KLHDC1

protein-coding

kelch domain containing 1

Gene summary

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Is active in Cul5-RING ubiquitin ligase complex and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_172193.3

Inheritance

—

ClinVar variants

U:64

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr14:49,693,105-49,753,150

External References & Databases

Ensembl (ENSG00000197776)

Transcript & Mutation Effects

hg38 • Region Span ~60.0 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 KLHDC1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 61

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172193.3. 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						0
missense			63 clinvar			63
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	64	0	0	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172193.3	RefSeq	NP_751943.1	13	MANE Select
ENST00000359332.7	Ensembl	ENSP00000352282.2	13	MANE Select
ENST00000553274.1	Ensembl	ENSP00000452543.2	6	Standard
ENST00000555704.5	Ensembl	ENSP00000451819.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359332
Coding exons: 13
Length: 60048
Individuals with no LoFs: 125688
Homozygous LoFs: 1
Heterozygous LoFs: 58
Defined: 125747
p: 0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.397	189	205	0.922	0.00000992	2675
Missense (PolyPhen)		68	74.186	0.91662		901
Synonymous	0.900	58	67.4	0.861	0.00000329	682
Loss of Function	1.96	16	27.0	0.593	0.00000135	322

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00016	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00018	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00035	0.00032	rare
South Asian	0.00034	0.00033	rare
Other	0.00037	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.105

Intolerance Scores

RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.225

Gene Damage Prediction

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