YKT6

Summary

YKT6 (YKT6 vesicular SNARE protein, HGNC:16959) is a protein-coding gene on chromosome 7p13, encoding Synaptobrevin homolog YKT6 (O15498). Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

This gene product is one of the SNARE recognition molecules implicated in vesicular transport between secretory compartments. It is a membrane associated, isoprenylated protein that functions at the endoplasmic reticulum-Golgi transport step. This protein is highly conserved from yeast to human and can functionally complement the loss of the yeast homolog in the yeast secretory pathway.

Source: NCBI Gene 10652 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic disease (Moderate, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16959
Approved symbol	YKT6
Name	YKT6 vesicular SNARE protein
Location	7p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106636
Ensembl biotype	protein_coding
OMIM	606209
Entrez	10652

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 nonsense_mediated_decay, 5 protein_coding, 5 retained_intron

ENST00000223369, ENST00000421621, ENST00000424864, ENST00000447123, ENST00000463014, ENST00000478411, ENST00000496112, ENST00000677090, ENST00000677436, ENST00000677851, ENST00000678359, ENST00000678497, ENST00000679020, ENST00000679209, ENST00000679310, ENST00000877770

RefSeq mRNA: 3 — MANE Select: NM_006555 NM_001363678, NM_001410874, NM_006555

CCDS: CCDS5482, CCDS87497, CCDS94093

Canonical transcript exons

ENST00000223369 — 7 exons

Exon	Start	End
ENSE00001899844	44212247	44214294
ENSE00001943685	44200978	44201239
ENSE00003460180	44207388	44207492
ENSE00003461998	44206385	44206485
ENSE00003616962	44204568	44204650
ENSE00003620259	44208133	44208198
ENSE00003631014	44211023	44211124

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.9427 / max 203.2813, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78409	57.9427	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.67	gold quality
islet of Langerhans	UBERON:0000006	95.43	gold quality
cortical plate	UBERON:0005343	95.20	gold quality
lower esophagus mucosa	UBERON:0035834	94.62	gold quality
body of pancreas	UBERON:0001150	94.46	gold quality
mucosa of transverse colon	UBERON:0004991	94.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.08	gold quality
ganglionic eminence	UBERON:0004023	93.74	gold quality
granulocyte	CL:0000094	93.71	gold quality
esophagus mucosa	UBERON:0002469	93.50	gold quality
body of stomach	UBERON:0001161	93.42	gold quality
smooth muscle tissue	UBERON:0001135	93.24	gold quality
right frontal lobe	UBERON:0002810	93.22	gold quality
pancreas	UBERON:0001264	93.20	gold quality
rectum	UBERON:0001052	93.19	gold quality
amygdala	UBERON:0001876	93.17	gold quality
apex of heart	UBERON:0002098	93.15	gold quality
gastrocnemius	UBERON:0001388	93.08	gold quality
adenohypophysis	UBERON:0002196	92.92	gold quality
cingulate cortex	UBERON:0003027	92.91	gold quality
prefrontal cortex	UBERON:0000451	92.86	gold quality
anterior cingulate cortex	UBERON:0009835	92.77	gold quality
ventricular zone	UBERON:0003053	92.75	gold quality
muscle of leg	UBERON:0001383	92.69	gold quality
esophagus	UBERON:0001043	92.58	gold quality
spinal cord	UBERON:0002240	92.53	gold quality
metanephros cortex	UBERON:0010533	92.51	gold quality
right coronary artery	UBERON:0001625	92.48	gold quality
monocyte	CL:0000576	92.43	gold quality
thoracic aorta	UBERON:0001515	92.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting YKT6, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4757-5P	99.12	64.51	981

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• abnormalities in the SNARE complex could represent a molecular substrate for abnormalities of neural connectivity in severe mental disorders (PMID:11884350)
• Data suggest that GS15 exists in a distinct SNARE complex that contains syntaxin5, GS28, and Ykt6, and may be involved in both ER-to-Golgi and intra-Golgi transport. (PMID:12388752)
• N-ethylmaleimide-sensitive factor-dependent SNARE-priming complex disassembly is required for efficient exocytosis from mast cells. (PMID:14607937)
• mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. (PMID:16821082)
• YKT6 is a key molecule in the regulation of exosome release in lung cancer cells and is in turn precisely regulated by miR-134 and miR-135b. Moreover, YKT6 levels impact prognosis of resected Non small cell lung cancer patients. (PMID:27285987)
• YKT6 forms a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. (PMID:29789439)
• The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. (PMID:30010460)
• Parkinson’s disease alpha-synuclein perturbs the physiological response to lysosomal stress by impeding the SNARE protein ykt6 (PMID:31648898)
• A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. (PMID:32128853)
• Proinflammatory macrophage-derived microvesicles exhibit tumor tropism dependent on CCL2/CCR2 signaling axis and promote drug delivery via SNARE-mediated membrane fusion. (PMID:32550891)
• YKT6, as a potential predictor of prognosis and immunotherapy response for oral squamous cell carcinoma, is related to cell invasion, metastasis, and CD8+ T cell infiltration. (PMID:34221701)
• High expression of YKT6 associated with progression and poor prognosis of hepatocellular carcinoma. (PMID:34396876)
• A pan-cancer analysis of the oncogenic role of YKT6 in human tumors. (PMID:37058019)
• Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion. (PMID:38340317)
• Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma. (PMID:38522068)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ykt6	ENSDARG00000038308
mus_musculus	Ykt6	ENSMUSG00000002741
rattus_norvegicus	Ykt6	ENSRNOG00000014785
drosophila_melanogaster	Ykt6	FBGN0260858
caenorhabditis_elegans		WBGENE00015164

Paralogs (10): VAMP3 (ENSG00000049245), SEC22C (ENSG00000093183), VAMP4 (ENSG00000117533), VAMP8 (ENSG00000118640), SEC22A (ENSG00000121542), VAMP7 (ENSG00000124333), VAMP1 (ENSG00000139190), VAMP5 (ENSG00000168899), VAMP2 (ENSG00000220205), SEC22B (ENSG00000265808)

Protein

Protein identifiers

Synaptobrevin homolog YKT6 — O15498 (reviewed: O15498)

All UniProt accessions (8): O15498, A0A7I2V3A1, A0A7I2V3S2, A0A7I2V3V7, A0A7I2V4L6, A0A7I2V530, A4D2J0, H7C3K7

UniProt curated annotations — full annotation on UniProt →

Function. Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. Functions in endoplasmic reticulum to Golgi transport; as part of a SNARE complex composed of GOSR1, GOSR2 and STX5. Functions in early/recycling endosome to TGN transport; as part of a SNARE complex composed of BET1L, GOSR1 and STX5. Has a S-palmitoyl transferase activity. Essential for the structural and functional organization of the Golgi apparatus.

Subunit / interactions. Identified in 2 different SNARE complexes; the first one composed of GOSR1, GOSR2 and STX5 and the second one composed of BET1L, GOSR1 and STX5.

Subcellular location. Cytoplasm. Cytosol. Cytoplasmic vesicle membrane. Golgi apparatus membrane.

Post-translational modifications. Palmitoylated; catalyzes its own palmitoylation. Palmitoylation is required for Golgi targeting. Farnesylation at Cys-195 is required for Golgi targeting. Geranylgeranylation at Cys-194 is mediated by the GGTase-3 complex and is required for Golgi SNARE complex assembly.

Domain organisation. The longin domain regulates palmitoylation and membrane targeting. The CAAX motif is a signal for farnesylation at Cys-195 and the subsequent geranylgeranylation at Cys-194; the double prenylation is essential for the structural and functional organization of the Golgi apparatus.

Similarity. Belongs to the synaptobrevin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15498-1	1	yes
O15498-2	2

RefSeq proteins (3): NP_001350607, NP_001397803, NP_006546* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010908	Longin_dom	Domain
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR042855	V_SNARE_CC	Domain
IPR045848	R-SNARE_YKT6	Domain

Pfam: PF00957, PF13774

UniProt features (43 total): strand 10, mutagenesis site 8, helix 7, turn 4, sequence conflict 3, lipid moiety-binding region 3, domain 2, modified residue 2, chain 1, propeptide 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6J7X	X-RAY DIFFRACTION	2.75
6J7F	X-RAY DIFFRACTION	2.88
6J74	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15498-F1	91.09	0.78

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 (5): 159, 195, 194, 194, 195

Mutagenesis-validated functional residues (8):

Position	Phenotype
30	impairs geranylgeranylation by ggtase-3 complex.
31	impairs geranylgeranylation by ggtase-3 complex.
42	increases palmitoylation. targeted to golgi membranes. targeted to golgi and cytosol; when associated with s-194. target
84	impairs geranylgeranylation by ggtase-3 complex.
86	impairs geranylgeranylation by ggtase-3 complex.
133	impairs geranylgeranylation by ggtase-3 complex.
194	decreases palmitoylation by 55%. prevents palmitoylation; when associated with s-195. targeted to golgi and cytosol; whe
195	prevents farnesylation. targeted to cytosol; when associated with e-42. decreases palmitoylation by 13%. prevents palmit

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811438	Intra-Golgi traffic
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 193 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MEMBRANE_FUSION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_VESICLE_TARGETING, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MEMBRANE_DOCKING, PATIL_LIVER_CANCER, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (7): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), obsolete vesicle targeting (GO:0006903), obsolete vesicle docking involved in exocytosis (GO:0006904), protein transport (GO:0015031), retrograde transport, endosome to Golgi (GO:0042147), vesicle-mediated transport (GO:0016192), membrane fusion (GO:0061025)

GO Molecular Function (5): SNAP receptor activity (GO:0005484), protein-cysteine S-palmitoyltransferase activity (GO:0019706), cadherin binding (GO:0045296), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (18): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), transport vesicle (GO:0030133), cytoplasmic vesicle membrane (GO:0030659), SNARE complex (GO:0031201), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), neuronal cell body (GO:0043025), apical dendrite (GO:0097440), basal dendrite (GO:0097441), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	5
ER to Golgi Anterograde Transport	2
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	7
cellular anatomical structure	4
endomembrane system	4
intracellular membrane-bounded organelle	3
cytoplasmic vesicle	3
intercellular transport	2
transport	2
bounding membrane of organelle	2
dendrite	2
intracellular transport	1
Golgi vesicle transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
cytosolic transport	1
cellular process	1
membrane organization	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
palmitoyltransferase activity	1
protein-cysteine S-acyltransferase activity	1
cell adhesion molecule binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
vesicle membrane	1
membrane protein complex	1
endoplasmic reticulum-Golgi intermediate compartment	1
somatodendritic compartment	1
cell body	1
vacuole	1
plasma membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

1862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YKT6	STX5	Q13190	999
YKT6	GOSR1	O95249	994
YKT6	STX7	O15400	990
YKT6	VTI1B	Q9UEU0	979
YKT6	SNAP29	O95721	966
YKT6	SEC22B	O75396	953
YKT6	TRAPPC2	P0DI81	928
YKT6	STX17	P56962	914
YKT6	BET1	O15155	881
YKT6	NSF	P46459	867
YKT6	VAMP8	Q9BV40	852
YKT6	VAMP7	P51809	845
YKT6	PFN4	Q8NHR9	814
YKT6	SNAP25	P13795	785
YKT6	PFN3	P60673	783

IntAct

133 interactions, top by confidence:

A	B	Type	Score
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
RABGGTB	YKT6	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
STX6	GOSR2	psi-mi:“MI:0914”(association)	0.670
STX3	SNAP23	psi-mi:“MI:0914”(association)	0.660
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
YKT6	STX7	psi-mi:“MI:0915”(physical association)	0.560
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
RABGGTA	YKT6	psi-mi:“MI:0914”(association)	0.530
YKT6	C1QL1	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
STX3	YKT6	psi-mi:“MI:0914”(association)	0.530

BioGRID (340): YKT6 (Two-hybrid), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), YKT6 (Affinity Capture-MS), CNN3 (Co-fractionation), CRIP1 (Co-fractionation), CRYZ (Co-fractionation), DBI (Co-fractionation), ETFA (Co-fractionation), FKBP1A (Co-fractionation)

ESM2 similar proteins: A8WVD0, O08547, O08595, O15498, O16000, O60073, O74824, O75396, P22214, P36015, P47192, P48612, Q16932, Q24547, Q32N70, Q3T000, Q4KM74, Q58DV0, Q5EGY4, Q5RAI9, Q5RCE3, Q5TX47, Q5XIP1, Q5ZJW4, Q5ZK01, Q6BSL0, Q6C537, Q6C880, Q6CJA0, Q6CSA2, Q6DDU7, Q6FW27, Q6FWT0, Q6P7L4, Q6P816, Q74ZD2, Q757A4, Q7SXP0, Q7ZUN8, Q7ZV15

Diamond homologs: O15498, O60073, P36015, Q32N70, Q3T000, Q54ES8, Q5EGY4, Q6BSL0, Q6C537, Q6CSA2, Q6DDU7, Q6FW27, Q6P816, Q757A4, Q7ZUN8, Q86AQ7, Q9CQW1, Q9LVM9, Q9ZRD6, O70480, O75379, Q32L97, Q6C880, Q94AU2, Q6FWT0, Q9Y7L0, Q92356, Q9MAS5, Q9M376

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
RAS processing	5	29.4×	5e-05
Intra-Golgi traffic	7	22.4×	1e-05
FLT3 Signaling	5	21.4×	1e-04
Signaling by SCF-KIT	6	18.4×	6e-05
COPII-mediated vesicle transport	6	12.1×	3e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	8	10.3×	7e-05
ER to Golgi Anterograde Transport	5	8.2×	3e-03
COPI-mediated anterograde transport	6	8.1×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	7	52.1×	2e-08
vesicle fusion	8	46.8×	4e-09
membrane fusion	5	30.3×	1e-04
Ras protein signal transduction	5	10.0×	7e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	7	9.2×	1e-03
MAPK cascade	6	8.9×	3e-03
neuron projection development	6	7.1×	9e-03
intracellular protein transport	11	6.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527356	GRCh37/hg19 7p14.1-12.2(chr7:40778439-50228656)	Pathogenic

SpliceAI

1112 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44201238:AGGTG:A	donor_loss	1.0000
7:44201240:GT:G	donor_loss	1.0000
7:44201241:T:G	donor_loss	1.0000
7:44204566:A:AG	acceptor_gain	1.0000
7:44204567:G:GG	acceptor_gain	1.0000
7:44204567:GC:G	acceptor_gain	1.0000
7:44204567:GCGT:G	acceptor_gain	1.0000
7:44204649:AGGT:A	donor_loss	1.0000
7:44204651:G:C	donor_loss	1.0000
7:44206380:CTTA:C	acceptor_loss	1.0000
7:44206381:TTAGA:T	acceptor_loss	1.0000
7:44206383:A:AG	acceptor_gain	1.0000
7:44206383:AGA:A	acceptor_loss	1.0000
7:44206384:G:GA	acceptor_gain	1.0000
7:44206384:GA:G	acceptor_gain	1.0000
7:44206384:GAC:G	acceptor_gain	1.0000
7:44206384:GACT:G	acceptor_gain	1.0000
7:44206384:GACTA:G	acceptor_gain	1.0000
7:44206482:GAAG:G	donor_gain	1.0000
7:44206486:G:GG	donor_gain	1.0000
7:44208131:A:AG	acceptor_gain	1.0000
7:44208132:G:GG	acceptor_gain	1.0000
7:44211021:A:AG	acceptor_gain	1.0000
7:44211022:G:GG	acceptor_gain	1.0000
7:44211022:GCAC:G	acceptor_gain	1.0000
7:44211125:G:GG	donor_gain	1.0000
7:44212245:A:G	acceptor_gain	1.0000
7:44201182:T:TA	donor_gain	0.9900
7:44201183:G:GA	donor_gain	0.9900
7:44201240:G:GG	donor_gain	0.9900

AlphaMissense

1289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44208197:T:C	L153P	0.998
7:44211051:G:C	R163P	0.998
7:44211083:T:C	S174P	0.998
7:44212248:C:A	A188D	0.998
7:44211042:T:C	L160P	0.997
7:44211072:T:C	L170S	0.997
7:44211104:T:C	S181P	0.997
7:44211113:T:C	F184L	0.997
7:44211115:C:A	F184L	0.997
7:44211115:C:G	F184L	0.997
7:44212247:G:C	A188P	0.997
7:44204570:T:A	V36D	0.996
7:44204587:T:C	F42L	0.996
7:44204589:C:A	F42L	0.996
7:44204589:C:G	F42L	0.996
7:44204639:T:A	V59D	0.996
7:44211038:T:C	S159P	0.996
7:44211114:T:C	F184S	0.996
7:44211114:T:G	F184C	0.996
7:44201158:T:A	V8D	0.995
7:44207427:T:A	W110R	0.995
7:44207427:T:C	W110R	0.995
7:44208176:T:C	L146P	0.995
7:44211063:T:A	L167Q	0.995
7:44211084:C:T	S174F	0.995
7:44204600:T:C	L46P	0.994
7:44206393:T:C	C66R	0.994
7:44211045:T:C	L161S	0.994
7:44211116:T:G	Y185D	0.994
7:44206450:T:G	Y85D	0.993

dbSNP variants (sampled 300 via entrez): RS1000422828 (7:44211177 C>T), RS1000647512 (7:44204749 C>G,T), RS1000943044 (7:44209811 C>A,T), RS1000993699 (7:44210179 A>T), RS1001071967 (7:44200167 T>A), RS1001441557 (7:44203959 C>T), RS1001549769 (7:44203452 G>A), RS1001607557 (7:44213378 C>T), RS1001666769 (7:44210410 T>A), RS1001720671 (7:44207215 A>C,G), RS1002066901 (7:44207003 A>T), RS1002151169 (7:44202197 A>G), RS1002153239 (7:44202417 G>A,T), RS1002360416 (7:44205412 C>T), RS1002446086 (7:44205860 C>T)

Disease associations

OMIM: gene MIM:606209 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic disease	Moderate	Autosomal recessive

Mondo (1): syndromic disease (MONDO:0002254)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004206_12	Fasting plasma glucose	1.000000e-28
GCST004206_3	Fasting plasma glucose	3.000000e-24
GCST005146_6	Birth weight	1.000000e-26
GCST006001_11	Hemoglobin A1c levels	4.000000e-11
GCST006002_10	Blood sugar levels	7.000000e-16
GCST006867_59	Type 2 diabetes	4.000000e-09
GCST007096_125	Pulse pressure	3.000000e-08
GCST008362_168	Birth weight	4.000000e-61
GCST008363_60	Offspring birth weight	2.000000e-13
GCST009240_211	Serum metabolite levels (CMS)	3.000000e-08
GCST009242_181	Serum metabolite levels	7.000000e-10
GCST010724_14	HOMA-B (corrected for HOMA-IR)	3.000000e-07
GCST90013406_229	Liver enzyme levels (alkaline phosphatase)	2.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004541	HbA1c measurement
EFO:0004468	glucose measurement
EFO:0005763	pulse pressure measurement
EFO:0005939	parental genotype effect measurement
EFO:0004469	HOMA-B
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Acetaminophen	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
beauvericin	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
periodate-oxidized adenosine	affects expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
tamibarotene	affects expression	1
enniatins	affects cotreatment, increases expression	1
monomethylarsonous acid	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
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
Arsenic	affects methylation	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome