KLHDC8A

protein-coding

kelch domain containing 8A

Gene summary

This gene encodes a kelch domain-containing protein which is upregulated in cancer. Upregulated expression of the encoded protein may provide an alternative pathway for tumors to maintain aggressiveness in the absence of epidermal growth factor receptor dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

MANE transcript

NM_018203.3

Inheritance

—

ClinVar variants

U:53B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr1:205,336,061-205,357,090

External References & Databases

Ensembl (ENSG00000162873)

Transcript & Mutation Effects

hg38 • Region Span ~21.0 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 KLHDC8A variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 54

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018203.3. 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 clinvar		2
missense			51 clinvar	2 clinvar		53
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	3	0	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018203.3	RefSeq	NP_060673.1	5	MANE Select
ENST00000367155.8	Ensembl	ENSP00000356123.3	5	MANE Select
NM_001271863.2	RefSeq	NP_001258792.1	5	Standard
NM_001271864.2	RefSeq	NP_001258793.1	5	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367156
Coding exons: 5
Length: 20999
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.896	200	239	0.837	0.0000154	2249
Missense (PolyPhen)		49	66.572	0.73605		624
Synonymous	-0.0245	98	97.7	1.00	0.00000619	735
Loss of Function	0.964	12	16.2	0.741	0.00000106	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: -1.11
RVIS percentile EVS: 6.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.219

Gene Damage Prediction

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