KLHL1

protein-coding

kelch like family member 1, the group of Kelch like|BTB domain containing

Gene summary

The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

MANE transcript

NM_020866.3

Inheritance

—

ClinVar variants

U:109B:5

Top phenotype

KLHL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr13:69,700,594-70,108,493

External References & Databases

Ensembl (ENSG00000150361)

Transcript & Mutation Effects

hg38 • Region Span ~407.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLHL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 105

not providedTotal: 5

KLHL1-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020866.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	1 clinvar	3
missense			109 clinvar	2 clinvar		111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	109	4	1	114

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020866.3	RefSeq	NP_065917.1	11	MANE Select
ENST00000377844.9	Ensembl	ENSP00000367075.4	11	MANE Select
NM_001286725.2	RefSeq	NP_001273654.1	10	Standard
ENST00000545028.2	Ensembl	ENSP00000439602.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

adult walking behavior
dendrite development
cerebellar Purkinje cell layer development
actin cytoskeleton organization

Molecular Function

actin binding

Cellular Component

cytoplasm
cytoskeleton
dendrite
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377844
Coding exons: 11
Length: 407866
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0797	392	396	0.989	0.0000184	4887
Missense (PolyPhen)		111	146.96	0.75532		1810
Synonymous	-1.26	165	146	1.13	0.00000714	1454
Loss of Function	2.89	16	34.3	0.467	0.00000166	415

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00017	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in organizing the actin cytoskeleton of the brain cells.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.417
RVIS EVS: -0.44
RVIS percentile EVS: 24.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.342

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium