KCTD7

Summary

KCTD7 (potassium channel tetramerization domain containing 7, HGNC:21957) is a protein-coding gene on chromosome 7q11.21, encoding BTB/POZ domain-containing protein KCTD7 (Q96MP8). May be involved in the control of excitability of cortical neurons.

This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 154881 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive myoclonus epilepsy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 441 total — 21 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 34
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_153033

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21957
Approved symbol	KCTD7
Name	potassium channel tetramerization domain containing 7
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32069, EPM3, CLN14
Ensembl gene	ENSG00000243335
Ensembl biotype	protein_coding
OMIM	611725
Entrez	154881

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 nonsense_mediated_decay

ENST00000275532, ENST00000443322, ENST00000449064, ENST00000638524, ENST00000638540, ENST00000639828, ENST00000639879, ENST00000640234, ENST00000640385, ENST00000640601, ENST00000640851

RefSeq mRNA: 2 — MANE Select: NM_153033 NM_001167961, NM_153033

CCDS: CCDS55117, CCDS5534

Canonical transcript exons

ENST00000639828 — 4 exons

Exon	Start	End
ENSE00000976772	66633275	66633444
ENSE00003513191	66638253	66638431
ENSE00003804569	66628881	66629208
ENSE00003811316	66638856	66643047

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 94.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4692 / max 92.7374, expressed in 1754 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78874	3.0574	973
78873	2.9631	1395
78872	2.9487	1238
78870	1.0135	482
78871	0.4866	251

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.56	gold quality
ganglionic eminence	UBERON:0004023	91.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.01	gold quality
middle frontal gyrus	UBERON:0002702	90.34	gold quality
spinal cord	UBERON:0002240	90.14	gold quality
ventricular zone	UBERON:0003053	89.97	gold quality
stromal cell of endometrium	CL:0002255	89.81	gold quality
buccal mucosa cell	CL:0002336	87.80	gold quality
substantia nigra	UBERON:0002038	86.80	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.71	gold quality
midbrain	UBERON:0001891	86.22	gold quality
tendon of biceps brachii	UBERON:0008188	86.08	gold quality
nucleus accumbens	UBERON:0001882	85.94	gold quality
inferior vagus X ganglion	UBERON:0005363	85.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.66	gold quality
left ovary	UBERON:0002119	85.62	gold quality
right ovary	UBERON:0002118	85.48	gold quality
frontal pole	UBERON:0002795	85.36	silver quality
paraflocculus	UBERON:0005351	85.25	silver quality
prefrontal cortex	UBERON:0000451	85.24	gold quality
cerebellar hemisphere	UBERON:0002245	85.14	gold quality
cerebellar cortex	UBERON:0002129	85.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.06	gold quality
amygdala	UBERON:0001876	85.04	gold quality
cingulate cortex	UBERON:0003027	84.87	gold quality
caudate nucleus	UBERON:0001873	84.86	gold quality
Ammon’s horn	UBERON:0001954	84.84	gold quality
right frontal lobe	UBERON:0002810	84.80	gold quality
putamen	UBERON:0001874	84.79	gold quality
hypothalamus	UBERON:0001898	84.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

125 targeting KCTD7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7856-5P	99.75	69.99	2901

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• We found a C to T mutation in exon 2 of the potassium channel tetramerization domain containing 7 gene(KCTD7)in a progressive myoclonic epilepsy family affecting a highly conserved segment of the predicted protein changing an arginine codon to a stop. (PMID:17455289)
• The KCTD7 gene, previously associated with progressive myoclonus epilepsies (PMEs) in a single inbred family, was screened for mutations in 18 Turkish PME patients. (PMID:22693283)
• this study clearly demonstrates that KCTD7 mutations also cause a rare, infantile-onset NCL subtype designated as CLN14. (PMID:22748208)
• This study identified that novel KCTD7 mutation in patients with progressive myoclonus epilepsy with ataxia. (PMID:25060828)
• reviews the phenotype of progressive myoclonic epilepsy associated with KCTD7 mutations [review] (PMID:27629772)
• KCTD7 has an impact on K+ fluxes, neurotransmitter synthesis and neuronal function, and that malfunction of the encoded protein may lead to progressive myoclonus epilepsy. (PMID:27742667)
• Biallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders (PMID:30295347)
• Compound heterozygous KCTD7 variants in progressive myoclonus epilepsy. (PMID:33970744)
• Nonsyndromic Early-Onset Epileptic Encephalopathies: Two Novel KCTD7 Pathogenic Variants and a Literature Review. (PMID:34469883)
• BTB/POZ domain-containing protein 7/hypoxia-inducible factor 1 alpha signalling axis modulates hepatocellular carcinoma metastasis. (PMID:34709740)
• KCTD7-related progressive myoclonic epilepsy: report of three Indian families and review of literature. (PMID:34866617)
• KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses. (PMID:35921411)
• KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature. (PMID:38231304)
• KCTD Proteins Have Redundant Functions in Controlling Cellular Growth. (PMID:38732215)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd7	ENSDARG00000061580
mus_musculus	Kctd7	ENSMUSG00000034110
rattus_norvegicus	Kctd7	ENSRNOG00000042384
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD1 (ENSG00000134504), KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD18 (ENSG00000155729), KCTD6 (ENSG00000168301), KCTD19 (ENSG00000168676), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD11 (ENSG00000213859)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD7 — Q96MP8 (reviewed: Q96MP8)

All UniProt accessions (10): Q96MP8, A0A1W2PP71, A0A1W2PQ65, A0A1W2PQB2, A0A1W2PQL2, A0A1W2PQM8, A0A1W2PR57, A0A1W2PS30, A0A1X7SBW1, C9JTB6

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the control of excitability of cortical neurons.

Subunit / interactions. Interacts with CUL3.

Subcellular location. Cell membrane. Cytoplasm. Cytosol.

Disease relevance. Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (EPM3) [MIM:611726] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM3 is an autosomal recessive, severe, form 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 intellectual disability, 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. The disease is caused by variants affecting the gene represented in this entry. 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96MP8-1	1	yes
Q96MP8-2	2

RefSeq proteins (2): NP_001161433, NP_694578* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR057890	KCTD7/14_C	Domain
IPR057891	BTB_KCTD7	Domain

Pfam: PF02214, PF25611

UniProt features (10 total): sequence variant 6, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MP8-F1	81.67	0.65

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 196 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_INTRACELLULAR_POTASSIUM_ION_HOMEOSTASIS, TTGGAGA_MIR5155P_MIR519E, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_MEMBRANE_HYPERPOLARIZATION, chr7q11, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_MACROPHAGE, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_ENDOTHELIUM, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_FIBROBLAST

GO Biological Process (4): intracellular potassium ion homeostasis (GO:0030007), protein homooligomerization (GO:0051260), membrane hyperpolarization (GO:0060081), intracellular glutamate homeostasis (GO:0090461)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular monoatomic cation homeostasis	1
potassium ion homeostasis	1
protein complex oligomerization	1
regulation of membrane potential	1
intracellular amino acid homeostasis	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD7	PPT1	P50897	897
KCTD7	PRICKLE1	Q96MT3	812
KCTD7	CLN6	Q9NWW5	798
KCTD7	CLN5	O75503	790
KCTD7	CLN8	Q9UBY8	788
KCTD7	MFSD8	Q8NHS3	770
KCTD7	CLN3	Q13286	728
KCTD7	NHLRC1	Q6VVB1	725
KCTD7	DNAJC5	Q9H3Z4	713
KCTD7	CTSF	Q9UBX1	665
KCTD7	ATP13A2	Q9NQ11	665
KCTD7	KCNA1	Q09470	620
KCTD7	CUL3	Q13618	596
KCTD7	TPP1	O14773	593
KCTD7	CSTB	P04080	533

IntAct

7 interactions, top by confidence:

A	B	Type	Score
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
KCTD7	SHKBP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): KCTD7 (Affinity Capture-MS), KCTD7 (Affinity Capture-MS), KCTD7 (Reconstituted Complex), KCTD7 (Affinity Capture-RNA), CUL3 (Affinity Capture-Western), KCTD7 (Affinity Capture-Western), KCTD7 (Affinity Capture-MS), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid), KCTD7 (Two-hybrid)

ESM2 similar proteins: A3KMV1, A4IFB4, A5PKG7, A9ULR9, B1WC97, B5DEL1, O70479, O73916, P0C5J9, Q01820, Q0VD00, Q0VFV7, Q12259, Q13829, Q28DC9, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q5EAX2, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q6DC02, Q6DCX3, Q6DG99, Q6P3P4, Q6P7W2, Q719H9, Q7TNY1, Q7TPL3, Q7Z3E5, Q863D4, Q8BGV7, Q8BJK1, Q8BNL5, Q8K0E1

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, B1WC97, B5DEL1, D5SHR0, G5EFC3, O65555, P0C5J9, P15388, P17971, P17972, P25122, P48547, P59994, P59995, Q01956, Q03607, Q03719, Q0VD00, Q0VFV7, Q14003, Q14681, Q29RJ0, Q2HJ48, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q52PG9, Q54KH0, Q5DTY9, Q5M956, Q5XJ34, Q5ZJP7, Q62897, Q63881, Q63959, Q68DU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

441 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	17
Uncertain significance	200
Likely benign	144
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069708	NM_153033.5(KCTD7):c.339_340del (p.Asp115fs)	Pathogenic
1075621	NC_000007.13:g.(?66094052)(66104219_?)del	Pathogenic
1252047	NM_153033.5(KCTD7):c.696del (p.Phe232fs)	Pathogenic
1332817	NM_153033.5(KCTD7):c.205C>G (p.Leu69Val)	Pathogenic
1405546	NM_153033.5(KCTD7):c.388C>T (p.Gln130Ter)	Pathogenic
1452016	NC_000007.13:g.(?66103220)(66104219_?)del	Pathogenic
206016	NM_153033.5(KCTD7):c.536_543del (p.Val179fs)	Pathogenic
2164909	NM_153033.5(KCTD7):c.367C>T (p.Arg123Ter)	Pathogenic
253379	GRCh37/hg19 7q11.21(chr7:66103208-66105624)x3	Pathogenic
2722390	NM_153033.5(KCTD7):c.130dup (p.Leu44fs)	Pathogenic
3245776	NC_000007.13:g.(?66068499)(66098288_?)del	Pathogenic
3652794	NM_153033.5(KCTD7):c.514G>T (p.Glu172Ter)	Pathogenic
37009	NM_153033.5(KCTD7):c.594del (p.Ile199fs)	Pathogenic
37011	NM_153033.5(KCTD7):c.818A>T (p.Asn273Ile)	Pathogenic
37012	NM_153033.5(KCTD7):c.343G>T (p.Asp115Tyr)	Pathogenic
37013	NM_153033.5(KCTD7):c.322C>A (p.Leu108Met)	Pathogenic
4731709	NM_153033.5(KCTD7):c.338C>G (p.Ser113Ter)	Pathogenic
583587	NC_000007.14:g.(?66638233)(66639252_?)del	Pathogenic
831752	NC_000007.14:g.(?66629045)(66640414_?)del	Pathogenic
843	NM_153033.5(KCTD7):c.295C>T (p.Arg99Ter)	Pathogenic
860762	NM_153033.5(KCTD7):c.331del (p.Leu111fs)	Pathogenic
1188829	NM_153033.5(KCTD7):c.685G>T (p.Asp229Tyr)	Likely pathogenic
1324611	NM_153033.5(KCTD7):c.493+2_493+6del	Likely pathogenic
1329067	NM_153033.5(KCTD7):c.731del (p.Leu244fs)	Likely pathogenic
1332794	NM_153033.5(KCTD7):c.458G>C (p.Arg153Pro)	Likely pathogenic
1705254	NM_153033.5(KCTD7):c.604del (p.Tyr202fs)	Likely pathogenic
2168099	NM_153033.5(KCTD7):c.520G>A (p.Ala174Thr)	Likely pathogenic
2501012	NM_153033.5(KCTD7):c.393C>G (p.Tyr131Ter)	Likely pathogenic
2502292	NM_153033.5(KCTD7):c.207_214del (p.Cys71fs)	Likely pathogenic
2671704	NM_153033.5(KCTD7):c.294C>T (p.Asp98=)	Likely pathogenic

SpliceAI

555 predictions. Top by Δscore:

Variant	Effect	Δscore
7:66629205:GGAG:G	donor_gain	1.0000
7:66629206:G:GT	donor_gain	1.0000
7:66633443:GG:G	donor_gain	1.0000
7:66633444:GG:G	donor_gain	1.0000
7:66633444:GGTA:G	donor_loss	1.0000
7:66633445:G:GG	donor_gain	1.0000
7:66633445:GTAT:G	donor_loss	1.0000
7:66638251:A:AG	acceptor_gain	1.0000
7:66638252:G:GG	acceptor_gain	1.0000
7:66638252:GA:G	acceptor_gain	1.0000
7:66638252:GAGAT:G	acceptor_gain	1.0000
7:66638853:TA:T	acceptor_loss	1.0000
7:66638854:A:AG	acceptor_gain	1.0000
7:66638855:G:GC	acceptor_loss	1.0000
7:66638855:G:GG	acceptor_gain	1.0000
7:66638855:GA:G	acceptor_gain	1.0000
7:66638855:GAC:G	acceptor_gain	1.0000
7:66638855:GACC:G	acceptor_gain	1.0000
7:66638855:GACCA:G	acceptor_gain	1.0000
7:66639224:TGGTG:T	donor_gain	1.0000
7:66639225:GGTGG:G	donor_gain	1.0000
7:66639226:GTG:G	donor_gain	1.0000
7:66629206:G:T	donor_gain	0.9900
7:66629206:GAGGT:G	donor_loss	0.9900
7:66629210:T:G	donor_loss	0.9900
7:66633273:A:AG	acceptor_gain	0.9900
7:66633274:G:GA	acceptor_gain	0.9900
7:66638246:T:A	acceptor_gain	0.9900
7:66638248:CTTA:C	acceptor_loss	0.9900
7:66638251:A:T	acceptor_loss	0.9900

AlphaMissense

1884 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:66639060:G:A	G233E	1.000
7:66639065:T:A	W235R	1.000
7:66639065:T:C	W235R	1.000
7:66639093:T:C	L244P	1.000
7:66639161:T:C	C267R	1.000
7:66639213:T:C	F284S	1.000
7:66633288:T:A	V53D	0.999
7:66633294:T:A	L55H	0.999
7:66633303:G:A	G58E	0.999
7:66633360:T:C	L77S	0.999
7:66633372:T:C	F81S	0.999
7:66633420:T:A	I97N	0.999
7:66633426:G:C	R99P	0.999
7:66638261:T:C	L108P	0.999
7:66638323:G:C	A129P	0.999
7:66638404:T:C	F156L	0.999
7:66638405:T:C	F156S	0.999
7:66638406:T:A	F156L	0.999
7:66638406:T:G	F156L	0.999
7:66638883:C:A	A174D	0.999
7:66638931:T:A	V190D	0.999
7:66638937:T:A	V192D	0.999
7:66638944:G:C	K194N	0.999
7:66638944:G:T	K194N	0.999
7:66639059:G:A	G233R	0.999
7:66639059:G:C	G233R	0.999
7:66639067:G:C	W235C	0.999
7:66639067:G:T	W235C	0.999
7:66639089:G:C	D243H	0.999
7:66639090:A:C	D243A	0.999

dbSNP variants (sampled 300 via entrez): RS1000021329 (7:66642295 T>C), RS1000046524 (7:66642615 A>C,G), RS1000099581 (7:66628972 C>A,G,T), RS1000188320 (7:66631957 T>C,G), RS1000327828 (7:66626900 T>C), RS1000402904 (7:66627245 T>G), RS1000666083 (7:66628211 A>G), RS1001073964 (7:66635874 G>A), RS1001142106 (7:66628437 G>A), RS1001198650 (7:66630701 A>G), RS1001285171 (7:66636784 GAAA>G,GAA,GAAAA), RS1001405364 (7:66628466 G>C), RS1002307000 (7:66640771 A>C,G), RS1002370737 (7:66631285 T>G), RS1002388851 (7:66641040 G>A,C,T)

Disease associations

OMIM: gene MIM:611725 | disease phenotypes: MIM:611726, MIM:256730, MIM:254800

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive myoclonic epilepsy type 3	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive myoclonus epilepsy	Definitive	AR

Mondo (4): progressive myoclonic epilepsy type 3 (MONDO:0012721), neuronal ceroid lipofuscinosis (MONDO:0016295), intellectual disability (MONDO:0001071), progressive myoclonus epilepsy (MONDO:0020074)

Orphanet (7): Progressive myoclonic epilepsy type 3 (Orphanet:263516), Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263), Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261), CLN14 disease (Orphanet:699708), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000504	Abnormality of vision
HP:0000572	Visual loss
HP:0000648	Optic atrophy
HP:0000726	Dementia
HP:0001249	Intellectual disability
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001327	Photosensitive myoclonic seizure
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002073	Progressive cerebellar ataxia
HP:0002078	Truncal ataxia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002123	Generalized myoclonic seizure
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0003208	Fingerprint intracellular accumulation of autofluorescent lipopigment storage material
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0007221	Progressive truncal ataxia
HP:0007272	Progressive psychomotor deterioration
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0007370	Aplasia/Hypoplasia of the corpus callosum
HP:0011166	Focal myoclonic seizure
HP:0011185	EEG with focal epileptiform discharges
HP:0011188	Focal EEG discharges with secondary generalization

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000943_4	Aortic root size	4.000000e-07
GCST002652_7	Cotinine glucuronidation	5.000000e-09
GCST008059_195	Estimated glomerular filtration rate	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006508	cotinine glucuronidation measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650
C567095	Epilepsy, Progressive Myoclonic 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D5EX	HeLa::TMEM192-3xHA KCTD7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

204 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00337636	PHASE1	COMPLETED	Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL)
NCT01238315	PHASE1	WITHDRAWN	Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT07582484	PHASE1/PHASE2	NOT_YET_RECRUITING	Gene Therapy Trial for CLN6 Batten Disease
NCT01873924	Not specified	RECRUITING	Clinical and Neuropsychological Investigations in Batten Disease
NCT01966757	Not specified	COMPLETED	Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities
NCT06844877	Not specified	RECRUITING	Italian NCL Registry: a Registry for NCL as an Integration Tool for Future Therapeutic Strategies
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients