KLHL30

Summary

KLHL30 (kelch like family member 30, HGNC:24770) is a protein-coding gene on chromosome 2q37.3, encoding Kelch-like protein 30 (Q0D2K2).

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 377007 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_198582

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24770
Approved symbol	KLHL30
Name	kelch like family member 30
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43374
Ensembl gene	ENSG00000168427
Ensembl biotype	protein_coding
Entrez	377007

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000409223, ENST00000964871, ENST00000964872, ENST00000964873

RefSeq mRNA: 1 — MANE Select: NM_198582 NM_198582

CCDS: CCDS46555

Canonical transcript exons

ENST00000409223 — 8 exons

Exon	Start	End
ENSE00001373233	238144902	238144988
ENSE00001387818	238142799	238142931
ENSE00001503794	238149007	238149152
ENSE00001503795	238147834	238148022
ENSE00001503796	238145677	238145832
ENSE00001578675	238150814	238152947
ENSE00001582411	238138668	238138758
ENSE00001586298	238140685	238141528

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 96.13.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2143 / max 139.9450, expressed in 293 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26325	0.7213	242
26326	0.4353	171
26327	0.0427	11
202626	0.0150	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.13	gold quality
skeletal muscle tissue	UBERON:0001134	95.36	gold quality
quadriceps femoris	UBERON:0001377	95.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.23	gold quality
muscle of leg	UBERON:0001383	93.98	gold quality
apex of heart	UBERON:0002098	87.83	gold quality
cerebellar vermis	UBERON:0004720	87.65	gold quality
muscle tissue	UBERON:0002385	85.14	gold quality
heart left ventricle	UBERON:0002084	83.69	gold quality
right atrium auricular region	UBERON:0006631	82.43	gold quality
heart	UBERON:0000948	81.77	gold quality
right coronary artery	UBERON:0001625	81.02	gold quality
popliteal artery	UBERON:0002250	80.68	gold quality
tibial artery	UBERON:0007610	80.66	gold quality
ascending aorta	UBERON:0001496	78.93	gold quality
thoracic aorta	UBERON:0001515	78.73	gold quality
left coronary artery	UBERON:0001626	77.81	gold quality
descending thoracic aorta	UBERON:0002345	75.42	gold quality
mucosa of stomach	UBERON:0001199	71.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.10	gold quality
thymus	UBERON:0002370	67.22	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	66.36	gold quality
adipose tissue	UBERON:0001013	65.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.43	gold quality
lower esophagus	UBERON:0013473	63.31	gold quality
endocervix	UBERON:0000458	62.98	gold quality
myometrium	UBERON:0001296	61.10	gold quality
urinary bladder	UBERON:0001255	60.89	gold quality
colonic epithelium	UBERON:0000397	60.67	silver quality
omental fat pad	UBERON:0010414	60.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting KLHL30, 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-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-6787-3P	97.75	66.17	1233

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl30	ENSDARG00000076094
mus_musculus	Klhl30	ENSMUSG00000026308
rattus_norvegicus	Klhl30	ENSRNOG00000020105

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), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 30 — Q0D2K2 (reviewed: Q0D2K2)

All UniProt accessions (1): Q0D2K2

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_940984* (*=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
IPR030582	KLHL30_BACK	Domain

Pfam: PF00651, PF07707, PF24681

UniProt features (13 total): repeat 6, sequence conflict 4, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0D2K2-F1	87.12	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, 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, GOCC_UBIQUITIN_LIGASE_COMPLEX, LI_INDUCED_T_TO_NATURAL_KILLER_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, KATSANOU_ELAVL1_TARGETS_UP, SUNG_METASTASIS_STROMA_DN, GSE14415_NATURAL_TREG_VS_FOXP3_KO_NATURAL_TREG_DN

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

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL30	NIF3L1	Q9GZT8	536
KLHL30	NANP	Q8TBE9	505
KLHL30	DIPK1C	Q0P6D2	465
KLHL30	METTL8	Q9H825	462
KLHL30	WDR33	Q9C0J8	453
KLHL30	PRPF40A	O75400	445
KLHL30	SUSD4	Q5VX71	444
KLHL30	DRC8	Q5VUJ9	442
KLHL30	C1orf50	Q9BV19	396
KLHL30	TRIM55	Q9BYV6	389
KLHL30	UBR3	Q6ZT12	376
KLHL30	HEATR9	A2RTY3	370
KLHL30	HRC	P23327	367
KLHL30	KATNAL2	Q8IYT4	357
KLHL30	FBXO40	Q9UH90	351

IntAct

0 interactions, top by confidence:

BioGRID (1): KLHL30 (Affinity Capture-Western)

ESM2 similar proteins: A6NED2, D2HEW7, D3ZZC3, D4A2K4, E1BNS0, E2RKN7, O35709, O60294, O94819, Q08BL9, Q08DS0, Q0D2K2, Q2TBA0, Q2WGJ6, Q3B7M1, Q3U410, Q4R828, Q53GT1, Q53HC5, Q5BK60, Q5U575, Q5ZJ37, Q66HD2, Q6DEL7, Q6E804, Q6INL2, Q6NYM1, Q6PF15, Q6TDP4, Q8BFQ9, Q8BGY4, Q8BNW9, Q8BSF5, Q8BYR1, Q8C3F7, Q8N239, Q8N4N3, Q8NEP7, Q8R2P1, Q8TD43

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, E9Q4F2, O15062, O15156, O15209, O43167, O88282, O88939, O93567, O94889, O95365, P10074, P24278, P41182, P41183, P52739, P97302, Q0D2K2, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q3B725, Q3B7M1, Q3B7N9, Q3SWU4, Q53HC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2071 predictions. Top by Δscore:

Variant	Effect	Δscore
2:238140681:CTA:C	acceptor_loss	1.0000
2:238140682:TA:T	acceptor_loss	1.0000
2:238140683:A:AC	acceptor_loss	1.0000
2:238140683:A:AG	acceptor_gain	1.0000
2:238140683:AG:A	acceptor_gain	1.0000
2:238140684:G:GT	acceptor_gain	1.0000
2:238140684:GG:G	acceptor_gain	1.0000
2:238140684:GGA:G	acceptor_gain	1.0000
2:238140684:GGAGC:G	acceptor_gain	1.0000
2:238142932:G:GG	donor_gain	1.0000
2:238144896:T:A	acceptor_gain	1.0000
2:238144899:CAGA:C	acceptor_loss	1.0000
2:238144900:A:AC	acceptor_loss	1.0000
2:238144901:GA:G	acceptor_gain	1.0000
2:238144901:GAGA:G	acceptor_gain	1.0000
2:238147832:A:AG	acceptor_gain	1.0000
2:238147832:AG:A	acceptor_gain	1.0000
2:238147832:AGG:A	acceptor_loss	1.0000
2:238147833:G:GA	acceptor_gain	1.0000
2:238147833:GG:G	acceptor_gain	1.0000
2:238147833:GGC:G	acceptor_gain	1.0000
2:238147833:GGCA:G	acceptor_gain	1.0000
2:238147833:GGCAC:G	acceptor_gain	1.0000
2:238148018:CACAG:C	donor_loss	1.0000
2:238148021:AGGT:A	donor_loss	1.0000
2:238148022:GG:G	donor_loss	1.0000
2:238148023:G:GA	donor_loss	1.0000
2:238148024:T:A	donor_loss	1.0000
2:238149043:A:G	acceptor_gain	1.0000
2:238140326:G:GT	donor_gain	0.9900

AlphaMissense

3710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:238140917:A:C	S55R	0.996
2:238140919:C:A	S55R	0.996
2:238140919:C:G	S55R	0.996
2:238149012:T:A	W449R	0.996
2:238149012:T:C	W449R	0.996
2:238149123:T:G	Y486D	0.995
2:238145782:G:C	R367P	0.993
2:238140927:T:C	F58S	0.992
2:238140939:T:C	F62S	0.991
2:238145796:A:C	S372R	0.991
2:238145798:C:A	S372R	0.991
2:238145798:C:G	S372R	0.991
2:238141361:T:A	W203R	0.990
2:238141361:T:C	W203R	0.990
2:238147887:T:A	W402R	0.990
2:238147887:T:C	W402R	0.990
2:238149144:T:A	W493R	0.990
2:238149144:T:C	W493R	0.990
2:238141047:T:A	I98N	0.988
2:238141159:C:G	C135W	0.988
2:238141223:T:C	F157L	0.988
2:238141225:C:A	F157L	0.988
2:238141225:C:G	F157L	0.988
2:238144983:T:A	V330D	0.988
2:238141022:T:C	F90L	0.987
2:238141024:C:A	F90L	0.987
2:238141024:C:G	F90L	0.987
2:238141363:G:C	W203C	0.987
2:238141363:G:T	W203C	0.987
2:238141131:T:C	L126P	0.986

dbSNP variants (sampled 300 via entrez): RS1000022282 (2:238144331 T>C), RS1000322075 (2:238143817 G>A,T), RS1000366279 (2:238137427 G>T), RS1000371939 (2:238150617 C>T), RS1000503421 (2:238140536 A>G,T), RS1000559754 (2:238144837 G>A), RS1001221499 (2:238138696 G>A,T), RS1001394677 (2:238146483 T>C,G), RS1001464796 (2:238145294 T>C,G), RS1001723710 (2:238143008 T>TG), RS1002172606 (2:238139589 T>G), RS1002271984 (2:238148626 G>A,T), RS1002341512 (2:238140311 G>A,T), RS1002405846 (2:238148429 T>C), RS1002714429 (2:238152168 G>A)

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

1 associations (top):

Study	Trait	p-value
GCST004379_13	Red blood cell density in sickle cell anemia	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
deoxynivalenol	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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