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HKDC1

gene
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Also known as FLJ37767FLJ22761

Summary

HKDC1 (hexokinase domain containing 1, HGNC:23302) is a protein-coding gene on chromosome 10q22.1, encoding Hexokinase HKDC1 (Q2TB90). Catalyzes the phosphorylation of hexose to hexose 6-phosphate, although at very low level compared to other hexokinases.

This gene encodes a member of the hexokinase protein family. The encoded protein is involved in glucose metabolism, and reduced expression may be associated with gestational diabetes mellitus. High expression of this gene may also be associated with poor prognosis in hepatocarcinoma.

Source: NCBI Gene 80201 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): retinitis pigmentosa 92 (Limited, GenCC) — +1 more curated relationship
  • GWAS associations: 14
  • Clinical variants (ClinVar): 207 total — 6 likely-pathogenic
  • Phenotypes (HPO): 8
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_025130

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:23302
Approved symbolHKDC1
Namehexokinase domain containing 1
Location10q22.1
Locus typegene with protein product
StatusApproved
AliasesFLJ37767, FLJ22761
Ensembl geneENSG00000156510
Ensembl biotypeprotein_coding
OMIM617221
Entrez80201

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000354624, ENST00000470920, ENST00000488706, ENST00000953956, ENST00000953957

RefSeq mRNA: 1 — MANE Select: NM_025130 NM_025130

CCDS: CCDS7288

Canonical transcript exons

ENST00000354624 — 18 exons

ExonStartEnd
ENSE000010269296926661069267552
ENSE000010963086926113969261294
ENSE000010963096926558569265818
ENSE000013464336925877669258959
ENSE000016992666922033269220498
ENSE000017294826922720769227369
ENSE000017298436923301469233133
ENSE000017732716923904269239137
ENSE000017752766923276469232912
ENSE000032321416924842469248728
ENSE000032499026924065269240751
ENSE000032560416925703669257131
ENSE000032747386925053369250652
ENSE000032759876925029069250435
ENSE000032787996924318269243365
ENSE000032976606924607969246234
ENSE000033657126925732769257426
ENSE000033836256924736069247593

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 94.79.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1230 / max 300.8988, expressed in 384 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1053332.0515213
1053320.3580118
1053360.352372
1053340.3315101
1053350.02987

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
jejunal mucosaUBERON:000039994.79gold quality
duodenumUBERON:000211493.61gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047387.09gold quality
ileal mucosaUBERON:000033186.53gold quality
metanephros cortexUBERON:001053385.47gold quality
small intestine Peyer’s patchUBERON:000345484.69gold quality
small intestineUBERON:000210884.49gold quality
mucosa of transverse colonUBERON:000499184.32gold quality
jejunumUBERON:000211583.42gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451181.15gold quality
cerebellar vermisUBERON:000472080.06gold quality
islet of LangerhansUBERON:000000679.99gold quality
gall bladderUBERON:000211079.08gold quality
body of pancreasUBERON:000115077.86gold quality
pancreasUBERON:000126477.25gold quality
right uterine tubeUBERON:000130277.25gold quality
adult mammalian kidneyUBERON:000008276.09gold quality
tibial nerveUBERON:000132375.67gold quality
spermCL:000001975.42gold quality
vena cavaUBERON:000408774.95silver quality
rectumUBERON:000105274.63gold quality
male germ cellCL:000001573.37gold quality
gingival epitheliumUBERON:000194973.00gold quality
gingivaUBERON:000182872.38gold quality
parotid glandUBERON:000183171.89gold quality
colonic mucosaUBERON:000031771.84gold quality
sural nerveUBERON:001548871.75gold quality
deciduaUBERON:000245071.58silver quality
body of tongueUBERON:001187671.11gold quality
kidneyUBERON:000211370.53gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes8.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting HKDC1, 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-314899.9775.066478
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-6809-3P99.9171.453814
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-612499.8769.783551
HSA-MIR-130B-5P99.8368.501888
HSA-MIR-808099.8267.521342
HSA-MIR-7156-5P99.6468.811369
HSA-MIR-3136-3P99.5766.59781
HSA-MIR-7155-3P99.5766.48794
HSA-MIR-312399.4767.152693
HSA-MIR-427399.4567.931206
HSA-MIR-446498.9567.73820
HSA-MIR-474898.9567.53810
HSA-MIR-4742-5P98.8968.411542
HSA-MIR-4711-5P98.8968.00965
HSA-MIR-942-3P98.8169.04876
HSA-MIR-216B-3P98.5567.191223
HSA-MIR-211798.4867.971307
HSA-MIR-4691-3P98.1166.831204
HSA-MIR-1212098.0568.441768
HSA-MIR-6817-5P97.9567.861026
HSA-MIR-4712-5P97.2467.79775
HSA-MIR-770-5P97.2468.10758
HSA-MIR-124397.0765.44719
HSA-MIR-3622A-3P97.0666.431000
HSA-MIR-3622B-3P96.8266.36988
HSA-MIR-3194-5P96.8064.901027
HSA-MIR-397696.6767.791187
HSA-MIR-324-5P95.6865.20560

Literature-anchored findings (GeneRIF, showing 17)

  • Data identified two novel genome-wide significant associations: 2-h plasma glucose and HKDC1, and fasting C-peptide and BACE2. (PMID:23903356)
  • Association of HKDC1 genetic variants with susceptibility to gestational diabetes mellitus. (PMID:27346736)
  • Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied Keratoconus family (PMID:27703147)
  • These studies indicate that the tissues with highest HKDC1 expression were the brush border epithelium of the intestines, parts of the pancreas, and lung alveolar macrophages. (PMID:29401404)
  • results suggest a conditional regulation of KRT16 gene by ATF4 that may be inhibited in normal cells, but engaged during cancer progression. Potential roles of KRT16, FAM129A and HKDC1 genes upregulation in adaptive stress responses and pathologies are discussed (PMID:29420561)
  • bsence of HKDC1 expression in the Hkdc1 KO retina was confirmed by western blot and immunostaning using HKDC1 antibody. Hkdc1 KO mice exhibited reduced scotopic electroretinogram response and thinner outer nuclear layer, similar to some of the human patient phenotypes. (PMID:30085091)
  • expression in hepatocytes results in defective mitochondrial function and altered hepatocellular metabolism (PMID:30517626)
  • Hepatic HKDC1 contributes to whole body glucose disposal, insulin sensitivity, and aspects of nutrient balance during pregnancy. (PMID:30543855)
  • Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis. (PMID:33309778)
  • The Role of Hexokinase Domain Containing Protein-1 in Glucose Regulation During Pregnancy. (PMID:34232412)
  • The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment. (PMID:35485648)
  • HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex. (PMID:37423558)
  • HKDC1 in Gastric Cancer: A New Diagnostic, Prognostic Biomarker, and Novel Therapeutic Target. (PMID:37945018)
  • CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer. (PMID:38009649)
  • HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression. (PMID:38351096)
  • Hepatitis B virus X protein promotes tumor glycolysis by downregulating lncRNA OIP5-AS1/HKDC1 in HCC. (PMID:38636768)
  • HKDC1 promotes autophagy and proliferation in pancreatic adenocarcinoma through interaction with PARP1 and poly(ADP-ribosyl)ation. (PMID:39424110)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriohkdc1ENSDARG00000038703
mus_musculusHkdc1ENSMUSG00000020080
rattus_norvegicusHkdc1ENSRNOG00000049045

Paralogs (4): GCK (ENSG00000106633), HK1 (ENSG00000156515), HK2 (ENSG00000159399), HK3 (ENSG00000160883)

Protein

Protein identifiers

Hexokinase HKDC1 — Q2TB90 (reviewed: Q2TB90)

Alternative names: Hexokinase domain-containing protein 1

All UniProt accessions (1): Q2TB90

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of hexose to hexose 6-phosphate, although at very low level compared to other hexokinases. Has low glucose phosphorylating activity compared to other hexokinases. Involved in glucose homeostasis and hepatic lipid accumulation. Required to maintain whole-body glucose homeostasis during pregnancy; however additional evidences are required to confirm this role.

Subcellular location. Cytoplasm. Mitochondrion membrane. Photoreceptor inner segment.

Tissue specificity. Widely expressed. Highly expressed in the brush border, surface epithelium and the myenteric plexus of the small and large intestines; the acinar centrocytes and interlobular ducts of the pancreas; and the alveolar macrophages in the lungs (at protein level). Present at moderate level in the thyroid follicular epithelium (at protein level).

Disease relevance. Retinitis pigmentosa 92 (RP92) [MIM:619614] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP92 is an autosomal recessive, mild form with onset of night blindness and vision loss in the third to sixth decades of life. The disease may be caused by variants affecting the gene represented in this entry.

Pathway. Carbohydrate metabolism; hexose metabolism. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4.

Similarity. Belongs to the hexokinase family.

Isoforms (3)

UniProt IDNamesCanonical?
Q2TB90-11yes
Q2TB90-22
Q2TB90-33

RefSeq proteins (1): NP_079406* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001312HexokinaseFamily
IPR019807Hexokinase_BSBinding_site
IPR022672Hexokinase_NDomain
IPR022673Hexokinase_CDomain
IPR043129ATPase_NBDHomologous_superfamily

Pfam: PF00349, PF03727

Enzyme classification (BRENDA):

  • EC 2.7.1.1 — hexokinase (BRENDA: 77 organisms, 225 substrates, 336 inhibitors, 483 Km, 134 kcat entries)

Substrate kinetics (BRENDA)

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

SubstrateKm (mM)Measurements
ATP—184
D-GLUCOSE0.003–45112
D-FRUCTOSE0.025–151046
D-MANNOSE0.014–25.4136
2-DEOXY-D-GLUCOSE0.033–19.224
D-GLUCOSAMINE0.06–212
UTP0.288–307
ITP1.9–16.66
CTP0.52–55
GTP0.231–0.7884
N-ACETYL-D-GLUCOSAMINE0.32–41.62
1,5-ANHYDRO-D-GLUCITOL201
1-THIO-D-GLUCOSE51
2-DEOXY-2-FLUORO-D-GLUCOSE0.21
2-DEOXYGLUCOSE181

Catalyzed reactions (Rhea), 2 shown:

  • D-glucose + ATP = D-glucose 6-phosphate + ADP + H(+) (RHEA:17825)
  • a D-hexose + ATP = a D-hexose 6-phosphate + ADP + H(+) (RHEA:22740)

UniProt features (48 total): binding site 30, sequence variant 6, region of interest 5, splice variant 4, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q2TB90-F193.370.83

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 (30): 84–89; 155; 172–173; 208–209; 209; 232; 235; 260; 291–294; 413–415; 425–426; 449 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-70171Glycolysis

MSigDB gene sets: 139 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WOO_LIVER_CANCER_RECURRENCE_UP, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, LIAO_METASTASIS

GO Biological Process (9): intracellular glucose homeostasis (GO:0001678), glucose metabolic process (GO:0006006), glycolytic process (GO:0006096), glucose 6-phosphate metabolic process (GO:0051156), carbohydrate metabolic process (GO:0005975), hexose metabolic process (GO:0019318), organophosphate metabolic process (GO:0019637), carbohydrate phosphorylation (GO:0046835), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (9): glucokinase activity (GO:0004340), ATP binding (GO:0005524), D-glucose binding (GO:0005536), fructokinase activity (GO:0008865), nucleotide binding (GO:0000166), hexokinase activity (GO:0004396), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, alcohol group as acceptor (GO:0016773)

GO Cellular Component (6): photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Glucose metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
hexokinase activity2
transferase activity, transferring phosphorus-containing groups2
cytoplasm2
glucose homeostasis1
intracellular chemical homeostasis1
hexose metabolic process1
phosphoglycerate kinase activity1
phosphoglycerate mutase activity1
phosphopyruvate hydratase activity1
pyruvate kinase activity1
pyruvate metabolic process1
generation of precursor metabolites and energy1
aerobic respiration1
carbohydrate catabolic process1
pyridine nucleotide catabolic process1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity1
ADP catabolic process1
ATP metabolic process1
nicotinamide nucleotide metabolic process1
organophosphate metabolic process1
carbohydrate derivative metabolic process1
primary metabolic process1
monosaccharide metabolic process1
phosphorus metabolic process1
carbohydrate metabolic process1
phosphorylation1
metabolic process1
glucose 6-phosphate metabolic process1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
monosaccharide binding1
nucleoside phosphate binding1
heterocyclic compound binding1
phosphotransferase activity, alcohol group as acceptor1
carbohydrate kinase activity1
catalytic activity1
intracellular anatomical structure1
intracellular membrane-bounded organelle1
mitochondrion1

Protein interactions and networks

STRING

1288 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HKDC1G6PDP11413573
HKDC1PFKLP17858545
HKDC1PKMP14618542
HKDC1H6PDO95479526
HKDC1PFKPQ01813507
HKDC1PFKMP08237503
HKDC1PKLRP11973480
HKDC1G6PC1P35575474
HKDC1G6PC3Q9BUM1463
HKDC1BACE2Q9Y5Z0447
HKDC1MTNR1BP49286446
HKDC1AKR1B10O60218445
HKDC1GPIP06744445
HKDC1G6PC2Q9NQR9436
HKDC1PGDP52209431

IntAct

49 interactions, top by confidence:

ABTypeScore
CA10WDHD1psi-mi:“MI:0914”(association)0.640
HK3HK1psi-mi:“MI:0914”(association)0.530
PBXIP1KCNN4psi-mi:“MI:0914”(association)0.530
DNAJA1DNAJA2psi-mi:“MI:0914”(association)0.530
HK3HK2psi-mi:“MI:0914”(association)0.530
HK1HK2psi-mi:“MI:0914”(association)0.530
HKDC1LARS2psi-mi:“MI:0915”(physical association)0.400
HKDC1H2BC9psi-mi:“MI:0915”(physical association)0.400
HSCBRBP5psi-mi:“MI:0914”(association)0.350
HK3HK1psi-mi:“MI:0914”(association)0.350
HK1SNCApsi-mi:“MI:0914”(association)0.350
PADDX39Apsi-mi:“MI:0914”(association)0.350
ITM2BILVBLpsi-mi:“MI:0914”(association)0.350
rs27_rs27l_humanHBDpsi-mi:“MI:0914”(association)0.350
PPP2R2BA2ML1psi-mi:“MI:0914”(association)0.350
SUPT5Hpsi-mi:“MI:0914”(association)0.350
GTPBP10psi-mi:“MI:0914”(association)0.350
GTPBP1psi-mi:“MI:0914”(association)0.350
KLRB1ESYT2psi-mi:“MI:0914”(association)0.350
UCN3VWA8psi-mi:“MI:0914”(association)0.350
GMLPOTEFpsi-mi:“MI:0914”(association)0.350
LDLRAD1ZNF316psi-mi:“MI:0914”(association)0.350
SDC2ELAPOR2psi-mi:“MI:0914”(association)0.350
CA6QSOX1psi-mi:“MI:0914”(association)0.350
ADAM7RIOK3psi-mi:“MI:0914”(association)0.350
VSTM1ACOT8psi-mi:“MI:0914”(association)0.350
SNX21ACOT8psi-mi:“MI:0914”(association)0.350
CD83TNFRSF10Bpsi-mi:“MI:0914”(association)0.350

BioGRID (56): HKDC1 (Synthetic Growth Defect), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), HKDC1 (Proximity Label-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-RNA), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K0JFP3, A2PYL6, A2PYL7, A2PYL8, O08528, O64390, P05708, P17710, P17712, P19367, P27595, P27881, P27926, P33284, P35557, P50506, P50521, P52789, P52790, P52792, P80581, P83776, P93834, Q04409, Q09756, Q1W674, Q1WM15, Q1WM16, Q26609, Q2KNB4, Q2KNB7, Q2KNB9, Q2TB90, Q3TRM8, Q42525, Q5RC71, Q5W676, Q69TF4, Q6CUZ3, Q6Q8A5

Diamond homologs: A0A0K0JFP3, A2PYL6, A2PYL7, A2PYL8, O08528, O64390, P04806, P04807, P05708, P17709, P17710, P17712, P19367, P27595, P27881, P27926, P33284, P35557, P50506, P52789, P52790, P52792, P80581, P83776, P93834, Q04409, Q09756, Q1W674, Q1WM15, Q1WM16, Q26609, Q2KNB4, Q2KNB5, Q2KNB7, Q2KNB9, Q2TB90, Q3TRM8, Q42525, Q56XE8, Q5RC71

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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.

GO biological processes:

GO termPartnersFoldFDR
protein transport85.1×1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic6
Uncertain significance169
Likely benign9
Benign3

Top pathogenic / likely-pathogenic (6)

Variant IDHGVSClassification
1321242NM_025130.4(HKDC1):c.173C>T (p.Thr58Met)Likely pathogenic
3065416NM_025130.4(HKDC1):c.1250A>G (p.Tyr417Cys)Likely pathogenic
3065578NM_025130.4(HKDC1):c.250G>A (p.Asp84Asn)Likely pathogenic
599515NM_025130.4(HKDC1):c.301G>T (p.Gly101Trp)Likely pathogenic
599516NM_025130.4(HKDC1):c.1009C>T (p.Arg337Trp)Likely pathogenic
617836NM_025130.4(HKDC1):c.2302C>T (p.Arg768Ter)Likely pathogenic

SpliceAI

3590 predictions. Top by Δscore:

VariantEffectΔscore
10:69220495:GAAG:Gdonor_gain1.0000
10:69220498:GGT:Gdonor_loss1.0000
10:69220499:G:GAdonor_loss1.0000
10:69220500:T:Gdonor_loss1.0000
10:69232762:A:AGacceptor_gain1.0000
10:69232763:G:GGacceptor_gain1.0000
10:69232910:GAG:Gdonor_gain1.0000
10:69232910:GAGGT:Gdonor_loss1.0000
10:69232911:AG:Adonor_loss1.0000
10:69232912:GG:Gdonor_loss1.0000
10:69232913:GT:Gdonor_loss1.0000
10:69233013:GCT:Gacceptor_gain1.0000
10:69240646:C:Aacceptor_gain1.0000
10:69240650:AG:Aacceptor_gain1.0000
10:69240651:GG:Gacceptor_gain1.0000
10:69240651:GGAC:Gacceptor_gain1.0000
10:69240733:G:GTdonor_gain1.0000
10:69240750:CG:Cdonor_loss1.0000
10:69240751:GG:Gdonor_loss1.0000
10:69240752:G:GGdonor_gain1.0000
10:69240752:G:Tdonor_loss1.0000
10:69240753:T:Gdonor_loss1.0000
10:69243357:A:Tdonor_gain1.0000
10:69243363:ACT:Adonor_gain1.0000
10:69243366:G:GGdonor_gain1.0000
10:69246232:GAA:Gdonor_gain1.0000
10:69246235:G:GGdonor_gain1.0000
10:69247590:CTCA:Cdonor_gain1.0000
10:69247591:TCA:Tdonor_gain1.0000
10:69247594:G:GGdonor_gain1.0000

AlphaMissense

6045 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
10:69250612:T:CF599S1.000
10:69257358:A:TN655I1.000
10:69257359:T:AN655K1.000
10:69257359:T:GN655K1.000
10:69257361:A:CD656A1.000
10:69257361:A:GD656G1.000
10:69257361:A:TD656V1.000
10:69266698:G:TG899W1.000
10:69243201:T:GC237W0.999
10:69243271:T:AW261R0.999
10:69243271:T:CW261R0.999
10:69250308:C:AA530D0.999
10:69250311:T:CL531P0.999
10:69250314:A:TD532V0.999
10:69250317:T:CL533P0.999
10:69250335:G:CR539P0.999
10:69250341:T:CL541P0.999
10:69250534:T:CL573P0.999
10:69250536:T:CF574L0.999
10:69250538:T:AF574L0.999
10:69250538:T:GF574L0.999
10:69250566:T:CF584L0.999
10:69250568:C:AF584L0.999
10:69250568:C:GF584L0.999
10:69250608:G:CG598R0.999
10:69250609:G:AG598D0.999
10:69250611:T:CF599L0.999
10:69250613:C:AF599L0.999
10:69250613:C:GF599L0.999
10:69250617:T:CF601L0.999

dbSNP variants (sampled 300 via entrez): RS1000064595 (10:69255438 G>A,C), RS1000065133 (10:69265942 G>A), RS1000077165 (10:69219634 C>A,T), RS1000202029 (10:69260956 G>A), RS1000300550 (10:69249714 T>G), RS1000326093 (10:69236125 T>A,C), RS1000332094 (10:69267947 C>A), RS1000378572 (10:69235870 C>A,T), RS1000474932 (10:69233823 G>A,T), RS1000533007 (10:69219245 C>T), RS1000548653 (10:69233689 G>C), RS1000573971 (10:69261197 G>A,T), RS1000626337 (10:69230398 C>G,T), RS1000659955 (10:69234951 T>A), RS1000738411 (10:69244935 T>G)

Disease associations

OMIM: gene MIM:617221 | disease phenotypes: MIM:619614, MIM:148300

GenCC curated gene-disease

DiseaseClassificationInheritance
retinitis pigmentosa 92LimitedAutosomal recessive
retinitis pigmentosaLimitedAutosomal recessive

Mondo (4): retinitis pigmentosa 92 (MONDO:0030619), long QT syndrome (MONDO:0002442), keratoconus 1 (MONDO:0007851), retinitis pigmentosa (MONDO:0019200)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000505Visual impairment
HP:0000580Pigmentary retinopathy
HP:0000662Nyctalopia
HP:0001133Constriction of peripheral visual field
HP:0003596Middle age onset
HP:0011462Young adult onset
HP:0030528Paracentral scotoma

GWAS associations

14 associations (top):

StudyTraitp-value
GCST002110_3Glycemic traits (pregnancy)1.000000e-22
GCST004627_11Lymphocyte count3.000000e-10
GCST008362_193Birth weight2.000000e-18
GCST008363_72Offspring birth weight5.000000e-10
GCST90002383_486Hematocrit7.000000e-17
GCST90002384_190Hemoglobin2.000000e-17
GCST90002388_560Lymphocyte count3.000000e-18
GCST90002390_490Mean corpuscular hemoglobin1.000000e-17
GCST90002392_614Mean corpuscular volume7.000000e-22
GCST90002397_713Mean spheric corpuscular volume1.000000e-24
GCST90011898_74Alanine aminotransferase levels8.000000e-27
GCST90011899_88Aspartate aminotransferase levels2.000000e-14
GCST90013663_43Alanine aminotransferase levels1.000000e-39
GCST90013664_67Aspartate aminotransferase levels3.000000e-22

EFO canonical traits (8, from GWAS)

EFO IDTrait name
EFO:0004307glucose tolerance test
EFO:0004587lymphocyte count
EFO:0004344birth weight
EFO:0005939parental genotype effect measurement
EFO:0004348hematocrit
EFO:0004509hemoglobin measurement
EFO:0004527mean corpuscular hemoglobin
EFO:0004736aspartate aminotransferase measurement

MeSH disease descriptors (3)

DescriptorNameTree numbers
D008133Long QT SyndromeC14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D012174Retinitis PigmentosaC11.270.684; C11.768.585.658.500; C16.320.290.684
C563649Keratoconus 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741200 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 98,290 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL790CHLORHEXIDINE485,053
CHEMBL51085EBSELEN313,237

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

Binding affinities (BindingDB)

237 measured of 268 human assays (319 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
1,4-diketo-3-(4-methoxyphenyl)naphthalene-2-carboxylic acid ethyl esterIC50322 nM
MLS000374486IC50348 nM
4-[(E)-[3-(2-methylanilino)-4-oxo-1-naphthalenylidene]amino]sulfonylbenzoic acidIC50522 nM
3-[[(4E)-1-keto-4-tosylimino-2-naphthyl]amino]benzoic acidIC50524 nM
cid_3005734EC50615 nM
4-[(E)-[3-(2-fluoroanilino)-4-keto-1-naphthylidene]amino]sulfonylbenzoic acidIC50638 nM
(NZ)-N-[3-(4-hydroxyanilino)-4-keto-1-naphthylidene]thiophene-2-sulfonamideIC50656 nM
1H-Benzo[a]carbazole-1,4(11H)-dione, 8-methoxy-IC50919 nM
3-[[(4E)-4-(2,4-dimethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acidIC50919 nM
3-[[(4E)-4-(4-ethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acidIC50926 nM
4-[[(4E)-4-(4-ethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acidIC50966 nM
4-({(4Z)-1-oxo-4-[(phenylsulfonyl)imino]-1,4-dihydronaphthalen-2-yl}amino)benzoic acidIC50967 nM
(5E)-1-(2,5-dimethoxyphenyl)-5-(2-furanylmethylidene)-2-sulfanylidene-1,3-diazinane-4,6-dioneIC501230 nM
4-[(E)-[3-(2-carbomethoxyanilino)-4-keto-1-naphthylidene]amino]sulfonylbenzoic acidIC501260 nM
SMR000516584IC501270 nM
2-[4-[[[4-[2-(4-chloroanilino)-1,3-thiazol-4-yl]benzoyl]hydrazinylidene]methyl]phenoxy]acetic acidIC501300 nM
(NZ)-4-isopropyl-N-[4-keto-3-(1H-1,2,4-triazol-5-ylthio)-1-naphthylidene]benzenesulfonamideIC501350 nM
2,5-bis(diethylaminomethyl)benzene-1,4-diolIC501580 nM
(phenylmethyl) N-(1-pyridin-2-ylethylideneamino)carbamodithioateEC501610 nM
MLS000686315IC501610 nM
MLS001002736IC501610 nM
4-[[(4E)-1-keto-4-mesitylsulfonylimino-2-naphthyl]amino]benzoic acidIC501680 nM
(4Z)-4-[[5-(2,4-dichlorophenyl)-2-furanyl]methylidene]-3-methyl-5-isoxazoloneIC501700 nM
3-[[phenyl(pyridin-2-yl)methylidene]amino]-1,1-bis(pyridin-2-ylmethyl)thioureaEC501780 nM
N-[1-(1,3-thiazol-2-yl)ethylideneamino]-3-azabicyclo[3.2.2]nonane-3-carbothioamideEC501830 nM
MLS000565792EC501980 nM
MLS000390413IC502020 nM
4-piperidin-1-ylnaphthalene-1,2-dioneIC502120 nM
ethyl 4-[2-(6-pyridin-2-ylpyridazin-3-yl)sulfanylethanoylamino]benzoateIC502150 nM
SMR001565176IC502150 nM
N’-[1-(1-isoquinolinyl)ethyl]-4-(2-pyridinyl)-1-piperazinecarbothiohydrazideEC502190 nM
SMR000294066EC502200 nM
MLS000769398EC502230 nM
MLS002701599IC502230 nM
MLS002702209EC502270 nM
2,5-bis(chloranyl)-3-piperidin-1-yl-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dioneEC502320 nM
MLS000084034IC502360 nM
3-chloranyl-N-(3,3-dimethylbutan-2-yl)-6-nitro-1-benzothiophene-2-carboxamideEC502470 nM
MLS002207260IC502490 nM
SMR000439524IC502500 nM
SMR001527280IC502560 nM
MLS002207255IC502690 nM
SMR000439744IC502820 nM
1-(2-methoxyphenyl)-3-[1-(2-pyridinyl)ethylideneamino]thioureaEC503030 nM
2-Methyl-8-morpholin-4-yl-5,6-dioxo-5,6-dihydro-quinoline-4-carboxylic acid methyl esterIC503210 nM
SMR000298430IC503450 nM
(4E)-5-methyl-2-phenyl-4-[[(5-phenyl-1,2,4-triazin-3-yl)hydrazo]methylidene]-3-pyrazoloneIC503500 nM
(2Z,3E)-3-(3-methoxy-5-nitro-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)-2-(5-methyl-1,3-dihydrobenzimidazol-2-ylidene)propanenitrileIC503580 nM
N-[[[[3-(4-methoxyphenyl)-1H-pyrazol-5-yl]-oxomethyl]hydrazo]-sulfanylidenemethyl]-5-methyl-3-phenyl-4-isoxazolecarboxamideEC503620 nM
5,7-dimethyl-2-[({5-[(2-methylbenzyl)sulfanyl]-1,3,4-thiadiazol-2-yl}methyl)sulfanyl][1,2,4]triazolo[1,5-a]pyrimidineIC503710 nM

ChEMBL bioactivities

199 potent at pChembl≥5 of 459 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.67EC50212nMCHEMBL1713955
6.21EC50615nMCHEMBL1725990
5.99IC501020nMCHEMBL1454614
5.90IC501270nMCHEMBL1454614
5.87IC501340nMCHEMBL1395907
5.81IC501560nMCHEMBL1728280
5.79IC501610nMCHEMBL1362935
5.79IC501630nMCHEMBL1998302
5.79EC501610nMCHEMBL1708020
5.78IC501680nMCHEMBL3199539
5.75IC501800nMCHEMBL1968732
5.75EC501780nMCHEMBL1702026
5.74IC501830nMCHEMBL1728280
5.74EC501830nMCHEMBL1705535
5.72IC501900nMCHEMBL1451931
5.68IC502080nMCHEMBL1724454
5.67IC502150nMCHEMBL1368625
5.67IC502150nMCHEMBL27953
5.66IC502180nMCHEMBL27953
5.66EC502190nMCHEMBL169811
5.66EC502200nMCHEMBL1329129
5.65IC502230nMCHEMBL1724454
5.65EC502230nMCHEMBL1401989
5.65EC502240nMCHEMBL1701797
5.64IC502310nMCHEMBL1368625
5.64EC502270nMCHEMBL1709153
5.63IC502320nMCHEMBL1310221
5.63IC502360nMCHEMBL1401606
5.62IC502390nMCHEMBL1395907
5.61IC502470nMCHEMBL1721095
5.61IC502460nMCHEMBL592124
5.61IC502440nMCHEMBL1310221
5.60IC502500nMCHEMBL1451931
5.60IC502490nM2,6-DIMETHOXYQUINONE
5.60IC502530nMCHEMBL1999630
5.60IC502500nMCHEMBL1366206
5.59IC502560nMCHEMBL1706640
5.59IC502570nMCHEMBL1329141
5.57IC502690nMCHEMBL1964361
5.57IC502720nMCHEMBL1366206
5.56IC502740nMCHEMBL1998302
5.55IC502820nMCHEMBL1345851
5.55IC502840nMCHEMBL1999630
5.54IC502880nMCHEMBL1721986
5.54IC502850nMCHEMBL592124
5.53IC502960nMCHEMBL1342410
5.52IC503000nMCHEMBL2003651
5.52EC503030nMCHEMBL1717079
5.51IC503090nMCHEMBL1717890
5.51IC503060nMCHEMBL1704261

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148514: Binding affinity to human HKDC1 incubated for 45 mins by Kinobead based pull down assaykd4.8248uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects expression, decreases expression, increases expression4
Cyclosporineincreases expression3
sodium arsenitedecreases expression, increases expression2
Acetaminophendecreases expression2
Benzo(a)pyrenedecreases expression, increases expression2
Tetrachlorodibenzodioxindecreases expression2
Tobacco Smoke Pollutionincreases expression2
Valproic Acidincreases expression2
aristolochic acid Iincreases expression1
sotorasibaffects cotreatment, decreases expression1
propionaldehydeincreases expression1
lead acetateincreases expression1
tris(2-butoxyethyl) phosphateaffects expression1
2,4,5,2’,4’,5’-hexachlorobiphenyldecreases expression1
beta-lapachoneincreases expression1
sulforaphaneincreases expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
3,4,5,3’,4’-pentachlorobiphenyldecreases expression1
perfluorooctanoic aciddecreases expression1
cupric chlorideincreases expression1
yessotoxinincreases expression1
perfluorooctane sulfonic acidincreases expression1
2,3,5-(triglutathion-S-yl)hydroquinoneincreases ADP-ribosylation1
CGP 52608affects binding, increases reaction1
perfluoro-n-nonanoic acidincreases expression1
2-palmitoylglycerolincreases expression1
azaspiracidincreases expression1
K 7174increases expression1
belinostatdecreases expression1
ICG 001increases expression1

ChEMBL screening assays

7 unique, capped per target: 6 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1738313FunctionalPUBCHEM_BIOASSAY: Dose Response confirmation of activators of hexokinase domain containing I (HKDC1). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493187, AID493207]PubChem BioAssay data set
CHEMBL5651556BindingBinding affinity to human HKDC1 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_F1QFHyCyte HGC-27 KO-hHKDC1Cancer cell lineSex unspecified
CVCL_F1TTHyCyte SW620 KO-hHKDC1Cancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00717080PHASE4COMPLETEDThe Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT02513940PHASE4COMPLETEDInfluence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883PHASE4COMPLETEDReducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100PHASE4UNKNOWNNovel Form of Acquired Long QT Syndrome
NCT04675788PHASE4COMPLETEDNovel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00000114PHASE3COMPLETEDRandomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116PHASE3COMPLETEDRandomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333PHASE3COMPLETEDClinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395PHASE3TERMINATEDPhase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207PHASE3COMPLETEDManagement of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853PHASE3COMPLETEDCB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220PHASE3ACTIVE_NOT_RECRUITINGOral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301PHASE3COMPLETEDManagement of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583PHASE3ACTIVE_NOT_RECRUITINGA Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200PHASE3ACTIVE_NOT_RECRUITINGA Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855PHASE3NOT_YET_RECRUITINGA Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530PHASE3NOT_YET_RECRUITING24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230PHASE2COMPLETEDDHA and X-Linked Retinitis Pigmentosa
NCT00447980PHASE2COMPLETEDA Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993PHASE2COMPLETEDA Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609PHASE2COMPLETEDTrial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515PHASE2COMPLETEDEfficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659PHASE2COMPLETEDRetinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715PHASE2COMPLETEDAutologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165PHASE2COMPLETEDNerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711PHASE2COMPLETEDAflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360PHASE2UNKNOWNIntravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640PHASE2UNKNOWNStudying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733PHASE2COMPLETEDSafety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207PHASE2COMPLETEDMinocycline Treatment in Retinitis Pigmentosa
NCT04356716PHASE2COMPLETEDSildenafil for Treatment of Choroidal Ischemia
NCT04604899PHASE2COMPLETEDSafety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369PHASE2UNKNOWNInvestigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496PHASE2UNKNOWNEffects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772PHASE2COMPLETEDEfficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964PHASE2TERMINATEDAn Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179PHASE2COMPLETEDA Study in Subjects With Retinitis Pigmentosa
NCT06627179PHASE2RECRUITINGStudy to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947PHASE2RECRUITINGA Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633PHASE2RECRUITINGSafety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)

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
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Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot