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.

• Intellectual disability, autosomal dominant 33 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	14	41
missense			36	9	7	52
nonsense			3			3
start loss			1			1
frameshift						0
inframe indel			1	2		3
splice donor/acceptor (+/-2bp)	1		2			3
splice region			3	2	1	6
non coding			1	8	115	124
Total	1	0	44	46	136

Variants in DPP6

This is a list of pathogenic ClinVar variants found in the DPP6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-153748987-T-A		Intellectual disability, autosomal dominant 33	Uncertain significance (Sep 23, 2020)
7-153887698-C-T		DPP6-related disorder	Benign (Apr 18, 2024)
7-153887702-A-G		Intellectual disability, autosomal dominant 33	Uncertain significance (Feb 13, 2019)
7-153887728-CGTGATGGTGA-C		DPP6-related disorder	Uncertain significance (Mar 25, 2024)
7-153887729-G-A			Uncertain significance (Dec 01, 2023)
7-154052113-GGGGC-G			Benign (Jun 18, 2021)
7-154052119-C-G			Benign (Jun 18, 2021)
7-154052206-A-C			Benign (May 11, 2021)
7-154052343-G-C			Benign (May 23, 2021)
7-154052668-C-T			Benign (May 11, 2021)
7-154052720-CT-C			Benign (May 12, 2021)
7-154052823-G-A		Intellectual disability, autosomal dominant 33	Uncertain significance (Oct 17, 2023)
7-154052847-T-C			Likely benign (Jul 01, 2022)
7-154052878-G-A		Ventricular fibrillation, paroxysmal familial, 2;Intellectual disability, autosomal dominant 33	Uncertain significance (Nov 03, 2021)
7-154052908-G-A		Intellectual disability, autosomal dominant 33	Uncertain significance (Oct 25, 2018)
7-154052919-C-G			Likely benign (Jul 01, 2024)
7-154052929-G-T		Intellectual disability, autosomal dominant 33	Uncertain significance (Jan 10, 2020)
7-154052934-C-T		not specified	Benign (May 04, 2021)
7-154052947-C-G			Uncertain significance (Sep 01, 2021)
7-154052952-C-T			Likely benign (Jun 01, 2022)
7-154052956-C-T			Uncertain significance (Feb 01, 2024)
7-154052960-G-T			Likely benign (-)
7-154052961-G-T			Likely benign (-)
7-154052966-AGGCGGCGGCGCCCCGGGAGCGCGGCGGC-A		See cases	Conflicting classifications of pathogenicity (Dec 21, 2022)
7-154052970-G-A			Likely benign (Jun 01, 2022)

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_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