UXS1

Summary

UXS1 (UDP-glucuronate decarboxylase 1, HGNC:17729) is a protein-coding gene on chromosome 2q12.2, encoding UDP-glucuronic acid decarboxylase 1 (Q8NBZ7). Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose. It is a selective cancer dependency (DepMap: 29.6% of cell lines).

This gene encodes an enzyme found in the perinuclear Golgi which catalyzes the synthesis of UDP-xylose used in glycosaminoglycan (GAG) synthesis on proteoglycans. The GAG chains are covalently attached to proteoglycans which participate in signaling pathways during development. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80146 — RefSeq curated summary.

At a glance

• Gene–disease (curated): skeletal dysplasia (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 29.6% of screened cell lines
• MANE Select transcript: NM_001253875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17729
Approved symbol	UXS1
Name	UDP-glucuronate decarboxylase 1
Location	2q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23591, UGD, SDR6E1
Ensembl gene	ENSG00000115652
Ensembl biotype	protein_coding
OMIM	609749
Entrez	80146

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 25 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000283148, ENST00000409032, ENST00000409501, ENST00000416298, ENST00000436241, ENST00000441952, ENST00000444193, ENST00000457835, ENST00000470053, ENST00000473338, ENST00000474920, ENST00000479621, ENST00000479774, ENST00000483426, ENST00000497604, ENST00000903962, ENST00000903963, ENST00000903964, ENST00000903965, ENST00000903966, ENST00000903967, ENST00000903968, ENST00000903969, ENST00000903970, ENST00000903971, ENST00000937935, ENST00000937936, ENST00000937937, ENST00000937938

RefSeq mRNA: 9 — MANE Select: NM_001253875 NM_001253875, NM_001253876, NM_001377504, NM_001377505, NM_001377506, NM_001377507, NM_001377508, NM_001377509, NM_025076

CCDS: CCDS46378, CCDS58720, CCDS58721

Canonical transcript exons

ENST00000283148 — 15 exons

Exon	Start	End
ENSE00000772528	106122970	106123091
ENSE00000772530	106125620	106125679
ENSE00000963432	106112646	106112765
ENSE00000963433	106101058	106101118
ENSE00001184974	106194148	106194301
ENSE00001576574	106164736	106164799
ENSE00001837304	106093311	106094157
ENSE00003500330	106096718	106096821
ENSE00003513401	106098716	106098773
ENSE00003523784	106129674	106129778
ENSE00003524105	106166056	106166083
ENSE00003642044	106145190	106145370
ENSE00003642631	106158058	106158118
ENSE00003756477	106163667	106163710
ENSE00003788619	106104794	106104837

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.7011 / max 386.9765, expressed in 1817 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30054	30.3341	1817
30055	1.4074	1046
30053	0.5548	81
30051	0.1300	56
30050	0.1151	52
30049	0.0987	53
30052	0.0609	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.81	gold quality
renal medulla	UBERON:0000362	97.78	gold quality
oocyte	CL:0000023	97.22	gold quality
cartilage tissue	UBERON:0002418	96.65	gold quality
tibia	UBERON:0000979	96.54	gold quality
visceral pleura	UBERON:0002401	96.10	gold quality
decidua	UBERON:0002450	95.00	gold quality
germinal epithelium of ovary	UBERON:0001304	94.56	gold quality
dorsal root ganglion	UBERON:0000044	94.38	gold quality
trigeminal ganglion	UBERON:0001675	93.76	gold quality
stromal cell of endometrium	CL:0002255	93.53	gold quality
placenta	UBERON:0001987	93.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.33	gold quality
epithelium of nasopharynx	UBERON:0001951	93.29	gold quality
nasopharynx	UBERON:0001728	93.27	gold quality
metanephros cortex	UBERON:0010533	93.02	gold quality
lower lobe of lung	UBERON:0008949	93.01	gold quality
monocyte	CL:0000576	92.79	gold quality
mononuclear cell	CL:0000842	92.74	gold quality
olfactory bulb	UBERON:0002264	92.74	silver quality
pleura	UBERON:0000977	92.72	gold quality
leukocyte	CL:0000738	92.71	gold quality
adult mammalian kidney	UBERON:0000082	92.52	gold quality
right lung	UBERON:0002167	92.46	gold quality
calcaneal tendon	UBERON:0003701	92.23	gold quality
lung	UBERON:0002048	92.18	gold quality
parietal pleura	UBERON:0002400	92.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.02	gold quality
palpebral conjunctiva	UBERON:0001812	91.93	gold quality
upper lobe of lung	UBERON:0008948	91.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	26.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• UDP-glucuronate decarboxylase, a key enzyme in proteoglycan synthesis: cloning, characterization, and localization. (PMID:11877387)
• Complementation was achieved by expression of a cytoplasmic variant of UDP-xylose Synthase, which proves the existence of a functional Golgi UDP-xylose transporter[UDP-xylose Synthase] (PMID:19028698)
• hUXS forms a tetramer in solution that is important for activity. The higher activity of the tetramer coupled with the relative instability of the dimeric complex suggests that an association-dissociation mechanism may regulate hUXS activity. (PMID:23656592)
• The persistence of a latent hexamer-building interface in the human enzyme suggests that the ancestral UXS may have been a hexamer. (PMID:25521717)
• UXS1: a sweet spot for cell death. (PMID:38030856)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	uxs1	ENSDARG00000056102
mus_musculus	Uxs1	ENSMUSG00000057363
rattus_norvegicus	Uxs1	ENSRNOG00000045605
drosophila_melanogaster	Uxs	FBGN0035848
caenorhabditis_elegans		WBGENE00005019

Paralogs (10): TGDS (ENSG00000088451), HSD3B7 (ENSG00000099377), GFUS (ENSG00000104522), GMDS (ENSG00000112699), GALE (ENSG00000117308), NSDHL (ENSG00000147383), SDR42E2 (ENSG00000183921), SDR42E1 (ENSG00000184860), HSD3B1 (ENSG00000203857), HSD3B2 (ENSG00000203859)

Protein

Protein identifiers

UDP-glucuronic acid decarboxylase 1 — Q8NBZ7 (reviewed: Q8NBZ7)

Alternative names: UDP-glucuronate decarboxylase 1

All UniProt accessions (9): A0A6Q8PGM4, A0A6Q8PGN2, A0A6Q8PH60, C9J3T9, C9JCB7, C9JE50, C9JFU6, C9JW33, Q8NBZ7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose. Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis. Catalyzes the synthesis of UDP-xylose in two steps: the hydroxyl group of UDP-glucuronic acid is first oxidized using an enzyme-bound NAD(+) as electron acceptor, favoring the decarboxylation yielding a UDP-4-ketoxylose reaction intermediate and a reduced cofactor NADH bound to the catalytic pocket. In the second step, the 4-keto group is reduced resulting in UDP-xylose and the restoration of the enzyme to its NAD(+)-bound form.

Subunit / interactions. Homodimer and homotetramer. Interacts with AKT1.

Subcellular location. Golgi apparatus. Golgi stack membrane. Endoplasmic reticulum membrane.

Disease relevance. UXS1 defects may be a cause of short stature phenotype, characterized by short long bones, normal epiphysis, and subtle metaphyseal changes especially in his legs.

Activity regulation. Under low NAD(+) conditions, UXS1 forms an inactive UDP-4-ketoxylose intermediate bound to NADH, impairing the synthesis of core tetrasaccharide. The inactive NADH-bound UXS1 can be rescued by UDP-4-keto-6-deoxyglucose, produced by TGDS, which mimics the UDP-4-ketoxylose intermediate and acts as an enzyme-rescue metabolite. UDP-4-keto-6-deoxyglucose is used by the inactive NADH-bound UXS1 to produce UDP-6-deoxyglucose and NAD(+) within the catalytic pocket of UXS1, regenerating the essential cofactor NAD(+).

Pathway. Nucleotide-sugar biosynthesis; UDP-alpha-D-xylose biosynthesis; UDP-alpha-D-xylose from UDP-alpha-D-glucuronate: step 1/1.

Similarity. Belongs to the NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NBZ7-1	1	yes
Q8NBZ7-2	2
Q8NBZ7-3	3

RefSeq proteins (9): NP_001240804, NP_001240805, NP_001364433, NP_001364434, NP_001364435, NP_001364436, NP_001364437, NP_001364438, NP_079352 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016040	NAD(P)-bd_dom	Domain
IPR021761	UXS1_N	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR044516	UXS-like	Family

Pfam: PF11803, PF16363

Catalyzed reactions (Rhea), 1 shown:

• UDP-alpha-D-glucuronate + H(+) = UDP-alpha-D-xylose + CO2 (RHEA:23916)

UniProt features (71 total): binding site 29, strand 14, helix 12, mutagenesis site 4, topological domain 2, modified residue 2, splice variant 2, chain 1, transmembrane region 1, glycosylation site 1, sequence variant 1, active site 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2B69	X-RAY DIFFRACTION	1.21
4GLL	X-RAY DIFFRACTION	2.5
4LK3	X-RAY DIFFRACTION	2.64
4M55	X-RAY DIFFRACTION	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBZ7-F1	89.59	0.71

Functional residue map

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

Catalytic / active sites (1): 231 (proton acceptor)

Ligand- & substrate-binding residues (29): 122; 123; 124; 144; 145; 149; 150; 159; 161; 177; 178; 185 …

Post-translational modifications (2): 1, 94

Glycosylation sites (1): 316

Mutagenesis-validated functional residues (4):

Position	Phenotype
204	reduced udp-glucuronic acid decarboxylase activity.
231	abolished udp-glucuronic acid decarboxylase activity.
236	strongly reduced udp-glucuronic acid decarboxylase activity, caused by a local unfolding of the active site that allows
361	strongly reduced udp-glucuronic acid decarboxylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-173599	Formation of the active cofactor, UDP-glucuronate
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis

MSigDB gene sets: 224 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_BIOLOGICAL_OXIDATIONS, chr2q12, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, CTATGCA_MIR153, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, PATIL_LIVER_CANCER, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, MODULE_239, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (3): glycosaminoglycan biosynthetic process (GO:0006024), UDP-D-xylose biosynthetic process (GO:0033320), D-xylose metabolic process (GO:0042732)

GO Molecular Function (6): identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), UDP-glucuronate decarboxylase activity (GO:0048040), NAD+ binding (GO:0070403), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (8): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), Golgi cisterna membrane (GO:0032580), extracellular exosome (GO:0070062), catalytic complex (GO:1902494), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucuronidation	1
Glycosaminoglycan metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
organelle membrane	2
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
nucleotide-sugar biosynthetic process	1
UDP-D-xylose metabolic process	1
pentose metabolic process	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
carboxy-lyase activity	1
anion binding	1
NAD binding	1
catalytic activity	1
carbon-carbon lyase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi cisterna	1
extracellular vesicle	1
protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UXS1	UGDH	O60701	775
UXS1	FAM20B	O75063	653
UXS1	XYLT1	Q86Y38	649
UXS1	B3GAT3	O94766	648
UXS1	EXTL3	O43909	593
UXS1	EXT2	Q93063	592
UXS1	XYLT2	Q9H1B5	587
UXS1	UGP2	Q16851	565
UXS1	B4GALT7	Q9UBV7	559
UXS1	SLC35B2	Q8TB61	543
UXS1	WDR64	B1ANS9	517
UXS1	B3GALT6	Q96L58	492
UXS1	EXT1	Q16394	480
UXS1	SH3RF3	Q8TEJ3	476
UXS1	UNC50	Q53HI1	467

IntAct

85 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
UXS1	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
PA	UXS1	psi-mi:“MI:0915”(physical association)	0.370
UXS1	FXR1	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
IGF2R	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): UXS1 (Affinity Capture-MS), UXS1 (Affinity Capture-MS), UXS1 (Affinity Capture-MS), UXS1 (Affinity Capture-MS), SPSB3 (Affinity Capture-MS), TSKU (Affinity Capture-MS), UXS1 (Affinity Capture-MS), NOP9 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), XPO4 (Affinity Capture-MS), VPS8 (Affinity Capture-MS), FAM98A (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), UXS1 (Affinity Capture-MS), UXS1 (Affinity Capture-MS)

ESM2 similar proteins: A1JPN5, A2Z7B3, A3C4S4, A4TIM4, A4WAM3, A7FHH4, A8FRR2, A8GDR7, A9R093, B1JJ30, B2K5L3, B4ETL7, B5XTK9, B7LM76, C6DAW5, O48917, O64749, P37744, P55579, P93031, Q1C742, Q1CIH7, Q2R1V8, Q4K4U8, Q4KC82, Q5PQX0, Q5R885, Q5UPS5, Q6DF08, Q6GMI9, Q7N3Q7, Q84KI6, Q8NBZ7, Q8S8T4, Q8S9Z2, Q8VZC0, Q8ZDX8, Q91XL3, Q93PD8, Q93VR3

Diamond homologs: A6QLW2, A6TF98, A7GKX7, B0RVL0, B4SYX1, B5BCP6, B5FNT9, B5XTK9, C0Q069, D4GU72, F8C4X8, O34886, O95455, P0C0R6, P0C7J0, P35675, P45602, Q0A4T8, Q2NRV7, Q54WS6, Q57664, Q5PNA6, Q5PQX0, Q5R885, Q5UR12, Q6DF08, Q6E7F2, Q6GMI9, Q7N3Q7, Q8NBZ7, Q8S8T4, Q8VDR7, Q8VZC0, Q8Z540, Q91XL3, Q9EQC1, Q9FIE8, Q9H2F3, Q9LZI2, Q9SN95

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EPHA3	“up-regulates activity”	UXS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Neutrophil degranulation	13	4.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	6	40.5×	2e-06
intracellular zinc ion homeostasis	8	37.0×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2840 predictions. Top by Δscore:

Variant	Effect	Δscore
2:106094156:ACCT:A	acceptor_loss	1.0000
2:106094157:CCTGT:C	acceptor_loss	1.0000
2:106094158:C:CA	acceptor_loss	1.0000
2:106096711:CACT:C	donor_loss	1.0000
2:106096712:ACTT:A	donor_loss	1.0000
2:106096713:CTTA:C	donor_loss	1.0000
2:106096714:TTACC:T	donor_loss	1.0000
2:106096715:TA:T	donor_loss	1.0000
2:106096716:A:AC	donor_gain	1.0000
2:106096716:A:C	donor_loss	1.0000
2:106096717:C:CC	donor_gain	1.0000
2:106096717:CCA:C	donor_gain	1.0000
2:106096831:T:C	acceptor_gain	1.0000
2:106096831:T:TC	acceptor_gain	1.0000
2:106101116:TCG:T	acceptor_gain	1.0000
2:106101117:CG:C	acceptor_gain	1.0000
2:106101117:CGC:C	acceptor_gain	1.0000
2:106101119:C:CC	acceptor_gain	1.0000
2:106112640:ACCT:A	donor_loss	1.0000
2:106112641:CCTA:C	donor_loss	1.0000
2:106112642:CTAC:C	donor_loss	1.0000
2:106112643:TACCG:T	donor_loss	1.0000
2:106112644:A:AG	donor_loss	1.0000
2:106112645:C:A	donor_loss	1.0000
2:106112762:CTTC:C	acceptor_gain	1.0000
2:106112766:C:CA	acceptor_loss	1.0000
2:106112766:C:CC	acceptor_gain	1.0000
2:106112767:T:C	acceptor_loss	1.0000
2:106129667:AACTT:A	donor_loss	1.0000
2:106129668:ACTTA:A	donor_loss	1.0000

AlphaMissense

2810 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:106096729:A:G	W374R	1.000
2:106096729:A:T	W374R	1.000
2:106096766:T:A	R361S	1.000
2:106096766:T:G	R361S	1.000
2:106098772:C:T	G324E	1.000
2:106098773:C:A	G324W	1.000
2:106101061:G:C	N322K	1.000
2:106101061:G:T	N322K	1.000
2:106104812:C:A	R297M	1.000
2:106112722:C:T	G263E	1.000
2:106112730:G:C	N260K	1.000
2:106112730:G:T	N260K	1.000
2:106112733:G:C	F259L	1.000
2:106112733:G:T	F259L	1.000
2:106112735:A:G	F259L	1.000
2:106112740:C:G	R257T	1.000
2:106112743:G:T	A256D	1.000
2:106123007:C:G	R236P	1.000
2:106123008:G:T	R236S	1.000
2:106123010:T:A	K235I	1.000
2:106123014:C:G	G234R	1.000
2:106123023:A:G	Y231H	1.000
2:106123056:C:G	G220R	1.000
2:106125622:C:A	G207V	1.000
2:106125622:C:T	G207E	1.000
2:106125623:C:G	G207R	1.000
2:106125623:C:T	G207R	1.000
2:106125631:T:A	E204V	1.000
2:106125632:C:T	E204K	1.000
2:106129691:C:T	G182E	1.000

dbSNP variants (sampled 300 via entrez): RS1000132611 (2:106187855 C>T), RS1000135890 (2:106115367 T>C), RS1000153509 (2:106156421 C>T), RS1000185493 (2:106115573 T>C), RS1000195677 (2:106149043 T>C), RS1000243618 (2:106137663 C>T), RS1000244488 (2:106164430 GTTTGTAC>G), RS1000283697 (2:106143205 G>A,C,T), RS1000288726 (2:106110112 C>G,T), RS1000289748 (2:106106526 A>G), RS1000327094 (2:106191594 G>A,T), RS1000337136 (2:106142990 T>C), RS1000341524 (2:106100072 G>A), RS1000363258 (2:106095698 T>C), RS1000442105 (2:106177125 A>G)

Disease associations

OMIM: gene MIM:609749 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
skeletal dysplasia	Limited	Autosomal dominant

Mondo (1): skeletal dysplasia (MONDO:0018230)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005024_3	Pursuit maintenance gain	4.000000e-07
GCST005028_10	Pursuit maintenance gain in psychotic disorders	3.000000e-07
GCST006224_3	Right lateral prefrontal cortical growth	7.000000e-06
GCST006585_2353	Blood protein levels	2.000000e-09
GCST90020028_69	Hip circumference adjusted for BMI	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
tibolone	decreases expression	1
thymidine 5’-diphosphate	affects binding, affects cotreatment	1
K 7174	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Bilirubin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
NAD	affects cotreatment, affects binding	1
Paraquat	decreases expression	1
Uridine Diphosphate Galactose	affects binding, affects cotreatment	1
Uridine Diphosphate Glucose	affects binding, affects cotreatment	1
Uridine Diphosphate Glucuronic Acid	affects binding, affects cotreatment	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients