CISD2

Chr 4AR

CDGSH iron sulfur domain 2

ENSG00000145354UniProt: Q8N5K1OMIM: 611507

Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Wolfram syndrome 2MIM #604928
AR

Clinical highlights

Gene-disease validity (ClinGen)
Wolfram syndrome · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
38
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.91
LOEUF
LOF
Mechanism· G2P
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.91LOEUF
pLI 0.416
Z-score 1.71
OE 0.19 (0.07–0.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.27Z-score
OE missense 0.58 (0.45–0.75)
42 obs / 72.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.19 (0.07–0.91)
0≤0.351.4
Missense OE?0.58 (0.45–0.75)
0≤0.61.4
Synonymous OE?1.16
0≤1.21.6
LoF obs/exp: 1 / 5.2Missense obs/exp: 42 / 72.4Syn Z: -0.66

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

CISD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients