PISD

Chr 22AR

phosphatidylserine decarboxylase

Also known as: DJ858B16, LIBF, PSD, PSDC, PSSC, dJ858B16.2

NCBI Gene: 23761ENSG00000241878UniProt: Q9UG56

The protein encoded by this gene catalyzes the conversion of phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane. The encoded protein is active in phospholipid metabolism and interorganelle trafficking of phosphatidylserine. [provided by RefSeq, May 2016]

Primary Disease Associations & Inheritance

Liberfarb syndromeMIM #618889
AR
91
ClinVar variants
7
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— PISD
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 46 VUS of 91 total submissions
Some data sources returned errors (1)

clinvarCount: 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
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.222
Z-score 2.76
OE 0.25 (0.12–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.68Z-score
OE missense 0.88 (0.79–0.98)
221 obs / 251.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.12–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.79–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 4 / 15.8Missense obs/exp: 221 / 251.2Syn Z: -2.05

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic4
VUS46
Likely Benign36
Benign2
3
Pathogenic
4
Likely Pathogenic
46
VUS
36
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
1
0
3
Likely Pathogenic
4
0
0
0
4
VUS
0
44
1
1
46
Likely Benign
0
0
7
29
36
Benign
0
0
1
1
2
Total644103191

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PISD · protein map & ClinVar variants

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

Gene2Phenotype Curations

PISD-related spondyloepimetaphyseal dysplasia with large epiphyses and disturbed mitochondrial function

limited
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
splice region variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Liberfarb syndrome

MIM #618889

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Mechanism of PISD/SPG7-mediated mPTP opening in necroptosis of inflammatory HaCaT cells induced by nano-zinc oxide.
Wang M et al.·Toxicology
2025Functional
Nano polystyrene accelerated the reproductive toxicity induced by the Tris(1,3-dichloro-2-propyl) phosphate via Nhr-69-PISD-Drp-1-mediated mitochondrial fragmentation in Caenorhabditis elegans.
Wang J et al.·Environ Pollut
2025
Novel biallelic PISD missense variants cause spondyloepimetaphyseal dysplasia with disproportionate short stature and fragmented mitochondrial morphology.
Aagaard Nolting L et al.·Clin Genet
2024
Knockdown of TFAM in Tumor Cells Retarded Autophagic Flux through Regulating p53 Acetylation and PISD Expression.
Jiang X et al.·Cancers (Basel)
2020🔓 Open Access
The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene.
Peter VG et al.·Genet Med
2019🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools