KLHL34

Summary

KLHL34 (kelch like family member 34, HGNC:26634) is a protein-coding gene on chromosome Xp22.12, encoding Kelch-like protein 34 (Q8N239).

Located in extracellular space.

Source: NCBI Gene 257240 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 79 total — 1 pathogenic
• MANE Select transcript: NM_153270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26634
Approved symbol	KLHL34
Name	kelch like family member 34
Location	Xp22.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34960, RP11-450P7.3
Ensembl gene	ENSG00000185915
Ensembl biotype	protein_coding
Entrez	257240

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000379499

RefSeq mRNA: 1 — MANE Select: NM_153270 NM_153270

CCDS: CCDS14199

Canonical transcript exons

ENST00000379499 — 1 exons

Exon	Start	End
ENSE00001481325	21654690	21658330

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 95.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0732 / max 27.1738, expressed in 21 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198696	0.0330	12
198694	0.0278	10
198695	0.0124	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.56	gold quality
biceps brachii	UBERON:0001507	92.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.09	gold quality
quadriceps femoris	UBERON:0001377	88.23	gold quality
vastus lateralis	UBERON:0001379	87.93	gold quality
skeletal muscle tissue	UBERON:0001134	87.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.55	gold quality
cerebellar vermis	UBERON:0004720	85.62	silver quality
buccal mucosa cell	CL:0002336	85.15	gold quality
deltoid	UBERON:0001476	83.18	gold quality
muscle tissue	UBERON:0002385	81.57	gold quality
gastrocnemius	UBERON:0001388	80.38	gold quality
muscle of leg	UBERON:0001383	80.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.01	gold quality
body of tongue	UBERON:0011876	75.81	gold quality
jejunum	UBERON:0002115	69.48	gold quality
tendon of biceps brachii	UBERON:0008188	66.54	silver quality
tongue	UBERON:0001723	66.44	gold quality
jejunal mucosa	UBERON:0000399	65.10	gold quality
heart left ventricle	UBERON:0002084	64.13	gold quality
superior surface of tongue	UBERON:0007371	64.07	gold quality
cardiac ventricle	UBERON:0002082	63.55	gold quality
apex of heart	UBERON:0002098	61.76	gold quality
duodenum	UBERON:0002114	61.17	gold quality
prefrontal cortex	UBERON:0000451	60.12	gold quality
pigmented layer of retina	UBERON:0001782	59.83	gold quality
mucosa of transverse colon	UBERON:0004991	59.19	gold quality
myocardium	UBERON:0002349	58.18	gold quality
heart	UBERON:0000948	57.07	gold quality
endothelial cell	CL:0000115	56.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting KLHL34, 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-4682	100.00	68.89	1258
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-8083	95.93	67.55	694

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klhl34	ENSMUSG00000047485
rattus_norvegicus	Klhl34	ENSRNOG00000024479

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 34 — Q8N239 (reviewed: Q8N239)

All UniProt accessions (1): Q8N239

RefSeq proteins (1): NP_695002* (*=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, PF07707, PF24681

UniProt features (11 total): repeat 6, domain 2, chain 1, compositionally biased region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N239-F1	87.15	0.71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GATA1_01, YRTCANNRCGC_UNKNOWN, 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, ER_Q6_02, GOCC_UBIQUITIN_LIGASE_COMPLEX, chrXp22, RAO_BOUND_BY_SALL4, MIR182_5P, MIR96_5P

GO Biological Process (0):

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

GO Cellular Component (1): obsolete extracellular space (GO:0005615)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL34	LSMEM2	Q8N112	488
KLHL34	BAIAP3	O94812	482
KLHL34	KCNN1	Q92952	467
KLHL34	DAB2IP	Q5VWQ8	432
KLHL34	FABP3	P05413	430
KLHL34	SHANK1	Q9Y566	365
KLHL34	ABTB3	A6QL63	364
KLHL34	DZIP1	Q86YF9	350
KLHL34	RBM44	Q6ZP01	350
KLHL34	KCTD2	Q14681	345
KLHL34	KCTD4	Q8WVF5	340
KLHL34	HELB	Q8NG08	335
KLHL34	BTBD6	Q96KE9	328
KLHL34	TINAG	Q9UJW2	327
KLHL34	ARHGAP6	O43182	321

IntAct

7 interactions, top by confidence:

A	B	Type	Score
KLHL34	BAG3	psi-mi:“MI:0914”(association)	0.530
KLHL34	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
NUDCD3	KLHL34	psi-mi:“MI:0915”(physical association)	0.400
NUDC	KLHL34	psi-mi:“MI:0915”(physical association)	0.400
KLHL34	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): HSPA8 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), HSPA1B (Affinity Capture-MS), STIP1 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), HSPA1B (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), STIP1 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS)

ESM2 similar proteins: A6NE02, A8MY62, C9JR72, D3Z7H8, D3ZU57, O09017, O15197, O19179, O95382, P0C0K6, P10588, P43136, P55203, Q02846, Q08DG4, Q15628, Q2KHV9, Q3U0S6, Q3UH93, Q5BK61, Q5U651, Q5W7P8, Q5ZMM1, Q6ZNJ1, Q6ZQA0, Q6ZVZ8, Q80ZD5, Q86WK7, Q8BH02, Q8BH83, Q8C828, Q8CIG9, Q8IUL8, Q8IYS2, Q8JGM4, Q8K2J9, Q8N239, Q8VHA6, Q91X21, Q96CD0

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	77
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2661882	GRCh37/hg19 Xp22.12(chrX:21393016-21675906)x1	Pathogenic

SpliceAI

125 predictions. Top by Δscore:

Variant	Effect	Δscore
X:21657763:T:C	acceptor_gain	0.9700
X:21657763:T:TC	acceptor_gain	0.9700
X:21657767:A:T	acceptor_gain	0.9700
X:21657761:CTT:C	acceptor_gain	0.7500
X:21657762:TTT:T	acceptor_gain	0.7500
X:21658168:A:T	donor_gain	0.7300
X:21657763:T:G	acceptor_gain	0.7100
X:21658138:C:T	donor_gain	0.7000
X:21658137:A:T	donor_gain	0.6900
X:21658049:C:A	donor_gain	0.6800
X:21657766:C:CT	acceptor_gain	0.6600
X:21658048:T:TA	donor_gain	0.6600
X:21658165:TGCA:T	donor_gain	0.6100
X:21657761:C:CC	acceptor_gain	0.5500
X:21658172:CATCA:C	donor_loss	0.5400
X:21658173:ATCAC:A	donor_loss	0.5400
X:21658174:TCACC:T	donor_loss	0.5400
X:21658176:ACCTG:A	donor_loss	0.5400
X:21658177:CC:C	donor_loss	0.5400
X:21658178:C:G	donor_loss	0.5400
X:21658179:T:C	donor_loss	0.5300
X:21657789:T:TA	acceptor_gain	0.5200
X:21657760:G:C	acceptor_gain	0.4900
X:21658268:G:T	donor_gain	0.4700
X:21657762:T:C	acceptor_gain	0.4600
X:21658135:C:CA	donor_gain	0.4600
X:21658169:C:T	donor_gain	0.4600
X:21657766:C:G	acceptor_gain	0.4500
X:21658169:CACCA:C	donor_gain	0.4500
X:21657768:G:GC	acceptor_gain	0.4400

AlphaMissense

4091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:21656138:A:G	W551R	0.996
X:21656138:A:T	W551R	0.996
X:21657636:A:C	S51R	0.995
X:21657636:A:T	S51R	0.995
X:21657638:T:G	S51R	0.995
X:21655985:A:G	W602R	0.994
X:21655985:A:T	W602R	0.994
X:21656136:C:A	W551C	0.994
X:21656136:C:G	W551C	0.994
X:21655983:C:A	W602C	0.993
X:21655983:C:G	W602C	0.993
X:21656430:C:A	W453C	0.993
X:21656430:C:G	W453C	0.993
X:21656432:A:G	W453R	0.993
X:21656432:A:T	W453R	0.993
X:21656159:A:C	Y544D	0.992
X:21656006:A:C	Y595D	0.991
X:21656576:A:G	W405R	0.990
X:21656576:A:T	W405R	0.990
X:21657531:G:C	F86L	0.989
X:21657531:G:T	F86L	0.989
X:21657533:A:G	F86L	0.989
X:21657628:A:G	F54S	0.989
X:21657106:A:T	V228D	0.986
X:21657472:G:T	A106D	0.986
X:21657616:A:G	F58S	0.986
X:21656137:C:G	W551S	0.985
X:21656356:A:T	I478N	0.985
X:21656574:C:A	W405C	0.985
X:21656574:C:G	W405C	0.985

dbSNP variants (sampled 300 via entrez): RS1001765910 (X:21660251 G>C,T), RS1002683955 (X:21659701 G>A), RS1003304266 (X:21657477 C>T), RS1003657552 (X:21658396 A>C), RS1004977735 (X:21660250 G>C), RS1005375887 (X:21659754 G>A), RS1005716312 (X:21658387 T>A), RS1006979758 (X:21656153 G>A), RS1007225236 (X:21658861 C>T), RS1007379122 (X:21655657 ACC>A,AC,ACCC), RS1008234104 (X:21659202 C>A,T), RS1008449809 (X:21656215 C>A,T), RS1008900228 (X:21655774 A>G), RS1009199657 (X:21658032 G>A,C), RS1009676653 (X:21659096 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
sodium arsenite	decreases methylation	1
Acetaminophen	increases expression	1
Niclosamide	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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