KCMF1

protein-coding

potassium channel modulatory factor 1, the group of Zinc fingers ZZ-type

Gene summary

Enables ubiquitin protein ligase activity. Involved in several processes, including HRI-mediated signaling; negative regulation of HRI-mediated signaling; and protein polyubiquitination. Located in cytosol. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_020122.5

Inheritance

—

ClinVar variants

U:26B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr2:84,971,093-85,059,472

External References & Databases

Ensembl (ENSG00000176407)

Transcript & Mutation Effects

hg38 • Region Span ~88.4 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 KCMF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 23

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020122.5. 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					2 clinvar	2
missense			23 clinvar			23
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	26	0	2	28

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020122.5	RefSeq	NP_064507.3	7	MANE Select
ENST00000409785.9	Ensembl	ENSP00000386738.3	7	MANE Select
ENST00000428691.5	Ensembl	ENSP00000409499.1	2	Standard
ENST00000453448.1	Ensembl	ENSP00000391340.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

protein ubiquitination
neutrophil degranulation

Molecular Function

nucleic acid binding
zinc ion binding
ubiquitin protein ligase activity

Cellular Component

extracellular region
cytosol
ficolin-1-rich granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409785
Coding exons: 7
Length: 88380
Individuals with no LoFs: 124590
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 124592
p: 0.00000803

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.68	113	227	0.499	0.0000135	2474
Missense (PolyPhen)		34	90.915	0.37398		910
Synonymous	1.74	57	76.4	0.746	0.00000433	759
Loss of Function	3.48	1	16.0	0.0625	7.36e-7	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. {ECO:0000269|PubMed:15581609}.;

Recessive Scores

pRec: 0.0923

Intolerance Scores

RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.251

Gene Damage Prediction

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