KCTD7

potassium channel tetramerization domain containing 7, the group of KCTD family

Basic information

Region (hg38): 7:66628881-66649067

Links

ENSG00000243335 ∙ NCBI:154881 ∙ OMIM:611725 ∙ HGNC:21957 ∙ Uniprot:Q96MP8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive myoclonic epilepsy type 3 (Definitive), mode of inheritance: AR
• progressive myoclonic epilepsy type 3 (Strong), mode of inheritance: AR
• progressive myoclonic epilepsy type 3 (Strong), mode of inheritance: AR
• progressive myoclonic epilepsy type 3 (Moderate), mode of inheritance: AR
• progressive myoclonic epilepsy type 3 (Supportive), mode of inheritance: AR
• progressive myoclonus epilepsy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic 3, with or without intracellular inclusions	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Neurologic	17455289; 22606975; 22638565; 22693283; 22748208
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCTD7 gene.

• Progressive_myoclonic_epilepsy_type_3 (310 variants)
• not_provided (61 variants)
• Inborn_genetic_diseases (40 variants)
• not_specified (28 variants)
• KCTD7-related_disorder (6 variants)
• Neuronal_ceroid_lipofuscinosis (6 variants)
• Intellectual_disability (4 variants)
• Epileptic_encephalopathy (2 variants)
• Epilepsy,_progressive_myoclonic,_3,_with_intracellular_inclusions (2 variants)
• Progressive_myoclonic_epilepsy (1 variants)
• Neuronal_ceroid_lipofuscinosis_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCTD7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153033.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	2	92	1	97
missense	4	20	142	2		168
nonsense	5	2	1			8
start loss						0
frameshift	6	3				9
splice donor/acceptor (+/-2bp)		3				3
Total	15	30	145	94	1

Highest pathogenic variant AF is 0.000104728

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCTD7	protein_coding	protein_coding	ENST00000510829	8	182579

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000631	0.999	125736	0	10	125746	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	210	279	0.753	0.0000158	3274
Missense in Polyphen		20	64.958	0.30789		772
Synonymous	0.754	91	101	0.904	0.00000596	875
Loss of Function	2.90	10	25.9	0.385	0.00000149	296

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000721	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the control of excitability of cortical neurons. {ECO:0000250}.
• Disease: DISEASE: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (EPM3) [MIM:611726]: An autosomal recessive, severe, progressive myoclonic epilepsy with early onset. Multifocal myoclonic seizures begin between 16 and 24 months of age after normal initial development. Neurodegeneration and regression occur with seizure onset. Other features include mental retardation, dysarthria, truncal ataxia, and loss of fine finger movements. EEG shows slow dysrhythmia, multifocal and occasionally generalized epileptiform discharges. In some patients, ultrastructural findings on skin biopsies identify intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis. {ECO:0000269|PubMed:17455289, ECO:0000269|PubMed:22606975, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:22693283, ECO:0000269|PubMed:22748208}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in KCTD7 are a cause of opsoclonus-myoclonus ataxia-like syndrome. Opsoclonus myoclonus ataxia syndrome (OMS) is a rare pervasive and frequently permanent disorder that usually develops in previously healthy children with normal premorbid psychomotor development and characterized by association of abnormal eye movements (opsoclonus), severe dyskinesia (myoclonus), cerebellar ataxia, functional regression, and behavioral problems. The syndrome is considered to be an immune- mediated disorder and may be tumor-associated or idiopathic. OMS is one of a few steroid responsive disorders of childhood. KCTD7 mutations have been found in a patient with an atypical clinical presentation characterized by non-epileptic myoclonus and ataxia commencing in early infancy, abnormal opsoclonus-like eye movements, improvement of clinical symptoms under steroid treatment, and subsequent development of generalized epilepsy (PubMed:22638565). {ECO:0000269|PubMed:22638565}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Intolerance Scores

• loftool: 0.606
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.265
• hipred: N
• hipred_score: 0.322
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.540

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kctd7

Gene ontology

• Biological process: cellular potassium ion homeostasis;positive regulation of transporter activity;post-translational protein modification;protein homooligomerization;membrane hyperpolarization;glutamate homeostasis
• Cellular component: cytoplasm;cytosol;plasma membrane
• Molecular function: protein binding