Lipodystrophy, congenital generalized, type 5

Summary

Lipodystrophy, congenital generalized, type 5 (MONDO:0958023) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lipodystrophy, congenital generalized, type 5
Mondo ID	MONDO:0958023
OMIM	620680
UMLS	C5882745
MedGen	1847991
GARD	0026914
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › lipodystrophy › hereditary lipodystrophy › congenital generalized lipodystrophy › lipodystrophy, congenital generalized, type 5

Related subtypes (4): congenital generalized lipodystrophy type 2, congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy type 3, congenital generalized lipodystrophy type 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2691732	NM_001312673.2(PCYT1A):c.424G>A (p.Val142Met)	LOC126806932	Pathogenic	no assertion criteria provided
4072072	NM_001312673.2(PCYT1A):c.413A>G (p.His138Arg)	LOC126806932	Likely pathogenic	criteria provided, single submitter
1004313	NM_001312673.2(PCYT1A):c.835GAG[1] (p.Glu280del)	PCYT1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3589113	NM_001312673.2(PCYT1A):c.36G>T (p.Arg12Ser)	PCYT1A	Uncertain significance	criteria provided, single submitter
942178	NM_001312673.2(PCYT1A):c.996del (p.Ser333fs)	PCYT1A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PCYT1A	Orphanet:65	Leber congenital amaurosis
PCYT1A	Orphanet:85167	Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PCYT1A	HGNC:8754	ENSG00000161217	P49585	Choline-phosphate cytidylyltransferase A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PCYT1A	Choline-phosphate cytidylyltransferase A	Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PCYT1A	Enzyme (other)	yes	2.7.7.15	Cyt_trans-like, Rossmann-like_a/b/a_fold, CCT

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	1
skin of leg	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PCYT1A	274	ubiquitous	marker	sural nerve, monocyte, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCYT1A	2,004

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PCYT1A	P49585	76.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of PC	1	407.9×	0.002	PCYT1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
CDP-choline pathway	1	3370.4×	0.001	PCYT1A
isotype switching	1	842.6×	0.002	PCYT1A
phosphatidylcholine biosynthetic process	1	802.5×	0.002	PCYT1A
B cell proliferation	1	481.5×	0.002	PCYT1A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PCYT1A	ENCORAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PCYT1A	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENCORAFENIB	4	PCYT1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PCYT1A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PCYT1A	2.7.7.15	choline-phosphate cytidylyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ENCORAFENIB	4	PCYT1A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PCYT1A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.