CIDEC

protein-coding

cell death inducing DFFA like effector c

Gene summary

This gene encodes a member of the cell death-inducing DNA fragmentation factor-like effector family. Members of this family play important roles in apoptosis. The encoded protein promotes lipid droplet formation in adipocytes and may mediate adipocyte apoptosis. This gene is regulated by insulin and its expression is positively correlated with insulin sensitivity. Mutations in this gene may contribute to insulin resistant diabetes. A pseudogene of this gene is located on the short arm of chromosome 3. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MANE transcript

NM_001321142.2

Inheritance

ClinVar variants

P:3U:44B:17

Top phenotype

Lipodystrophy, familial partial, type 5

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr3:9,866,711-9,880,255

External References & Databases

Ensembl (ENSG00000187288)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

CIDEC-related familial partial lipodystrophyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014098

Submitter: Labcorp Genetics (formerly Invitae)

CIDEC-related familial partial lipodystrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014098

Submitter: Orphanet

CIDEC-related familial partial lipodystrophyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014098

Submitter: ClinGen

*CIDEC*, also known as *FSP27*, was first reported in association with autosomal recessive *CIDEC*-related familial partial lipodystrophy in 2009 (Rubio-Cabezas et al., PMID: 20049731). The affected individual was an Ecuadorean female with adolescent-onset lipodystrophy who was homozygous for the nonsense variant NM_001321142.2:c.556G>T (p.Glu186Ter). The inheritance pattern was curated as autosomal recessive, consistent with the homozygous loss-of-function variant identified in the affected individual. The reported patient had partial lipodystrophy affecting the limbs, femorogluteal region, and abdominal subcutaneous fat, accompanied by severe insulin-resistant diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and reduced circulating adiponectin (PMID: 20049731). Another patient was reported to have partial lipodystrophy, acanthosis nigricans, and marked insulin resistance and was found to be homozygous for the rare *CIDEC* missense variant NM_001199623.2:c.224G>T (p.Ser75Ile) (PMID: 41596298). However, she also carried a novel homozygous *WRN* missense variant, NM_000553.4:c.1856T>G (p.Leu619Arg), and both variants were classified as variants of uncertain significance. Because *WRN*-associated disease may also present with partial lipodystrophy phenotype and insulin resistance (PMID: 23849162) and both variants were novel missense variants, the specific contributions of both the *CIDEC* and *WRN *variants to this patient’s phenotype remain uncertain. Therefore, this case does not provide unequivocal independent evidence for *CIDEC*-related disease. Per the ClinGen Lumping and Splitting guidelines, the available evidence supports evaluation under a single disease entity: autosomal recessive CIDEC-related familial partial lipodystrophy. One homozygous variant reported in one proband was included in this curation (PMID: 20049731). The case-level evidence received 3 points. This gene-disease relationship is further supported by expression studies, biochemical function, protein interaction, functional alteration, and mouse model data (PMIDs: 17884815, 20049731, 22144693, 23399566, 24627478, 18654663, 18682832, 25565658, 34508658, 35963433, 36800289). Total points for experimental evidence are 5, and the combined genetic and experimental evidence totals 8 points. In summary, there is moderate evidence supporting the relationship between *CIDEC* and autosomal recessive *CIDEC*-related familial partial lipodystrophy. This classification was approved by the ClinGen Monogenic Diabetes GCEP on the meeting date July 15, 2026 (SOP Version 12).

Clinical Genomic Database (CGD)

Lipodystrophy, familial partial, type 5AR

Manifestation: Cardiovascular; Endocrine; Gastrointestinal

Intervention: Cardiovascular; Endocrine; Gastrointestinal

Rationale: Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality; Recognition and treatment of hypertriglyceridemia can help avoid sequelae such as acute pancreatitis

Refs: 20049731

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CIDEC variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 20

CIDEC-related disorderTotal: 11

CIDEC-related familial partial lipodystrophyTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321142.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar		7
missense			42 clinvar	9 clinvar	1 clinvar	52
nonsense	1 clinvar					1
start loss						0
frameshift		2 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	2	44	16	1	64

Highest pathogenic variant AF is 0.00009044885

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321142.2	RefSeq	NP_001308071.1	5	MANE Select
ENST00000336832.7	Ensembl	ENSP00000338642.2	5	MANE Select
NM_001199551.2	RefSeq	NP_001186480.1	6	Standard
NM_001199552.2	RefSeq	NP_001186481.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Plasma lipoprotein assembly, remodeling, and clearance
Metabolism of lipids
Metabolism
Lipid particle organization

Biological Process

apoptotic process
lipid droplet organization
execution phase of apoptosis

Molecular Function

molecular_function

Cellular Component

nucleus
endoplasmic reticulum
lipid droplet
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000430427
Coding exons: 6
Length: 13541
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125747
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.669	163	141	1.16	0.00000855	1591
Missense (PolyPhen)		45	43.058	1.0451		519
Synonymous	-1.02	68	58.1	1.17	0.00000347	501
Loss of Function	1.71	5	11.2	0.448	5.48e-7	125

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00066	0.00067	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00026	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment. As mature adipocytes, that express high CIDEC levels, are quite resistant to apoptotic stimuli, the physiological significance of its role in apoptosis is unclear. May play a role in the modulation of the response to osmotic stress by preventing NFAT5 to translocate into the nucleus and activate its target genes expression. {ECO:0000269|PubMed:12429024, ECO:0000269|PubMed:18334488, ECO:0000269|PubMed:19843876, ECO:0000269|PubMed:20049731, ECO:0000269|PubMed:23399566}.;
Disease: DISEASE: Note=In omental adipose tissue of obese patients matched for BMI, expression levels tend to correlate with insulin sensitivity. Expression is increased 2-3 fold in the group of patients with high insulin sensitivity, compared to the insulin- resistant group. This observation is consistent with the idea that triglyceride storage in adipocytes plays an important role in sequestering triglycerides and fatty acids away from the circulation and peripheral tissues, thus enhancing insulin sensitivity in liver and muscle. This effect is not significant in subcutaneous adipose tissue (PubMed:18509062). In subcutaneous adipose tissue of diabetic patients, tends to negatively correlate with body mass index and total fat mass, independently of insulin sensitivity (PubMed:18334488). {ECO:0000269|PubMed:18334488, ECO:0000269|PubMed:18509062}.; DISEASE: Lipodystrophy, familial partial, 5 (FPLD5) [MIM:615238]: A form of lipodystrophy characterized by loss of subcutaneous adipose tissue affecting limb, femorogluteal and subcutaneous abdominal fat, preservation of visceral, neck and axilliary fat, hepatomegaly, hepatic steatosis and insulin-resistant diabetes. {ECO:0000269|PubMed:20049731}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.569
RVIS EVS: 0.26
RVIS percentile EVS: 70.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.454

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium