WNT8B

gene
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Summary

WNT8B (Wnt family member 8B, HGNC:12789) is a protein-coding gene on chromosome 10q24.31, encoding Protein Wnt-8b (Q93098). Ligand for members of the frizzled family of seven transmembrane receptors.

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 95%, 86% and 71% amino acid identity to the mouse, zebrafish and Xenopus Wnt8B proteins, respectively. The expression patterns of the human and mouse genes appear identical and are restricted to the developing brain. The chromosomal location of this gene to 10q24 suggests it as a candidate gene for partial epilepsy.

Source: NCBI Gene 7479 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 28 total
  • MANE Select transcript: NM_003393

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12789
Approved symbolWNT8B
NameWnt family member 8B
Location10q24.31
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000075290
Ensembl biotypeprotein_coding
OMIM601396
Entrez7479

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000343737

RefSeq mRNA: 1 — MANE Select: NM_003393 NM_003393

CCDS: CCDS7494

Canonical transcript exons

ENST00000343737 — 6 exons

ExonStartEnd
ENSE00000720926100479874100480012
ENSE00000720931100480998100481123
ENSE00000720936100481912100482054
ENSE00001374161100463009100463236
ENSE00001387303100482271100483744
ENSE00002503538100479052100479085

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 80.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.5145 / max 605.1031, expressed in 123 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1065864.4862123
1065850.028317

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
diaphragmUBERON:000110380.91gold quality
tendon of biceps brachiiUBERON:000818872.24gold quality
buccal mucosa cellCL:000233669.00gold quality
endometrium epitheliumUBERON:000481168.69gold quality
triceps brachiiUBERON:000150968.59gold quality
secondary oocyteCL:000065567.98silver quality
tongue squamous epitheliumUBERON:000691967.75gold quality
cervix squamous epitheliumUBERON:000692266.69gold quality
hair follicleUBERON:000207365.25gold quality
left ventricle myocardiumUBERON:000656663.86gold quality
CA1 field of hippocampusUBERON:000388163.01gold quality
vastus lateralisUBERON:000137962.09gold quality
quadriceps femorisUBERON:000137761.28gold quality
heart right ventricleUBERON:000208060.99gold quality
olfactory bulbUBERON:000226460.93gold quality
oocyteCL:000002360.68gold quality
type B pancreatic cellCL:000016960.68gold quality
mucosa of urinary bladderUBERON:000125959.95gold quality
gluteal muscleUBERON:000200059.91gold quality
epithelial cell of pancreasCL:000008359.74gold quality
deciduaUBERON:000245059.15gold quality
nasal cavity epitheliumUBERON:000538459.13gold quality
periodontal ligamentUBERON:000826658.52gold quality
parotid glandUBERON:000183158.47gold quality
myocardiumUBERON:000234958.46gold quality
gingival epitheliumUBERON:000194958.07gold quality
cerebellar vermisUBERON:000472057.81gold quality
squamous epitheliumUBERON:000691457.70gold quality
endothelial cellCL:000011556.26gold quality
cervix epitheliumUBERON:000480155.63gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DMRT3, ETV4, GLI3, SIX3, ZIC1

miRNA regulators (miRDB)

56 targeting WNT8B, 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-453199.9969.703181
HSA-MIR-433-3P99.9869.371203
HSA-MIR-211099.9666.681930
HSA-MIR-477999.8666.501583
HSA-MIR-76599.8468.242442
HSA-MIR-6739-5P99.8067.872806
HSA-MIR-4668-5P99.7970.583782
HSA-MIR-11181-3P99.7566.382205
HSA-MIR-6733-5P99.7467.942759
HSA-MIR-430699.7270.503630
HSA-MIR-509399.6769.262291
HSA-MIR-29899.6367.561916
HSA-MIR-451699.6167.783390
HSA-MIR-432899.5771.064094
HSA-MIR-18A-3P99.5665.681092
HSA-MIR-315399.5567.592337
HSA-MIR-7106-5P99.5367.473574
HSA-MIR-671-5P99.5267.111277
HSA-MIR-1213199.4868.721673
HSA-MIR-132499.4666.571302
HSA-MIR-6871-3P99.4368.85741
HSA-MIR-6507-3P99.3567.321059
HSA-MIR-520F-5P99.3470.401632
HSA-MIR-149-5P99.2567.161315
HSA-MIR-4758-3P99.1263.96869
HSA-MIR-443499.1067.011984
HSA-MIR-570399.1067.092053
HSA-MIR-570198.9769.541502
HSA-MIR-6770-5P98.9766.761853
HSA-MIR-315498.9466.551455

Literature-anchored findings (GeneRIF, showing 6)

  • significantly up-regulated in gastric cancer cell lines KATO-III (signet-ring cell carcinoma) and MKN45 (poorly differentiated adenocarcinoma), and also in 5 out of 10 cases of primary gastric cancer (PMID:11788899)
  • Expression and regulation of WNT8B mRNA in human tumor cell lines (PMID:11956596)
  • WNT8B expression in hepatocyte progenitors derived from human ES cells is due to POU5F1 (OCT3/OCT4) and GATA3, and WNT8B expression in diffuse-type gastric cancer is due to POU5F1 and GATA6 (PMID:17390031)
  • WNT8b and SHH mutations and abnormal expressions are present in the peripheral blood of children with sporadic Hirschsprung disease. (PMID:20972907)
  • Wnt8B, transcriptionally regulated by ZNF191, promotes cell proliferation of hepatocellular carcinoma via Wnt signaling. (PMID:33197287)
  • WNT8B as an Independent Prognostic Marker for Nasopharyngeal Carcinoma. (PMID:34287269)

Cross-species orthologs

9 orthologs

OrganismSymbolGene ID
danio_reriownt8bENSDARG00000006911
mus_musculusWnt8bENSMUSG00000036961
rattus_norvegicusWnt8bENSRNOG00000013817
drosophila_melanogasterWnt2FBGN0004360
drosophila_melanogasterWnt5FBGN0010194
drosophila_melanogasterWnt10FBGN0031903
caenorhabditis_elegansWBGENE00000857
caenorhabditis_elegansWBGENE00000858
caenorhabditis_eleganslin-44WBGENE00003029

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-8bQ93098 (reviewed: Q93098)

All UniProt accessions (2): Q93098, A0A384NKY7

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expression is restricted to the brain, and more specifically to the forebrain.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition. Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT8B.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_003384* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR005817WntFamily
IPR013301Wnt8Family
IPR018161Wnt_CSConserved_site
IPR043158Wnt_CHomologous_superfamily

Pfam: PF00110

UniProt features (20 total): disulfide bond 11, sequence variant 2, sequence conflict 2, glycosylation site 2, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q93098-F184.880.64

Functional residue map

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

Post-translational modifications (1): 186

Disulfide bonds (11): 256–294, 272–287, 291–333, 309–324, 311–321, 316–317, 54–65, 104–112, 114–132, 180–194, 182–189

Glycosylation sites (2): 103, 259

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-201681TCF dependent signaling in response to WNT
R-HSA-3238698WNT ligand biogenesis and trafficking
R-HSA-373080Class B/2 (Secretin family receptors)
R-HSA-4641262Disassembly of the destruction complex and recruitment of AXIN to the membrane

MSigDB gene sets: 145 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_RESPONSE_TO_ESTRADIOL, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIPID, NKX25_02, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, LHX3_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, NKX61_01, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_CELLULAR_RESPONSE_TO_RETINOIC_ACID, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY

GO Biological Process (12): signal transduction (GO:0007165), gastrulation (GO:0007369), nervous system development (GO:0007399), neuron differentiation (GO:0030182), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), cell fate commitment (GO:0045165), determination of dorsal identity (GO:0048263), canonical Wnt signaling pathway (GO:0060070), cellular response to retinoic acid (GO:0071300), multicellular organism development (GO:0007275), Wnt signaling pathway (GO:0016055)

GO Molecular Function (4): frizzled binding (GO:0005109), cytokine activity (GO:0005125), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Signaling by WNT2
GPCR ligand binding1
TCF dependent signaling in response to WNT1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cell differentiation2
response to lipid2
response to oxygen-containing compound2
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
ectoderm formation1
endoderm formation1
mesoderm formation1
embryonic morphogenesis1
system development1
generation of neurons1
cellular developmental process1
dorsal/ventral pattern formation1
determination of dorsal/ventral asymmetry1
Wnt signaling pathway1
response to retinoic acid1
cellular response to lipid1
cellular response to oxygen-containing compound1
multicellular organismal process1
anatomical structure development1
cell surface receptor signaling pathway1
G protein-coupled receptor binding1
receptor ligand activity1
signaling receptor binding1
signal transduction1
signaling receptor activator activity1
protein binding1
cellular anatomical structure1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
WNT8BSFRP5Q5T4F7849
WNT8BSFRP1Q8N474801
WNT8BLCN1P31025794
WNT8BRYKP34925786
WNT8BFZD2Q14332712
WNT8BLRP5O75197638
WNT8BLRP6O75581608
WNT8BDKK1O94907554
WNT8BFZD1Q9UP38545
WNT8BCTNNB1P35222543
WNT8BFZD9O00144531
WNT8BFZD5Q13467506
WNT8BLEF1Q9UJU2505
WNT8BFZD8Q9H461503
WNT8BAXIN2Q9Y2T1489

IntAct

4 interactions, top by confidence:

ABTypeScore
WNT8BRPL18Apsi-mi:“MI:0915”(physical association)0.400
WNT8BWLSpsi-mi:“MI:0915”(physical association)0.400
WNT8BHALpsi-mi:“MI:0914”(association)0.350

BioGRID (5): WNT8B (Proximity Label-MS), SDR9C7 (Affinity Capture-MS), ALOXE3 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), HAL (Affinity Capture-MS)

ESM2 similar proteins: A4D7S0, A8XEH1, O00755, O14904, O15978, O42280, P09544, P24383, P28026, P28047, P28107, P28111, P28130, P28144, P28465, P31291, P34888, P34889, P51028, P51029, P51030, P56706, Q07DW8, Q07DX7, Q07DY7, Q09YI4, Q09YJ6, Q10459, Q1KYK4, Q1KYK5, Q1KYK6, Q1KYK7, Q1KYK9, Q1KYL1, Q1KYL3, Q27886, Q2IBB0, Q2IBE2, Q2QL76, Q2QL96

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, O00744, O00755, O13267, O14904, O14905, O15978, O35468, O42280, O70283, P04426, P04628, P09544, P10108, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31286, P33945, P40589, P41221, P43446, P47793, P48614, P49337, P49338, P49339, P49340, P51029

SIGNOR signaling

3 interactions.

AEffectBMechanism
WNT8Bup-regulatesFZD3binding
WNT8Bup-regulatesLRP6binding
EXT1“up-regulates activity”WNT8B

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance24
Likely benign0
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1047 predictions. Top by Δscore:

VariantEffectΔscore
10:100479047:TATAG:Tacceptor_loss1.0000
10:100479049:TAGGT:Tacceptor_loss1.0000
10:100479050:A:AGacceptor_gain1.0000
10:100479050:AGGT:Aacceptor_loss1.0000
10:100479051:G:GCacceptor_loss1.0000
10:100479051:G:GGacceptor_gain1.0000
10:100479086:G:GCdonor_loss1.0000
10:100479087:T:Adonor_loss1.0000
10:100479863:T:Gacceptor_gain1.0000
10:100479870:ACAG:Aacceptor_gain1.0000
10:100479871:C:Gacceptor_gain1.0000
10:100479871:CA:Cacceptor_loss1.0000
10:100479872:A:AGacceptor_gain1.0000
10:100479872:A:Cacceptor_loss1.0000
10:100479872:AG:Aacceptor_gain1.0000
10:100479873:G:GTacceptor_gain1.0000
10:100479873:GG:Gacceptor_gain1.0000
10:100479873:GGC:Gacceptor_gain1.0000
10:100479873:GGCT:Gacceptor_gain1.0000
10:100479873:GGCTT:Gacceptor_gain1.0000
10:100480010:GTG:Gdonor_gain1.0000
10:100480985:T:TAacceptor_gain1.0000
10:100480986:G:Aacceptor_gain1.0000
10:100480992:T:Aacceptor_gain1.0000
10:100480996:A:AGacceptor_gain1.0000
10:100480997:G:GGacceptor_gain1.0000
10:100480997:GC:Gacceptor_gain1.0000
10:100480997:GCC:Gacceptor_gain1.0000
10:100480997:GCCA:Gacceptor_gain1.0000
10:100480997:GCCAA:Gacceptor_gain1.0000

AlphaMissense

2287 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
10:100479907:G:TG46C1.000
10:100479931:T:AC54S1.000
10:100479932:G:CC54S1.000
10:100479958:T:AW63R1.000
10:100479958:T:CW63R1.000
10:100479960:G:CW63C1.000
10:100479960:G:TW63C1.000
10:100481024:G:CA90P1.000
10:100481066:T:AC104S1.000
10:100481067:G:AC104Y1.000
10:100481067:G:CC104S1.000
10:100481068:C:GC104W1.000
10:100481931:G:CW129C1.000
10:100481931:G:TW129C1.000
10:100481938:T:AC132S1.000
10:100481939:G:CC132S1.000
10:100482036:C:AN164K1.000
10:100482036:C:GN164K1.000
10:100482050:G:CR169P1.000
10:100482304:T:AC182S1.000
10:100482305:G:CC182S1.000
10:100482310:G:TG184C1.000
10:100482325:T:AC189S1.000
10:100482326:G:CC189S1.000
10:100482345:G:CW195C1.000
10:100482345:G:TW195C1.000
10:100482383:T:CL208P1.000
10:100482691:T:AC311S1.000
10:100482692:G:CC311S1.000
10:100482697:T:CF313L1.000

dbSNP variants (sampled 300 via entrez): RS1000191400 (10:100464335 T>G), RS1000287935 (10:100463862 G>A,T), RS1000383006 (10:100475067 C>G), RS1000623963 (10:100462093 G>A), RS1000920933 (10:100469431 A>G), RS1000955055 (10:100483318 C>T), RS1000998777 (10:100470142 A>C,G), RS1001040882 (10:100476340 A>G), RS1001112204 (10:100462908 C>T), RS1001137208 (10:100483407 A>T), RS1001199396 (10:100483927 C>G,T), RS1001371221 (10:100474780 G>T), RS1001533949 (10:100482688 A>G), RS1001687318 (10:100481539 G>C), RS1001725611 (10:100481108 C>T)

Disease associations

OMIM: gene MIM:601396 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST001841_4Palmitoleic acid (16:1n-7) levels6.000000e-09
GCST007856_1Colorectal cancer or advanced adenoma4.000000e-06
GCST007856_18Colorectal cancer or advanced adenoma7.000000e-15
GCST010703_13Brain morphology (MOSTest)1.000000e-09

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004346neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

ChemicalActions (top 5)PubMed papers
aristolochic acid Iincreases expression1
sotorasibaffects cotreatment, decreases expression1
decabromobiphenyl etherdecreases expression1
tetrachlorodiandecreases expression1
CGP 52608affects binding, increases reaction1
2,2’,4,4’-tetrabromodiphenyl etherincreases expression1
trametinibaffects cotreatment, decreases expression1
NVP-BKM120affects cotreatment, decreases expression1
Resveratroldecreases expression, affects cotreatment1
Microplasticsincreases abundance, increases expression1
Benzo(a)pyreneincreases methylation1
Diethylhexyl Phthalatedecreases expression1
Niclosamideincreases expression1
Plant Extractsdecreases expression, affects cotreatment1
Polystyrenesincreases abundance, increases expression1
Acrylamidedecreases expression1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

CellosaurusNameCategorySex
CVCL_A7W9SEES3-1V human WNT8B, clone1Embryonic stem cellMale
CVCL_A7X0SEES3-1V human WNT8B, clone2Embryonic stem cellMale
CVCL_A7X1SEES3-1V human WNT8B, clone3Embryonic stem cellMale

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): colorectal adenoma