CISD2

Protein identityUniProt · HPA

UniProt accession

Q8N5K1

Gene

CISD2

Ensembl

ENSG00000145354

Chromosome

4

Canonical length

135 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Endoplasmic reticulum

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein binds an iron/sulfur cluster and may be involved in calcium homeostasis. Defects in this gene are a cause of Wolfram syndrome 2. [provided by RefSeq, Mar 2011]

Canonical amino-acid sequenceUniProt

135 residues, UniProt reviewed canonical sequence.

>Q8N5K1|CISD2
     1  MVLESVARIV KVQLPAYLKR LPVPESITGF ARLTVSEWLR LLPFLGVLAL LGYLAVRPFL
    61  PKKKQQKDSL INLKIQKENP KVVNEINIED LCLTKAAYCR CWRSKTFPAC DGSHNKHNEL
   121  TGDNVGPLIL KKKEV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CISD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CISD2.

Disease | AllUniProt

Conditions CISD2 is implicated in, by any mechanism.

• Wolfram syndrome 2 (WFS2) MIM:604928

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 85 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Wolfram syndrome 2

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.91

gnomAD pLI

0.42

gnomAD missense Z

1.27

DepMap mean gene effect

0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy of mitochondrion
• regulation of autophagy

Molecular functions

• 2 iron, 2 sulfur cluster binding
• metal ion binding
• protein homodimerization activity
• RNA binding

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• membrane
• mitochondrial outer membrane
• perinuclear endoplasmic reticulum
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Iron-binding zinc finger, CDGSH type
• Iron sulphur domain-containing, mitoNEET, N-terminal
• MitoNEET, CDGSH iron-sulfur domain
• CDGSH iron-sulfur domain-containing protein 1/2
• Iron-binding zinc finger CDGSH type
• Iron-containing outer mitochondrial membrane protein N-terminus

KeywordsUniProt

• 2Fe-2S
• Autophagy
• Deafness
• Diabetes mellitus
• Endoplasmic reticulum
• Iron
• Iron-sulfur
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion outer membrane
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CISD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BCL2
• BCL2L1
• ITPR1
• ATG9A
• EMD
• SEC61B
• STX7