KLHL32

Summary

KLHL32 (kelch like family member 32, HGNC:21221) is a protein-coding gene on chromosome 6q16.1, encoding Kelch-like protein 32 (Q96NJ5).

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_052904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21221
Approved symbol	KLHL32
Name	kelch like family member 32
Location	6q16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186231
Ensembl biotype	protein_coding
Entrez	114792

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000369254, ENST00000369261, ENST00000447886, ENST00000536676, ENST00000539200, ENST00000544166, ENST00000620278, ENST00000859766, ENST00000859767, ENST00000951638, ENST00000951639

RefSeq mRNA: 17 — MANE Select: NM_052904 NM_001286250, NM_001286251, NM_001286252, NM_001286254, NM_001323252, NM_001323253, NM_001323254, NM_001323255, NM_001323256, NM_001323257, NM_001323258, NM_001323259, NM_001323260, NM_001323261, NM_001323263, NM_001323264, NM_052904

CCDS: CCDS5038, CCDS69154, CCDS69155, CCDS75495

Canonical transcript exons

ENST00000369261 — 11 exons

Exon	Start	End
ENSE00001338741	97085126	97085341
ENSE00001863015	96924728	96925026
ENSE00002437187	97132653	97132747
ENSE00002498781	97113783	97114509
ENSE00002535103	97130757	97130949
ENSE00003479806	97127404	97127462
ENSE00003484435	97064628	97064726
ENSE00003502937	96975997	96976177
ENSE00003597268	96966996	96967083
ENSE00003605185	97041492	97041599
ENSE00003847558	97139121	97140753

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 93.05.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2416 / max 976.9348, expressed in 381 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68951	4.3465	262
68953	0.5580	151
68949	0.5065	120
68947	0.4651	101
68952	0.3512	112
68955	0.3145	102
68950	0.2389	90
68957	0.1152	36
68954	0.1042	64
68946	0.0871	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.05	gold quality
corpus callosum	UBERON:0002336	90.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.52	gold quality
spinal cord	UBERON:0002240	87.43	gold quality
substantia nigra	UBERON:0002038	84.36	gold quality
endothelial cell	CL:0000115	84.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.26	gold quality
prefrontal cortex	UBERON:0000451	83.23	gold quality
midbrain	UBERON:0001891	83.16	gold quality
hypothalamus	UBERON:0001898	83.07	gold quality
oocyte	CL:0000023	81.50	gold quality
caudate nucleus	UBERON:0001873	81.18	gold quality
amygdala	UBERON:0001876	81.09	gold quality
Ammon’s horn	UBERON:0001954	80.73	gold quality
putamen	UBERON:0001874	80.68	gold quality
anterior cingulate cortex	UBERON:0009835	80.56	gold quality
inferior vagus X ganglion	UBERON:0005363	80.43	gold quality
secondary oocyte	CL:0000655	80.35	gold quality
right uterine tube	UBERON:0001302	80.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.01	gold quality
subthalamic nucleus	UBERON:0001906	79.68	gold quality
neocortex	UBERON:0001950	79.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	79.36	gold quality
frontal cortex	UBERON:0001870	79.26	gold quality
right frontal lobe	UBERON:0002810	79.23	gold quality
nucleus accumbens	UBERON:0001882	79.00	gold quality
cerebral cortex	UBERON:0000956	78.81	gold quality
globus pallidus	UBERON:0001875	78.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.77	gold quality
medial globus pallidus	UBERON:0002477	78.76	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	74.63
E-ANND-3	no	3.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting KLHL32, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl32	ENSDARG00000003576
mus_musculus	Klhl32	ENSMUSG00000040387
rattus_norvegicus	Klhl32	ENSRNOG00000007441

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 32 — Q96NJ5 (reviewed: Q96NJ5)

Alternative names: BTB and kelch domain-containing protein 5

All UniProt accessions (5): A0A087WYQ8, Q96NJ5, Q5THS9, Q5THT1, Q8IXH0

Isoforms (3)

UniProt ID	Names	Canonical?
Q96NJ5-1	1	yes
Q96NJ5-2	2
Q96NJ5-3	3

RefSeq proteins (17): NP_001273179, NP_001273180, NP_001273181, NP_001273183, NP_001310181, NP_001310182, NP_001310183, NP_001310184, NP_001310185, NP_001310186, NP_001310187, NP_001310188, NP_001310189, NP_001310190, NP_001310192, NP_001310193, NP_443136* (*=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
IPR030570	BTB_POZ_KLHL32	Domain
IPR047028	KLHL32_BACK	Domain
IPR056737	Beta-prop_ATRN-MKLN-like	Domain

Pfam: PF00651, PF07707, PF24981

UniProt features (14 total): repeat 6, sequence variant 3, splice variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NJ5-F1	90.01	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, AACTTT_UNKNOWN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, CTTTGTA_MIR524, MODULE_95, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_CUL3_RING_UBIQUITIN_LIGASE_COMPLEX, WGTTNNNNNAAA_UNKNOWN, GOCC_UBIQUITIN_LIGASE_COMPLEX, ROVERSI_GLIOMA_COPY_NUMBER_DN, TCANNTGAY_SREBP1_01

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL32	GPR63	Q9BZJ6	668
KLHL32	MMS22L	Q6ZRQ5	593
KLHL32	COXFA4	O00483	557
KLHL32	ZFAND4	Q86XD8	535
KLHL32	NDUFAF4	Q9P032	532
KLHL32	GALNT10	Q86SR1	477
KLHL32	C3orf22	Q8N5N4	475
KLHL32	XPNPEP1	Q9NQW7	456
KLHL32	ANTXRL	A6NF34	452
KLHL32	FUT6	P51993	446
KLHL32	SMAD1	Q15797	442
KLHL32	MANEA	Q5SRI9	441
KLHL32	RNASE12	Q5GAN4	437
KLHL32	SMIM17	P0DL12	435
KLHL32	BLOC1S2	Q6QNY1	430

IntAct

18 interactions, top by confidence:

A	B	Type	Score
KLHL32	MAPK3	psi-mi:“MI:0915”(physical association)	0.560
KLHL32	ICAM5	psi-mi:“MI:0915”(physical association)	0.560
KLF11	KLHL32	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	KLHL32	psi-mi:“MI:0915”(physical association)	0.560
HSP90AB1	KLHL32	psi-mi:“MI:0915”(physical association)	0.400
KLHL32	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
KLHL32	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	KLHL32	psi-mi:“MI:0915”(physical association)	0.370
KLHL32	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), KLHL32 (Two-hybrid), APP (Reconstituted Complex), KLHL32 (Affinity Capture-Luminescence), CDK4 (Affinity Capture-MS)

ESM2 similar proteins: A1A5C7, A5D7B1, A6H7A0, A6NCF5, A6QLN9, A8MUP2, D3YYU8, D3ZZ80, O43688, O75147, O88843, P08887, Q14CX5, Q3SZQ2, Q3UHH2, Q58CT4, Q5EA19, Q5R4Q7, Q5R7S9, Q5RCI5, Q5RFN0, Q5SP67, Q5SUV1, Q642A6, Q6IA17, Q6PCB0, Q7TPB4, Q86TI4, Q8BGR6, Q8BZI6, Q8K5A4, Q8N5I2, Q8N653, Q8R2Z5, Q8TBF2, Q8VE98, Q92737, Q969P0, Q96NJ5, Q96NT3

Diamond homologs: A0A0A6YY25, B2RXH4, E0CZ16, E1B932, E7F6F9, F1LZ52, F1LZF0, F1MBP6, O88282, O93567, O95198, P10074, P17789, P42282, P42283, P42284, Q01295, Q1H9T6, Q24174, Q24206, Q3B7M1, Q52KG4, Q53G59, Q53HC5, Q5R633, Q5REP9, Q5U374, Q66HD2, Q6NRH0, Q7KQZ4, Q7KRI2, Q867Z4, Q86B87, Q8BGY4, Q8BZM0, Q8CA72, Q8IN81, Q8JZP3, Q8K0L9, Q8N143

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3693 predictions. Top by Δscore:

Variant	Effect	Δscore
6:96967079:CTCAG:C	donor_loss	1.0000
6:96967080:TCAG:T	donor_loss	1.0000
6:96967081:CAG:C	donor_loss	1.0000
6:96967082:AG:A	donor_loss	1.0000
6:96967083:GG:G	donor_loss	1.0000
6:96967084:G:A	donor_loss	1.0000
6:96967085:T:G	donor_loss	1.0000
6:96975995:A:AG	acceptor_gain	1.0000
6:96975996:G:GG	acceptor_gain	1.0000
6:96976174:CCGGG:C	donor_loss	1.0000
6:96976175:CGGGT:C	donor_loss	1.0000
6:96976176:GG:G	donor_gain	1.0000
6:96976177:GG:G	donor_gain	1.0000
6:96976178:G:GG	donor_gain	1.0000
6:96976178:GTA:G	donor_loss	1.0000
6:96976179:T:G	donor_loss	1.0000
6:97064617:A:AG	acceptor_gain	1.0000
6:97064618:A:G	acceptor_gain	1.0000
6:97113782:GCTA:G	acceptor_gain	1.0000
6:97130755:A:AG	acceptor_gain	1.0000
6:97130756:G:GG	acceptor_gain	1.0000
6:97130756:GA:G	acceptor_gain	1.0000
6:97130756:GAAT:G	acceptor_gain	1.0000
6:97130756:GAATA:G	acceptor_gain	1.0000
6:96925023:TCGGG:T	donor_loss	0.9900
6:96925025:GG:G	donor_gain	0.9900
6:96925025:GGGTA:G	donor_loss	0.9900
6:96925026:GG:G	donor_gain	0.9900
6:96925026:GGT:G	donor_loss	0.9900
6:96925027:G:GA	donor_loss	0.9900

AlphaMissense

4084 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:97114210:G:A	G352E	1.000
6:97114365:G:T	G404W	1.000
6:97114366:G:A	G404E	1.000
6:97114431:T:A	W426R	1.000
6:97114431:T:C	W426R	1.000
6:97114433:G:C	W426C	1.000
6:97114433:G:T	W426C	1.000
6:97127404:G:A	G452D	1.000
6:97127407:G:A	G453E	1.000
6:97130763:T:A	W474R	1.000
6:97130763:T:C	W474R	1.000
6:97130842:G:A	G500E	1.000
6:97130845:G:T	G501V	1.000
6:97130898:T:G	Y519D	1.000
6:97130919:T:A	W526R	1.000
6:97130919:T:C	W526R	1.000
6:97130921:G:C	W526C	1.000
6:97130921:G:T	W526C	1.000
6:97132707:G:A	G554E	1.000
6:96976110:T:A	L46Q	0.999
6:96976110:T:C	L46P	0.999
6:96976137:C:A	A55D	0.999
6:96976149:T:A	V59D	0.999
6:96976152:T:C	L60P	0.999
6:96976163:A:C	S64R	0.999
6:96976165:T:A	S64R	0.999
6:96976165:T:G	S64R	0.999
6:97041562:G:A	G92D	0.999
6:97041582:T:C	F99L	0.999
6:97041584:T:A	F99L	0.999

dbSNP variants (sampled 300 via entrez): RS1000025984 (6:97054903 C>G,T), RS1000037189 (6:97130008 T>C), RS1000051152 (6:97109640 C>T), RS1000058964 (6:97005769 T>G), RS1000103869 (6:96915830 C>A), RS1000106987 (6:97022017 C>G), RS1000124157 (6:97004166 T>C), RS1000129765 (6:97138176 C>A,G,T), RS1000144871 (6:96929417 AG>A), RS1000174978 (6:96914203 T>A), RS1000177960 (6:97079706 CAAAT>C), RS1000182519 (6:97091101 C>G), RS1000193048 (6:97048176 G>C), RS1000194295 (6:96941489 T>G), RS1000195395 (6:96999401 C>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

17 associations (top):

Study	Trait	p-value
GCST001967_6	Body mass index	6.000000e-06
GCST002072_1	Multiple sclerosis (OCB status)	9.000000e-07
GCST002497_10	Blood pressure	5.000000e-07
GCST003263_53	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST003263_55	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST003263_56	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST003263_57	Post bronchodilator FEV1 in COPD	1.000000e-06
GCST003265_257	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_258	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_259	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_260	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST004519_15	Body mass index (adult)	6.000000e-09
GCST004519_22	Body mass index (adult)	6.000000e-09
GCST004519_5	Body mass index (adult)	2.000000e-07
GCST009391_819	Metabolite levels	7.000000e-07
GCST011122_61	Walking pace	2.000000e-10
GCST011176_3	Stroke	2.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0010398	sphingomyelin 24:1 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.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis, affects methylation	3
Arsenic	affects methylation, increases methylation	2
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
ferrous chloride	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Caffeine	decreases phosphorylation	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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