GNPNAT1

Summary

GNPNAT1 (glucosamine-phosphate N-acetyltransferase 1, HGNC:19980) is a protein-coding gene on chromosome 14q22.1, encoding Glucosamine 6-phosphate N-acetyltransferase (Q96EK6). It is a selective cancer dependency (DepMap: 21.4% of cell lines).

Enables identical protein binding activity. Predicted to be involved in UDP-N-acetylglucosamine biosynthetic process. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in endoplasmic reticulum-Golgi intermediate compartment and late endosome.

Source: NCBI Gene 64841 — RefSeq curated summary.

At a glance

• Gene–disease (curated): rhizomelic dysplasia, Ain-Naz type (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 29 total — 1 pathogenic
• Phenotypes (HPO): 41
• Cancer dependency (DepMap): dependent in 21.4% of screened cell lines
• MANE Select transcript: NM_198066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19980
Approved symbol	GNPNAT1
Name	glucosamine-phosphate N-acetyltransferase 1
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	Gpnat1, FLJ10607
Ensembl gene	ENSG00000100522
Ensembl biotype	protein_coding
OMIM	616510
Entrez	64841

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216410, ENST00000553987, ENST00000554230, ENST00000554421, ENST00000557604, ENST00000650397, ENST00000875202, ENST00000875203, ENST00000875204, ENST00000875205, ENST00000875206, ENST00000875207, ENST00000875208, ENST00000875209, ENST00000875210, ENST00000875211, ENST00000875212, ENST00000916811, ENST00000916812, ENST00000916813, ENST00000916815

RefSeq mRNA: 1 — MANE Select: NM_198066 NM_198066

CCDS: CCDS9712

Canonical transcript exons

ENST00000216410 — 6 exons

Exon	Start	End
ENSE00000657480	52780679	52780740
ENSE00000657482	52781784	52781911
ENSE00001147742	52784497	52784664
ENSE00001255425	52791428	52791607
ENSE00001255438	52775193	52778458
ENSE00003529190	52783423	52783485

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6544 / max 398.8763, expressed in 1792 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143267	14.0579	1765
143265	7.0851	1547
143266	0.4121	204
143264	0.0993	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	96.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.85	gold quality
colonic mucosa	UBERON:0000317	92.69	gold quality
liver	UBERON:0002107	92.48	gold quality
epithelial cell of pancreas	CL:0000083	92.39	silver quality
oviduct epithelium	UBERON:0004804	92.28	gold quality
gingival epithelium	UBERON:0001949	90.97	silver quality
nasal cavity epithelium	UBERON:0005384	90.18	gold quality
stromal cell of endometrium	CL:0002255	90.06	gold quality
gingiva	UBERON:0001828	89.88	gold quality
islet of Langerhans	UBERON:0000006	89.81	gold quality
rectum	UBERON:0001052	89.48	gold quality
endometrium	UBERON:0001295	89.37	gold quality
right lobe of liver	UBERON:0001114	89.30	gold quality
cartilage tissue	UBERON:0002418	89.26	gold quality
pancreas	UBERON:0001264	89.13	gold quality
body of pancreas	UBERON:0001150	88.72	gold quality
calcaneal tendon	UBERON:0003701	88.57	gold quality
adrenal tissue	UBERON:0018303	87.97	gold quality
esophagus squamous epithelium	UBERON:0006920	87.72	gold quality
duodenum	UBERON:0002114	87.69	gold quality
tibia	UBERON:0000979	86.49	gold quality
kidney epithelium	UBERON:0004819	86.26	silver quality
corpus epididymis	UBERON:0004359	86.18	gold quality
tendon	UBERON:0000043	86.02	gold quality
jejunal mucosa	UBERON:0000399	85.96	gold quality
palpebral conjunctiva	UBERON:0001812	85.53	gold quality
nasal cavity mucosa	UBERON:0001826	85.12	gold quality
smooth muscle tissue	UBERON:0001135	84.73	gold quality
amniotic fluid	UBERON:0000173	84.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting GNPNAT1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10523-5P	99.91	69.22	2038

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• Crystal structures of human GNA1, including apo GNA1, the GNA1-GlcN6P complex and an E156A mutant were reported. (PMID:18675810)
• The Glucosamine-6-phosphate N-acetyltransferase1 (GNA1) catalyses the transfer of an acetyl group from acetyl coenzyme A to glucosamine-6-phosphate to form N-acetylglucosamine-6-phosphate which is an essential intermediate in UDP-GlcNAc biosynthesis. (PMID:26935656)
• Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1. (PMID:32591345)
• Independent Prognostic Potential of GNPNAT1 in Lung Adenocarcinoma. (PMID:33178836)
• Potential role of glucosamine-phosphate N-acetyltransferase 1 in the development of lung adenocarcinoma. (PMID:33686019)
• GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer. (PMID:37215111)
• GNPNAT1 promotes the stemness of breast cancer and serves as a potential prognostic biomarker. (PMID:37387422)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnpnat1	ENSDARG00000039892
mus_musculus	Gnpnat1	ENSMUSG00000037722
rattus_norvegicus	AABR07059877.1	ENSRNOG00000039626
drosophila_melanogaster	Gnpnat	FBGN0039690
caenorhabditis_elegans		WBGENE00001646
caenorhabditis_elegans	gna-2	WBGENE00001647

Protein

Protein identifiers

Glucosamine 6-phosphate N-acetyltransferase — Q96EK6 (reviewed: Q96EK6)

Alternative names: Phosphoglucosamine acetylase, Phosphoglucosamine transacetylase

All UniProt accessions (3): Q96EK6, G3V4W4, G3V5E4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer.

Subcellular location. Golgi apparatus membrane. Endosome membrane.

Disease relevance. Rhizomelic dysplasia, Ain-Naz type (RHZDAN) [MIM:619598] An autosomal recessive skeletal dysplasia characterized by short stature, marked rhizomelic shortening of the limbs, platyspondyly, hip dysplasia, and large hands and feet relative to height. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-glucosamine biosynthesis; N-acetyl-alpha-D-glucosamine 1-phosphate from alpha-D-glucosamine 6-phosphate (route I): step 1/2.

Similarity. Belongs to the acetyltransferase family. GNA1 subfamily.

RefSeq proteins (1): NP_932332* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR039143	GNPNAT1-like	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.4 — glucosamine-phosphate N-acetyltransferase (BRENDA: 30 organisms, 11 substrates, 22 inhibitors, 57 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCOSAMINE 6-PHOSPHATE	0.03–7.1	31
ACETYL-COA	0.012–0.78	23
COENZYME A	0.038	1
GLUCOSAMINE 6-PHOSPHATE	0.071	1
PROPIONYL-COA	0.13	1

Catalyzed reactions (Rhea), 1 shown:

• D-glucosamine 6-phosphate + acetyl-CoA = N-acetyl-D-glucosamine 6-phosphate + CoA + H(+) (RHEA:10292)

UniProt features (34 total): helix 10, strand 8, binding site 8, turn 3, mutagenesis site 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2O28	X-RAY DIFFRACTION	1.8
3CXP	X-RAY DIFFRACTION	2.01
3CXQ	X-RAY DIFFRACTION	2.3
2HUZ	X-RAY DIFFRACTION	2.67
3CXS	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EK6-F1	97.49	0.97

Functional residue map

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

Ligand- & substrate-binding residues (8): 61; 108–111; 120–122; 130–135; 151–152; 165–167; 175; 181

Mutagenesis-validated functional residues (2):

Position	Phenotype
156	reduces affinity for glucosamine-6-phosphate 6-fold.
156	slightly reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-446210	Synthesis of UDP-N-acetyl-glucosamine

MSigDB gene sets: 298 (showing top): FREAC2_01, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, MARTIN_VIRAL_GPCR_SIGNALING_UP, GOBP_AMINO_SUGAR_METABOLIC_PROCESS

GO Biological Process (2): UDP-N-acetylglucosamine biosynthetic process (GO:0006048), cellular response to leukemia inhibitory factor (GO:1990830)

GO Molecular Function (6): glucosamine 6-phosphate N-acetyltransferase activity (GO:0004343), identical protein binding (GO:0042802), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (9): Golgi membrane (GO:0000139), late endosome (GO:0005770), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), cytosol (GO:0005829), endosome membrane (GO:0010008), cytoplasm (GO:0005737), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
bounding membrane of organelle	2
endosome	2
intracellular membrane-bounded organelle	2
endomembrane system	2
UDP-N-acetylglucosamine metabolic process	1
nucleotide-sugar biosynthetic process	1
amino sugar biosynthetic process	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
N-acetyltransferase activity	1
protein binding	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
Golgi apparatus	1
cytoplasmic vesicle membrane	1
intracellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNPNAT1	UAP1	Q16222	861
GNPNAT1	PGM3	O95394	841
GNPNAT1	GFPT1	Q06210	808
GNPNAT1	NAGK	Q9UJ70	791
GNPNAT1	GFPT2	O94808	770
GNPNAT1	GALE	Q14376	662
GNPNAT1	GNPDA1	P46926	646
GNPNAT1	UAP1L1	Q3KQV9	624
GNPNAT1	GPI	P06744	618
GNPNAT1	STYX	Q8WUJ0	565
GNPNAT1	GNPDA2	Q8TDQ7	531
GNPNAT1	ESCO1	Q5FWF5	513
GNPNAT1	ESCO2	Q56NI9	512
GNPNAT1	OGA	O60502	511
GNPNAT1	ZNF518B	Q9C0D4	495

IntAct

24 interactions, top by confidence:

A	B	Type	Score
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
GNPNAT1	GNPNAT1	psi-mi:“MI:0915”(physical association)	0.590
GNPNAT1	GNPNAT1	psi-mi:“MI:0407”(direct interaction)	0.590
FABP1	GNPNAT1	psi-mi:“MI:0915”(physical association)	0.560
PSMB8	GNPNAT1	psi-mi:“MI:0915”(physical association)	0.560
MAPT	DENR	psi-mi:“MI:0914”(association)	0.560
OR5F1	UBA6	psi-mi:“MI:0914”(association)	0.530
HSD17B6	NME2P1	psi-mi:“MI:0914”(association)	0.530
RDH5	NME2P1	psi-mi:“MI:0914”(association)	0.530
GNPNAT1	MSRB2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
GNPNAT1	C1QA	psi-mi:“MI:0915”(physical association)	0.370
GNPNAT1	NAGK	psi-mi:“MI:0915”(physical association)	0.370
MRPL4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
MAPT	NME2	psi-mi:“MI:0914”(association)	0.350
FABP1	NME2P1	psi-mi:“MI:0914”(association)	0.350
NTNG1	UBA6	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
LARS2	CREB1	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350
PSMB8	GNPNAT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): GNPNAT1 (Two-hybrid), ASPDH (Co-fractionation), GNPNAT1 (Co-fractionation), GNPNAT1 (Co-fractionation), GNPNAT1 (Co-fractionation), GNPNAT1 (Co-fractionation), GNPNAT1 (Co-fractionation), PCBP2 (Co-fractionation), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS), GNPNAT1 (Affinity Capture-MS)

ESM2 similar proteins: B0BN85, B4G0F3, B8BKI7, C6JS30, O00244, O08997, O74735, O76003, O81187, P07178, P07311, P13439, P19356, P22907, P24540, P31754, P38636, P41500, P55142, P55143, P56376, Q0V9A9, Q28C69, Q28ID3, Q2KIK0, Q2R483, Q3T0E0, Q53H82, Q54PZ2, Q5R514, Q5RAL9, Q5XGR8, Q5XJ54, Q5XK67, Q61035, Q6DBT3, Q8L8T2, Q8W1X2, Q94BT9, Q96EK6

Diamond homologs: C7IZ16, E3Q1H1, O13738, O93806, P43577, Q17427, Q54WR8, Q5RAL9, Q5U9F2, Q5UPZ9, Q96EK6, Q9JK38, Q9LFU9, Q9VAI0, A0A0R0IHP4, A2Y5T7, C7MRC4, K7MTW9, Q58604, Q5EDG0, Q5KQI6, Q7X9V3, Q9C666, Q7PCJ9, Q6Z1Y6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1302024	NM_198066.4(GNPNAT1):c.226G>A (p.Glu76Lys)	Pathogenic

SpliceAI

1301 predictions. Top by Δscore:

Variant	Effect	Δscore
14:52771032:GGCA:G	acceptor_gain	1.0000
14:52781779:CATA:C	donor_loss	1.0000
14:52781780:ATACC:A	donor_loss	1.0000
14:52781781:TA:T	donor_loss	1.0000
14:52781782:A:AC	donor_gain	1.0000
14:52781783:C:CA	donor_loss	1.0000
14:52781783:C:CC	donor_gain	1.0000
14:52781907:AGATT:A	acceptor_gain	1.0000
14:52781908:GATT:G	acceptor_gain	1.0000
14:52781909:ATT:A	acceptor_gain	1.0000
14:52781909:ATTC:A	acceptor_loss	1.0000
14:52781910:TT:T	acceptor_gain	1.0000
14:52781910:TTCT:T	acceptor_loss	1.0000
14:52781912:C:CC	acceptor_gain	1.0000
14:52781913:T:C	acceptor_loss	1.0000
14:52781914:G:C	acceptor_gain	1.0000
14:52781914:G:GC	acceptor_gain	1.0000
14:52781921:T:TC	acceptor_gain	1.0000
14:52783415:GTACT:G	donor_loss	1.0000
14:52783416:TACTT:T	donor_loss	1.0000
14:52783417:ACTT:A	donor_loss	1.0000
14:52783418:CTT:C	donor_loss	1.0000
14:52783419:TT:T	donor_loss	1.0000
14:52783420:TACT:T	donor_loss	1.0000
14:52783421:A:AC	donor_gain	1.0000
14:52783421:A:T	donor_loss	1.0000
14:52783422:C:CA	donor_gain	1.0000
14:52783422:CT:C	donor_gain	1.0000
14:52783422:CTCAT:C	donor_gain	1.0000
14:52784493:TTACC:T	donor_loss	1.0000

AlphaMissense

1204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:52778431:G:C	S145R	0.996
14:52778431:G:T	S145R	0.996
14:52778433:T:G	S145R	0.996
14:52780736:C:T	G117E	0.996
14:52781806:T:A	K108I	0.996
14:52781833:G:T	A99D	0.996
14:52781821:A:G	L103P	0.995
14:52781827:G:T	A101E	0.995
14:52781828:C:G	A101P	0.995
14:52781834:C:G	A99P	0.995
14:52781866:A:T	V88D	0.995
14:52784526:C:A	R42M	0.995
14:52784526:C:G	R42T	0.995
14:52778395:A:C	C157W	0.994
14:52778416:A:C	C150W	0.994
14:52780715:A:T	V124D	0.994
14:52778374:G:C	F164L	0.993
14:52778374:G:T	F164L	0.993
14:52778376:A:G	F164L	0.993
14:52780685:C:T	G134D	0.993
14:52784525:C:A	R42S	0.993
14:52784525:C:G	R42S	0.993
14:52778410:C:A	K152N	0.992
14:52778410:C:G	K152N	0.992
14:52780737:C:G	G117R	0.992
14:52780737:C:T	G117R	0.992
14:52778397:A:G	C157R	0.991
14:52778402:A:T	L155H	0.991
14:52780718:A:T	V123D	0.991
14:52780732:T:A	R118S	0.991

dbSNP variants (sampled 300 via entrez): RS1000094415 (14:52784456 G>A), RS1000209817 (14:52788392 C>T), RS1000240844 (14:52788143 C>T), RS1000696964 (14:52781924 G>A,C), RS1000760132 (14:52789540 T>C), RS1001107720 (14:52782317 C>T), RS1001886287 (14:52786611 C>A,T), RS1002000137 (14:52788437 A>G), RS1002039765 (14:52779742 A>C), RS1002051065 (14:52788744 T>C), RS1002586653 (14:52783142 AC>A), RS1002677852 (14:52785151 C>G,T), RS1002786826 (14:52792430 G>A), RS1003557780 (14:52785230 TATC>T), RS1003615295 (14:52779768 A>G)

Disease associations

OMIM: gene MIM:616510 | disease phenotypes: MIM:619598

GenCC curated gene-disease

Disease	Classification	Inheritance
rhizomelic dysplasia, Ain-Naz type	Moderate	Autosomal recessive
osteochondrodysplasia	Limited	Autosomal recessive

Mondo (2): rhizomelic dysplasia, Ain-Naz type (MONDO:0859203), osteochondrodysplasia (MONDO:0005516)

Orphanet (0):

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000316	Hypertelorism
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000767	Pectus excavatum
HP:0000904	Flaring of rib cage
HP:0000926	Platyspondyly
HP:0001176	Large hands
HP:0001249	Intellectual disability
HP:0001288	Gait disturbance
HP:0001376	Limitation of joint mobility
HP:0001385	Hip dysplasia
HP:0001538	Protuberant abdomen
HP:0001822	Hallux valgus
HP:0001833	Long foot
HP:0001845	Overlapping toe
HP:0002007	Frontal bossing
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002938	Lumbar hyperlordosis
HP:0003037	Enlarged joints
HP:0003097	Short femur
HP:0003177	Squared iliac bones
HP:0003180	Flat acetabular roof
HP:0003510	Severe short stature
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003951	Distal humeral metaphyseal irregularity

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_15	Prostate cancer	2.000000e-14
GCST005959_32	Waist-to-hip ratio adjusted for BMI x sex interaction	4.000000e-06
GCST006585_1865	Blood protein levels	7.000000e-11

EFO canonical traits (2, from GWAS)

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

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010009	Osteochondrodysplasias	C05.116.099.708; C16.320.728

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression	3
Valproic Acid	decreases methylation, increases expression	3
sodium arsenite	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diazinon	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
beta-Naphthoflavone	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06067425	PHASE2	TERMINATED	Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
NCT05846009	PHASE1	COMPLETED	A First-in-human Single and Repeated Dose Escalation Study of SAR442501 in Healthy Adults Subjects
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