KLHDC10

protein-coding

kelch domain containing 10

Gene summary

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in rescue of stalled cytosolic ribosome and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Is active in Cul2-RING ubiquitin ligase complex and cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014997.4

Inheritance

—

ClinVar variants

U:32

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr7:130,070,534-130,135,705

External References & Databases

Ensembl (ENSG00000128607)

Transcript & Mutation Effects

hg38 • Region Span ~65.2 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 KLHDC10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 27

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014997.4. 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						0
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	32	0	0	32

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014997.4	RefSeq	NP_055812.1	10	MANE Select
ENST00000335420.10	Ensembl	ENSP00000334140.4	10	MANE Select
ENST00000463413.1	Ensembl	ENSP00000420083.1	3	Standard
ENST00000468226.1	Ensembl	ENSP00000420034.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of stress-activated MAPK cascade

Molecular Function

protein binding

Cellular Component

nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335420
Coding exons: 10
Length: 65211
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125742
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.41	90	238	0.378	0.0000127	2858
Missense (PolyPhen)		19	84.658	0.22443		916
Synonymous	0.490	81	86.8	0.933	0.00000459	876
Loss of Function	3.99	4	25.9	0.154	0.00000166	269

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in the oxidative stress-induced cell death through MAP3K5 activation. Inhibits PPP5C phosphatase activity on MAP3K5. {ECO:0000269|PubMed:23102700}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.205
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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