FITM2

Chr 20AR

fat storage inducing transmembrane protein 2

Also known as: C20orf142, Fit2, SIDDIS, dJ881L22.2

NCBI Gene: 128486ENSG00000197296UniProt: Q8N6M3

Enables coenzyme A diphosphatase activity. Involved in several processes, including fatty-acyl-CoA catabolic process; lipid droplet formation; and lipid homeostasis. Predicted to be located in endoplasmic reticulum and membrane. Predicted to be active in endoplasmic reticulum membrane. Implicated in Siddiqi syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Siddiqi syndromeMIM #618635
AR
73
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FITM2
🧬
Gene-Disease Validity (ClinGen)
Siddiqi syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 36 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.55LOEUF
pLI 0.000
Z-score 0.29
OE 0.90 (0.54–1.55)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.60Z-score
OE missense 0.86 (0.74–1.00)
122 obs / 142.0 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.0.90 (0.54–1.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.74–1.00)
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.1.11
0≤1.21.6
LoF obs/exp: 9 / 10.0Missense obs/exp: 122 / 142.0Syn Z: -0.72

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic7
VUS36
Likely Benign13
Benign3
Conflicting1
13
Pathogenic
7
Likely Pathogenic
36
VUS
13
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
12
0
13
Likely Pathogenic
1
2
4
0
7
VUS
0
34
2
0
36
Likely Benign
0
5
2
6
13
Benign
0
0
3
0
3
Conflicting
—1
Total24123673

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

View in ClinVar →

Protein Context — Lollipop Plot

FITM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Siddiqi syndrome

MIM #618635

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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