PNKD PNKD metallo-beta-lactamase domain containing [Homo sapiens (human)] - Gene

Summary

Official Symbol: PNKDprovided by HGNC
Official Full Name: PNKD metallo-beta-lactamase domain containingprovided by HGNC
Primary source: HGNC:HGNC:9153
See related: Ensembl:ENSG00000127838 MIM:609023; AllianceGenome:HGNC:9153
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: R1; MR1; PDC; DYT8; FPD1; MR-1; BRP17; MR-1S; PKND1; PNKD1; FKSG19; TAHCCP2; KIPP1184
Summary: This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Expression: Ubiquitous expression in prostate (RPKM 19.3), kidney (RPKM 16.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q35

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (218270519..218346793)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (218756220..218832888)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (219135242..219211516)

Chromosome 2 - NC_000002.12 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?

Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.
Title: Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.
A rare heterozygous nonsense mutation (C to T transition) was identified in a Tourette Disorder multiplex family by whole exome sequencing. Tourette or Tic Disorder-affected family members shared a heterozygous nonsense mutation (chr2: 219204814 C/T), which is not present in the unaffected individuals and absent in the background sample
Title: The PNKD gene is associated with Tourette Disorder or Tic disorder in a multiplex family.
The short isoform of the myofibrillogenesis regulator 1 (MR-1S) as a new COX assembly factor, which works with the highly conserved PET100 and PET117 chaperones to assist COX biogenesis in higher eukaryotes.
Title: MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase.
The combined analysis identified a new risk association for colorectal cancer (CRC) at 2q35 marked by rs992157 which is intronic to PNKD and TMBIM1.Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r(2) = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD).
Title: Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.
study highlights the frequency, novel mutations and clinical and molecular spectrum of PRRT2, SLC2A1 and PNKD mutations as well as the phenotype-genotype overlap among these paroxysmal movement disorders.
Title: The clinical and genetic heterogeneity of paroxysmal dyskinesias.
This study present the pedigree is the first PNKD family from Chinese Mainland, which is also the largest PNKD family among those reported across the globe. It included 5 generations and 26 patients.
Title: A case of familial paroxysmal nonkinesigenic dyskinesia due to mutation of the PNKD gene in Chinese Mainland.
MR-1 functions as a tumor promoter in MCF7 cells by activating the MEK/ERK signaling
Title: Phosphorylation of myofibrillogenesis regulator-1 activates the MAPK signaling pathway and induces proliferation and migration in human breast cancer MCF7 cells.
MR-1 overexpression was tightly associated with more aggressive tumor behavior and a poor prognosis in pancreatic ductal adenocarcinoma.
Title: Clinicopathological and prognostic significance of myofibrillogenesis regulator-1 protein expression in pancreatic ductal adenocarcinoma.
MR-1 was up-regulated in gastric cancer tissues. High expression of MR-1 in gastric cancer was significantly correlated with clinical stage. Postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group.
Title: Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients.
A Taiwanese family with paroxysmal nonkinesigenic dyskinesia has a heterozygous c.20 C>T (p.Ala7Val) mutation which was clearly segregated in the five affected patients.
Title: Familial paroxysmal nonkinesigenic dyskinesia: clinical and genetic analysis of a Taiwanese family.

Submit: New GeneRIF Correction See all GeneRIFs (21)

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
Paroxysmal nonkinesigenic dyskinesia 1 MedGen: C4551506 OMIM: 118800 GeneReviews: Familial Paroxysmal Nonkinesigenic Dyskinesia	not available

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. 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

RH12007 (e-PCR)
- UniSTS:31236

D2S173 (e-PCR), detects polymorphism
- UniSTS:44805

RH64881 (e-PCR)
- UniSTS:84274

D2S126 (e-PCR), detects polymorphism
- UniSTS:72000

RH80510 (e-PCR)
- UniSTS:86596

RH78114 (e-PCR)
- UniSTS:25927

RH68260 (e-PCR)
- UniSTS:54346

AI854243 (e-PCR)
- UniSTS:181078

D2S128 (e-PCR), detects polymorphism
- UniSTS:1117

RH41829 (e-PCR)
- UniSTS:52062

D2S120 (e-PCR), detects polymorphism
- UniSTS:68996

HSC2KC082 (e-PCR)
- UniSTS:66255

RH98595 (e-PCR)
- UniSTS:86232

RH128628 (e-PCR)
- UniSTS:211936

337G113' (e-PCR)
- UniSTS:186600

SHGC-84670 (e-PCR)
- UniSTS:103154

D2S102 (e-PCR)
- UniSTS:60916

WI-17411 (e-PCR)
- UniSTS:49661

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables hydroxyacylglutathione hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neurotransmitter secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromuscular process controlling posture	IEA Inferred from Electronic Annotation more info
involved_in regulation of dopamine metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, dopaminergic	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in presynaptic cytosol	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: probable hydrolase PNKD

Names: PNKD, MBL domain containing; brain protein 17; myofibrillogenesis regulator 1; trans-activated by hepatitis C virus core protein 2

NP_001070867.1

EC 3.1.2.6

NP_056303.3

EC 3.1.2.6

NP_072094.1

EC 3.1.2.6

XP_016859260.1

EC 3.1.2.6

XP_016859261.1

EC 3.1.2.6

XP_054197290.1

EC 3.1.2.6

XP_054197291.1

EC 3.1.2.6

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_017060.1 RefSeqGene

Range

5128..81402

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001077399.3 → NP_001070867.1 probable hydrolase PNKD isoform 3 precursor

See identical proteins and their annotated locations for NP_001070867.1

Status: REVIEWED

Description

Transcript Variant: This variant (3), alternately referred to as the short form (MR-1S), differs in the 3' UTR and has multiple coding region differences, compared to variant 1. This results in a frameshift in isoform 3, which has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AF318057, BQ028777

Consensus CDS

CCDS42816.1

UniProtKB/Swiss-Prot

Q8N490

Related

ENSP00000248451.3, ENST00000248451.7

Conserved Domains (1) summary

pfam15932
Location:71 → 121

DUF4748; Domain of unknown function (DUF4748)
NM_015488.5 → NP_056303.3 probable hydrolase PNKD isoform 1 precursor

See identical proteins and their annotated locations for NP_056303.3

Status: REVIEWED

Description

Transcript Variant: This variant (1), alternately referred to as the long form (MR-1L), represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB033010, AF318057, BC002937, BC036457

Consensus CDS

CCDS2411.1

UniProtKB/Swiss-Prot

A8K1F2, Q8N490, Q96A48, Q9BU26, Q9NSX4, Q9ULN6, Q9Y4T1

UniProtKB/TrEMBL

A0A8J8ZTU4

Related

ENSP00000273077.4, ENST00000273077.9

Conserved Domains (1) summary

TIGR03413
Location:121 → 380

GSH_gloB; hydroxyacylglutathione hydrolase
NM_022572.4 → NP_072094.1 probable hydrolase PNKD isoform 2

See identical proteins and their annotated locations for NP_072094.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), alternately referred to as the medium form (MR-1M), differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC021016, BC002937, BC036457, BU553179

Consensus CDS

CCDS2413.1

UniProtKB/Swiss-Prot

Q8N490

Related

ENSP00000258362.3, ENST00000258362.7

Conserved Domains (1) summary

TIGR03413
Location:97 → 356

GSH_gloB; hydroxyacylglutathione hydrolase