrane (GO:0030672), glutamatergic synapse (GO:0098978), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Hyaluronan metabolism	1
Synthesis of substrates in N-glycan biosythesis	1
SLC-mediated transport of organic anions	1
SLC transporter disorders	1
Transport of small molecules	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Disorders of transmembrane transporters	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	4
transmembrane transport	2
glucuronate transmembrane transport	2
solute:proton symporter activity	2
cytoplasm	2
cellular anatomical structure	2
plasma membrane region	2
monoatomic ion transport	1
response to other organism	1
carboxylic acid transport	1
neurotransmitter transport	1
intercellular transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
carbohydrate transport	1
organic acid transport	1
cellular process	1
monoatomic cation transmembrane transport	1
carbohydrate:monoatomic cation symporter activity	1
uronic acid transmembrane transporter activity	1
sialic acid transport	1
carbohydrate derivative transmembrane transporter activity	1
sialic acid transmembrane transporter activity	1
glucuronate transmembrane transporter activity	1
D-glucuronate transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
basal plasma membrane	1
apical part of cell	1
synaptic vesicle	1
exocytic vesicle membrane	1
synapse	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC17A5	GNE	Q9Y223	848
SLC17A5	SLC16A3	O15427	778
SLC17A5	SLC16A8	O95907	775
SLC17A5	SLC16A7	O60669	772
SLC17A5	LAMP1	P11279	769
SLC17A5	TOPBP1	Q92547	526
SLC17A5	CTNS	O60931	521
SLC17A5	SLC18B1	Q6NT16	510
SLC17A5	ASAH1	Q13510	508
SLC17A5	GINS3	Q9BRX5	505
SLC17A5	CCL21	O00585	486
SLC17A5	NEU1	Q99519	486
SLC17A5	CMAS	Q8NFW8	471
SLC17A5	WDFY2	Q96P53	464
SLC17A5	CDC123	O75794	461

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
TMEM258	TMEM223	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC17A5	YPMT1.25Ac	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (73): SLC17A5 (Affinity Capture-MS), SLC17A5 (Affinity Capture-MS), SLC17A5 (Affinity Capture-MS), SLC17A5 (Affinity Capture-RNA), SLC17A5 (Affinity Capture-RNA), SLC17A5 (Affinity Capture-MS), SLC17A5 (Affinity Capture-MS), SLC17A5 (Affinity Capture-MS), SLC17A5 (Proximity Label-MS), SLC17A5 (Co-fractionation), SLC17A5 (Co-fractionation), SLC17A5 (Co-fractionation), ACADSB (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ADPGK (Affinity Capture-MS)

ESM2 similar proteins: A5LGM7, A9ZSY2, A9ZSY3, B0WC46, B4HNS1, B4QBN3, O62786, O62787, P11166, P11167, P11168, P11169, P12336, P13355, P14142, P14246, P14672, P17809, P19357, P20303, P22732, P27674, P28568, P32037, P43427, P46896, P47842, P47843, P58351, P58352, P58353, P79365, Q07647, Q27994, Q28ES4, Q5Q0U0, Q5R608, Q5RET7, Q6PDF3, Q863Y9

Diamond homologs: A4FV52, A6QLI1, O00476, O00624, O61369, O82390, P34644, Q03567, Q05B21, Q0IZQ3, Q10046, Q14916, Q1L8X9, Q28722, Q2QWW7, Q32LF0, Q3E9A0, Q3TXX4, Q53P54, Q5NCM1, Q5Q0U0, Q5SZA1, Q5W8I7, Q5W8I8, Q61983, Q62634, Q62795, Q652N5, Q66GI9, Q6INC8, Q7TSF2, Q8BFU8, Q8BLE7, Q8BN82, Q8GX78, Q8NDX2, Q9FKV1, Q9JI12, Q9MZD1, Q9NRA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

672 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	51
Likely pathogenic	75
Uncertain significance	195
Likely benign	245
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071719	NC_000006.11:g.(?74345095)(74345233_?)del	Pathogenic
1073504	NM_012434.5(SLC17A5):c.157del (p.Val53fs)	Pathogenic
1073614	NC_000006.11:g.(?74345095)(74346440_?)del	Pathogenic
1074913	NM_012434.5(SLC17A5):c.146del (p.Gly49fs)	Pathogenic
1075886	NM_012434.5(SLC17A5):c.976G>T (p.Glu326Ter)	Pathogenic
1285238	NG_008272.1:g.(37212_43567)_(48616_58573)del	Pathogenic
1364804	NM_012434.5(SLC17A5):c.579_580insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCCCCCCCCCCCTCCCTCCCGGACGGGGCGGCTGGCCGGGCAGAGGGGCTCCTCACTTCCCAGTAGGGGCGGCCGGGCAGAGGGGGCTCCCCCTCTT (p.Leu193_Glu194insPhePhePhePhePhePheXaaXaaXaaXaaProProProProProSerArgThrGlyArgLeuAlaGlyGlnArgGlySerSerLeuProSerArgGlyGlyArgAlaGluGlyAlaProProLeu)	Pathogenic
1412336	NM_012434.5(SLC17A5):c.860_863dup (p.Leu289fs)	Pathogenic
1420974	NC_000006.11:g.(?74325018)(74325190_?)del	Pathogenic
1447940	NM_012434.5(SLC17A5):c.964_976del (p.Phe322fs)	Pathogenic
1460030	NC_000006.11:g.(?74304790)(74354336_?)del	Pathogenic
1460247	NC_000006.11:g.(?74304790)(74310174_?)del	Pathogenic
1460316	NC_000006.11:g.(?74331507)(74331705_?)del	Pathogenic
1978583	NM_012434.5(SLC17A5):c.916del (p.Tyr306fs)	Pathogenic
1997291	NM_012434.5(SLC17A5):c.683_698del (p.Tyr228fs)	Pathogenic
2002193	NM_012434.5(SLC17A5):c.908G>A (p.Trp303Ter)	Pathogenic
2026744	NM_012434.5(SLC17A5):c.1039C>T (p.Gln347Ter)	Pathogenic
2098722	NM_012434.5(SLC17A5):c.479del (p.Gly160fs)	Pathogenic
2102539	NM_012434.5(SLC17A5):c.575del (p.Pro192fs)	Pathogenic
21493	NM_012434.5(SLC17A5):c.406A>G (p.Lys136Glu)	Pathogenic
2425810	NC_000006.11:g.(?74363496)(74363609_?)del	Pathogenic
2425811	NC_000006.11:g.(?74320103)(74320290_?)del	Pathogenic
2425813	NC_000006.11:g.(?74310064)(74310174_?)del	Pathogenic
2581347	NM_012434.5(SLC17A5):c.952G>T (p.Glu318Ter)	Pathogenic
2678766	NM_012434.5(SLC17A5):c.1341del (p.Thr448fs)	Pathogenic
2698513	NM_012434.5(SLC17A5):c.532dup (p.Thr178fs)	Pathogenic
2708289	NM_012434.5(SLC17A5):c.267del (p.Pro89_Ile90insTer)	Pathogenic
2720497	NM_012434.5(SLC17A5):c.1019dup (p.Leu340fs)	Pathogenic
2740618	NM_012434.5(SLC17A5):c.994del (p.Ser332fs)	Pathogenic
2751329	NM_012434.5(SLC17A5):c.699dup (p.Gly234fs)	Pathogenic

SpliceAI

2054 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73600349:A:AC	donor_gain	1.0000
6:73600350:C:CC	donor_gain	1.0000
6:73610398:A:AC	donor_gain	1.0000
6:73610399:C:CA	donor_gain	1.0000
6:73610399:CGA:C	donor_gain	1.0000
6:73610399:CGAAG:C	donor_gain	1.0000
6:73610554:T:C	acceptor_gain	1.0000
6:73610554:T:TC	acceptor_gain	1.0000
6:73610562:T:C	acceptor_gain	1.0000
6:73610562:T:TC	acceptor_gain	1.0000
6:73610564:A:AC	acceptor_gain	1.0000
6:73610564:A:C	acceptor_gain	1.0000
6:73635376:CCATA:C	donor_loss	1.0000
6:73635377:CATA:C	donor_loss	1.0000
6:73635378:ATAC:A	donor_loss	1.0000
6:73635379:TA:T	donor_loss	1.0000
6:73635380:A:C	donor_loss	1.0000
6:73635381:CCTG:C	donor_loss	1.0000
6:73635502:T:C	acceptor_gain	1.0000
6:73641686:ATTAC:A	donor_loss	1.0000
6:73641687:TTACC:T	donor_loss	1.0000
6:73641688:TA:T	donor_loss	1.0000
6:73641689:ACCTC:A	donor_loss	1.0000
6:73641690:CCT:C	donor_gain	1.0000
6:73641834:AT:A	donor_gain	1.0000
6:73641923:CC:C	acceptor_gain	1.0000
6:73641924:CC:C	acceptor_gain	1.0000
6:73653792:CCGG:C	donor_gain	1.0000
6:73595215:C:CC	acceptor_gain	0.9900
6:73600350:CAT:C	donor_gain	0.9900

AlphaMissense

3194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73595197:C:A	W456C	0.999
6:73595197:C:G	W456C	0.999
6:73636695:C:T	G209E	0.999
6:73636696:C:A	G209W	0.999
6:73638460:A:G	W189R	0.999
6:73638460:A:T	W189R	0.999
6:73641701:C:T	G172E	0.999
6:73641702:C:G	G172R	0.999
6:73641702:C:T	G172R	0.999
6:73641868:A:C	F116L	0.999
6:73641868:A:T	F116L	0.999
6:73641870:A:G	F116L	0.999
6:73641871:A:C	F115L	0.999
6:73641871:A:T	F115L	0.999
6:73641873:A:G	F115L	0.999
6:73641907:C:A	W103C	0.999
6:73641907:C:G	W103C	0.999
6:73641909:A:G	W103R	0.999
6:73641909:A:T	W103R	0.999
6:73644515:A:C	S61R	0.999
6:73644515:A:T	S61R	0.999
6:73644517:T:G	S61R	0.999
6:73644529:G:T	R57S	0.999
6:73595110:C:A	W485C	0.998
6:73595110:C:G	W485C	0.998
6:73600411:A:C	N430K	0.998
6:73600411:A:T	N430K	0.998
6:73621875:A:G	W303R	0.998
6:73621875:A:T	W303R	0.998
6:73635483:A:G	W240R	0.998

dbSNP variants (sampled 300 via entrez): RS1000064604 (6:73598714 C>T), RS1000074212 (6:73595983 T>G), RS1000102835 (6:73652099 C>T), RS1000115139 (6:73598487 C>T), RS1000129375 (6:73644868 A>T), RS1000136780 (6:73639030 GA>G,GAA), RS1000263313 (6:73606127 C>T), RS1000270006 (6:73624328 C>T), RS1000321405 (6:73624617 A>T), RS1000330696 (6:73612721 C>G,T), RS1000534802 (6:73641361 G>A,T), RS1000556486 (6:73617126 C>A), RS1000638573 (6:73623278 A>G), RS1000668251 (6:73611048 G>C), RS1000705002 (6:73602440 A>G)

Disease associations

OMIM: gene MIM:604322 | disease phenotypes: MIM:604369, MIM:269920, MIM:263800, MIM:268100

GenCC curated gene-disease

Disease	Classification	Inheritance
Salla disease	Definitive	Autosomal recessive
free sialic acid storage disease, infantile form	Strong	Autosomal recessive
intermediate severe Salla disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
free sialic acid storage disease	Definitive	AR

Mondo (7): Salla disease (MONDO:0011449), free sialic acid storage disease, infantile form (MONDO:0010027), Gitelman syndrome (MONDO:0009904), enhanced S-cone syndrome (MONDO:0100288), intermediate severe Salla disease (MONDO:0017737), free sialic acid storage disease (MONDO:0019366), focal segmental glomerulosclerosis (MONDO:0100313)

Orphanet (7): Salla disease (Orphanet:309334), Free sialic acid storage disease (Orphanet:834), Free sialic acid storage disease, infantile form (Orphanet:309324), Gitelman syndrome (Orphanet:358), Goldmann-Favre syndrome (Orphanet:53540), Intermediate severe Salla disease (Orphanet:309331), (Orphanet:10870)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000100	Nephrotic syndrome
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000463	Anteverted nares
HP:0000508	Ptosis
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000765	Abnormal thorax morphology
HP:0000938	Osteopenia
HP:0001010	Hypopigmentation of the skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001541	Ascites
HP:0001622	Premature birth
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_326	Refractive error	3.000000e-205

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D053579	Gitelman Syndrome	C12.050.351.968.419.815.491; C12.200.777.419.815.491; C12.950.419.815.491; C16.320.831.491
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
C564835	Enhanced S-Cone Syndrome (supp.)
C538523	Free sialic acid storage disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630859 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Sialic acid transporter

ChEMBL bioactivities

2 potent at pChembl≥5 of 5 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.62	IC50	2400	nM	CHEMBL4646356
5.11	Ki	7800	nM	CHEMBL4646356

PubChem BioAssay actives

2 with measured affinity, of 56 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(7-hydroxy-2-oxochromen-4-yl)methylsulfanyl]propanoic acid	1669222: Inhibition of human recombinant-Sialin expressed in HEK293 cells assessed as reduction in [3H]Neu5Ac uptake at 30 to 300 uM incubated for 15 mins by liquid scintillation counting method	ic50	2.4000	uM

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
sodium arsenite	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
benazol P	affects expression	1
diallyl trisulfide	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
3,4,5,4’-tetramethoxystilbene	affects expression	1
3-iodothyronamine	affects uptake	1
bisphenol B	increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4630260	Binding	Inhibition of human recombinant-Sialin expressed in HEK293 cells assessed as reduction in [3H]Neu5Ac uptake at 30 to 300 uM incubated for 15 mins by liquid scintillation counting method	Amino Acids Bearing Aromatic or Heteroaromatic Substituents as a New Class of Ligands for the Lysosomal Sialic Acid Transporter Sialin. — J Med Chem

Cellosaurus cell lines

10 cell lines: 7 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AB39	GM17721	Transformed cell line	Female
CVCL_AB40	GM17722	Transformed cell line	Female
CVCL_AB41	GM17723	Transformed cell line	Male
CVCL_B2FJ	Abcam HeLa SLC17A5 KO	Cancer cell line	Female
CVCL_D4ID	HCT116-SLC17A5-KO-c3	Cancer cell line	Male
CVCL_D4IE	HCT116-SLC17A5-KO-c4	Cancer cell line	Male
CVCL_D5FB	HeLa::TMEM192-3xHA SLC17A5 partial KO	Cancer cell line	Female
CVCL_E0NM	Ubigene HeLa SLC17A5 KO	Cancer cell line	Female
CVCL_TL71	HAP1 SLC17A5 (-) 1	Cancer cell line	Male
CVCL_TL72	HAP1 SLC17A5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

84 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02297048	PHASE4	COMPLETED	Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT00550342	PHASE2	WITHDRAWN	Rituximab Treatment of Focal Segmental Glomerulosclerosis
NCT00814255	PHASE2	COMPLETED	Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
NCT01613118	PHASE2	COMPLETED	Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT03366337	PHASE2	COMPLETED	A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
NCT03448692	PHASE2	TERMINATED	A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT03536754	PHASE2	COMPLETED	A Study of CCX140-B in Subjects With FSGS
NCT03598036	PHASE2	TERMINATED	Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
NCT03649152	PHASE2	COMPLETED	Safety and Effectiveness of Propagermanium in Focal Segmental Glomerulosclerosis Participants Receiving Irbesartan
NCT03703908	PHASE2	TERMINATED	A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome
NCT04009668	PHASE2	COMPLETED	Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
NCT04573920	PHASE2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT05003986	PHASE2	RECRUITING	Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05267262	PHASE2	COMPLETED	Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis
NCT05441826	PHASE2	TERMINATED	Efficacy and Safety of VB119 in Subjects With Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)
NCT06500702	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease
NCT06664814	PHASE2	RECRUITING	An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT07268638	PHASE2	RECRUITING	A Study of Praliciguat in Participants With Focal Segmental Glomerulosclerosis (FSGS)
NCT07614477	PHASE2	RECRUITING	Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EVER001 in Participants With Selected Proteinuric Glomerular Diseases
NCT00464321	PHASE1	COMPLETED	Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS
NCT00782561	PHASE1	TERMINATED	Safety and Pharmacokinetics of FG-3019 in Adolescents and Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT00816478	PHASE1	TERMINATED	Effect of Oral Galactose on Focal Segmental Glomerulosclerosis (FSGS) Permeability Factor
NCT00816504	PHASE1	WITHDRAWN	Effect of Galactose on Permeblity Factor in Patients With FSGS and CKD Stage 5
NCT02382874	PHASE1	UNKNOWN	Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)
NCT02693366	PHASE1	COMPLETED	Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis
NCT05942625	PHASE1	RECRUITING	A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10390 in Healthy Subjects
NCT05955872	PHASE1	COMPLETED	A Study Evaluating the Relative Bioavailability and Food Effect of a Tablet Formulation of VX-147