KLHL3 - kelch like family member 3 Gene

Homo sapiens

Also known as PHA2D

Gene ID: 26249 | Gene type: protein coding

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	Reference	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	Reference	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	Reference	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 Cross Intra	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	Reference
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

Bioactive Molecules (1)

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

Name
Email *

	Sorry, but the email address you supplied was invalid.