KLHL14

protein-coding

kelch like family member 14, the group of BTB domain containing|Kelch like

Gene summary

The protein encoded by this gene is a member of the Kelch-like gene family, whose members contain a BTB/POZ domain, a BACK domain, and several Kelch domains. The encoded protein possesses six Kelch domains and localizes to the endoplasmic reticulum, where it interacts with torsin-1A. [provided by RefSeq, Sep 2015]

MANE transcript

NM_020805.3

Inheritance

—

ClinVar variants

U:61B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr18:32,672,673-32,773,023

External References & Databases

Ensembl (ENSG00000197705)

Transcript & Mutation Effects

hg38 • Region Span ~100.4 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 KLHL14 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 59

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020805.3. 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				1 clinvar		1
missense			61 clinvar			61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	61	1	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020805.3	RefSeq	NP_065856.1	8	MANE Select
ENST00000359358.9	Ensembl	ENSP00000352314.4	8	MANE Select
ENST00000358095.4	Ensembl	ENSP00000350808.4	3	Standard
ENST00000358095.5	Ensembl	ENSP00000350808.4	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
cytosol
actin cytoskeleton
aggresome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359358
Coding exons: 8
Length: 100392
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	275	361	0.762	0.0000181	4075
Missense (PolyPhen)		98	150.98	0.64911		1638
Synonymous	-1.22	175	156	1.12	0.00000814	1253
Loss of Function	3.63	8	29.1	0.275	0.00000147	316

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.527
RVIS EVS: -0.98
RVIS percentile EVS: 8.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0286

Gene Damage Prediction

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