GUCD1

gene
On this page

Also known as MGC1842LLN4

Summary

GUCD1 (guanylyl cyclase domain containing 1, HGNC:14237) is a protein-coding gene on chromosome 22q11.23, encoding Protein GUCD1 (Q96NT3).

Predicted to be involved in liver regeneration and response to cAMP.

Source: NCBI Gene 83606 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 37 total
  • MANE Select transcript: NM_001284254

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14237
Approved symbolGUCD1
Nameguanylyl cyclase domain containing 1
Location22q11.23
Locus typegene with protein product
StatusApproved
AliasesMGC1842, LLN4
Ensembl geneENSG00000138867
Ensembl biotypeprotein_coding
OMIM619171
Entrez83606

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000398245, ENST00000402766, ENST00000404664, ENST00000407471, ENST00000407973, ENST00000435822, ENST00000447813, ENST00000468170, ENST00000480272, ENST00000490810, ENST00000490922, ENST00000493099, ENST00000621833, ENST00000894495, ENST00000951439

RefSeq mRNA: 8 — MANE Select: NM_001284254 NM_001284251, NM_001284252, NM_001284253, NM_001284254, NM_001284255, NM_001284256, NM_001284257, NM_031444

CCDS: CCDS33621, CCDS63426, CCDS63427, CCDS74831, CCDS74832, CCDS74833

Canonical transcript exons

ENST00000435822 — 6 exons

ExonStartEnd
ENSE000009357542454790824548073
ENSE000009357552454691424547005
ENSE000016673742455494924555138
ENSE000017890372454043824543097
ENSE000035455002454891724549001
ENSE000036848912454384224544083

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7014 / max 374.5581, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
19338319.52981802
1933855.84871725
1933861.40651026
1933841.3770981
1933820.5394285

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
apex of heartUBERON:000209898.82gold quality
oocyteCL:000002398.51gold quality
ileal mucosaUBERON:000033198.36gold quality
right lobe of liverUBERON:000111498.02gold quality
secondary oocyteCL:000065597.83gold quality
hindlimb stylopod muscleUBERON:000425297.75gold quality
pancreatic ductal cellCL:000207997.42gold quality
mucosa of transverse colonUBERON:000499197.40gold quality
kidney epitheliumUBERON:000481997.37gold quality
heart left ventricleUBERON:000208497.33gold quality
gastrocnemiusUBERON:000138897.20gold quality
cardiac ventricleUBERON:000208297.20gold quality
left ventricle myocardiumUBERON:000656697.16gold quality
liverUBERON:000210797.15gold quality
small intestine Peyer’s patchUBERON:000345496.87gold quality
adult mammalian kidneyUBERON:000008296.67gold quality
muscle of legUBERON:000138396.67gold quality
small intestineUBERON:000210896.54gold quality
bloodUBERON:000017896.50gold quality
stromal cell of endometriumCL:000225596.39gold quality
tibialis anteriorUBERON:000138596.35gold quality
body of stomachUBERON:000116196.25gold quality
lower esophagus mucosaUBERON:003583496.17gold quality
transverse colonUBERON:000115796.12gold quality
lower esophagus muscularis layerUBERON:003583396.10gold quality
metanephros cortexUBERON:001053396.09gold quality
lower esophagusUBERON:001347396.09gold quality
duodenumUBERON:000211495.98gold quality
quadriceps femorisUBERON:000137795.97gold quality
jejunal mucosaUBERON:000039995.89gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes18.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting GUCD1, 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-1277-5P100.0073.955056
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-3163100.0077.238605
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-19A-3P99.9875.332762
HSA-MIR-19B-3P99.9875.442754
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-22-3P99.9368.13917
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-1343-3P99.8966.781815
HSA-MIR-444799.8567.812900
HSA-MIR-548AJ-5P99.7871.123085
HSA-MIR-548F-5P99.7871.023093
HSA-MIR-548G-5P99.7871.123085
HSA-MIR-548X-5P99.7871.123085
HSA-MIR-3156-3P99.7666.72939
HSA-MIR-431999.7669.832586
HSA-MIR-33A-3P99.7070.273362
HSA-MIR-453099.6966.471509
HSA-MIR-580-3P99.6769.231841
HSA-MIR-24-3P99.5969.971934
HSA-MIR-6758-3P99.5767.551078
HSA-MIR-1207-5P99.4969.112983
HSA-MIR-94099.3766.142064

Literature-anchored findings (GeneRIF, showing 2)

  • The expression and function of a ubiquitous protein, GUCD1, were characterized, it might have a role in regulating normal and abnormal cell growth in the liver. (PMID:24743017)
  • miR-370 suppressed Hepatocellular carcinoma cell metastasis and epithelial-mesenchymal transition via regulating GUCD1. (PMID:30799589)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriogucd1ENSDARG00000068438
mus_musculusGucd1ENSMUSG00000033416
rattus_norvegicusGucd1ENSRNOG00000049952
drosophila_melanogasterCG13760FBGN0040375

Protein

Protein identifiers

Protein GUCD1Q96NT3 (reviewed: Q96NT3)

Alternative names: Guanylyl cyclase domain-containing protein 1, Protein LLN4

All UniProt accessions (6): A0A087WVD9, B4DL90, B5MCF3, E7EX77, E9PGZ7, Q96NT3

UniProt curated annotations — full annotation on UniProt →

Isoforms (3)

UniProt IDNamesCanonical?
Q96NT3-11yes
Q96NT3-22
Q96NT3-33

RefSeq proteins (8): NP_001271180, NP_001271181, NP_001271182, NP_001271183, NP_001271184, NP_001271185, NP_001271186, NP_113632 (=MANE)

Domains & families (InterPro)

IDNameType
IPR018616GUCD1Family

Pfam: PF09778

UniProt features (4 total): splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96NT3-F186.920.67

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MORI_IMMATURE_B_LYMPHOCYTE_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, BURTON_ADIPOGENESIS_5, SENESE_HDAC3_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, LU_EZH2_TARGETS_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, BAKKER_FOXO3_TARGETS_UP, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_WITH_H4K20ME1_MARK, RAO_BOUND_BY_SALL4_ISOFORM_A, PECE_MAMMARY_STEM_CELL_UP, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_DN

GO Biological Process (2): response to cAMP (GO:0051591), liver regeneration (GO:0097421)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
response to purine-containing compound1
response to organophosphorus1
response to oxygen-containing compound1
liver development1
animal organ regeneration1
binding1

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GUCD1ZNF652Q9Y2D9603
GUCD1LRRC75BQ2VPJ9591
GUCD1C22orf15Q8WYQ4577
GUCD1DCTN4Q9UJW0499
GUCD1DRICH1Q6PGQ1474
GUCD1ADD3Q9UEY8432
GUCD1ZNF70Q9UC06393
GUCD1PALMDQ9NP74390
GUCD1GSTT4A0A1W2PR19376
GUCD1DDTLA6NHG4371
GUCD1CLUP10909371
GUCD1SMIM24O75264364
GUCD1TM4SF4P48230351
GUCD1RGL4Q8IZJ4349
GUCD1CLUL1Q15846348

IntAct

33 interactions, top by confidence:

ABTypeScore
GUCD1NGLY1psi-mi:“MI:0915”(physical association)0.670
NGLY1GUCD1psi-mi:“MI:0915”(physical association)0.670
CRXGUCD1psi-mi:“MI:0915”(physical association)0.560
TCF4GUCD1psi-mi:“MI:0915”(physical association)0.560
GUCD1CTHpsi-mi:“MI:0915”(physical association)0.560
GUCD1KRTAP10-7psi-mi:“MI:0915”(physical association)0.560
GUCD1KRT40psi-mi:“MI:0915”(physical association)0.560
GUCD1CRXpsi-mi:“MI:0915”(physical association)0.560
CTHGUCD1psi-mi:“MI:0915”(physical association)0.560
GUCD1TCF4psi-mi:“MI:0915”(physical association)0.560
KRTAP10-7GUCD1psi-mi:“MI:0915”(physical association)0.560
SLC31A1C2orf72psi-mi:“MI:0914”(association)0.530
IMPDH1BCAT2psi-mi:“MI:0914”(association)0.530
PCNAGUCD1psi-mi:“MI:0915”(physical association)0.370
IMPDH1LCMT2psi-mi:“MI:0914”(association)0.350
GORASP1CLASP2psi-mi:“MI:0914”(association)0.350
AMIGO1TMEM223psi-mi:“MI:0914”(association)0.350
GORASP1RTCApsi-mi:“MI:0914”(association)0.350
GUCD1HNRNPA1L2psi-mi:“MI:0914”(association)0.350
GORASP1PRORPpsi-mi:“MI:0914”(association)0.350
SLC15A1MEN1psi-mi:“MI:0914”(association)0.350

BioGRID (145): GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), GUCD1 (Affinity Capture-MS), GUCD1 (Affinity Capture-MS), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid), GUCD1 (Two-hybrid)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A8MUP2, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, F1LTR1, O43688, O94925, P17553, P52875, P55244, P56703, P57791, Q16763, Q1RML1, Q28D01, Q2HJ61, Q3UHH2, Q3ZCD7, Q4L208, Q4R8V4, Q4V899, Q5R6I6, Q5R890, Q5SP67, Q66H54, Q86YN1, Q8BZH0, Q8BZI6, Q8K593, Q8R4D1, Q8VDI9, Q91ZH7, Q96H72, Q96NT3, Q9DAX2

Diamond homologs: Q8BZI6, Q8L870, Q96NT3

SIGNOR signaling

1 interactions.

AEffectBMechanism
NEDD4“down-regulates quantity by destabilization”GUCD1polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance31
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1038 predictions. Top by Δscore:

VariantEffectΔscore
22:24543101:C:CCacceptor_gain1.0000
22:24543107:G:GCacceptor_gain1.0000
22:24543834:GCACT:Gdonor_loss1.0000
22:24543836:ACTCA:Adonor_loss1.0000
22:24543837:CTCA:Cdonor_loss1.0000
22:24543838:TCA:Tdonor_loss1.0000
22:24543839:CA:Cdonor_loss1.0000
22:24543840:A:ACdonor_gain1.0000
22:24543840:ACGG:Adonor_loss1.0000
22:24543840:ACGGT:Adonor_gain1.0000
22:24543841:C:CGdonor_gain1.0000
22:24543841:CG:Cdonor_gain1.0000
22:24543841:CGG:Cdonor_gain1.0000
22:24543841:CGGT:Cdonor_gain1.0000
22:24543841:CGGTC:Cdonor_gain1.0000
22:24544079:CTGTG:Cacceptor_gain1.0000
22:24544084:C:CCacceptor_gain1.0000
22:24546908:GCTC:Gdonor_loss1.0000
22:24546909:CTCA:Cdonor_loss1.0000
22:24546910:TCACC:Tdonor_loss1.0000
22:24546911:CAC:Cdonor_loss1.0000
22:24546912:A:ACdonor_gain1.0000
22:24546912:A:Tdonor_loss1.0000
22:24546913:C:CAdonor_loss1.0000
22:24546913:C:CCdonor_gain1.0000
22:24547001:AAGGA:Aacceptor_gain1.0000
22:24547002:AGGA:Aacceptor_gain1.0000
22:24547004:GA:Gacceptor_gain1.0000
22:24547006:C:CCacceptor_gain1.0000
22:24547904:TCA:Tdonor_loss1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000063217 (22:24542467 T>C), RS1000070163 (22:24555808 G>C), RS1000258656 (22:24542112 C>T), RS1000351879 (22:24554766 C>G,T), RS1000384492 (22:24555086 T>C), RS1000441110 (22:24547443 C>A,T), RS1000506272 (22:24553152 T>G), RS1000654850 (22:24553521 C>G), RS1000680578 (22:24546446 G>C), RS1001016809 (22:24546186 C>T), RS1001066748 (22:24543614 G>A), RS1001249058 (22:24549519 T>C), RS1001385860 (22:24556002 C>A,G,T), RS1002073795 (22:24544831 G>A), RS1002271642 (22:24544468 G>A)

Disease associations

OMIM: gene MIM:619171 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): cerebellar ataxia (MONDO:0000437)

Orphanet (1): Rare ataxia (Orphanet:102002)

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST002481_6Acne (severe)6.000000e-07
GCST90013407_62Liver enzyme levels (gamma-glutamyl transferase)5.000000e-32

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004532serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

DescriptorNameTree numbers
D002524Cerebellar AtaxiaC10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Sdecreases methylation, affects cotreatment, increases expression2
bisphenol Faffects cotreatment, increases expression1
triphenyl phosphateaffects expression1
alpha-pineneaffects cotreatment, increases expression, increases oxidation, increases abundance1
bisphenol Aaffects cotreatment, increases expression1
titanium dioxideincreases expression1
beta-lapachonedecreases expression, increases expression1
sodium arseniteincreases expression1
butyraldehydedecreases expression1
methacrylaldehydeaffects cotreatment, increases expression, increases oxidation, increases abundance1
pentanaldecreases expression1
perfluorooctane sulfonic aciddecreases expression1
abrinedecreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Temozolomidedecreases expression1
Acroleinincreases oxidation, increases abundance, affects cotreatment, increases expression1
Air Pollutantsaffects cotreatment, increases abundance, increases expression, increases oxidation1
Vehicle Emissionsdecreases expression, increases abundance1
Dexamethasoneaffects cotreatment, increases expression1
Doxorubicindecreases expression1
Indomethacinaffects cotreatment, increases expression1
Ozoneincreases expression, increases oxidation, increases abundance, affects cotreatment1
Quercetindecreases expression1
Smokedecreases expression1
Tobacco Smoke Pollutionincreases expression1
Valproic Acidaffects expression1
1-Methyl-3-isobutylxanthineaffects cotreatment, increases expression1
Cyclosporinedecreases expression1
Gold Compoundsincreases expression1
Okadaic Aciddecreases expression1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00950196PHASE4COMPLETEDAmantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740PHASE4COMPLETEDC-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098PHASE3COMPLETEDA Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111PHASE3COMPLETEDAn Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124PHASE3COMPLETEDA Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137PHASE3COMPLETEDA 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302PHASE3COMPLETEDAn Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080PHASE3ACTIVE_NOT_RECRUITINGOpen Pilot Trial of BHV-4157
NCT03701399PHASE3ACTIVE_NOT_RECRUITINGTroriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638PHASE3TERMINATEDTllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137PHASE3RECRUITINGConfirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242PHASE2COMPLETEDHigh-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397PHASE2COMPLETEDEffect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538PHASE2COMPLETEDPhase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016PHASE2COMPLETEDA Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440PHASE2COMPLETEDSafety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655PHASE2COMPLETEDEfficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669PHASE2COMPLETEDEffect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284PHASE2WITHDRAWNStudy of CAD-1883 for Spinocerebellar Ataxia
NCT05125666PHASE2UNKNOWNEfficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274PHASE2NOT_YET_RECRUITINGStemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943PHASE1COMPLETEDLithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064PHASE1UNKNOWNAn Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802PHASE1ACTIVE_NOT_RECRUITINGPromoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01104649PHASE2/PHASE3COMPLETEDEfficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893PHASE2/PHASE3COMPLETEDTrial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361PHASE1/PHASE2COMPLETEDEffectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687PHASE1/PHASE2COMPLETEDTreatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177PHASE1/PHASE2UNKNOWNClinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268PHASE1/PHASE2COMPLETEDA Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324Not specifiedCOMPLETEDPET Scan to Study Brain Control of Human Movement
NCT00006492Not specifiedCOMPLETEDGluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630Not specifiedCOMPLETEDNatural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829Not specifiedCOMPLETEDSPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272Not specifiedCOMPLETEDFall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251Not specifiedCOMPLETEDMeasuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861Not specifiedCOMPLETEDAutoimmunity in Neurologic Complications of Celiac Disease
NCT01037777Not specifiedCOMPLETEDRISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176Not specifiedCOMPLETEDExercise Training Program for Cerebellar Ataxia
NCT01428531Not specifiedCOMPLETEDSpecial Drug Use Investigation for Arixtra® (Fondaparinux) Venous Thromboembolism Treatment
  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): acne, cerebellar ataxia