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CHSY1

gene
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Also known as KIAA0990CSS1

Summary

CHSY1 (chondroitin sulfate synthase 1, HGNC:17198) is a protein-coding gene on chromosome 15q26.3, encoding Chondroitin sulfate synthase 1 (Q86X52). Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity.

This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome.

Source: NCBI Gene 22856 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): temtamy preaxial brachydactyly syndrome (Definitive, GenCC)
  • GWAS associations: 24
  • Clinical variants (ClinVar): 334 total — 7 pathogenic
  • Phenotypes (HPO): 64
  • Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
  • MANE Select transcript: NM_014918

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17198
Approved symbolCHSY1
Namechondroitin sulfate synthase 1
Location15q26.3
Locus typegene with protein product
StatusApproved
AliasesKIAA0990, CSS1
Ensembl geneENSG00000131873
Ensembl biotypeprotein_coding
OMIM608183
Entrez22856

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000254190, ENST00000543813, ENST00000559384, ENST00000560766, ENST00000561143, ENST00000561414, ENST00000968149

RefSeq mRNA: 1 — MANE Select: NM_014918 NM_014918

CCDS: CCDS10390

Canonical transcript exons

ENST00000254190 — 3 exons

ExonStartEnd
ENSE00000860485101235082101235577
ENSE00001176339101175727101178980
ENSE00001303865101251137101252048

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.4536 / max 590.7942, expressed in 1806 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
15181223.27591803
1518134.48591669
1518140.6061362
1518100.085737

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
tibiaUBERON:000097999.06gold quality
deciduaUBERON:000245098.79gold quality
visceral pleuraUBERON:000240198.32gold quality
endothelial cellCL:000011598.02gold quality
placentaUBERON:000198797.59gold quality
choroid plexus epitheliumUBERON:000391197.41gold quality
vena cavaUBERON:000408797.27gold quality
pleuraUBERON:000097796.97gold quality
hair follicleUBERON:000207396.85gold quality
cartilage tissueUBERON:000241896.77gold quality
gingival epitheliumUBERON:000194996.75gold quality
synovial jointUBERON:000221796.61gold quality
adrenal tissueUBERON:001830396.48gold quality
parietal pleuraUBERON:000240096.39gold quality
saphenous veinUBERON:000731896.19gold quality
cervix squamous epitheliumUBERON:000692296.11gold quality
cauda epididymisUBERON:000436096.08gold quality
gingivaUBERON:000182895.98gold quality
trabecular bone tissueUBERON:000248395.47gold quality
periodontal ligamentUBERON:000826695.44gold quality
pericardiumUBERON:000240795.42gold quality
urethraUBERON:000005795.39gold quality
epithelium of mammary glandUBERON:000324495.27gold quality
lower lobe of lungUBERON:000894995.05gold quality
mammary ductUBERON:000176594.99gold quality
skin of hipUBERON:000155494.92gold quality
layer of synovial tissueUBERON:000761694.92gold quality
squamous epitheliumUBERON:000691494.90gold quality
germinal epithelium of ovaryUBERON:000130494.80gold quality
palpebral conjunctivaUBERON:000181294.68gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes15.89
E-GEOD-83139yes6.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

170 targeting CHSY1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-29A-3P100.0073.111835
HSA-MIR-29B-3P100.0073.181833
HSA-MIR-29C-3P100.0073.151833
HSA-MIR-5692A100.0074.406850
HSA-MIR-200B-3P100.0073.312693
HSA-MIR-200C-3P100.0073.352685
HSA-MIR-429100.0073.442698
HSA-MIR-3646100.0073.565283
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-9-5P100.0072.282361
HSA-MIR-12118100.0065.881270
HSA-MIR-4789-3P99.9970.752484
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-428299.9975.366408
HSA-MIR-453199.9969.703181
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-539-3P99.9870.741616
HSA-MIR-485-3P99.9870.681585
HSA-MIR-1213699.9872.815713
HSA-MIR-6891-5P99.9866.531372
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-3173-3P99.9866.491217
HSA-MIR-548AN99.9770.912817
HSA-MIR-570-3P99.9672.414910
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

  • chondroitin polymerizing activity requires concomitant expression of a ChPF with ChSy; coexpression of the ChPF and ChSy yielded markedly augmented glycosyltransferase activities, whereas simple mixing of the two separately expressed proteins did not. (PMID:12716890)
  • conclude that CHSY1 is a secreted FRINGE enzyme required for adjustment of NOTCH signaling throughout human and fish embryogenesis and particularly during limb patterning (PMID:21129727)
  • unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation (PMID:21129728)
  • The present study focused on the expression of chondroitin-synthesizing enzymes in colorectal cancer. (PMID:21468578)
  • elongation of chondroitin sulfate chains may be tightly regulated by the cooperative expression of chondroitin synthase-1 and chondroitin N-acetylgalactosaminyltransferase-1 in peripheral neurons and peripheral neuropathies (PMID:23811343)
  • A novel missense mutation (c.1897 G > A) in the CHSY1 gene in two Temtamy preaxial brachydactyly syndrome patients from a consanguineous Pakistani family. (PMID:24269551)
  • CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance. (PMID:26997434)
  • CHSY1 overexpression in HCC contributes to the malignant behavior of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. (PMID:28652022)
  • CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration. (PMID:34412565)
  • LncRNA LINC01094 contributes to glioma progression by modulating miR-224-5p/CHSY1 axis. (PMID:34716872)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriochsy1ENSDARG00000079027
mus_musculusChsy1ENSMUSG00000032640
rattus_norvegicusChsy1ENSRNOG00000012698
drosophila_melanogasterChsyFBGN0030662
caenorhabditis_eleganssqv-5WBGENE00005023

Paralogs (7): CHPF2 (ENSG00000033100), CHPF (ENSG00000123989), B4GALNT3 (ENSG00000139044), CSGALNACT1 (ENSG00000147408), CSGALNACT2 (ENSG00000169826), B4GALNT4 (ENSG00000182272), CHSY3 (ENSG00000198108)

Protein

Protein identifiers

Chondroitin sulfate synthase 1 — Q86X52 (reviewed: Q86X52)

Alternative names: Chondroitin glucuronyltransferase 1, Chondroitin synthase 1, Glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase 1, N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase 1, N-acetylgalactosaminyltransferase 1

All UniProt accessions (2): A0A2R8Y7B7, Q86X52

UniProt curated annotations — full annotation on UniProt →

Function. Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Involved in the negative control of osteogenesis likely through the modulation of NOTCH signaling.

Subcellular location. Golgi apparatus. Golgi stack membrane. Secreted.

Tissue specificity. Ubiquitous, with the highest levels in placenta. Detected at low levels in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, adrenal gland, mammary gland, stomach, small intestine, lung and peripheral blood leukocytes.

Disease relevance. Temtamy preaxial brachydactyly syndrome (TPBS) [MIM:605282] A syndrome characterized by multiple congenital anomalies, intellectual disability, sensorineural deafness, talon cusps of upper central incisors, growth retardation, and bilateral symmetric digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Divalent metal cations. Highest activities are measured with Co(2+), Mn(2+) and Cd(2+).

Similarity. Belongs to the chondroitin N-acetylgalactosaminyltransferase family.

RefSeq proteins (1): NP_055733* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR008428Chond_GalNAcFamily
IPR029044Nucleotide-diphossugar_transHomologous_superfamily
IPR051227CS_glycosyltransferaseFamily

Pfam: PF05679

Enzyme classification (BRENDA):

  • EC 2.4.1.175 — glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase (BRENDA: 8 organisms, 92 substrates, 7 inhibitors, 8 Km, 1 kcat entries)
  • EC 2.4.1.226 — N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase (BRENDA: 6 organisms, 31 substrates, 4 inhibitors, 6 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
UDP-N-ACETYL-BETA-D-GALACTOSAMINE0.0059–0.053
UDP-GALNAC0.221–9.2752
UDP-GLUCURONIC ACID0.051–0.08242
CHONDROITIN SULFATE CS-110.361
UDP-N-ACETYL-ALPHA-D-GLUCOSAMINE0.00591
C11-OLIGOSACCHARIDE OF CHONDROITIN SULFATE A0.0271
CHONDROITIN SULFATE UNDECASACCHARIDE0.06531
UDP-ALPHA-D-GLUCURONATE0.2631

Catalyzed reactions (Rhea), 4 shown:

  • 3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP + H(+) (RHEA:20800)
  • 3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP + H(+) (RHEA:23428)
  • 3-O-{beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-{beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-[protein] + UDP + H(+) (RHEA:54996)
  • 3-O-{beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-{beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-[protein] + UDP + H(+) (RHEA:55000)

UniProt features (18 total): sequence variant 4, glycosylation site 3, topological domain 2, sequence conflict 2, compositionally biased region 2, binding site 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q86X52-F184.200.59

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 (2): 633; 747

Glycosylation sites (3): 623, 796, 189

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-2022870CS-GAG biosynthesis
R-HSA-3595177Defective CHSY1 causes TPBS

MSigDB gene sets: 468 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, AAGCCAT_MIR135A_MIR135B, AP2_Q3, GOBP_CHONDROCYTE_DEVELOPMENT, GOBP_SULFATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GTGCCTT_MIR506, GOBP_PROXIMAL_DISTAL_PATTERN_FORMATION

GO Biological Process (9): chondrocyte development (GO:0002063), proximal/distal pattern formation (GO:0009954), negative regulation of ossification (GO:0030279), response to nutrient levels (GO:0031667), positive regulation of smoothened signaling pathway (GO:0045880), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), sulfation (GO:0051923), bone morphogenesis (GO:0060349), cartilage development (GO:0051216)

GO Molecular Function (6): metal ion binding (GO:0046872), glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity (GO:0047238), N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity (GO:0050510), acetylgalactosaminyltransferase activity (GO:0008376), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): Golgi membrane (GO:0000139), extracellular region (GO:0005576), membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Chondroitin sulfate/dermatan sulfate metabolism1
Diseases associated with glycosaminoglycan metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure2
chondrocyte differentiation1
cell development1
regionalization1
ossification1
regulation of ossification1
negative regulation of multicellular organismal process1
response to stimulus1
smoothened signaling pathway1
regulation of smoothened signaling pathway1
positive regulation of signal transduction1
proteoglycan biosynthetic process1
chondroitin sulfate proteoglycan metabolic process1
protein O-linked glycosylation via xylose1
sulfur compound metabolic process1
animal organ morphogenesis1
skeletal system morphogenesis1
bone development1
skeletal system development1
animal organ development1
connective tissue development1
cation binding1
acetylgalactosaminyltransferase activity1
glucuronosyltransferase activity1
UDP-glycosyltransferase activity1
hexosyltransferase activity1
catalytic activity1
transferase activity1
Golgi apparatus1
bounding membrane of organelle1
organelle membrane1
Golgi cisterna1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CHSY1CHPFQ8IZ52899
CHSY1B4GALNT1Q00973835
CHSY1B4GALT2O60909790
CHSY1B4GALT7Q9UBV7662
CHSY1CHST11Q9NPF2661
CHSY1CHST3Q7LGC8635
CHSY1XYLT1Q86Y38633
CHSY1EXTL3O43909616
CHSY1CHST13Q8NET6604
CHSY1CHST12Q9NRB3604
CHSY1B3GAT3O94766601
CHSY1THBDP07204578
CHSY1XYLT2Q9H1B5565
CHSY1EXTL1Q92935561
CHSY1CHST14Q8NCH0560

IntAct

80 interactions, top by confidence:

ABTypeScore
NIPAL1ESYT2psi-mi:“MI:0914”(association)0.640
SLC1A1AGPAT2psi-mi:“MI:0914”(association)0.640
KCNA10GAPDHSpsi-mi:“MI:0914”(association)0.530
PEX19FAM20Bpsi-mi:“MI:0914”(association)0.530
DCNKLHL17psi-mi:“MI:0914”(association)0.530
SLC39A5TMEM223psi-mi:“MI:0914”(association)0.530
HLA-DPA1TYW5psi-mi:“MI:0914”(association)0.530
CSGALNACT2GOLIM4psi-mi:“MI:0914”(association)0.530
PLAURXRCC3psi-mi:“MI:0914”(association)0.530
MYCBPAPCHSY3psi-mi:“MI:0914”(association)0.530
SLC39A4TMEM120Bpsi-mi:“MI:0914”(association)0.530
CSGALNACT2TPST1psi-mi:“MI:0914”(association)0.530
CHSY3CHSY1psi-mi:“MI:0914”(association)0.530
CREB3MYO9Apsi-mi:“MI:0914”(association)0.530
ZMYM2HDAC3psi-mi:“MI:0914”(association)0.480
GOLT1Bpsi-mi:“MI:0914”(association)0.350
FOXN3FOXN3psi-mi:“MI:0914”(association)0.350
HLA-DPA1GXYLT2psi-mi:“MI:0914”(association)0.350
SCGB2A2GXYLT2psi-mi:“MI:0914”(association)0.350
SLC39A12POM121Cpsi-mi:“MI:0914”(association)0.350
PLAURDDX11L8psi-mi:“MI:0914”(association)0.350
ATP2B2GPR89Apsi-mi:“MI:0914”(association)0.350
CSGALNACT2CLASP2psi-mi:“MI:0914”(association)0.350
PTCH1PLXNB2psi-mi:“MI:0914”(association)0.350
CHSY3STK17Bpsi-mi:“MI:0914”(association)0.350
ATP2B2ESYT2psi-mi:“MI:0914”(association)0.350

BioGRID (81): CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O35757, O62650, O75882, O95980, P07225, P09858, P10669, P17247, P19883, P21214, P21674, P26012, P26013, P27090, P30371, P31514, P31515, P47931, P49767, P50291, P61811, P61812, P97299, P97953, Q07257, Q0VBD0, Q17QD6, Q38L25, Q5RA73, Q6NW40, Q6V9H4, Q6ZQ11, Q863H1, Q86X52, Q8BFR2, Q8CI19, Q8JG54, Q8N475

Diamond homologs: A0A2C9JXL4, Q08BL3, Q0VC84, Q18515, Q3SX46, Q5DTK1, Q5F3G7, Q66GS2, Q6GNL1, Q70JA7, Q7K237, Q7SYI5, Q86X52, Q9JJ05, Q9JJ06, Q9NS00, Q6ZQ11, Q7Z1Z1, Q8BJQ9, Q8C1F4, Q8N6G5, Q8TDX6, Q76KP1, A0A1S6M251, A8Y1P7, O43286, O60512, O60513, O60909, O88419, P08037, P15291, P15535, P34548, Q09323, Q3YL68, Q5EA87, Q5NVN3, Q66HH1, Q6P768

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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:

PathwayPartnersFoldFDR
Metal ion SLC transporters549.3×4e-06
R-HSA-425366617.8×6e-05
SLC-mediated transmembrane transport98.7×6e-05
Transport of small molecules114.5×1e-03

GO biological processes:

GO termPartnersFoldFDR
zinc ion transmembrane transport865.3×7e-11
intracellular monoatomic cation homeostasis565.3×1e-06
intracellular zinc ion homeostasis739.2×9e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic7
Likely pathogenic0
Uncertain significance189
Likely benign79
Benign39

Top pathogenic / likely-pathogenic (7)

Variant IDHGVSClassification
30710NM_014918.5(CHSY1):c.55_84del (p.Gly19_Leu28del)Pathogenic
30711NM_014918.5(CHSY1):c.14del (p.Gly5fs)Pathogenic
30712NM_014918.5(CHSY1):c.205C>T (p.Gln69Ter)Pathogenic
30713NM_014918.5(CHSY1):c.321-3C>GPathogenic
30714NM_014918.5(CHSY1):c.1616C>G (p.Pro539Arg)Pathogenic
30715NM_014918.5(CHSY1):c.96del (p.Glu33fs)Pathogenic
522064NM_014918.5(CHSY1):c.1423C>T (p.Gln475Ter)Pathogenic

SpliceAI

1177 predictions. Top by Δscore:

VariantEffectΔscore
15:101235076:TCTTA:Tdonor_loss0.9900
15:101235077:CTTA:Cdonor_loss0.9900
15:101235078:TTA:Tdonor_loss0.9900
15:101235079:TA:Tdonor_loss0.9900
15:101235080:A:ATdonor_loss0.9900
15:101235143:T:TAdonor_gain0.9900
15:101251131:GCTCA:Gdonor_loss0.9900
15:101251132:CTCAC:Cdonor_loss0.9900
15:101251133:TCA:Tdonor_loss0.9900
15:101251134:CA:Cdonor_loss0.9900
15:101178981:C:CCacceptor_gain0.9800
15:101178988:A:Tacceptor_gain0.9800
15:101235129:TTCCC:Tdonor_gain0.9800
15:101235574:TGTT:Tacceptor_gain0.9800
15:101235584:T:TCacceptor_gain0.9800
15:101248323:A:Cdonor_gain0.9800
15:101178980:TCTG:Tacceptor_loss0.9700
15:101178981:C:CGacceptor_loss0.9700
15:101219315:A:ACdonor_gain0.9700
15:101235130:TCCC:Tdonor_gain0.9700
15:101235576:TT:Tacceptor_gain0.9700
15:101235578:C:CCacceptor_gain0.9700
15:101251834:T:TAdonor_gain0.9700
15:101235081:CCT:Cdonor_gain0.9600
15:101235178:G:Adonor_gain0.9600
15:101235574:TGTTC:Tacceptor_loss0.9600
15:101235576:TTC:Tacceptor_loss0.9600
15:101235577:TC:Tacceptor_loss0.9600
15:101235578:CT:Cacceptor_loss0.9600
15:101235579:T:Aacceptor_loss0.9600

AlphaMissense

5314 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
15:101177649:C:AW716C1.000
15:101177649:C:GW716C1.000
15:101177651:A:GW716R1.000
15:101177651:A:TW716R1.000
15:101178887:G:CH304D1.000
15:101235099:A:GC267R1.000
15:101235144:C:GD252H1.000
15:101235241:G:CC219W1.000
15:101235242:C:TC219Y1.000
15:101235243:A:GC219R1.000
15:101235383:T:AD172V1.000
15:101235384:C:GD172H1.000
15:101235402:A:GW166R1.000
15:101235402:A:TW166R1.000
15:101235573:A:GW109R1.000
15:101235573:A:TW109R1.000
15:101177508:G:CC763W0.999
15:101177509:C:GC763S0.999
15:101177510:A:GC763R0.999
15:101177510:A:TC763S0.999
15:101177545:C:TC751Y0.999
15:101177637:A:CD720E0.999
15:101177637:A:TD720E0.999
15:101177638:T:AD720V0.999
15:101177638:T:GD720A0.999
15:101177639:C:GD720H0.999
15:101177641:T:AE719V0.999
15:101177706:A:CC697W0.999
15:101177707:C:TC697Y0.999
15:101177708:A:GC697R0.999

dbSNP variants (sampled 300 via entrez): RS1000028313 (15:101194339 T>C), RS1000028794 (15:101202913 G>T), RS1000084973 (15:101236657 T>C), RS1000093126 (15:101189584 A>C), RS1000224450 (15:101245485 A>G), RS1000224850 (15:101250717 C>T), RS1000299447 (15:101245198 C>G,T), RS1000303703 (15:101209956 T>G), RS1000303797 (15:101217006 G>A), RS1000389220 (15:101192126 C>T), RS1000446194 (15:101202694 T>C), RS1000447901 (15:101237366 T>G), RS1000448834 (15:101221918 G>A,C), RS1000455480 (15:101186802 ACAAAAACAAAAAC>A), RS1000460004 (15:101188744 A>C,G)

Disease associations

OMIM: gene MIM:608183 | disease phenotypes: MIM:605282

GenCC curated gene-disease

DiseaseClassificationInheritance
temtamy preaxial brachydactyly syndromeDefinitiveAutosomal recessive

Mondo (3): temtamy preaxial brachydactyly syndrome (MONDO:0011533), primary ovarian failure (MONDO:0005387), hearing loss disorder (MONDO:0005365)

Orphanet (2): Temtamy preaxial brachydactyly syndrome (Orphanet:363417), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000160Narrow mouth
HP:0000164Abnormality of the dentition
HP:0000175Cleft palate
HP:0000311Round face
HP:0000316Hypertelorism
HP:0000327Hypoplasia of the maxilla
HP:0000347Micrognathia
HP:0000369Low-set ears
HP:0000517Abnormal lens morphology
HP:0000592Blue sclerae
HP:0000648Optic atrophy
HP:0000664Synophrys
HP:0000668Hypodontia
HP:0000677Oligodontia
HP:0000691Microdontia
HP:0000692Tooth malposition
HP:0000699Diastema
HP:0001090Abnormally large globe
HP:0001156Brachydactyly
HP:0001159Syndactyly
HP:0001234Hitchhiker thumb
HP:0001249Intellectual disability
HP:0001263Global developmental delay
HP:0001328Specific learning disability
HP:0001357Plagiocephaly
HP:0001510Growth delay
HP:0001566Widely-spaced maxillary central incisors
HP:0001773Short foot
HP:0001999Abnormal facial shape

GWAS associations

24 associations (top):

StudyTraitp-value
GCST001806_24Corneal structure2.000000e-09
GCST002183_3Relative hand skill in reading disability9.000000e-09
GCST004608_203Granulocyte percentage of myeloid white cells6.000000e-17
GCST004609_220Monocyte percentage of white cells9.000000e-13
GCST004613_45Sum neutrophil eosinophil counts4.000000e-12
GCST004614_23Granulocyte count3.000000e-12
GCST004620_93Sum basophil neutrophil counts3.000000e-13
GCST004626_134Myeloid white cell count1.000000e-10
GCST004629_144Neutrophil count5.000000e-13
GCST004633_36Neutrophil percentage of white cells1.000000e-13
GCST006366_10Central corneal thickness3.000000e-08
GCST007844_10Ankylosing spondylitis7.000000e-06
GCST009414_13Central corneal thickness2.000000e-07
GCST010396_60Gut microbiota (bacterial taxa, hurdle binary method)8.000000e-06
GCST012227_275Hip circumference adjusted for BMI9.000000e-09
GCST012227_276Hip circumference adjusted for BMI4.000000e-14
GCST90000025_243Appendicular lean mass1.000000e-12
GCST90002379_73Basophil count1.000000e-16
GCST90002389_305Lymphocyte percentage of white cells8.000000e-17
GCST90002394_528Monocyte percentage of white cells1.000000e-32
GCST90002398_289Neutrophil count2.000000e-36
GCST90002399_371Neutrophil percentage of white cells3.000000e-26
GCST90002407_599White blood cell count4.000000e-25
GCST90020028_1479Hip circumference adjusted for BMI1.000000e-10

EFO canonical traits (14, from GWAS)

EFO IDTrait name
EFO:0004345corneal topography
EFO:0009902handedness
EFO:0007997granulocyte percentage of myeloid white cells
EFO:0007989monocyte percentage of leukocytes
EFO:0004833neutrophil count
EFO:0004842eosinophil count
EFO:0007987granulocyte count
EFO:0005090basophil count
EFO:0007990neutrophil percentage of leukocytes
EFO:0005213central corneal thickness
EFO:0007874gut microbiome measurement
EFO:0008039BMI-adjusted hip circumference
EFO:0004980appendicular lean mass
EFO:0007993lymphocyte percentage of leukocytes

MeSH disease descriptors (3)

DescriptorNameTree numbers
D034381Hearing LossC09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D016649Primary Ovarian InsufficiencyC12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C536958Temtamy preaxial brachydactyly syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases expression, affects expression, affects cotreatment7
trichostatin Aaffects cotreatment, increases expression3
Cyclosporinedecreases expression, increases expression3
bisphenol Aincreases expression, decreases methylation2
Panobinostataffects cotreatment, increases expression2
Estradiolincreases expression2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases expression2
Cadmium Chloridedecreases expression, increases expression2
aristolochic acid Idecreases expression1
FR900359decreases reaction, increases expression1
triphenyl phosphateaffects expression1
pirinixic acidaffects binding, increases activity, increases expression1
cobaltous chlorideincreases expression1
di-n-butylphosphoric acidaffects expression1
chloropicrinincreases expression1
K 7174increases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, increases expression1
PCI 5002affects cotreatment, increases expression1
Sunitinibincreases expression1
Acetaminophenincreases expression1
Air Pollutantsdecreases expression, increases abundance1
Cisplatindecreases expression1
Dexamethasonedecreases expression1
Doxorubicindecreases expression1
Formaldehydedecreases expression1
Hydrogen Peroxideaffects expression1
Oxygenincreases expression1
Polychlorinated Biphenylsincreases expression1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00417066PHASE4COMPLETEDFlexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693PHASE4COMPLETEDEvaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616PHASE4COMPLETEDEstrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501PHASE4UNKNOWNEffects of ADSC Therapy in Women With POF
NCT02783937PHASE4COMPLETEDFilgrastim for Premature Ovarian Insufficiency
NCT03535480PHASE4UNKNOWNAutologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00205881PHASE4COMPLETEDBilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539PHASE4UNKNOWNRelationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307PHASE4UNKNOWNBilateral Cochlear Implant Benefit in Young Children
NCT00765635PHASE4COMPLETEDChlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006PHASE4COMPLETEDTreating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT00140998PHASE3COMPLETEDEstrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT01499901PHASE3WITHDRAWNComparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091PHASE3COMPLETEDAM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627PHASE3COMPLETEDSafety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657PHASE3ACTIVE_NOT_RECRUITINGACHIEVE Brain Health Follow-Up Study
NCT00001951PHASE2COMPLETEDHormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019PHASE2WITHDRAWNEffects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494PHASE2COMPLETEDGnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852PHASE2SUSPENDEDThe Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467PHASE2UNKNOWNPrevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982PHASE2COMPLETEDThe Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00013455PHASE2COMPLETEDQuantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427PHASE2COMPLETEDClinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786PHASE2COMPLETEDAntioxidation Medication for Noise-induced Hearing Loss
NCT00802425PHASE2COMPLETEDEfficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281PHASE2COMPLETEDThe Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853PHASE2UNKNOWNSPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925PHASE2COMPLETEDHearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278PHASE2RECRUITINGCholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128PHASE2COMPLETEDEvaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183PHASE2RECRUITINGAtorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773PHASE2COMPLETEDEvaluation of the Presence of SENS-401 in the Perilymph
NCT06340633PHASE2RECRUITINGSPI-1005 in Adults Receiving Cochlear Implant
NCT02912104PHASE1COMPLETEDA Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695PHASE1COMPLETEDInovium Ovarian Rejuvenation Trials
NCT04815213PHASE1ACTIVE_NOT_RECRUITINGThe Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367PHASE1COMPLETEDEffects of UCA-PSCs in Women With POF
NCT06132542PHASE1UNKNOWNAutologous ADMSC Transplantation in Patients With POI
NCT00582946PHASE1COMPLETEDWide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot