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

Gene ID: 1804, updated on 3-Apr-2024

Summary

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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
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Genomic context

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See DPP6 in Genome Data Viewer
Location:
7q36.2
Exon count:
32
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (153748133..154894285)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (154922684..156069555)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (153445218..154685995)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375579 Neighboring gene uncharacterized LOC107986750 Neighboring gene NANOG hESC enhancer GRCh37_chr7:153367335-153367836 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:153501631-153501821 Neighboring gene uncharacterized LOC107986722 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:153555187-153556386 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153583199-153583700 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:153632460-153632651 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153640855-153641356 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153641357-153641856 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153686082-153686582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153748374-153748976 Neighboring gene uncharacterized LOC101929998 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:153797461-153797962 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:153880891-153881704 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:153881705-153882518 Neighboring gene NANOG hESC enhancer GRCh37_chr7:153895575-153896144 Neighboring gene uncharacterized LOC105375582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:153991562-153992062 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:154376061-154376644 Neighboring gene uncharacterized LOC105375581 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:154451859-154453058 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:154455057-154456256 Neighboring gene Sharpr-MPRA regulatory region 9204 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:154541852-154542037 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:154559199-154559739 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:154574745-154575246 Neighboring gene uncharacterized LOC105375580 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr7:154649493-154650146 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr7:154648838-154649492 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:154660288-154661046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26886 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26887 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26888 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26889 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:154737734-154738933 Neighboring gene PAXIP1 antisense RNA 2 Neighboring gene uncharacterized LOC124901781 Neighboring gene PAX interacting protein 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. 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. Naujock M, et al. Stem Cells Dev, 2020 Dec. PMID 33143549
  2. Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma. Zhao X, et al. Biosci Rep, 2020 Jul 31. PMID 32701143, Free PMC Article
  3. A novel DPP6 variant in Chinese families causes early repolarization syndrome. Ji CC, et al. Exp Cell Res, 2019 Nov 1. PMID 31476289
  4. Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability. Cacace R, et al. Acta Neuropathol, 2019 Jun. PMID 30874922, Free PMC Article
  5. A novel mutation of dipeptidyl aminopeptidase-like protein-6 in a family with suspicious idiopathic ventricular fibrillation. Ding DB, et al. QJM, 2018 Jun 1. PMID 29474731

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. The slope of the activation curve of DPP6-L747P was slightly decreased.
    Title: A novel DPP6 variant in Chinese families causes early repolarization syndrome.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. DPP6 is critical for synaptic integration and excitation.
    Title: A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample.
Submit: New GeneRIF Correction See all GeneRIFs (38)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ55680, MGC46605

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 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
dipeptidyl aminopeptidase-like protein 6
Names
DPP VI
dipeptidyl aminopeptidase IV-related protein
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

  1. NG_033878.2 RefSeqGene

    Range
    309413..1151300
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001039350.3 → NP_001034439.1  dipeptidyl aminopeptidase-like protein 6 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

  2. NM_001290252.2 → NP_001277181.1  dipeptidyl aminopeptidase-like protein 6 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

  3. NM_001290253.2 → NP_001277182.1  dipeptidyl aminopeptidase-like protein 6 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

  4. NM_001364497.2 → NP_001351426.1  dipeptidyl aminopeptidase-like protein 6 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

  5. NM_001364498.2 → NP_001351427.1  dipeptidyl aminopeptidase-like protein 6 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

  6. NM_001364499.2 → NP_001351428.1  dipeptidyl aminopeptidase-like protein 6 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

  7. NM_001364500.2 → NP_001351429.1  dipeptidyl aminopeptidase-like protein 6 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

  8. NM_001364501.2 → NP_001351430.1  dipeptidyl aminopeptidase-like protein 6 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

  9. NM_001364502.2 → NP_001351431.1  dipeptidyl aminopeptidase-like protein 6 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

  10. NM_001936.5 → NP_001927.3  dipeptidyl aminopeptidase-like protein 6 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

  11. NM_130797.4 → NP_570629.2  dipeptidyl aminopeptidase-like protein 6 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

  1. NR_157195.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC005588, AC024239, AC024730, AC073336

  2. NR_157196.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC024239, AC024730, AC073336, AC099341

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    153748133..154894285
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419951.1 → XP_047275907.1  dipeptidyl aminopeptidase-like protein 6 isoform X2

    UniProtKB/TrEMBL
    A0A994J7K0

  2. XM_017011812.3 → XP_016867301.1  dipeptidyl aminopeptidase-like protein 6 isoform X1

    UniProtKB/TrEMBL
    Q75MF0
    Related
    ENSP00000516234.1, ENST00000706151.1

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_012132919.1 Reference GRCh38.p14 PATCHES

    Range
    23861..165626
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    154922684..156069555
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054357416.1 → XP_054213391.1  dipeptidyl aminopeptidase-like protein 6 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P42658.2 GenPept UniProtKB/Swiss-Prot:P42658

Gene LinkOut

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