KLHL23

Summary

KLHL23 (kelch like family member 23, HGNC:27506) is a protein-coding gene on chromosome 2q31.1, encoding Kelch-like protein 23 (Q8NBE8).

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

Source: NCBI Gene 151230 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_144711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27506
Approved symbol	KLHL23
Name	kelch like family member 23
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC2610, FLJ37812, MGC22679
Ensembl gene	ENSG00000213160
Ensembl biotype	protein_coding
Entrez	151230

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000272797, ENST00000392647, ENST00000437875, ENST00000448589, ENST00000494387, ENST00000498202, ENST00000602521, ENST00000919244, ENST00000962027

RefSeq mRNA: 2 — MANE Select: NM_144711 NM_001199290, NM_144711

Canonical transcript exons

ENST00000392647 — 4 exons

Exon	Start	End
ENSE00000964744	169735013	169736227
ENSE00001489823	169749422	169751878
ENSE00001512635	169733832	169734087
ENSE00003469676	169741385	169741537

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6886 / max 96.0136, expressed in 1087 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23564	5.7217	1471
23567	4.9632	941
23568	1.2235	508
23570	0.2291	94
23569	0.1680	73
23565	0.1048	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.06	gold quality
ganglionic eminence	UBERON:0004023	95.27	gold quality
embryo	UBERON:0000922	95.07	gold quality
ventricular zone	UBERON:0003053	94.62	gold quality
endothelial cell	CL:0000115	90.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.91	gold quality
sigmoid colon	UBERON:0001159	87.34	gold quality
myometrium	UBERON:0001296	86.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.56	gold quality
lower esophagus	UBERON:0013473	86.53	gold quality
germinal epithelium of ovary	UBERON:0001304	86.29	gold quality
colonic epithelium	UBERON:0000397	86.22	gold quality
body of uterus	UBERON:0009853	86.09	gold quality
smooth muscle tissue	UBERON:0001135	86.08	gold quality
middle temporal gyrus	UBERON:0002771	86.02	silver quality
cauda epididymis	UBERON:0004360	85.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.60	gold quality
saphenous vein	UBERON:0007318	85.48	gold quality
seminal vesicle	UBERON:0000998	85.17	gold quality
jejunum	UBERON:0002115	84.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.82	gold quality
ovary	UBERON:0000992	84.45	gold quality
rectum	UBERON:0001052	84.17	gold quality
pigmented layer of retina	UBERON:0001782	83.68	gold quality
left ovary	UBERON:0002119	83.58	gold quality
large intestine	UBERON:0000059	83.49	gold quality
heart right ventricle	UBERON:0002080	83.40	silver quality
colon	UBERON:0001155	83.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.32	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	248.45
E-ANND-3	yes	11.83
E-CURD-114	yes	10.44
E-CURD-112	yes	8.82
E-MTAB-6108	no	208.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting KLHL23, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-507	99.97	70.11	1915
HSA-LET-7D-5P	99.96	71.76	1632

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl23	ENSDARG00000078475
mus_musculus	Klhl23	ENSMUSG00000042155
rattus_norvegicus	Klhl23	ENSRNOG00000007981

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), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359)

Protein

Protein identifiers

Kelch-like protein 23 — Q8NBE8 (reviewed: Q8NBE8)

All UniProt accessions (5): Q8NBE8, H7C0F4, H7C1K9, S4R3P4, S4R452

RefSeq proteins (2): NP_001186219, NP_653312* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR030566	BTB_POZ_KLHL23	Domain
IPR047068	KLHL23_BACK	Domain

Pfam: PF00651, PF01344, PF07707, PF24681

UniProt features (9 total): repeat 6, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBE8-F1	90.19	0.69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): AREB6_03, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, MORF_RAD51L3, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, SCHLOSSER_SERUM_RESPONSE_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, MORF_THPO, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, YY1_01, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, MORF_ATF2, BIDUS_METASTASIS_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:

Category	Terms
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
enzyme-substrate adaptor activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL23	PHOSPHO2	Q8TCD6	608
KLHL23	ZNF551	P17034	599
KLHL23	DCDC2C	A8MYV0	506
KLHL23	A6NDT3	A6NDT3	505
KLHL23	KNCN	A6PVL3	485
KLHL23	A0A0A6YYL6	A0A0A6YYL6	479
KLHL23	DCDC2B	A2VCK2	478
KLHL23	H7C0V5	H7C0V5	447
KLHL23	FOXL3	A0A1W2PRP0	437
KLHL23	LSMEM2	Q8N112	418
KLHL23	SETD4	Q9NVD3	412
KLHL23	HHLA1	C9JL84	394
KLHL23	OR2T4	Q8NH00	377
KLHL23	C18orf32	Q8TCD1	366
KLHL23	C5orf24	Q7Z6I8	358

IntAct

54 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
OSBPL5	NAGLU	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
KLHL23	NUDCD3	psi-mi:“MI:0915”(physical association)	0.640
AMDHD1	KLHL23	psi-mi:“MI:0915”(physical association)	0.590
VHL	KLHL23	psi-mi:“MI:0915”(physical association)	0.560
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
CCN2	LRP2	psi-mi:“MI:0914”(association)	0.530
PLS3	PLS1	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
ACOT8	PML	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	KLHL23	psi-mi:“MI:0915”(physical association)	0.400
KLHL23	ANXA1	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	KLHL23	psi-mi:“MI:0915”(physical association)	0.370
BNIP3L	KLHL23	psi-mi:“MI:0915”(physical association)	0.370
CDKN1A	KLHL23	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (55): KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS)

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: A0A1B8YAB1, A2APT9, A6QQY2, C9JR72, O82374, O82378, Q2T9Z7, Q3B7M1, Q5R866, Q5RCQ9, Q5VTJ3, Q5ZLD3, Q6GQU2, Q6ZPT1, Q80TF4, Q8C828, Q8N239, Q8N4N3, Q8NBE8, Q9P2J3, Q9P2N7, A2AAX3, A4IFG2, B0WWP2, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, D3YUB6, D3Z8N4, D3ZA50, D4A0X3, D4A2K4, O22891

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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:

Pathway	Partners	Fold	FDR
Neddylation	7	7.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell differentiation	5	23.5×	1e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	7	6.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1527 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169694627:G:GG	donor_gain	1.0000
2:169741434:T:TA	acceptor_gain	1.0000
2:169749417:A:AG	acceptor_gain	0.9900
2:169749418:A:G	acceptor_gain	0.9900
2:169749420:A:G	acceptor_gain	0.9900
2:169694518:GGCTT:G	donor_gain	0.9800
2:169694519:GCTT:G	donor_gain	0.9800
2:169694519:GCTTG:G	donor_gain	0.9800
2:169694523:G:GG	donor_gain	0.9800
2:169694799:TG:T	donor_gain	0.9800
2:169694800:GG:G	donor_gain	0.9800
2:169701122:GTCTT:G	donor_gain	0.9800
2:169701123:TCTTT:T	donor_gain	0.9800
2:169741384:GGT:G	acceptor_gain	0.9800
2:169741415:AT:A	acceptor_gain	0.9800
2:169741416:T:G	acceptor_gain	0.9800
2:169741432:ATT:A	acceptor_gain	0.9800
2:169749419:AAG:A	acceptor_loss	0.9800
2:169749420:A:AT	acceptor_loss	0.9800
2:169749421:G:GG	acceptor_gain	0.9800
2:169749421:GA:G	acceptor_gain	0.9800
2:169694623:GTCA:G	donor_gain	0.9700
2:169694626:A:AG	donor_gain	0.9700
2:169695244:GCTG:G	donor_gain	0.9700
2:169695247:GGTA:G	donor_loss	0.9700
2:169695248:G:GG	donor_gain	0.9700
2:169695248:GT:G	donor_loss	0.9700
2:169695249:TAA:T	donor_loss	0.9700
2:169695249:TAAG:T	donor_loss	0.9700
2:169695250:A:AG	donor_loss	0.9700

AlphaMissense

3700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169735990:G:T	G326W	1.000
2:169749664:T:A	W537R	1.000
2:169749664:T:C	W537R	1.000
2:169735354:G:C	A114P	0.999
2:169735633:T:A	W207R	0.999
2:169735633:T:C	W207R	0.999
2:169735850:G:A	G279E	0.999
2:169735909:T:A	W299R	0.999
2:169735909:T:C	W299R	0.999
2:169735991:G:A	G326E	0.999
2:169736059:T:A	W349R	0.999
2:169736059:T:C	W349R	0.999
2:169736200:T:A	W396R	0.999
2:169736200:T:C	W396R	0.999
2:169736202:G:C	W396C	0.999
2:169736202:G:T	W396C	0.999
2:169741439:G:A	G423D	0.999
2:169741507:T:A	W446R	0.999
2:169741507:T:C	W446R	0.999
2:169749517:T:A	W488R	0.999
2:169749517:T:C	W488R	0.999
2:169749549:G:C	R498S	0.999
2:169749549:G:T	R498S	0.999
2:169749596:G:A	G514E	0.999
2:169749596:G:T	G514V	0.999
2:169749599:G:A	G515E	0.999
2:169749643:T:G	Y530D	0.999
2:169749666:G:C	W537C	0.999
2:169749666:G:T	W537C	0.999
2:169735189:A:C	S59R	0.998

dbSNP variants (sampled 300 via entrez): RS1000065296 (2:169734341 C>G), RS1000069295 (2:169746863 C>A,G), RS1000177785 (2:169740281 T>G), RS1000280247 (2:169737551 C>T), RS1000332388 (2:169737294 C>T), RS1000383592 (2:169733520 C>T), RS1001017526 (2:169748589 A>G), RS1001115117 (2:169745441 A>G), RS1001269478 (2:169742619 A>G), RS1001334061 (2:169738607 C>T), RS1001400913 (2:169745189 C>T), RS1001545828 (2:169745340 A>G), RS1001736090 (2:169748111 A>G), RS1001868002 (2:169744346 A>G), RS1001932640 (2:169745680 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

4 associations (top):

Study	Trait	p-value
GCST001762_716	Obesity-related traits	6.000000e-06
GCST005184_8	Common carotid intima-media thickness in HIV infection	5.000000e-06
GCST90002400_338	Plateletcrit	7.000000e-11
GCST90002402_281	Platelet count	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, decreases methylation, affects cotreatment	6
trichostatin A	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
alpha phellandrene	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
resorcinol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Demecolcine	decreases expression	1
Dietary Carbohydrates	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Oxygen	decreases expression	1
Ozone	affects expression, increases abundance	1
Rifampin	decreases expression	1
Urethane	decreases expression	1
Vincristine	decreases expression	1
Zinc	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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