DPP6 dipeptidyl peptidase like 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DPP6provided by HGNC
Official Full Name: dipeptidyl peptidase like 6provided by HGNC
Primary source: HGNC:HGNC:3010
See related: Ensembl:ENSG00000130226 MIM:126141; AllianceGenome:HGNC:3010
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: VF2; DPL1; DPPX; MRD33
Summary: This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Expression: Biased expression in brain (RPKM 22.2), endometrium (RPKM 11.9) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q36.2

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (153748133..154894285)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (154922684..156069555)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (153445218..154685995)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.
Title: Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.
Neuronal Differentiation of Induced Pluripotent Stem Cells from Schizophrenia Patients in Two-Dimensional and in Three-Dimensional Cultures Reveals Increased Expression of the Kv4.2 Subunit DPP6 That Contributes to Decreased Neuronal Activity.
Title: Neuronal Differentiation of Induced Pluripotent Stem Cells from Schizophrenia Patients in Two-Dimensional and in Three-Dimensional Cultures Reveals Increased Expression of the Kv4.2 Subunit DPP6 That Contributes to Decreased Neuronal Activity.
Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma.
Title: Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma.
In an unresolved autosomal dominant dementia family significantly linked to 7q36, there was a chromosomal inversion of ca. 4 Mb, segregating on the disease haplotype and disrupting the coding sequence of DPP6. The missense variants found in patients destabilize DPP6 and reduce its membrane expression. DPP6 loss plays a in dementia.
Title: Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability.
The slope of the activation curve of DPP6-L747P was slightly decreased.
Title: A novel DPP6 variant in Chinese families causes early repolarization syndrome.
A novel missense mutation (c.1578G>C/p.Q526H) of DPP6 was identified and co-segregated with affected patients in a family with suspicious idiopathic ventricular fibrillation.
Title: A novel mutation of dipeptidyl aminopeptidase-like protein-6 in a family with suspicious idiopathic ventricular fibrillation.
These data suggest that the proband's autism may be due to the inheritance of disruptions in both DPP6 and LRRC4C, and may highlight the importance of the netrin G family and potassium channel interacting molecules in neurodevelopmental disorders.
Title: Implication of LRRC4C and DPP6 in neurodevelopmental disorders.
we expanded our knowledge of familial IVF linked to the DPP6 gene and discuss its (extended) clinical characteristics. In addition, its relationship with the Purkinje network is further explored.
Title: Detailed characterization of familial idiopathic ventricular fibrillation linked to the DPP6 locus.
This first familial case provides evidence for association between DPP6 haploinsufficiency and Gilles de la Tourette syndrome.
Title: DPP6 gene disruption in a family with Gilles de la Tourette syndrome.
the cysteine-rich domain of DPP6 plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER
Title: DPP6 domains responsible for its localization and function.

Submit: New GeneRIF Correction See all GeneRIFs (39)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual disability, autosomal dominant 33 MedGen: C4225375 OMIM: 616311 GeneReviews: Not available	Compare labs
Ventricular fibrillation, paroxysmal familial, 2 MedGen: C2751829 OMIM: 612956 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2019-06-26) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2019-06-26) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of sporadic ALS in a homogenous Irish population. EBI GWAS Catalog EBI GWAS CatalogPubMed
DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Generalization of variants identified by genome-wide association studies for electrocardiographic traits in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of pancreatic cancer in Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide diet-gene interaction analyses for risk of colorectal cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed
Screening for replication of genome-wide SNP associations in sporadic ALS. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7S1521 (e-PCR)
- UniSTS:69903

D4S3205 (e-PCR)
- UniSTS:34842

G31776 (e-PCR)
- UniSTS:74271

SHGC-111688 (e-PCR)
- UniSTS:168482

D7S2812 (e-PCR)
- UniSTS:42018

D7S637 (e-PCR), detects polymorphism
- UniSTS:50466

G17192 (e-PCR)
- UniSTS:6441

SHGC-147175 (e-PCR)
- UniSTS:175658

D7S774 (e-PCR)
- UniSTS:69675

RH118819 (e-PCR)
- UniSTS:138801

FB16B4 (e-PCR)
- UniSTS:60725

D7S2546 (e-PCR)
- UniSTS:4921

GDB:4585477 (e-PCR)
- UniSTS:6973

GDB:1317556 (e-PCR)
- UniSTS:22079

D7S2106E (e-PCR)
- UniSTS:60993

D7S1823 (e-PCR)
- UniSTS:65866

RH26271 (e-PCR)
- UniSTS:87627

D7S1807 (e-PCR)
- UniSTS:68430

GDB:4585573 (e-PCR)
- UniSTS:59728

D7S2689 (e-PCR)
- UniSTS:69204

GDB:4584977 (e-PCR)
- UniSTS:80724

SHGC-83608 (e-PCR)
- UniSTS:100954

SHGC-146393 (e-PCR)
- UniSTS:175196

D7S2447 (e-PCR), detects polymorphism
- UniSTS:56929

D7S2141E (e-PCR)
- UniSTS:151138

D7S2447 (e-PCR), detects polymorphism
- UniSTS:56930

RH11433 (e-PCR)
- UniSTS:43110

DXYS116Y (e-PCR)
- UniSTS:8807

G09452 (e-PCR)
- UniSTS:20583

GDB:1318120 (e-PCR)
- UniSTS:56935

RH12730 (e-PCR)
- UniSTS:55916

D7S2546 (e-PCR)
- UniSTS:52080

SHGC-146060 (e-PCR)
- UniSTS:174972

D7S755 (e-PCR)
- UniSTS:39806

GDB:1318366 (e-PCR)
- UniSTS:41350

RH48507 (e-PCR)
- UniSTS:79239

SHGC-106057 (e-PCR)
- UniSTS:169614

RH92198 (e-PCR)
- UniSTS:91281

GDB:4585231 (e-PCR)
- UniSTS:7828

D7S1521 (e-PCR)
- UniSTS:54932

D7S2802 (e-PCR)
- UniSTS:3479

SHGC-151014 (e-PCR)
- UniSTS:173214

NIB1085 (e-PCR)
- UniSTS:4258

SHGC-77889 (e-PCR)
- UniSTS:96163

SHGC-148281 (e-PCR)
- UniSTS:176298

D7S1920 (e-PCR)
- UniSTS:39343

GDB:1317534 (e-PCR)
- UniSTS:28599

SHGC-111675 (e-PCR)
- UniSTS:184506

SHGC-112024 (e-PCR)
- UniSTS:184507

SHGC-112091 (e-PCR)
- UniSTS:184509

A006U34 (e-PCR)
- UniSTS:54210

D7S1807 (e-PCR)
- UniSTS:67269

D7S637 (e-PCR), detects polymorphism
- UniSTS:47047

SHGC-151035 (e-PCR)
- UniSTS:173258

D7S1953 (e-PCR)
- UniSTS:60367

SHGC-142328 (e-PCR)
- UniSTS:174033

GDB:1318372 (e-PCR)
- UniSTS:42450

SHGC-30940 (e-PCR)
- UniSTS:66260

G15940 (e-PCR)
- UniSTS:57302

RH35843 (e-PCR)
- UniSTS:72424

WI-7260 (e-PCR)
- UniSTS:8424

SHGC-149634 (e-PCR)
- UniSTS:177129

GDB:4585663 (e-PCR)
- UniSTS:66794

D7S2303 (e-PCR)
- UniSTS:26348

D20S170 (e-PCR), detects polymorphism
- UniSTS:78832

A006E05 (e-PCR)
- UniSTS:60402

G15992 (e-PCR)
- UniSTS:1277

D7S1544 (e-PCR)
- UniSTS:22525

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables dipeptidyl-peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel regulator activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type peptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of potassium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: A-type potassium channel modulatory protein DPP6

Names: DPP VI; dipeptidyl aminopeptidase IV-related protein; dipeptidyl aminopeptidase-like protein 6; dipeptidyl peptidase IV-related protein; dipeptidyl peptidase VI; dipeptidyl-peptidase 6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033878.2 RefSeqGene

Range

309413..1151300

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001039350.3 → NP_001034439.1 A-type potassium channel modulatory protein DPP6 isoform 3

See identical proteins and their annotated locations for NP_001034439.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5'-most exon and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC024239, AC073336, BC150304, BX647966, DA156107, HY037545

Consensus CDS

CCDS75682.1

UniProtKB/TrEMBL

A7E2E4, E9PF59

Related

ENSP00000385578.1, ENST00000404039.5

Conserved Domains (2) summary

pfam00930
Location:131 → 497

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:577 → 786

Abhydrolase; alpha/beta hydrolases
NM_001290252.2 → NP_001277181.1 A-type potassium channel modulatory protein DPP6 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5'-most exon, initiates translation at an alternate start codon, and lacks two exons in the central coding region, compared to variant 1. The encoded isoform (4) is shorter, compared to isoform 1.

Source sequence(s)

AC073336, AC099341, AK294483, AK308993, BC150304, DA156107

Consensus CDS

CCDS78291.1

UniProtKB/TrEMBL

B7Z299, E9PDL2

Related

ENSP00000397303.1, ENST00000427557.1

Conserved Domains (2) summary

pfam00930
Location:133 → 454

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:534 → 740

Abhydrolase; alpha/beta hydrolases
NM_001290253.2 → NP_001277182.1 A-type potassium channel modulatory protein DPP6 isoform 5

See identical proteins and their annotated locations for NP_001277182.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks several exons, and contains an alternate 3-terminal exon, compared to variant 1. The encoded isoform (5) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC006019, AK001153, BC035912

Consensus CDS

CCDS78290.1

UniProtKB/TrEMBL

Q8IYG9

Related

ENSP00000384393.1, ENST00000406326.5
NM_001364497.2 → NP_001351426.1 A-type potassium channel modulatory protein DPP6 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (6), as well as variants 7, 8, and 9, encodes isoform 6.

Source sequence(s)

AC005998, AC024239, AC024730, AC073336

Consensus CDS

CCDS94238.1

UniProtKB/TrEMBL

A0A994J7K0, A7E2E4

Related

ENSP00000516215.1, ENST00000706130.1

Conserved Domains (2) summary

pfam00930
Location:134 → 500

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:580 → 789

Abhydrolase; alpha/beta hydrolases
NM_001364498.2 → NP_001351427.1 A-type potassium channel modulatory protein DPP6 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (7), as well as variants 6, 8, and 9, encodes isoform 6.

Source sequence(s)

AC005998, AC024239, AC024730, AC073336

Consensus CDS

CCDS94238.1

UniProtKB/TrEMBL

A0A994J7K0, A7E2E4

Conserved Domains (2) summary

pfam00930
Location:134 → 500

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:580 → 789

Abhydrolase; alpha/beta hydrolases
NM_001364499.2 → NP_001351428.1 A-type potassium channel modulatory protein DPP6 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (8), as well as variants 6, 7, and 9, encodes isoform 6.

Source sequence(s)

AC005998, AC024239, AC024730, AC073336

Consensus CDS

CCDS94238.1

UniProtKB/TrEMBL

A0A994J7K0, A7E2E4

Conserved Domains (2) summary

pfam00930
Location:134 → 500

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:580 → 789

Abhydrolase; alpha/beta hydrolases
NM_001364500.2 → NP_001351429.1 A-type potassium channel modulatory protein DPP6 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (9), as well as variants 6, 7, and 8, encodes isoform 6.

Source sequence(s)

AC005998, AC024239, AC024730, AC073336

Consensus CDS

CCDS94238.1

UniProtKB/TrEMBL

A0A994J7K0, A7E2E4

Conserved Domains (2) summary

pfam00930
Location:134 → 500

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:580 → 789

Abhydrolase; alpha/beta hydrolases
NM_001364501.2 → NP_001351430.1 A-type potassium channel modulatory protein DPP6 isoform 7

Status: REVIEWED

Source sequence(s)

AC005588, AC024239, AC024730, AC073336

Conserved Domains (1) summary

pfam00930
Location:131 → 366

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
NM_001364502.2 → NP_001351431.1 A-type potassium channel modulatory protein DPP6 isoform 8

Status: REVIEWED

Source sequence(s)

AC024730, AC099341, AC142230

Consensus CDS

CCDS94239.1

UniProtKB/TrEMBL

A0A994J521, Q75MI7

Related

ENSP00000516214.1, ENST00000496611.2

Conserved Domains (1) summary

cl28622
Location:25 → 55

PLN02870; Probable galacturonosyltransferase
NM_001936.5 → NP_001927.3 A-type potassium channel modulatory protein DPP6 isoform 2

See identical proteins and their annotated locations for NP_001927.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5'-most exon and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2, also referred to as S) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC024239, AC073336, AC099341, AK308993, BC150304, DA156107, HY037545

Consensus CDS

CCDS75684.1

UniProtKB/TrEMBL

A7E2E4

Related

ENSP00000328226.3, ENST00000332007.7

Conserved Domains (2) summary

pfam00930
Location:133 → 499

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:579 → 788

Abhydrolase; alpha/beta hydrolases
NM_130797.4 → NP_570629.2 A-type potassium channel modulatory protein DPP6 isoform 1

See identical proteins and their annotated locations for NP_570629.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1, also referred to as L).

Source sequence(s)

AC006019, AC024239, AC073336, BC035912, BC150304, DA156107, HY037545

Consensus CDS

CCDS75683.1

UniProtKB/Swiss-Prot

P42658

UniProtKB/TrEMBL

A7E2E4

Related

ENSP00000367001.3, ENST00000377770.8

Conserved Domains (2) summary

pfam00930
Location:195 → 561

DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

cl21494
Location:641 → 850

Abhydrolase; alpha/beta hydrolases

RNA

NR_157195.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC005588, AC024239, AC024730, AC073336
NR_157196.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC024239, AC024730, AC073336, AC099341

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

153748133..154894285

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419951.1 → XP_047275907.1 A-type potassium channel modulatory protein DPP6 isoform X2

UniProtKB/TrEMBL

A0A994J7K0
XM_017011812.3 → XP_016867301.1 A-type potassium channel modulatory protein DPP6 isoform X1

UniProtKB/TrEMBL

Q75MF0

Related

ENSP00000516234.1, ENST00000706151.1