KLHL36

Summary

KLHL36 (kelch like family member 36, HGNC:17844) is a protein-coding gene on chromosome 16q24.1, encoding Kelch-like protein 36 (Q8N4N3). Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Enables cullin family protein binding activity. Predicted to be involved in protein ubiquitination.

Source: NCBI Gene 79786 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 146 total
• MANE Select transcript: NM_024731

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17844
Approved symbol	KLHL36
Name	kelch like family member 36
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12543
Ensembl gene	ENSG00000135686
Ensembl biotype	protein_coding
Entrez	79786

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000258157, ENST00000325279, ENST00000564159, ENST00000564996, ENST00000565743, ENST00000567410, ENST00000569472, ENST00000861561, ENST00000861562, ENST00000861563, ENST00000923923, ENST00000949874, ENST00000949875, ENST00000949876

RefSeq mRNA: 2 — MANE Select: NM_024731 NM_001303451, NM_024731

CCDS: CCDS10948, CCDS76909

Canonical transcript exons

ENST00000564996 — 5 exons

Exon	Start	End
ENSE00001175192	84650852	84650930
ENSE00001228516	84648511	84648649
ENSE00001228526	84656871	84657944
ENSE00003462776	84659760	84659917
ENSE00003849168	84661578	84667686

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3780 / max 223.1221, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155335	18.3780	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	94.64	gold quality
cardia of stomach	UBERON:0001162	93.32	gold quality
heart right ventricle	UBERON:0002080	93.05	gold quality
adult organism	UBERON:0007023	92.86	gold quality
renal medulla	UBERON:0000362	92.78	gold quality
skin of hip	UBERON:0001554	92.69	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.28	gold quality
germinal epithelium of ovary	UBERON:0001304	92.11	gold quality
oral cavity	UBERON:0000167	91.79	gold quality
pylorus	UBERON:0001166	91.64	gold quality
vena cava	UBERON:0004087	91.56	gold quality
colonic mucosa	UBERON:0000317	91.51	gold quality
superficial temporal artery	UBERON:0001614	91.51	gold quality
corpus epididymis	UBERON:0004359	91.50	gold quality
cerebellar vermis	UBERON:0004720	91.48	gold quality
jejunal mucosa	UBERON:0000399	91.38	gold quality
jejunum	UBERON:0002115	90.79	gold quality
cauda epididymis	UBERON:0004360	90.70	gold quality
parietal pleura	UBERON:0002400	90.69	gold quality
parotid gland	UBERON:0001831	90.63	gold quality
caput epididymis	UBERON:0004358	90.61	gold quality
pigmented layer of retina	UBERON:0001782	90.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.92	gold quality
saphenous vein	UBERON:0007318	89.91	gold quality
synovial joint	UBERON:0002217	89.84	gold quality
body of tongue	UBERON:0011876	89.71	gold quality
urethra	UBERON:0000057	89.63	gold quality
mammary duct	UBERON:0001765	89.58	gold quality
bronchial epithelial cell	CL:0002328	89.57	gold quality
eye	UBERON:0000970	89.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting KLHL36, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl36	ENSDARG00000030251
mus_musculus	Klhl36	ENSMUSG00000031828
rattus_norvegicus	Klhl36	ENSRNOG00000016422

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), 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), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 36 — Q8N4N3 (reviewed: Q8N4N3)

All UniProt accessions (4): Q8N4N3, H3BPB9, H3BQE9, H3BQW5

UniProt curated annotations — full annotation on UniProt →

Function. Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Subunit / interactions. Interacts with CUL3.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N4N3-1	1	yes
Q8N4N3-2	2

RefSeq proteins (2): NP_001290380, NP_079007* (*=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

Pfam: PF00651, PF01344, PF07707, PF24681

UniProt features (13 total): repeat 6, domain 2, chain 1, compositionally biased region 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4N3-F1	91.36	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): MODULE_255, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, TGACCTY_ERR1_Q2, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, AACTTT_UNKNOWN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, TGACCTTG_SF1_Q6, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX, LEIN_MEDULLA_MARKERS, MODULE_69, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX

GO Biological Process (1): protein ubiquitination (GO:0016567)

GO Molecular Function (2): cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification by small protein conjugation	1
protein binding	1
binding	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL36	KIAA0513	O60268	677
KLHL36	CIBAR2	Q6ZTR7	626
KLHL36	DCLK2	Q8N568	581
KLHL36	SLC15A5	A6NIM6	571
KLHL36	SSMEM1	Q8WWF3	447
KLHL36	CFAP77	Q6ZQR2	447
KLHL36	OR4D1	Q15615	436
KLHL36	REXO4	Q9GZR2	403
KLHL36	TMEM121B	Q9BXQ6	397
KLHL36	FAM114A2	Q9NRY5	350
KLHL36	IGDCC4	Q8TDY8	345
KLHL36	CCDC14	Q49A88	329
KLHL36	FBXW12	Q6X9E4	324
KLHL36	DDRGK1	Q96HY6	315
KLHL36	TMEM171	Q8WVE6	313

IntAct

62 interactions, top by confidence:

A	B	Type	Score
APEX1	KLHL36	psi-mi:“MI:0915”(physical association)	0.560
HEXB	KLHL36	psi-mi:“MI:0915”(physical association)	0.560
KLHL36		psi-mi:“MI:0915”(physical association)	0.560
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
AAR2	SNRNP200	psi-mi:“MI:0914”(association)	0.530
ITM2A	NDUFB5	psi-mi:“MI:0914”(association)	0.530
KLHL36	HSPA8	psi-mi:“MI:0914”(association)	0.530
EIF1AY	EIF1AX	psi-mi:“MI:0914”(association)	0.530
STEEP1	KLHL36	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
HMGN2	GBE1	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
SLC6A15	CLGN	psi-mi:“MI:0914”(association)	0.530
PDAP1	KLHL36	psi-mi:“MI:0915”(physical association)	0.500
PACRG	KLHL36	psi-mi:“MI:0915”(physical association)	0.400
SUN5	KLHL36	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (67): KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), KLHL36 (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: 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

146 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

895 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84648693:G:GT	donor_gain	1.0000
16:84656865:GTCCA:G	acceptor_loss	1.0000
16:84656866:TCCA:T	acceptor_loss	1.0000
16:84656867:CCAG:C	acceptor_loss	1.0000
16:84656868:CA:C	acceptor_loss	1.0000
16:84656869:A:AT	acceptor_loss	1.0000
16:84659867:GAC:G	donor_gain	1.0000
16:84661567:C:A	acceptor_gain	1.0000
16:84656869:A:AG	acceptor_gain	0.9900
16:84656870:G:GG	acceptor_gain	0.9900
16:84656870:GGT:G	acceptor_gain	0.9900
16:84656870:GGTAT:G	acceptor_gain	0.9900
16:84659754:CCACA:C	acceptor_loss	0.9900
16:84659755:CACA:C	acceptor_loss	0.9900
16:84659756:ACAGG:A	acceptor_loss	0.9900
16:84659757:CA:C	acceptor_loss	0.9900
16:84659759:G:A	acceptor_loss	0.9900
16:84659867:G:GT	donor_gain	0.9900
16:84659894:GTCC:G	donor_gain	0.9900
16:84659895:TCCT:T	donor_gain	0.9900
16:84659913:CCAAG:C	donor_loss	0.9900
16:84659914:CAAGG:C	donor_loss	0.9900
16:84659915:AAG:A	donor_loss	0.9900
16:84659916:AGGT:A	donor_loss	0.9900
16:84659917:GG:G	donor_loss	0.9900
16:84659918:G:GC	donor_loss	0.9900
16:84659919:T:A	donor_loss	0.9900
16:84661560:T:TA	acceptor_gain	0.9900
16:84661564:C:CA	acceptor_gain	0.9900
16:84661574:GCAG:G	acceptor_loss	0.9900

AlphaMissense

4038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84657936:T:A	W377R	0.999
16:84657936:T:C	W377R	0.999
16:84659781:C:A	R387S	0.999
16:84659790:T:C	F390L	0.999
16:84659792:C:A	F390L	0.999
16:84659792:C:G	F390L	0.999
16:84659892:T:A	W424R	0.999
16:84659892:T:C	W424R	0.999
16:84661631:G:A	G450E	0.999
16:84661699:T:A	W473R	0.999
16:84661699:T:C	W473R	0.999
16:84661858:T:A	W526R	0.999
16:84661858:T:C	W526R	0.999
16:84657009:A:C	S68R	0.998
16:84657011:C:A	S68R	0.998
16:84657011:C:G	S68R	0.998
16:84659833:G:A	G404D	0.998
16:84659833:G:T	G404V	0.998
16:84659836:G:C	R405P	0.998
16:84661630:G:T	G450W	0.998
16:84661634:G:A	G451D	0.998
16:84661701:G:C	W473C	0.998
16:84661701:G:T	W473C	0.998
16:84661729:C:A	R483S	0.998
16:84661730:G:C	R483P	0.998
16:84661735:T:A	W485R	0.998
16:84661735:T:C	W485R	0.998
16:84661778:G:A	G499E	0.998
16:84661781:G:A	G500D	0.998
16:84661860:G:C	W526C	0.998

dbSNP variants (sampled 300 via entrez): RS1000141679 (16:84651694 T>C), RS1000148983 (16:84663440 C>A,G,T), RS1000180647 (16:84663239 C>G,T), RS1000218197 (16:84649506 G>A), RS1000477222 (16:84653771 C>A,T), RS1000514496 (16:84664307 G>A), RS1000586433 (16:84658311 C>G,T), RS1000684906 (16:84666466 G>C), RS1000874256 (16:84656261 TTTTG>T,TTTTGTTTG), RS1000919570 (16:84662407 C>A,T), RS1001249811 (16:84666142 T>A), RS1001313149 (16:84651417 G>A,C), RS1001556826 (16:84649859 A>T), RS1001576901 (16:84667043 C>T), RS1001709386 (16:84654427 C>A,T)

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
GCST000838_4	Waist circumference	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
Tretinoin	increases expression	2
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects expression	1
Hydrogen Peroxide	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	increases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Serpentine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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