CANT1

Summary

CANT1 (calcium activated nucleotidase 1, HGNC:19721) is a protein-coding gene on chromosome 17q25.3, encoding Soluble calcium-activated nucleotidase 1 (Q8WVQ1). Calcium-dependent nucleotidase with a preference for UDP.

This protein encoded by this gene belongs to the apyrase family. It functions as a calcium-dependent nucleotidase with a preference for UDP. Mutations in this gene are associated with Desbuquois dysplasia with hand anomalies. Alternatively spliced transcript variants have been noted for this gene.

Source: NCBI Gene 124583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Desbuquois dysplasia 1 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 465 total — 30 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 86
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001159773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19721
Approved symbol	CANT1
Name	calcium activated nucleotidase 1
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	SHAPY, SCAN-1
Ensembl gene	ENSG00000171302
Ensembl biotype	protein_coding
OMIM	613165
Entrez	124583

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 56 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000302345, ENST00000392446, ENST00000586916, ENST00000587242, ENST00000588075, ENST00000588096, ENST00000588611, ENST00000590370, ENST00000591625, ENST00000591732, ENST00000591773, ENST00000591811, ENST00000592033, ENST00000592228, ENST00000592887, ENST00000620915, ENST00000907684, ENST00000907685, ENST00000907686, ENST00000907687, ENST00000907688, ENST00000907689, ENST00000907690, ENST00000907691, ENST00000907692, ENST00000907693, ENST00000907694, ENST00000907695, ENST00000907696, ENST00000907697, ENST00000907698, ENST00000907699, ENST00000907700, ENST00000907701, ENST00000907702, ENST00000907703, ENST00000907704, ENST00000907705, ENST00000907706, ENST00000907707, ENST00000907708, ENST00000907709, ENST00000907710, ENST00000907711, ENST00000907712, ENST00000907713, ENST00000907714, ENST00000907715, ENST00000907716, ENST00000907717, ENST00000907718, ENST00000907719, ENST00000907720, ENST00000907721, ENST00000907722, ENST00000907723, ENST00000907724, ENST00000937513, ENST00000964257, ENST00000964258, ENST00000964259

RefSeq mRNA: 3 — MANE Select: NM_001159773 NM_001159772, NM_001159773, NM_138793

CCDS: CCDS11760

Canonical transcript exons

ENST00000392446 — 5 exons

Exon	Start	End
ENSE00001164238	78995018	78995221
ENSE00001377424	78996992	78997644
ENSE00001511976	78997840	78997963
ENSE00002845437	79009664	79009764
ENSE00003845958	78991716	78993920

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5399 / max 234.5635, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168534	22.6670	1812
168535	3.2937	1613
168532	0.9445	601
168533	0.6347	355

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.68	gold quality
mucosa of transverse colon	UBERON:0004991	97.09	gold quality
colonic mucosa	UBERON:0000317	96.79	gold quality
rectum	UBERON:0001052	96.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.29	gold quality
ileal mucosa	UBERON:0000331	96.24	gold quality
lower esophagus mucosa	UBERON:0035834	95.54	gold quality
stromal cell of endometrium	CL:0002255	93.30	gold quality
tongue squamous epithelium	UBERON:0006919	93.16	gold quality
esophagus squamous epithelium	UBERON:0006920	92.94	gold quality
transverse colon	UBERON:0001157	92.92	gold quality
epithelium of esophagus	UBERON:0001976	92.66	gold quality
blood	UBERON:0000178	92.62	gold quality
tibia	UBERON:0000979	92.59	gold quality
placenta	UBERON:0001987	92.36	gold quality
germinal epithelium of ovary	UBERON:0001304	92.29	gold quality
gingival epithelium	UBERON:0001949	92.07	gold quality
squamous epithelium	UBERON:0006914	91.98	gold quality
prostate gland	UBERON:0002367	91.91	gold quality
gall bladder	UBERON:0002110	91.68	gold quality
gingiva	UBERON:0001828	91.58	gold quality
saliva-secreting gland	UBERON:0001044	91.53	gold quality
palpebral conjunctiva	UBERON:0001812	91.46	gold quality
esophagus mucosa	UBERON:0002469	91.46	gold quality
decidua	UBERON:0002450	91.44	gold quality
seminal vesicle	UBERON:0000998	91.38	gold quality
nasal cavity epithelium	UBERON:0005384	91.31	gold quality
duodenum	UBERON:0002114	91.19	gold quality
minor salivary gland	UBERON:0001830	91.18	gold quality
parotid gland	UBERON:0001831	90.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting CANT1, 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-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-657	99.48	66.02	848
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-1227-5P	98.65	65.32	1549

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 20)

• Cloning, expression, and characterization of this calcium-acdtivated enzyme, a human enzyme belonging to a new family of extracellular nucleotidases. (PMID:12234496)
• This soluble apyrase is a calcium-binding protein, as evident from saturable Ca2+-dependent changes in intrinsic tryptophan fluorescence, UV difference absorption spectra, and Ca2+-triggered transition from enzymatically inactive form to active enzyme. (PMID:12600208)
• The importance of the dimeric state for enzymatic activity and biological function in this nucleotidase by mutating isoleucine 170, is investigated. (PMID:18067325)
• human soluble calcium-activated nucleotidase inhibits coagulation in vitro and thrombosis in vivo (PMID:18222531)
• The two novel ETV4 fusion partners possess as predominant common characteristics androgen-induction and prostate-specific expression. (PMID:18451133)
• Mutations in CANT1 in Desbuquois dysplasia are identified. (PMID:19853239)
• The clinical-radiographic spectrum produced by CANT1 mutations must be extended to include Desbuquois dysplasia type 2 and Kim variant. (PMID:21037275)
• estimated the age of the founder mutation as approximately 1420 years (PMID:21412251)
• CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker (PMID:21435463)
• Novel mutations in the CANT1 gene are reported in three cases of Desbuquois dysplasia type I and fetal hydrops. (PMID:21654728)
• Data studied proteoglycan synthesis in CANT1 mutated patient fibroblasts, and found significant reduced GAG synthesis in presence of beta-D-xyloside, suggesting that CANT1 plays a role in proteoglycan metabolism. (PMID:22539336)
• a novel mutation of CANT1, c.467C>T (p.Ser156Phe) in 3 Indian patients with Desbuquois dysplasia, Kim type from 2 families (PMID:25486376)
• CANT1 long non-coding RNA triggers efficient therapeutic efficacy by correcting aberrant long non-coding cascade in malignant uveal melanoma. (PMID:28330694)
• The Multiple Epiphyseal Dysplasia (MED)phenotype is thus allelic to the more severe Desbuquois dysplasia phenotype and the results identify CANT1 as a second locus for recessively inherited MED (PMID:28742282)
• Knockdown of CANT1 expression can inhibit cell proliferation, migration, and invasion in human clear cell renal cell carcinoma cells, cause cell-cycle arrest in S phase and promote cell apoptosis. (PMID:31102300)
• Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis. (PMID:31988067)
• Cloning, expression and enzyme activity delineation of two novel CANT1 mutations: the disappearance of dimerization may indicate the change of protein conformation and even function. (PMID:32907608)
• Calcium-activated nucleotides 1 (CANT1)-driven nuclear factor-k-gene binding (NF-kB) signaling pathway facilitates the lung cancer progression. (PMID:35068336)
• Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma. (PMID:37858061)
• Pan-cancer analysis predicts CANT1 as a potential prognostic, immunologic biomarker. (PMID:38369265)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cant1a	ENSDARG00000012192
danio_rerio	cant1b	ENSDARG00000102977
mus_musculus	Cant1	ENSMUSG00000025575
rattus_norvegicus	Cant1	ENSRNOG00000003239
drosophila_melanogaster	CG5276	FBGN0037900
caenorhabditis_elegans		WBGENE00017244
caenorhabditis_elegans		WBGENE00044355

Protein

Protein identifiers

Soluble calcium-activated nucleotidase 1 — Q8WVQ1 (reviewed: Q8WVQ1)

Alternative names: Apyrase homolog, Putative MAPK-activating protein PM09, Putative NF-kappa-B-activating protein 107

All UniProt accessions (8): Q8WVQ1, K7EIP9, K7EKT2, K7EKW6, K7EMT2, K7EN15, K7EQD4, K7EQT4

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.

Subunit / interactions. Monomer. Homodimer; dimerization is Ca(2+)-dependent. Homodimer; disulfide-linked (membrane form).

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

Tissue specificity. Widely expressed.

Post-translational modifications. N-glycosylated.

Disease relevance. Desbuquois dysplasia 1 (DBQD1) [MIM:251450] A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a ‘Swedish key’ appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. The disease is caused by variants affecting the gene represented in this entry. Epiphyseal dysplasia, multiple, 7 (EDM7) [MIM:617719] A form of multiple epiphyseal dysplasia, a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. EDM7 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Not inhibited by azide.

Similarity. Belongs to the apyrase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WVQ1-1	1	yes
Q8WVQ1-2	2
Q8WVQ1-3	3

RefSeq proteins (3): NP_001153244, NP_001153245, NP_620148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009283	Apyrase	Family
IPR036258	Apyrase_sf	Homologous_superfamily

Pfam: PF06079

Enzyme classification (BRENDA):

• EC 3.6.1.5 — apyrase (BRENDA: 66 organisms, 384 substrates, 230 inhibitors, 158 Km, 64 kcat entries)

Substrate kinetics (BRENDA)

29 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0025–8.7	44
ADP	0.0025–5.3	42
UDP	0.0113–0.555	7
GDP	0.0114–0.357	6
UTP	0.01–0.207	5
N-[5-[4-CARBOXY-3-(3-OXO-9,9A-DIHYDRO-3H-XANTHEN	0.0133–0.105	4
DATP	0.018–0.89	3
DCTP	0.029–0.276	3
DGTP	0.028–0.16	3
IDP	0.0105–0.622	3
1,N6-ETHENO-ADP	0.073–0.114	2
1,N6-ETHENO-ATP	0.024–0.031	2
2’(3’)-O-(2,4,6-TRINITROPHENYL)ADENOSINE 5’-DIPH	0.009–0.019	2
2’(3’)-O-(2,4,6-TRINITROPHENYL)ADENOSINE 5’-TRIP	0.008–0.018	2
3’(2’)-O-(METHYLANTHRANOYL)ADENOSINE 5’-DIPHOSPH	0.014–0.017	2

Catalyzed reactions (Rhea), 1 shown:

• a ribonucleoside 5’-diphosphate + H2O = a ribonucleoside 5’-phosphate + phosphate + H(+) (RHEA:36799)

UniProt features (89 total): strand 27, mutagenesis site 22, sequence variant 14, binding site 6, site 4, helix 4, splice variant 3, turn 3, topological domain 2, chain 1, glycosylation site 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1S1D	X-RAY DIFFRACTION	1.6
1S18	X-RAY DIFFRACTION	1.7
2H2N	X-RAY DIFFRACTION	2.3
2H2U	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVQ1-F1	89.47	0.79

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 (4): 160 (important for dimer formation); 200 (important for dimer formation); 202 (important for dimer formation); 256 (important for dimer formation)

Ligand- & substrate-binding residues (6): 168; 169; 215; 284; 345; 396

Disulfide bonds (1): 60

Glycosylation sites (1): 88

Mutagenesis-validated functional residues (22):

Position	Phenotype
60	loss of dimer formation.
112	reduces activity by 99%.
114	reduces activity by 99%.
139	reduces gdpase and adpase activities 1.7-fold. severe loss of dimer formation; when associated with s-287.
152	slightly reduced activity.
160	increases gdpase activity 2-fold and adpase activity 5-fold. forms dimer even at suboptimal ca(2+) concentrations.
163	reduces activity by 98%.
166	reduces activity by 95%.
168	reduces activity by over 99.9%.
169	reduces activity by 96%.
181	loss of activity.
182	reduces activity by over 99.9%.
200	reduces gdpase activity 2-fold and adpase activity 2.5-fold. no effect on dimer formation; when associated with s-287.
202	reduces gdpase activity 1.7-fold and adpase activity 1.5-fold. no effect on dimer formation; when associated with s-287.
205	slightly reduced activity.
215	reduces activity by 99%.
246	increases activity 5-fold.
256	no effect on gdpase and adpase activities. no effect on dimer formation; when associated with s-287.
287	reduces gdpase and adpase activities 1.3-fold.
301	reduces activity by 99%.
308	reduces gdpase activity 1.3-fold and adpase activity 2-fold. severe loss of dimer formation; when associated with s-287.
317	reduces gdpase activity 1.7-fold and adpase activity 1.5-fold. severe loss of dimer formation; when associated with s-28

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 367 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, RODRIGUES_NTN1_TARGETS_DN, WEI_MYCN_TARGETS_WITH_E_BOX, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, KEGG_PURINE_METABOLISM, SENESE_HDAC1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, ACEVEDO_LIVER_CANCER_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON

GO Biological Process (2): proteoglycan biosynthetic process (GO:0030166), positive regulation of canonical NF-kappaB signal transduction (GO:0043123)

GO Molecular Function (9): GDP phosphatase activity (GO:0004382), calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), ADP phosphatase activity (GO:0043262), UDP phosphatase activity (GO:0045134), protein binding (GO:0005515), hydrolase activity (GO:0016787), nucleoside diphosphate phosphatase activity (GO:0017110), metal ion binding (GO:0046872)

GO Cellular Component (11): extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside diphosphate phosphatase activity	3
cellular anatomical structure	2
organelle membrane	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intracellular organelle lumen	2
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
metal ion binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
pyrophosphatase activity	1
cation binding	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
Golgi cisterna	1
secretory granule lumen	1
specific granule	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CANT1	SLC26A2	P50443	806
CANT1	XYLT1	Q86Y38	686
CANT1	ETV4	P43268	626
CANT1	BPNT2	Q9NX62	591
CANT1	SLC45A3	Q96JT2	585
CANT1	KLK2	P20151	505
CANT1	FAM20B	O75063	470
CANT1	ATIC	P31939	445
CANT1	AK8	Q96MA6	433
CANT1	ADK	P55263	428
CANT1	CHST14	Q8NCH0	424
CANT1	SLC10A7	Q0GE19	420
CANT1	ETV1	P50549	418
CANT1	ENTPD3	O75355	414
CANT1	B4GALT7	Q9UBV7	410

IntAct

73 interactions, top by confidence:

A	B	Type	Score
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
CLRN1	CANT1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	CANT1	psi-mi:“MI:0915”(physical association)	0.560
BZW2	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
RUSF1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
GINM1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
CANT1	ITGA6	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
GINM1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
KIR2DL4	GPR89A	psi-mi:“MI:0914”(association)	0.350
MSH5	GET1	psi-mi:“MI:0914”(association)	0.350
SAAL1	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): CANT1 (Affinity Capture-RNA), CANT1 (Affinity Capture-RNA), CANT1 (Affinity Capture-MS), PLXNA1 (Affinity Capture-MS), ENTPD6 (Affinity Capture-MS), LRIG1 (Affinity Capture-MS), ATF6B (Affinity Capture-MS), CELSR1 (Affinity Capture-MS), ITGA6 (Affinity Capture-MS), CANT1 (Proximity Label-MS), CANT1 (Affinity Capture-MS), CANT1 (Affinity Capture-MS), CANT1 (Affinity Capture-MS), CANT1 (Affinity Capture-MS), CANT1 (Affinity Capture-MS)

ESM2 similar proteins: A1KQY3, A4XES9, A5HV13, A8Y9I2, C3VA26, C3VEQ4, O24592, O43837, O49505, O49675, O77784, P17571, P41565, P51553, P70404, P74334, P9WPR4, P9WPR5, Q28479, Q4W9H1, Q58CP0, Q5MBR3, Q5MBR5, Q5MBR6, Q5RBT4, Q5RF16, Q68FX0, Q69NX5, Q6PBW5, Q6QT07, Q6YVJ0, Q80YA7, Q84K96, Q8AXN9, Q8HXG8, Q8K4Y7, Q8LIY8, Q8VCF1, Q8VY26, Q8WVQ1

Diamond homologs: O96559, Q06K77, Q19202, Q8K4Y7, Q8VCF1, Q8WVQ1, Q9GTP7

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ESCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	11
Uncertain significance	160
Likely benign	188
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1456837	NM_001159773.2(CANT1):c.675C>G (p.Tyr225Ter)	Pathogenic
195399	NM_001159773.2(CANT1):c.278del (p.Leu93fs)	Pathogenic
1971912	NM_001159773.2(CANT1):c.789_790del (p.Ser264fs)	Pathogenic
2736669	NM_001159773.2(CANT1):c.861C>A (p.Cys287Ter)	Pathogenic
2747171	NM_001159773.2(CANT1):c.486del (p.Arg163fs)	Pathogenic
277	5’UTR-exon 1 deletion (2703 bp)	Pathogenic
2779417	NM_001159773.2(CANT1):c.100delinsTT (p.Ala34fs)	Pathogenic
278	NM_001159773.2(CANT1):c.734del (p.Pro245fs)	Pathogenic
2780153	NM_001159773.2(CANT1):c.347_348del (p.Glu116fs)	Pathogenic
2809026	NM_001159773.2(CANT1):c.124del (p.Arg42fs)	Pathogenic
281	NM_001159773.2(CANT1):c.909_910insGCCGC (p.Gln304fs)	Pathogenic
2820692	NM_001159773.2(CANT1):c.648G>A (p.Trp216Ter)	Pathogenic
2821536	NM_001159773.2(CANT1):c.33G>A (p.Trp11Ter)	Pathogenic
2841703	NM_001159773.2(CANT1):c.798C>A (p.Tyr266Ter)	Pathogenic
2854905	NM_001159773.2(CANT1):c.549del (p.Thr184fs)	Pathogenic
2858771	NM_001159773.2(CANT1):c.103del (p.Ala35fs)	Pathogenic
2887549	NM_001159773.2(CANT1):c.316C>T (p.Arg106Ter)	Pathogenic
2993562	NM_001159773.2(CANT1):c.595del (p.Trp198_Val199insTer)	Pathogenic
3013338	NM_001159773.2(CANT1):c.112dup (p.Arg38fs)	Pathogenic
31015	NM_001159773.2(CANT1):c.277_278del (p.Leu93fs)	Pathogenic
31017	NM_001159773.2(CANT1):c.375G>C (p.Trp125Cys)	Pathogenic
31018	NM_001159773.2(CANT1):c.676G>A (p.Val226Met)	Pathogenic
31019	NM_001159773.2(CANT1):c.1079C>A (p.Ala360Asp)	Pathogenic
3366599	NM_001159773.2(CANT1):c.467C>T (p.Ser156Phe)	Pathogenic
3677302	NM_001159773.2(CANT1):c.441G>A (p.Trp147Ter)	Pathogenic
41426	NM_001159773.2(CANT1):c.-147+1G>A	Pathogenic
4692887	NM_001159773.2(CANT1):c.360_370del (p.Gln120fs)	Pathogenic
4696602	NM_001159773.2(CANT1):c.885G>A (p.Trp295Ter)	Pathogenic
4811816	NM_001159773.2(CANT1):c.350C>G (p.Ser117Ter)	Pathogenic
631792	NM_001159773.2(CANT1):c.643G>T (p.Glu215Ter)	Pathogenic

SpliceAI

803 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78993921:C:CC	acceptor_gain	1.0000
17:78995012:TCTTA:T	donor_loss	1.0000
17:78995013:CTTAC:C	donor_loss	1.0000
17:78995014:TTA:T	donor_loss	1.0000
17:78995015:TACCT:T	donor_loss	1.0000
17:78995016:A:AC	donor_gain	1.0000
17:78995016:A:C	donor_loss	1.0000
17:78995017:C:A	donor_loss	1.0000
17:78995017:C:CC	donor_gain	1.0000
17:78995017:CCTGG:C	donor_gain	1.0000
17:78996990:ACCT:A	donor_loss	1.0000
17:78996991:C:G	donor_loss	1.0000
17:78996991:CCTTT:C	donor_gain	1.0000
17:78993919:GC:G	acceptor_gain	0.9900
17:78993919:GCCTG:G	acceptor_loss	0.9900
17:78993920:CC:C	acceptor_gain	0.9900
17:78993922:T:A	acceptor_loss	0.9900
17:78995219:AGC:A	acceptor_gain	0.9900
17:78995222:C:CC	acceptor_gain	0.9900
17:78995222:C:CG	acceptor_loss	0.9900
17:78995223:T:C	acceptor_loss	0.9900
17:78996990:A:AC	donor_gain	0.9900
17:78996991:C:CC	donor_gain	0.9900
17:78993916:GTAGC:G	acceptor_gain	0.9800
17:78993917:TAGC:T	acceptor_gain	0.9800
17:78995217:GAAGC:G	acceptor_gain	0.9800
17:78995218:AAGC:A	acceptor_gain	0.9800
17:78996990:AC:A	donor_gain	0.9800
17:78996991:CC:C	donor_gain	0.9800
17:78998175:T:C	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000288626 (17:79007048 A>G), RS1000301800 (17:79001455 C>A), RS1000386032 (17:79001414 T>A), RS1000624367 (17:79000747 C>T), RS1000959549 (17:78996280 A>G), RS1001026016 (17:78997856 G>A), RS1001057027 (17:78997683 C>A,T), RS1001093756 (17:78993367 C>A,G,T), RS1001634571 (17:78997638 G>A), RS1001835148 (17:79002196 G>A), RS1002333779 (17:79006653 G>A), RS1002493448 (17:78998163 T>C), RS1002674598 (17:79002535 C>T), RS1002746124 (17:79009175 G>A,C), RS1002771742 (17:78993855 G>A,C,T)

Disease associations

OMIM: gene MIM:613165 | disease phenotypes: MIM:251450, MIM:617719, MIM:132400

GenCC curated gene-disease

Disease	Classification	Inheritance
Desbuquois dysplasia 1	Definitive	Autosomal recessive
Desbuquois dysplasia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Desbuquois dysplasia 1	Definitive	AR

Mondo (4): Desbuquois dysplasia 1 (MONDO:0009629), epiphyseal dysplasia, multiple, 7 (MONDO:0054680), multiple epiphyseal dysplasia (MONDO:0016648), Desbuquois dysplasia (MONDO:0015426)

Orphanet (3): Desbuquois syndrome (Orphanet:1425), Multiple epiphyseal dysplasia type 7 (Orphanet:647676), Multiple epiphyseal dysplasia (Orphanet:251)

HPO phenotypes

86 total (30 of 86 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000272	Malar flattening
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000592	Blue sclerae
HP:0000774	Narrow chest
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000944	Abnormal metaphysis morphology
HP:0001087	Developmental glaucoma
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001373	Joint dislocation
HP:0001382	Joint hypermobility
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
deguelin	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
PCI 5002	affects cotreatment, 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
Zoledronic Acid	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	affects response to substance	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Coumestrol	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	increases expression, increases abundance, affects cotreatment	1
Silicon Dioxide	decreases methylation	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Urethane	increases expression	1
Zinc	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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