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Atlas / Gene / KLHL38

KLHL38

gene
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Also known as C8ORFK36

Summary

KLHL38 (kelch like family member 38, HGNC:34435) is a protein-coding gene on chromosome 8q24.13, encoding Kelch-like protein 38 (Q2WGJ6).

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 340359 — RefSeq curated summary.

At a glance

  • GWAS associations: 31
  • Clinical variants (ClinVar): 133 total
  • MANE Select transcript: NM_001081675

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:34435
Approved symbolKLHL38
Namekelch like family member 38
Location8q24.13
Locus typegene with protein product
StatusApproved
AliasesC8ORFK36
Ensembl geneENSG00000175946
Ensembl biotypeprotein_coding
Entrez340359

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000325995, ENST00000684634

RefSeq mRNA: 1 — MANE Select: NM_001081675 NM_001081675

CCDS: CCDS43766

Canonical transcript exons

ENST00000684634 — 4 exons

ExonStartEnd
ENSE00001288008123646909123647014
ENSE00003916302123651577123652927
ENSE00003918098123644442123646028
ENSE00003920627123653586123653801

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 96.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5315 / max 123.2955, expressed in 96 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter IDTPM avgSamples expressed
947370.263459
947360.159141
947330.03759
947310.02588
947350.023013
947340.01055
2053070.00744
947320.00482

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
skeletal muscle tissueUBERON:000113496.63gold quality
hindlimb stylopod muscleUBERON:000425295.67gold quality
gastrocnemiusUBERON:000138895.50gold quality
muscle of legUBERON:000138393.90gold quality
apex of heartUBERON:000209890.25gold quality
muscle tissueUBERON:000238587.46gold quality
heart left ventricleUBERON:000208487.16gold quality
heartUBERON:000094882.39gold quality
right atrium auricular regionUBERON:000663180.98gold quality
popliteal arteryUBERON:000225069.83gold quality
tibial arteryUBERON:000761069.77gold quality
smooth muscle tissueUBERON:000113569.31gold quality
descending thoracic aortaUBERON:000234567.31gold quality
mucosa of stomachUBERON:000119966.39gold quality
left coronary arteryUBERON:000162665.20gold quality
right coronary arteryUBERON:000162565.18gold quality
thoracic aortaUBERON:000151564.91gold quality
placentaUBERON:000198764.83gold quality
ascending aortaUBERON:000149664.36gold quality
esophagogastric junction muscularis propriaUBERON:003584160.37gold quality
myometriumUBERON:000129659.99gold quality
body of uterusUBERON:000985359.75gold quality
lower esophagus muscularis layerUBERON:003583359.23gold quality
lower esophagusUBERON:001347359.13gold quality
muscle layer of sigmoid colonUBERON:003580557.83gold quality
gall bladderUBERON:000211057.80gold quality
urinary bladderUBERON:000125556.26gold quality
prefrontal cortexUBERON:000045154.24gold quality
stromal cell of endometriumCL:000225553.93silver quality
fundus of stomachUBERON:000116052.13gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-MTAB-5061no3.66
E-ANND-3no2.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

  • KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway. (PMID:34050138)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioklhl38aENSDARG00000031383
danio_rerioklhl38bENSDARG00000040278
mus_musculusKlhl38ENSMUSG00000022357
rattus_norvegicusKlhl38ENSRNOG00000007896

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 38 — Q2WGJ6 (reviewed: Q2WGJ6)

All UniProt accessions (1): Q2WGJ6

RefSeq proteins (1): NP_001075144* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000210BTB/POZ_domDomain
IPR006652Kelch_1Repeat
IPR011333SKP1/BTB/POZ_sfHomologous_superfamily
IPR011705BACKDomain
IPR015915Kelch-typ_b-propellerHomologous_superfamily
IPR017096BTB-kelch_proteinFamily
IPR030568KLHL38_BACKDomain
IPR056737Beta-prop_ATRN-MKLN-likeDomain

Pfam: PF00651, PF01344, PF07707, PF24981

UniProt features (16 total): sequence variant 6, repeat 6, domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q2WGJ6-F190.600.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_CUL3_RING_UBIQUITIN_LIGASE_COMPLEX, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOCC_UBIQUITIN_LIGASE_COMPLEX, chr8q24, GOMF_MOLECULAR_ADAPTOR_ACTIVITY, GOCC_INTRACELLULAR_PROTEIN_CONTAINING_COMPLEX, CUX1_TARGET_GENES, BPTF_TARGET_GENES, GSE9946_MATURE_STIMULATORY_VS_PROSTAGLANDINE2_TREATED_MATURE_DC_UP

GO Biological Process (1): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), Cul3-RING ubiquitin ligase complex (GO:0031463)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
ubiquitin-dependent protein catabolic process1
proteasomal protein catabolic process1
enzyme-substrate adaptor activity1
binding1
intracellular anatomical structure1
cellular anatomical structure1
cullin-RING ubiquitin ligase complex1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
KLHL38NUDCD3Q8IVD9528
KLHL38NEURL1BA8MQ27520
KLHL38STYXL2Q5VZP5519
KLHL38ACTR6Q9GZN1494
KLHL38CCDC141Q6ZP82469
KLHL38NUDCD2Q8WVJ2463
KLHL38SPSB3Q6PJ21450
KLHL38DLEC1Q9Y238442
KLHL38XKR9Q5GH70428
KLHL38UBR3Q6ZT12414
KLHL38TMEM68Q96MH6414
KLHL38PROCA1Q8NCQ7406
KLHL38ANKRD29Q8N6D5393
KLHL38FAM110BQ8TC76372
KLHL38DYNLT4Q5JR98370

IntAct

320 interactions, top by confidence:

ABTypeScore
TRIM42KLHL38psi-mi:“MI:0915”(physical association)0.720
KLHL38KRT38psi-mi:“MI:0915”(physical association)0.720
KLHL38KRTAP5-9psi-mi:“MI:0915”(physical association)0.720
MAGEA6KLHL38psi-mi:“MI:0915”(physical association)0.720
KLHL38KRTAP10-7psi-mi:“MI:0915”(physical association)0.720
KRTAP10-8KLHL38psi-mi:“MI:0915”(physical association)0.720
KLHL38KRT31psi-mi:“MI:0915”(physical association)0.720
USHBP1KLHL38psi-mi:“MI:0915”(physical association)0.720
TRIM54KLHL38psi-mi:“MI:0915”(physical association)0.720
KLHL38BLZF1psi-mi:“MI:0915”(physical association)0.720
KLHL38TRIM42psi-mi:“MI:0915”(physical association)0.720
KRT38KLHL38psi-mi:“MI:0915”(physical association)0.720
KRTAP5-9KLHL38psi-mi:“MI:0915”(physical association)0.720
KRTAP10-7KLHL38psi-mi:“MI:0915”(physical association)0.720
KRT31KLHL38psi-mi:“MI:0915”(physical association)0.720
KLHL38USHBP1psi-mi:“MI:0915”(physical association)0.720
KLHL38TRIM54psi-mi:“MI:0915”(physical association)0.720
KLHL38KRTAP10-8psi-mi:“MI:0915”(physical association)0.720
BLZF1KLHL38psi-mi:“MI:0915”(physical association)0.720

BioGRID (103): KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid), KLHL38 (Two-hybrid)

ESM2 similar proteins: A2AAX3, A2AUC9, B3DIV9, D2HEW7, D3ZA50, D3ZZC3, E9QJ30, G3X9X1, O14682, O35709, O60662, Q08BL9, Q0D2A9, Q1LYM6, Q2TBA0, Q2WGJ6, Q3B7M1, Q4KLM4, Q53GT1, Q56A24, Q5EB39, Q5RCQ9, Q5RDY3, Q5RGB8, Q5U504, Q5U575, Q5ZJU2, Q66HD2, Q6DEL7, Q6DFF7, Q6GQU2, Q6NYM1, Q6Q7X9, Q6TFL4, Q6V595, Q8BRG6, Q8BWA5, Q8CA72, Q8IY47, Q8N4N3

Diamond homologs: A0JN76, A1L2U9, A1YPR0, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, E1B932, G5E8B9, G5ED84, O14867, O15062, O15209, O35260, O43298, O88939, O93567, O95365, O95625, P28575, P41182, P41183, P97302, P97303, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q13939, Q14526, Q1L8W0, Q1LYM6, Q2WGJ6, Q3B7N9, Q3SWU4, Q53G59, Q562B4, Q5R5N5, Q5TC79

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Keratinization2325.1×3e-25
Formation of the cornified envelope813.8×4e-06

GO biological processes:

GO termPartnersFoldFDR
morphogenesis of an epithelium737.0×1e-07
intermediate filament organization829.6×7e-08
epithelial cell differentiation718.9×8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance123
Likely benign3
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

321 predictions. Top by Δscore:

VariantEffectΔscore
8:123646026:AACC:Aacceptor_loss1.0000
8:123646029:C:CCacceptor_gain1.0000
8:123646029:C:CGacceptor_loss1.0000
8:123647015:C:CAacceptor_loss1.0000
8:123646025:TAAC:Tacceptor_gain0.9900
8:123646027:AC:Aacceptor_gain0.9900
8:123646028:CC:Cacceptor_gain0.9900
8:123646030:T:Gacceptor_loss0.9900
8:123646037:C:Tacceptor_gain0.9900
8:123646903:ACTC:Adonor_loss0.9900
8:123646904:CT:Cdonor_loss0.9900
8:123646905:T:TCdonor_loss0.9900
8:123646906:C:CGdonor_loss0.9900
8:123646907:ACC:Adonor_loss0.9900
8:123646907:ACCTC:Adonor_gain0.9900
8:123646908:C:Tdonor_loss0.9900
8:123646908:CCT:Cdonor_gain0.9900
8:123646908:CCTCC:Cdonor_gain0.9900
8:123647010:TAAAC:Tacceptor_gain0.9900
8:123647012:AAC:Aacceptor_gain0.9900
8:123647015:C:CCacceptor_gain0.9900
8:123646024:GTAAC:Gacceptor_gain0.9800
8:123646036:CCAAA:Cacceptor_gain0.9800
8:123646744:T:TAdonor_gain0.9800
8:123646907:A:ACdonor_gain0.9800
8:123646907:ACCT:Adonor_gain0.9800
8:123646908:C:CCdonor_gain0.9800
8:123646908:CCTC:Cdonor_gain0.9800
8:123647011:AAAC:Aacceptor_gain0.9800
8:123647011:AAACC:Aacceptor_gain0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000221852 (8:123653212 T>C), RS1000223787 (8:123651717 A>C,G), RS1000854489 (8:123649301 A>C,G), RS1001136823 (8:123654059 G>A), RS1001364539 (8:123648630 A>T), RS1001382079 (8:123653636 C>A,G,T), RS1001567050 (8:123649138 T>C), RS1001846660 (8:123650334 A>G,T), RS1002210402 (8:123648426 G>A,T), RS1002237669 (8:123653307 A>C), RS1002299171 (8:123650116 C>T), RS1002907419 (8:123651335 G>T), RS1003568810 (8:123651287 G>T), RS1003668666 (8:123647458 G>A,T), RS1004184683 (8:123644719 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

StudyTraitp-value
GCST002542_6Electrocardiographic traits1.000000e-07
GCST006061_84Atrial fibrillation1.000000e-10
GCST006979_368Heel bone mineral density6.000000e-13
GCST007103_17QRS duration4.000000e-15
GCST007104_9QRS duration6.000000e-19
GCST007267_183Systolic blood pressure2.000000e-09
GCST009921_4Carotid intima media thickness (mean)3.000000e-12
GCST010321_123PR interval1.000000e-18
GCST010796_1884Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-08
GCST010796_1885Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-08
GCST010796_1886Electrocardiogram morphology (amplitude at temporal datapoints)4.000000e-08
GCST010796_1887Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-09
GCST010796_1888Electrocardiogram morphology (amplitude at temporal datapoints)4.000000e-08
GCST010796_1889Electrocardiogram morphology (amplitude at temporal datapoints)1.000000e-08
GCST010796_1890Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-09
GCST010796_1891Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-08
GCST010796_1892Electrocardiogram morphology (amplitude at temporal datapoints)5.000000e-09
GCST010796_385Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-16
GCST010796_386Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-18
GCST010796_387Electrocardiogram morphology (amplitude at temporal datapoints)5.000000e-18
GCST010796_388Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-16
GCST010796_389Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-14
GCST010796_390Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-13
GCST010796_391Electrocardiogram morphology (amplitude at temporal datapoints)6.000000e-12
GCST010796_392Electrocardiogram morphology (amplitude at temporal datapoints)1.000000e-11
GCST010796_393Electrocardiogram morphology (amplitude at temporal datapoints)9.000000e-12
GCST010796_394Electrocardiogram morphology (amplitude at temporal datapoints)1.000000e-12
GCST010796_395Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-14
GCST010796_396Electrocardiogram morphology (amplitude at temporal datapoints)1.000000e-14
GCST010796_397Electrocardiogram morphology (amplitude at temporal datapoints)5.000000e-14

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0009270heel bone mineral density
EFO:0006335systolic blood pressure
EFO:0004462PR interval
EFO:0004327electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases methylation1
Benzo(a)pyrenedecreases methylation1
Doxorubicindecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Valproic Acidincreases methylation1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

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
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 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_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot