FITM2

Chr 20AR

fat storage inducing transmembrane protein 2

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

The protein functions as a fatty acyl-coenzyme A diphosphatase in the endoplasmic reticulum, hydrolyzing fatty acyl-CoA substrates and maintaining ER structure and lipid droplet biogenesis for cellular lipid and energy homeostasis. Mutations cause Siddiqi syndrome, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.551 OMIM phenotype
Clinical SummaryFITM2
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.55LOEUF
pLI 0.000
Z-score 0.29
OE 0.90 (0.541.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.60Z-score
OE missense 0.86 (0.741.00)
122 obs / 142.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.90 (0.541.55)
00.351.4
Missense OE0.86 (0.741.00)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 9 / 10.0Missense obs/exp: 122 / 142.0Syn Z: -0.72
DN
0.6454th %ile
GOF
0.5660th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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