STX5

Summary

STX5 (syntaxin 5, HGNC:11440) is a protein-coding gene on chromosome 11q12.3, encoding Syntaxin-5 (Q13190). Mediates endoplasmic reticulum to Golgi transport. It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

This gene encodes a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for v-SNAREs (vesicle-SNAP receptors), permitting specific synaptic vesicle docking and fusion. The encoded protein regulates endoplasmic reticulum to Golgi transport and plays a critical role in autophagy. Autoantibodies targeting the encoded protein may be a diagnostic marker for endometriosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 6811 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 41 total
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_003164

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11440
Approved symbol	STX5
Name	syntaxin 5
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	SED5
Ensembl gene	ENSG00000162236
Ensembl biotype	protein_coding
OMIM	603189
Entrez	6811

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000294179, ENST00000377897, ENST00000394690, ENST00000431400, ENST00000486437, ENST00000488303, ENST00000491231, ENST00000492066, ENST00000677401, ENST00000858716, ENST00000858717, ENST00000858718, ENST00000858719, ENST00000858720, ENST00000911719

RefSeq mRNA: 3 — MANE Select: NM_003164 NM_001244666, NM_001330294, NM_003164

CCDS: CCDS58140, CCDS8038, CCDS81578

Canonical transcript exons

ENST00000294179 — 11 exons

Exon	Start	End
ENSE00001198081	62806860	62807628
ENSE00002147645	62831019	62831262
ENSE00003459187	62824166	62824287
ENSE00003484718	62827155	62827225
ENSE00003491669	62827561	62827631
ENSE00003508447	62825036	62825117
ENSE00003533541	62827343	62827398
ENSE00003540638	62825423	62825539
ENSE00003591255	62824459	62824565
ENSE00003666772	62825283	62825339
ENSE00003683546	62831954	62832051

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 94.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1587 / max 182.0481, expressed in 1820 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120243	29.2258	1820
120242	0.9329	544

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	94.81	gold quality
blood	UBERON:0000178	94.53	gold quality
granulocyte	CL:0000094	93.85	gold quality
bone marrow	UBERON:0002371	93.80	gold quality
bone element	UBERON:0001474	93.79	gold quality
body of pancreas	UBERON:0001150	93.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.73	gold quality
endocervix	UBERON:0000458	93.66	gold quality
ectocervix	UBERON:0012249	93.51	gold quality
lower esophagus mucosa	UBERON:0035834	93.39	gold quality
left ovary	UBERON:0002119	93.29	gold quality
left lobe of thyroid gland	UBERON:0001120	93.25	gold quality
saliva-secreting gland	UBERON:0001044	93.18	gold quality
prostate gland	UBERON:0002367	93.18	gold quality
skin of leg	UBERON:0001511	93.07	gold quality
thyroid gland	UBERON:0002046	93.02	gold quality
ovary	UBERON:0000992	93.01	gold quality
minor salivary gland	UBERON:0001830	92.98	gold quality
pancreas	UBERON:0001264	92.88	gold quality
right lobe of thyroid gland	UBERON:0001119	92.86	gold quality
stromal cell of endometrium	CL:0002255	92.79	gold quality
right lobe of liver	UBERON:0001114	92.75	gold quality
zone of skin	UBERON:0000014	92.73	gold quality
right ovary	UBERON:0002118	92.60	gold quality
body of stomach	UBERON:0001161	92.58	gold quality
placenta	UBERON:0001987	92.57	gold quality
uterine cervix	UBERON:0000002	92.53	gold quality
tibial nerve	UBERON:0001323	92.52	gold quality
skin of abdomen	UBERON:0001416	92.36	gold quality
tonsil	UBERON:0002372	92.35	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting STX5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-6731-5P	99.28	67.42	2375

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• Syx5 is required for the maintenance of the Golgi structures but may not play a major role in the transport of vesicles carrying proteins between the ER and the Golgi compartment. (PMID:16081076)
• hypothesize that syntaxin 5 also has trafficking-independent functions (PMID:17389686)
• depletion of GM130 by RNA interference slows the rate of ER to Golgi trafficking in vivo; interactions of GM130 with syntaxin 5 and Rab1 are regulated by mitotic phosphorylation (PMID:18167358)
• Study shows that the SM protein, Sly1, interacts directly with the conserved oligomeric Golgi (COG) tethering complex; Sly1-COG interaction is mediated by the Cog4 subunit, which also interacts with Syntaxin 5 through a different binding site. (PMID:19536132)
• Depletion of syntaxin-5 complex components results in the accumulation of autophagosomes as a result of lysosomal dysfunction, leading to decreased degradation of autophagic substrates. (PMID:21242315)
• serum anti-STX5 autoantibody, which was discovered by a proteomic approach, is a potential new serum marker for the diagnosis of endometriosis. (PMID:21715015)
• Stx5 might play a role in modulating VLDL-R physiology by participating in an abrasively described or completely novel Golgi-bypass pathway. (PMID:23701949)
• Together, these data strongly suggest that syntaxin 5-mediated retrograde transport to the Golgi apparatus is a broadly conserved feature of adeno-associated virus trafficking. (PMID:25410859)
• Expression of the Syn5 K270R mutant in cells impairs post-mitotic Golgi reassembly (PMID:27404360)
• Golgin45-Syntaxin5 Interaction Contributes to Structural Integrity of the Golgi Stack. (PMID:31462665)
• Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5. (PMID:34711829)
• Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture. (PMID:35081689)
• Human antigen R transfers miRNA to Syntaxin 5 to synergize miRNA export from activated macrophages. (PMID:38492777)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stx5al	ENSDARG00000003175
danio_rerio	stx5a	ENSDARG00000025033
mus_musculus	Stx5a	ENSMUSG00000010110
rattus_norvegicus	Stx5	ENSRNOG00000018847
drosophila_melanogaster	Syx5	FBGN0011708
caenorhabditis_elegans		WBGENE00006373

Paralogs (12): STX7 (ENSG00000079950), STX1B (ENSG00000099365), STX4 (ENSG00000103496), STX1A (ENSG00000106089), STX2 (ENSG00000111450), STX12 (ENSG00000117758), STX16 (ENSG00000124222), STX11 (ENSG00000135604), STX17 (ENSG00000136874), STX3 (ENSG00000166900), TSNARE1 (ENSG00000171045), STX19 (ENSG00000178750)

Protein

Protein identifiers

Syntaxin-5 — Q13190 (reviewed: Q13190)

All UniProt accessions (5): E9PNU4, E9PP18, E9PRW9, Q13190, H7C3X5

UniProt curated annotations — full annotation on UniProt →

Function. Mediates endoplasmic reticulum to Golgi transport. Together with p115/USO1 and GM130/GOLGA2, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Required for Golgi to endoplasmic reticulum retrogade transport, and for intra-Golgi transport. (Microbial infection) Required for the efficient production of infectious virion during human cytomegalovirus infection. Mechanistically, participates in the formation of the cytoplasmic viral assembly compartment where tegument acquisition and envelopment occur.

Subunit / interactions. Part of a ternary complex containing STX5A, NSFL1C and VCP. Identified in a unique SNARE complex composed of the Golgi SNAREs GOSR1, GOSR2, YKT6 and VTI1A. Component of a SNARE complex consisting of STX5, YKT6, GOSR1 and BET1L. Interacts with BET1L. Interacts with BET1. Interacts with COG4. Interacts with GM130/GOLGA2. Interacts (via IxM motif) with SEC24C and SEC24D; mediates STX5 packaging into COPII-coated vesicles. Interacts with VLDLR; this interaction mediates VLDLR translocation from the endoplasmic reticulum to the plasma membrane.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment membrane. Golgi apparatus membrane.

Disease relevance. Congenital disorder of glycosylation 2AA (CDG2AA) [MIM:620454] A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2AA is an autosomal recessive, early fatal form characterized by severe liver disease, skeletal abnormalities, and protein glycosylation defects. The disease may be caused by variants affecting the gene represented in this entry. A likely pathogenic nucleotide substitution affecting the translation initiation codon of isoform 2 has been found in a CDG2AA family, and fully abrogates isoform 2 production. Loss of isoform 2 results in altered morphology of the endoplasmic reticulum and Golgi apparatus, compromised intra-Golgi trafficking, mislocalization of glycosyltransferases, and protein glycosylation defects.

Induction. (Microbial infection) By human cytomegalovirus infection.

Miscellaneous. Produced by alternative initiation at Met-55 of isoform 1. Produced by alternative splicing and alternative initiation.

Similarity. Belongs to the syntaxin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13190-1	1	yes
Q13190-2	2
Q13190-3	3
Q13190-4	4

RefSeq proteins (3): NP_001231595, NP_001317223, NP_003155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR006012	Syntaxin/epimorphin_CS	Conserved_site
IPR010989	SNARE	Homologous_superfamily
IPR021538	Syntaxin-5_N	Domain
IPR045242	Syntaxin	Family

Pfam: PF05739, PF11416

UniProt features (20 total): sequence variant 5, topological domain 2, splice variant 2, mutagenesis site 2, compositionally biased region 2, chain 1, strand 1, transmembrane region 1, domain 1, region of interest 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3EFO	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13190-F1	71.23	0.16

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
245	loss of interaction with sec24c.
247	loss of interaction with sec24c.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-5694530	Cargo concentration in the ER
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811438	Intra-Golgi traffic
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-9012999	RHO GTPase cycle
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9609507	Protein localization
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 310 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, E2F_Q4_01, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, WWTAAGGC_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GCANCTGNY_MYOD_Q6, MAZ_Q6, GOBP_MEMBRANE_FUSION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, TTGGGAG_MIR150

GO Biological Process (11): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), vesicle fusion (GO:0006906), early endosome to Golgi transport (GO:0034498), retrograde transport, endosome to Golgi (GO:0042147), positive regulation of protein catabolic process (GO:0045732), obsolete vesicle docking (GO:0048278), Golgi disassembly (GO:0090166), regulation of Golgi organization (GO:1903358), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endomembrane system (GO:0012505), ER to Golgi transport vesicle membrane (GO:0012507), SNARE complex (GO:0031201), vesicle (GO:0031982), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020), bounding membrane of organelle (GO:0098588)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	3
RHO GTPase cycle	3
Membrane Trafficking	2
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Protein localization	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Signaling by Rho GTPases	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
Golgi vesicle transport	3
cellular anatomical structure	3
intracellular transport	2
intercellular transport	2
Golgi organization	2
bounding membrane of organelle	2
organelle membrane	2
intracellular protein localization	1
protein transport	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
retrograde transport, endosome to Golgi	1
endosomal transport	1
cytosolic transport	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
Golgi inheritance	1
organelle disassembly	1
regulation of organelle organization	1
transport	1
cellular process	1
protein binding	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
cell adhesion molecule binding	1
binding	1
Golgi apparatus	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1

Protein interactions and networks

STRING

1956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STX5	BET1	O15155	999
STX5	YKT6	O15498	999
STX5	GOSR1	O95249	999
STX5	GOSR2	O14653	999
STX5	SCFD1	Q8WVM8	998
STX5	SEC22B	O75396	997
STX5	VTI1B	Q9UEU0	982
STX5	VTI1A	Q96AJ9	972
STX5	VCPIP1	Q96JH7	941
STX5	COG4	Q9H9E3	940
STX5	VAMP7	P51809	934
STX5	VPS45	Q9NRW7	908
STX5	SEC22A	Q96IW7	877
STX5	USO1	O60763	845
STX5	VAMP4	O75379	835

IntAct

284 interactions, top by confidence:

A	B	Type	Score
GOSR2	BET1	psi-mi:“MI:0914”(association)	0.810
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
VAMP5	STX5	psi-mi:“MI:0915”(physical association)	0.740
STX5	STX3	psi-mi:“MI:0915”(physical association)	0.740
STX4	STX5	psi-mi:“MI:0915”(physical association)	0.720
KASH5	STX5	psi-mi:“MI:0915”(physical association)	0.720
STX5	NAPB	psi-mi:“MI:0915”(physical association)	0.720
NAPB	STX5	psi-mi:“MI:0915”(physical association)	0.720
STX5	KASH5	psi-mi:“MI:0915”(physical association)	0.720
STXBP1	STX5	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STX5	STX8	psi-mi:“MI:0915”(physical association)	0.670
GOSR2	STX5	psi-mi:“MI:0915”(physical association)	0.670
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
SEC22B	STX5	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640

BioGRID (429): STX5 (Two-hybrid), STX5 (Two-hybrid), TACC1 (Two-hybrid), NAPB (Two-hybrid), CCDC155 (Two-hybrid), STX5 (Affinity Capture-MS), STX5 (Affinity Capture-MS), STX5 (Affinity Capture-MS), STX5 (Affinity Capture-MS), STX5 (Affinity Capture-MS), STX5 (Affinity Capture-MS), RBM26 (Affinity Capture-MS), HMMR (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4P5, A1DGS2, A2R7Z2, B0BN18, O04350, O35685, O70591, O75347, O76031, P48427, P48428, P50502, P50503, P80584, Q07866, Q08851, Q08DB5, Q0VCY1, Q13190, Q15691, Q17QG2, Q3ZBD9, Q4SPU8, Q5D016, Q5R581, Q5R601, Q5R7N3, Q5R7Z5, Q5RF31, Q5U2U0, Q5ZLC7, Q5ZLF0, Q61166, Q63525, Q66HR2, Q66T82, Q68FJ8, Q6P848, Q6V291, Q8K1E0

Diamond homologs: O13644, Q01590, Q08851, Q08DB5, Q13190, Q20797, Q24509, Q8K1E0, Q9FFK1, Q9LK09, O16000, Q12241, Q16932, Q54JY7, Q5RBW6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“Caspase 3 complex”	“down-regulates activity”	STX5	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intra-Golgi traffic	6	19.5×	4e-05
trans-Golgi Network Vesicle Budding	5	15.9×	7e-04
Retrograde transport at the Trans-Golgi-Network	5	13.7×	1e-03
COPII-mediated vesicle transport	6	12.2×	5e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	9	11.8×	8e-06
Golgi-to-ER retrograde transport	7	11.6×	1e-04
COPI-dependent Golgi-to-ER retrograde traffic	8	11.1×	4e-05
ER to Golgi Anterograde Transport	6	10.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	8	55.2×	6e-10
vesicle fusion	8	43.4×	3e-09
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	6	18.2×	1e-04
intracellular protein transport	16	9.3×	3e-09
exocytosis	6	8.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1592 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62807629:C:CC	acceptor_gain	1.0000
11:62807636:C:CT	acceptor_gain	1.0000
11:62807637:A:T	acceptor_gain	1.0000
11:62807642:C:CT	acceptor_gain	1.0000
11:62807642:C:T	acceptor_gain	1.0000
11:62807643:G:T	acceptor_gain	1.0000
11:62824160:TCTCA:T	donor_loss	1.0000
11:62824161:CTCA:C	donor_loss	1.0000
11:62824162:TCA:T	donor_loss	1.0000
11:62824163:CA:C	donor_loss	1.0000
11:62824165:C:CT	donor_loss	1.0000
11:62824165:CCT:C	donor_gain	1.0000
11:62824181:T:TA	donor_gain	1.0000
11:62824283:GAATC:G	acceptor_gain	1.0000
11:62824285:ATCC:A	acceptor_loss	1.0000
11:62824286:TC:T	acceptor_gain	1.0000
11:62824286:TCC:T	acceptor_loss	1.0000
11:62824287:CC:C	acceptor_gain	1.0000
11:62824287:CCTT:C	acceptor_loss	1.0000
11:62824288:C:CC	acceptor_gain	1.0000
11:62824288:CTT:C	acceptor_loss	1.0000
11:62824291:C:CT	acceptor_gain	1.0000
11:62824292:A:T	acceptor_gain	1.0000
11:62824456:TA:T	donor_loss	1.0000
11:62824457:A:AC	donor_loss	1.0000
11:62824458:CCTG:C	donor_gain	1.0000
11:62824561:ACCGC:A	acceptor_gain	1.0000
11:62824562:CCGC:C	acceptor_gain	1.0000
11:62824562:CCGCC:C	acceptor_gain	1.0000
11:62824563:CGC:C	acceptor_gain	1.0000

AlphaMissense

2334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62825332:A:G	L183P	1.000
11:62825505:A:G	L153P	1.000
11:62827174:A:G	L135P	1.000
11:62827351:A:G	L115P	1.000
11:62807585:C:G	A318P	0.999
11:62824213:A:C	F287L	0.999
11:62824213:A:T	F287L	0.999
11:62824215:A:G	F287L	0.999
11:62824226:A:G	L283S	0.999
11:62824242:A:G	S278P	0.999
11:62824266:C:G	A270P	0.999
11:62824268:C:G	R269P	0.999
11:62825113:A:G	L201P	0.999
11:62825310:G:C	F190L	0.999
11:62825310:G:T	F190L	0.999
11:62825311:A:G	F190S	0.999
11:62825312:A:G	F190L	0.999
11:62825321:A:G	S187P	0.999
11:62825330:C:G	A184P	0.999
11:62825339:A:G	S181P	0.999
11:62825526:A:G	L146P	0.999
11:62827203:A:C	F125L	0.999
11:62827203:A:T	F125L	0.999
11:62827205:A:G	F125L	0.999
11:62827223:C:G	A119P	0.999
11:62827351:A:T	L115Q	0.999
11:62827360:A:G	L112P	0.999
11:62827381:A:G	L105P	0.999
11:62827564:G:T	A98D	0.999
11:62831053:A:G	F64S	0.999

dbSNP variants (sampled 300 via entrez): RS1000074062 (11:62818516 C>T), RS1000109023 (11:62826835 G>A,C), RS1000484155 (11:62816943 ATTGCTCT>A), RS1000551267 (11:62815528 G>A), RS1000605816 (11:62821923 G>A), RS1000655075 (11:62822140 G>A), RS1000660191 (11:62810046 G>A), RS1000871249 (11:62833991 C>A,G), RS1000899786 (11:62815328 A>T), RS1001000694 (11:62824003 A>G), RS1001044305 (11:62817231 T>C), RS1001134683 (11:62828692 C>T), RS1001193529 (11:62812154 A>G,T), RS1001396879 (11:62817809 T>C), RS1001445437 (11:62820889 T>C)

Disease associations

OMIM: gene MIM:603189 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation	Moderate	Autosomal recessive
congenital disorder of glycosylation, type IIaa	Limited	Autosomal recessive

Mondo (2): congenital disorder of glycosylation, type IIaa (MONDO:0957540), congenital disorder of glycosylation (MONDO:0015286)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Cyclosporine	increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
sulphoraphene	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression, increases expression	1
bisphenol S	decreases methylation	1
bisphenol AF	increases expression	1
Irinotecan	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects reaction, decreases uptake	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism