KLHL4

protein-coding

kelch like family member 4, the group of BTB domain containing|Kelch like

Gene summary

This gene encodes a member of the kelch family of proteins, which are characterized by kelch repeat motifs and a POZ/BTB protein-binding domain. It is thought that kelch repeats are actin binding domains. However, the specific function of this protein has not been determined. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_019117.5

Inheritance

—

ClinVar variants

U:103B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chrX:87,517,409-87,670,050

External References & Databases

Ensembl (ENSG00000102271)

Transcript & Mutation Effects

hg38 • Region Span ~152.6 kb

Loading mutation effect viewer...

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 KLHL4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019117.5. 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			12 clinvar	3 clinvar		15
missense			83 clinvar	1 clinvar		84
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	103	4	0	107

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019117.5	RefSeq	NP_061990.2	11	MANE Select
ENST00000373119.9	Ensembl	ENSP00000362211.4	11	MANE Select
NM_057162.3	RefSeq	NP_476503.1	11	Standard
ENST00000373114.4	Ensembl	ENSP00000362206.4	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

molecular_function
actin binding

Cellular Component

cytoplasm
microtubule organizing center
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373114
Coding exons: 11
Length: 152299
Individuals with no LoFs: 125594
Homozygous LoFs: 3
Heterozygous LoFs: 3
Defined: 125600
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.892	220	261	0.845	0.0000187	4732
Missense (PolyPhen)		82	106.8	0.76776		1954
Synonymous	-0.898	103	92.0	1.12	0.00000665	1384
Loss of Function	3.44	4	21.0	0.191	0.00000152	394

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000040	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000025	0.000018	rare
South Asian	0.00016	0.000065	rare
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0858

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -0.36
RVIS percentile EVS: 28.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0747

Gene Damage Prediction

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