DPP6

dipeptidyl peptidase like 6, the group of DASH family|Potassium voltage-gated channel regulatory subunits

Basic information

Region (hg38): 7:153748133-154894285

Links

ENSG00000130226

∙ NCBI:1804 ∙ OMIM:126141 ∙ HGNC:3010 ∙ Uniprot:P42658 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal dominant 33 (Limited), mode of inheritance: AD
ventricular fibrillation, paroxysmal familial, 2 (Limited), mode of inheritance: AD
autosomal dominant primary microcephaly (Supportive), mode of inheritance: AD
paroxysmal familial ventricular fibrillation (Supportive), mode of inheritance: AD
intellectual disability, autosomal dominant 33 (Limited), mode of inheritance: Unknown
complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ventricular fibrillation, paroxysmal familial, 2	AD	Cardiovascular	Preventive measures and medical management may be helpful to help decrease morbidity; sudden cardiac death has been reported, including shortly following a normal cardiac examination	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	19285295; 23832105

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPP6 gene.

not_provided (94 variants)
DPP6-related_disorder (30 variants)
Intellectual_disability,_autosomal_dominant_33 (26 variants)
not_specified (17 variants)
Ventricular_fibrillation,_paroxysmal_familial,_2 (9 variants)
Complex_neurodevelopmental_disorder (4 variants)
Wolff-Parkinson-White_pattern (2 variants)
Collapse_(finding) (1 variants)
Long_QT_syndrome (1 variants)
See_cases (1 variants)
HP:0000729_Autistic_spectrum_disorder (1 variants)
Sudden_cardiac_death (1 variants)
Ventricular_tachycardia (1 variants)
Primary_dilated_cardiomyopathy (1 variants)
Ventricular_fibrillation,_paroxysmal_familial,_type_1 (1 variants)
Neurodevelopmental_abnormality (1 variants)
Cardiac_arrest (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPP6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000130797.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	34 clinvar	3 clinvar	38
missense	1 clinvar		47 clinvar	11 clinvar	3 clinvar	62
nonsense			3 clinvar			3
start loss			1			1
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	1	57	45	6

Highest pathogenic variant AF is 0.0000030989238

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPP6	protein_coding	protein_coding	ENST00000377770	26	1101814

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.340	0.660	124654	0	22	124676	0.0000882

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	324	459	0.705	0.0000259	5600
Missense in Polyphen		95	189.67	0.50087		2209
Synonymous	-1.23	211	189	1.11	0.0000127	1592
Loss of Function	4.97	11	48.3	0.228	0.00000232	592

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000938	0.0000934
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000564	0.0000556
Finnish	0.0000931	0.0000928
European (Non-Finnish)	0.000152	0.000142
Middle Eastern	0.0000564	0.0000556
South Asian	0.0000332	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Promotes cell surface expression of the potassium channel KCND2 (PubMed:15454437, PubMed:19441798). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:18364354). Has no dipeptidyl aminopeptidase activity (PubMed:8103397, PubMed:15476821). {ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:18364354, ECO:0000269|PubMed:8103397, ECO:0000305|PubMed:15476821}.;
Disease: DISEASE: Familial paroxysmal ventricular fibrillation 2 (VF2) [MIM:612956]: A cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity. {ECO:0000269|PubMed:19285295}. Note=The disease is caused by mutations affecting the gene represented in this entry. A genetic variation 340 bases upstream from the ATG start site of the DPP6 gene is the cause of familial paroxysmal ventricular fibrillation type 2.; DISEASE: Mental retardation, autosomal dominant 33 (MRD33) [MIM:616311]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD33 patients manifest microcephaly and intellectual disability. {ECO:0000269|PubMed:23832105}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.125

Haploinsufficiency Scores

pHI: 0.123
hipred: Y
hipred_score: 0.736
ghis: 0.570

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.221

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dpp6
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process: proteolysis;protein localization to plasma membrane;regulation of potassium ion transmembrane transport
Cellular component: plasma membrane;voltage-gated potassium channel complex;integral component of membrane
Molecular function: serine-type peptidase activity;dipeptidyl-peptidase activity;potassium channel regulator activity