KLHL31

Summary

KLHL31 (kelch like family member 31, HGNC:21353) is a protein-coding gene on chromosome 6p12.1, encoding Kelch-like protein 31 (Q9H511). Transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions.

Involved in negative regulation of JNK cascade and negative regulation of protein phosphorylation. Located in cytoplasm and nucleus.

Source: NCBI Gene 401265 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_001003760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21353
Approved symbol	KLHL31
Name	kelch like family member 31
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	bA345L23.2, BKLHD6
Ensembl gene	ENSG00000124743
Ensembl biotype	protein_coding
OMIM	610749
Entrez	401265

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370905, ENST00000407079

RefSeq mRNA: 1 — MANE Select: NM_001003760 NM_001003760

CCDS: CCDS34478

Canonical transcript exons

ENST00000370905 — 3 exons

Exon	Start	End
ENSE00000850562	53647916	53652330
ENSE00001551352	53654101	53655305
ENSE00001564191	53665601	53665756

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9947 / max 373.4550, expressed in 125 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74027	0.6439	73
74026	0.4580	56
74030	0.3134	69
74025	0.2752	53
74029	0.1326	44
74031	0.1199	43
74028	0.0517	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.56	gold quality
vastus lateralis	UBERON:0001379	99.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.41	gold quality
biceps brachii	UBERON:0001507	99.39	gold quality
heart right ventricle	UBERON:0002080	99.30	gold quality
quadriceps femoris	UBERON:0001377	99.20	gold quality
myocardium	UBERON:0002349	99.16	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.13	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.99	gold quality
deltoid	UBERON:0001476	98.30	gold quality
skeletal muscle tissue	UBERON:0001134	97.42	gold quality
tibialis anterior	UBERON:0001385	95.10	silver quality
body of tongue	UBERON:0011876	94.63	gold quality
cardiac ventricle	UBERON:0002082	92.73	gold quality
heart left ventricle	UBERON:0002084	92.58	gold quality
muscle tissue	UBERON:0002385	92.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.34	gold quality
cardiac atrium	UBERON:0002081	91.72	gold quality
right atrium auricular region	UBERON:0006631	91.23	gold quality
apex of heart	UBERON:0002098	89.25	gold quality
vena cava	UBERON:0004087	88.76	gold quality
heart	UBERON:0000948	88.11	gold quality
gastrocnemius	UBERON:0001388	86.77	gold quality
muscle of leg	UBERON:0001383	86.74	gold quality
tongue	UBERON:0001723	85.85	gold quality
oviduct epithelium	UBERON:0004804	85.12	gold quality
parietal pleura	UBERON:0002400	79.05	gold quality
germinal epithelium of ovary	UBERON:0001304	78.34	silver quality
pancreatic ductal cell	CL:0002079	77.07	silver quality
superior surface of tongue	UBERON:0007371	74.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

191 targeting KLHL31, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
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-7F-5P	99.98	72.56	1784
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

Literature-anchored findings (GeneRIF, showing 1)

• These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. (PMID:18719355)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl31	ENSDARG00000039066
mus_musculus	Klhl31	ENSMUSG00000044938
rattus_norvegicus	Klhl31	ENSRNOG00000006224

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), 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), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 31 — Q9H511 (reviewed: Q9H511)

Alternative names: BTB and kelch domain-containing protein 6, Kelch repeat and BTB domain-containing protein 1, Kelch-like protein KLHL

All UniProt accessions (1): Q9H511

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. Overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE).

Tissue specificity. Strongly expressed in skeletal muscle and weakly in heart. According to PubMed:15302408, not expressed in other tissues. According to PubMed:18719355, abundantly expressed in both embryonic skeletal and heart tissues.

Post-translational modifications. N-terminus is methylated by METTL11A/NTM1.

RefSeq proteins (1): NP_001003760* (*=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
IPR030604	BTB_POZ_KLHL31	Domain

Pfam: PF00651, PF01344, PF07707, PF24681

UniProt features (14 total): repeat 6, sequence variant 3, domain 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H511-F1	90.25	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, chr6p12, GOBP_JNK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_JNK_CASCADE, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORYLATION, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_MODIFICATION_PROCESS, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (2): negative regulation of protein phosphorylation (GO:0001933), negative regulation of JNK cascade (GO:0046329)

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
JNK cascade	1
negative regulation of MAPK cascade	1
regulation of JNK cascade	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL31	NTMT1	Q9BV86	882
KLHL31	RPL23A	P29316	798
KLHL31	CUL3	Q13618	736
KLHL31	PRODH	O43272	667
KLHL31	RCC1	P18754	607
KLHL31	TMEM214	Q6NUQ4	600
KLHL31	TMEM38A	Q9H6F2	542
KLHL31	TMEM161A	Q9NX61	491
KLHL31	KLHDC1	Q8N7A1	466
KLHL31	TMEM116	Q8NCL8	457
KLHL31	KLHL3	Q9UH77	445
KLHL31	ALKBH4	Q9NXW9	443
KLHL31	ARSJ	Q5FYB0	438
KLHL31	PALMD	Q9NP74	433
KLHL31	POPDC2	Q9HBU9	433

IntAct

2 interactions, top by confidence:

A	B	Type	Score
KLHL31	CDC37	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A1B8YAB1, B1H285, B3DIV9, E9QIN8, E9QJ30, F1QEG2, O88879, Q08CL3, Q08CY1, Q0D2A9, Q13939, Q28068, Q3UQV5, Q3ZCT8, Q503R4, Q5F3N5, Q5R4S6, Q5R663, Q5RG82, Q5XHZ6, Q5XI58, Q5ZI33, Q69ZK5, Q6DFF7, Q6DFU2, Q6Q7X9, Q6V595, Q7ZVQ8, Q86V97, Q8BHI4, Q8BUL5, Q8BWA5, Q8CA72, Q8CDE2, Q8CE33, Q8IXQ5, Q8NAB2, Q8NFY9, Q8R179, Q8WVZ9

Diamond homologs: A0JN76, A1YPR0, A6QQY2, B0WWP2, B1WBS3, B2RXF5, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D2HEW7, D3ZZC3, E0CZ16, E9Q4F2, F1LZ52, F1MBP6, O14867, O15062, O43167, O88282, O88939, O93567, O94889, O95365, P97302, P97303, Q08CY1, Q0IJ29, Q0P4X6, Q13105, Q16RL8, Q1L8W0, Q2M0J9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

500 predictions. Top by Δscore:

Variant	Effect	Δscore
6:53652326:CGTAT:C	acceptor_gain	1.0000
6:53652328:TAT:T	acceptor_gain	1.0000
6:53652328:TATCT:T	acceptor_loss	1.0000
6:53652329:AT:A	acceptor_gain	1.0000
6:53652330:TCTG:T	acceptor_loss	1.0000
6:53652331:C:CC	acceptor_gain	1.0000
6:53655302:CTTG:C	acceptor_gain	1.0000
6:53655303:TTG:T	acceptor_gain	1.0000
6:53655306:C:CC	acceptor_gain	1.0000
6:53665599:AC:A	donor_gain	1.0000
6:53665599:ACCCT:A	donor_gain	1.0000
6:53665600:CC:C	donor_gain	1.0000
6:53665600:CCCT:C	donor_gain	1.0000
6:53665600:CCCTC:C	donor_gain	1.0000
6:53665603:T:A	donor_gain	1.0000
6:53652327:GTAT:G	acceptor_gain	0.9900
6:53652337:A:AC	acceptor_gain	0.9900
6:53654096:AGTAC:A	donor_loss	0.9900
6:53654097:GTA:G	donor_loss	0.9900
6:53654098:TA:T	donor_loss	0.9900
6:53654099:A:AG	donor_loss	0.9900
6:53654100:CC:C	donor_loss	0.9900
6:53655304:TG:T	acceptor_gain	0.9900
6:53664454:C:T	acceptor_gain	0.9900
6:53665596:CTTAC:C	donor_loss	0.9900
6:53665597:TTA:T	donor_loss	0.9900
6:53665598:T:TG	donor_loss	0.9900
6:53665599:A:AC	donor_gain	0.9900
6:53665599:A:AG	donor_loss	0.9900
6:53665600:C:A	donor_loss	0.9900

AlphaMissense

4181 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:53652165:C:A	W446C	1.000
6:53652165:C:G	W446C	1.000
6:53652167:A:G	W446R	1.000
6:53652167:A:T	W446R	1.000
6:53652308:A:G	W399R	1.000
6:53652308:A:T	W399R	1.000
6:53654555:A:G	W240R	1.000
6:53654555:A:T	W240R	1.000
6:53651687:C:G	G606R	0.999
6:53651723:A:G	W594R	0.999
6:53651723:A:T	W594R	0.999
6:53651784:C:A	W573C	0.999
6:53651784:C:G	W573C	0.999
6:53651786:A:G	W573R	0.999
6:53651786:A:T	W573R	0.999
6:53651788:C:A	G572V	0.999
6:53651788:C:T	G572D	0.999
6:53651791:C:T	G571E	0.999
6:53651870:A:G	W545R	0.999
6:53651870:A:T	W545R	0.999
6:53651944:C:T	G520D	0.999
6:53651988:C:A	W505C	0.999
6:53651988:C:G	W505C	0.999
6:53651990:A:G	W505R	0.999
6:53651990:A:T	W505R	0.999
6:53652047:A:C	Y486D	0.999
6:53652085:C:T	G473D	0.999
6:53652088:C:T	G472E	0.999
6:53652166:C:G	W446S	0.999
6:53652188:A:C	Y439D	0.999

dbSNP variants (sampled 300 via entrez): RS1000250309 (6:53648152 A>C), RS1000301291 (6:53648378 A>G,T), RS1000826008 (6:53666307 G>A,T), RS1001174716 (6:53666495 G>A), RS1001198070 (6:53659580 T>G), RS1001247271 (6:53659247 C>A), RS1001262985 (6:53651033 G>C,T), RS1001367682 (6:53647629 G>A,C), RS1001455530 (6:53664891 C>T), RS1001598189 (6:53653910 T>C,G), RS1001998936 (6:53665832 C>G), RS1002031081 (6:53647856 A>G), RS1002144459 (6:53654063 T>C), RS1002212568 (6:53652610 C>T), RS1002285843 (6:53665578 C>T)

Disease associations

OMIM: gene MIM:610749 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001762_208	Obesity-related traits	6.000000e-06
GCST003518_85	Daytime sleep phenotypes	4.000000e-06
GCST004067_41	Hip circumference adjusted for BMI	1.000000e-08
GCST009365_2	LDL cholesterol levels x short total sleep time interaction (2df test)	7.000000e-11
GCST012137_3	Motor coordination	9.000000e-06
GCST90002401_530	Platelet distribution width	2.000000e-12
GCST90007319_4	circulating leptin levels adjusted for BMI	4.000000e-06
GCST90007321_7	circulating leptin levels adjusted for BMI	1.000000e-07
GCST90007322_3	circulating leptin levels adjusted for BMI	4.000000e-06
GCST90007324_4	circulating leptin levels adjusted for BMI	2.000000e-07
GCST90007325_6	circulating leptin levels adjusted for BMI	2.000000e-06
GCST90007327_3	circulating leptin levels adjusted for BMI	1.000000e-07
GCST90007328_3	circulating leptin levels adjusted for BMI	1.000000e-06
GCST90007330_4	circulating leptin levels adjusted for BMI	2.000000e-07
GCST90020026_132	Hip index	8.000000e-12
GCST90020026_321	Hip index	2.000000e-21
GCST90020026_322	Hip index	4.000000e-13
GCST90020028_599	Hip circumference adjusted for BMI	2.000000e-16
GCST90020028_600	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_601	Hip circumference adjusted for BMI	3.000000e-12
GCST90020028_602	Hip circumference adjusted for BMI	1.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0007828	daytime rest measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0010749	motor function measurement
EFO:0007984	platelet component distribution width
EFO:0007793	BMI-adjusted leptin 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
Nickel	decreases expression	2
bisphenol A	decreases methylation	1
sodium arsenite	affects splicing, decreases expression	1
perfluorooctanoic acid	increases expression	1
hydroquinone	decreases expression	1
tofacitinib	increases expression	1
N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine	increases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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