KLHL3 - kelch like family member 3 Gene

Also Known as PHA2D

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 26249

About KLHL3

Cytogenetic location: 5q31.2 Genomic coordinates (GRCh38): 5:137,617,500-137,736,089 (from NCBI)

This gene has 14 transcripts (splice variants), 205 orthologues, 54 paralogues and is associated with 2 phenotypes. Broad expression in thyroid (RPKM 5.9), heart (RPKM 4.0) and 23 other tissues.

Summary

This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin Ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

KLHL3 Products (3)

mRNA	Protein	Name
NM_001257194.1	NP_001244123.1	kelch-like protein 3 isoform 2
NM_001257195.2	NP_001244124.1	kelch-like protein 3 isoform 3
NM_017415.3	NP_059111.2	kelch-like protein 3 isoform 1

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables cullin family protein binding	IPI IPI: Inferred from physical interaction	14528312	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	22406640	GOA
enables ubiquitin-like ligase-substrate adaptor activity	IDA IDA: Inferred from direct assay	23387299	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in distal tubule morphogenesis	IMP IMP: Inferred from mutant phenotype	22406640	GOA
involved in monoatomic ion homeostasis	IMP IMP: Inferred from mutant phenotype	23453970	GOA
involved in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	35093948	GOA
involved in protein K48-linked ubiquitination	IDA IDA: Inferred from direct assay	23576762	GOA
involved in protein ubiquitination	IDA IDA: Inferred from direct assay	23453970	GOA
involved in renal sodium ion absorption	IDA IDA: Inferred from direct assay	35093948	GOA
involved in renal sodium ion absorption	IMP IMP: Inferred from mutant phenotype	22406640	GOA
involved in ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	23453970	GOA
involved in ubiquitin-dependent protein catabolic process	IMP IMP: Inferred from mutant phenotype	35093948	GOA

Cellular Component GO Annotation	Evidence	References	Source
part of Cul3-RING ubiquitin ligase complex	IDA IDA: Inferred from direct assay	23453970	GOA
located in cytosol	IDA IDA: Inferred from direct assay	22406640	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

KLHL3 Protein Structure

BTB

BACK

Kelch_1

0
100
200
300
400
500
587 a.a.

Protein Preferred Names	Protein Names
kelch-like protein 3

KLHL3 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	KLHL3	Q9UH77	LAMP2	Homo sapiens	P13473-2	Y2H Array	32814053
Intra	KLHL3	Q9UH77	LAMP2	Homo sapiens	P13473-2	Validated Y2H	32814053
Intra	KLHL3	Q9UH77	LAMP2	Homo sapiens	P13473-2	Y2H Pooling	32814053
Intra	KLHL3	Q9UH77	FGFR3	Homo sapiens	P22607	Y2H Array	32814053
Intra	KLHL3	Q9UH77	FGFR3	Homo sapiens	P22607	Y2H Pooling	32814053
Intra	KLHL3	Q9UH77	FGFR3	Homo sapiens	P22607	Validated Y2H	32814053
Intra	KLHL3	Q9UH77	HRAS	Homo sapiens	P01112	Validated Y2H	32814053
Intra	KLHL3	Q9UH77	HRAS	Homo sapiens	P01112	Y2H Array	32814053
Intra	KLHL3	Q9UH77	HRAS	Homo sapiens	P01112	Y2H Pooling	32814053
Intra	KLHL3	Q9UH77	GSN	Homo sapiens	P06396	Validated Y2H	32814053
Intra	KLHL3	Q9UH77	GSN	Homo sapiens	P06396	Y2H Array	32814053
Intra	KLHL3	Q9UH77	GSN	Homo sapiens	P06396	Y2H Pooling	32814053
Intra	KLHL3	Q9UH77	CUL3	Homo sapiens	Q13618	Pull Down	23665031
Intra	KLHL3	Q9UH77	CUL3	Homo sapiens	Q13618	Y2H Array	31515488
Intra	KLHL3	Q9UH77	CUL3	Homo sapiens	Q13618	Anti Tag CoIP	33961781
Intra	KLHL3	Q9UH77	CASP6	Homo sapiens	P55212	Validated Y2H	32814053
Intra	KLHL3	Q9UH77	CASP6	Homo sapiens	P55212	Y2H Array	32814053
Intra	KLHL3	Q9UH77	CASP6	Homo sapiens	P55212	Y2H Pooling	32814053
Intra	KLHL3	Q9UH77	KLHL12	Homo sapiens	Q53G59	Y2H Prey Pooling	32296183
Intra	KLHL3	Q9UH77	KLHL12	Homo sapiens	Q53G59	Y2H Array	32296183
Intra	KLHL3	Q9UH77	KLHL12	Homo sapiens	Q53G59	Anti Tag CoIP	33961781
Intra	KLHL3	Q9UH77	KLHL2	Homo sapiens	O95198	Anti Tag CoIP	33961781
Intra	KLHL3	Q9UH77	KEAP1	Homo sapiens	Q14145	Y2H Prey Pooling	32296183
Intra	KLHL3	Q9UH77	KEAP1	Homo sapiens	Q14145	Anti Tag CoIP	33961781
Intra	KLHL3	Q9UH77	KEAP1	Homo sapiens	Q14145	Y2H Array	32296183

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Diseases

Diseases	Alias
Pseudohypoaldosteronism, Type Iid	Pseudohypoaldosteronism Type 2d PHA2D Familial Hyperkalemic Hypertension Fhht Pseudohypoaldosteronism 2d
Pseudohypoaldosteronism, Type Iia	Pseudohypoaldosteronism Type 2a PHA2A Hyperpotassemia And Hypertension, Familial Hypertensive Hyperkalemia, Familial Gordon Hyperkalemia-Hypertension Syndrome Pseudohypoaldosteronism, Type Ii
Pseudohypoaldosteronism, Type Iie	Pseudohypoaldosteronism Type 2e PHA2E Familial Hyperkalemic Hypertension Gordon'S Syndrome Phaii Pseudohypoaldosteronism Type 2 Gordon Hyperkalemia-Hypertension Syndrome Pseudohypoaldosteronism Type Ii Chloride Shunt Syndrome Hyperpotassemia And Hypertension Familial Pha2 Familial Hyperpotassemia And Hypertension Familial Hypertensive Hyperkalemia Fhht Hyperkalemia-Hypertension Syndrome, Gordon Type Hypertensive Hyperkalemia Mineralocorticoid Resistant Hyperkalemia Spitzer-Weinstein Syndrome Pseudohypoaldosteronism 2e Pseudohypoaldosteronism, Type Ii Pseudohypoaldosteronism, Type Iid Hyperpotassemia And Hypertension, Familial
Metabolic Acidosis
Pseudohypoaldosteronism
Cerebral Palsy	Infantile Cerebral Palsy Mixed Cerebral Palsy Palsy Cerebral Palsy, Cerebral Cerebral Palsy, Mixed
Arthrogryposis, Distal, Type 3	Gordon Syndrome DA3 Distal Arthrogryposis Type 3 Arthrogryposis Multiplex Congenita, Distal, Type Iia Camptodactyly, Cleft Palate, And Clubfoot Camptodactyly-Cleft Palate-Clubfoot Syndrome Distal Arthrogryposis Multiplex Congenita Type Iia Arthrogryposis Distal Type 3 Distal Arthrogryposis Type Iia Arthrogryposis, Distal, 3 Pseudohypoaldosteronism, Type Ii
Renal Tubular Transport Disease	Renal Tubular Transport, Inborn Errors Inborn Renal Tubular Transport Disorder
Hypomagnesemia 3, Renal	HOMG3 Renal Hypomagnesemia 3 Fhhnc Without Severe Ocular Involvement Renal Hypomagnesemia Type 3 Hypomagnesemia, Primary, Due To Defect In Renal Tubular Transport Of Magnesium Hypomagnesemia, Isolated Renal Hypomagnesemia, Familial, With Hypercalciuria And Nephrocalcinosis Familial Primary Hypomagnesemia With Hypercalciuria And Nephrocalcinosis Without Severe Ocular Involvement Isolated Renal Hypomagnesemia Primary Hypomagnesemia Due To Defect In Renal Tubular Transport Of Magnesium Primary Hypomagnesemia With Hypercalciuria And Nephrocalcinosis Without Severe Ocular Involvement Hypomagnesemia 3 Familial Hypomagnesemia With Hypercalciuria And Nephrocalcinosis Fhhnc Hhn Renal Hypomagnesemia Hypercalciuria Nephrocalcinosis Hypomagnesemia, Type 3, Renal Primary Hypomagnesemia
Gitelman Syndrome	Familial Hypokalemia-Hypomagnesemia Hypomagnesemia-Hypokalemia, Primary Renotubular, With Hypocalciuria Potassium And Magnesium Depletion GTLMNS Gitelman'S Syndrome Gs Hypokalemia-Hypomagnesemia, Primary Renotubular, With Hypocalciuria Tubular Hypomagnesemia-Hypokalemia With Hypocalcuria Bartter Syndrome Gitelman Variant Bartter Syndrome Hypocalciuric Variant Primary Renotubular Hypomagnesemia-Hypokalemia With Hypocalciuria
Miliaria	Eccrine Miliaria Heat Rash Sweat Rash Sweat Retention Syndrome
Miliaria Rubra	Miliaria Prickly Heat Miliaria Crystallina
Glomeruloid Hemangioma
Liddle Syndrome 1	Liddle Syndrome Pseudoaldosteronism Liddle'S Syndrome LIDLS1 Lidls Pseudohyperaldosteronism Pseudoprimary Hyperaldosteronism Pseudohyperaldosteronism Type 1 Liddles Syndrome
Bartter Disease	Bartter Syndrome Bartter'S Syndrome Aldosteronism With Hyperplasia Of The Adrenal Cortex Hypokalemic Alkalosis With Hypercalciuria Potassium Wasting Juxtaglomerular Hyperplasia With Secondary Aldosteronism Renal Tubular Normotensive Hypokalemic Alkalosis With Hypercalciuria Salt-Losing Tubular Disorder, Henle'S Loop Type Salt-Wasting Tubulopathy, Henle'S Loop Type Bartters Syndrome
Distal Arthrogryposis	Arthrogryposis Multiplex Congenita Arthrogryposis Congenital Multiple Arthrogryposis Congenital Arthromyodysplasia Fibrous Ankylosis Of Multiple Joints Guerin-Stern Syndrome Guérin-Stern Syndrome Myodystrophia Fetalis Deformans Otto Syndrome Rocher-Sheldon Syndrome Rossi Syndrome Amc Multiple Congenital Arthrogryposis Arthrogryposis Syndrome Arthrogryposis, Distal Distal Arthrogryposis Syndrome Freeman-Sheldon Syndrome Arthrogryposis, Distal, Type 2b Congenital Multiplex Arthrogryposis Amyoplasia Congenita Congenital Amyoplasia Amc - [Arthrogryposis Multiplex Congenita]
Hypertension, Essential	Essential Hypertension Hypertension High Blood Pressure Hypertension, Essential, Susceptibility To Hypertensive Disease Primary Hypertension EHT Hypertension, Salt-Sensitive Essential, Susceptibility To Hyperpiesia Idiopathic Hypertension Hypertensive Disorder Hypertension, Essential, Susceptibility To, 3 Hypertension, Essential 3 Hypertension, Essential, Salt-Sensitive Hypertension, Essential, Susceptibility To, 6 Hypertension, Essential 6 Hypertension, Salt-Sensitive Essential Hypertension, Susceptibility To Hypertension, Essential, Susceptibility To, 4 Hypertension, Essential 4 Hypertension, Essential, Susceptibility To, 2 Hypertension, Essential 2 Hypertension, Essential, Susceptibility To, 1 Hypertension, Essential 1 Hypertension, Essential, Susceptibility To, 5 Hypertension, Essential 5 Htn Vascular Hypertensive Disorder Systemic Primary Arterial Hypertension Hbp - [High Blood Pressure] Systemic Arterial Hypertensive Disorder Elevated Blood Pressure Arterial Hypertension Nos Hypertension Nos Benign Hypertension Systemic Arterial Hypertension Systemic Hypertension Artery Htn Benign Htn Vascular Htn Vascular Hypertension Cholesterol Hypertension Cholesterol Htn Idiopathic Htn Malignant Hypertension Malignant Htn Raised Blood Pressure Cardiovascular Hypertension Primary Htn - [Hypertension] High Arterial Tension High Blood Pressure Disorder Ht - [Hypertension] Htn - [Hypertension] Hypertensive Vascular Disease Hypertensive Vascular Degeneration
Retinitis Pigmentosa	RP Rod-Cone Dystrophy Autosomal Recessive Retinitis Pigmentosa Non-Syndromic Retinitis Pigmentosa Pericentral Pigmentary Retinopathy Pigmentary Retinopathy Tapetoretinal Degeneration Rcd Retinitis Pigmentosa Autosomal Recessive ARRP Retinitis Pigmentosa, Autosomal Recessive Retinitis Pigmentosa 1

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (1)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-RS07366	KLHL3 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Rattus norvegicus	KLHL3	RGD	RGD:1565218
Mus musculus	KLHL3	MGD	MGI:2445185
Macaca mulatta	KLHL3	VGNC	VGNC:74186
Felis catus	KLHL3	VGNC	VGNC:67959
Bos taurus	KLHL3	VGNC	VGNC:30657
Canis familiaris	KLHL3	VGNC	VGNC:42463
Others	KLHL3	NCBI