Garg-Mishra progeroid syndrome

Summary

Garg-Mishra progeroid syndrome (MONDO:0957953) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Garg-Mishra progeroid syndrome
Mondo ID	MONDO:0957953
OMIM	620601
UMLS	C5882717
MedGen	1847272
GARD	0026896
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › progeroid syndrome › Garg-Mishra progeroid syndrome

Related subtypes (15): Hutchinson-Gilford progeria syndrome, Wiedemann-Rautenstrauch syndrome, Werner syndrome, progeroid facial appearance with hand anomalies, XFE progeroid syndrome, Fontaine progeroid syndrome, Nestor-Guillermo progeria syndrome, mandibular hypoplasia-deafness-progeroid syndrome, progeroid and marfanoid aspect-lipodystrophy syndrome, Cockayne syndrome, mandibuloacral dysplasia progeroid syndrome, achalasia-progeroid syndrome, Fischer-Zirnsak progeroid syndrome, Marbach-Rustad progeroid syndrome, RECON progeroid syndrome

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679423	NM_019059.5(TOMM7):c.73T>C (p.Trp25Arg)	TOMM7	Pathogenic/Likely pathogenic	no assertion criteria provided
2628316	NM_019059.5(TOMM7):c.86C>T (p.Pro29Leu)	TOMM7	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TOMM7	Moderate	Autosomal recessive	Garg-Mishra progeroid syndrome	3

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
TOMM7	HGNC:21648	ENSG00000196683	Q9P0U1	Mitochondrial import receptor subunit TOM7 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TOMM7	Mitochondrial import receptor subunit TOM7 homolog	Component of the translocase of the outer membrane of mitochondria (TOM) complex essential for the recognition and translocation of cytosolically synthesized mitochondrial preproteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TOMM7	Other/Unknown	no		Tom7

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
medial globus pallidus	1
skeletal muscle tissue of rectus abdominis	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TOMM7	295	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, medial globus pallidus, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TOMM7	1,712

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TOMM7	Q9P0U1	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
PINK1-PRKN Mediated Mitophagy	1	356.9×	0.006	TOMM7
Mitochondrial protein import	1	167.9×	0.006	TOMM7

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
positive regulation of type 2 mitophagy	1	1532.0×	0.002	TOMM7
protein insertion into mitochondrial outer membrane	1	1296.3×	0.002	TOMM7
protein import into mitochondrial matrix	1	702.2×	0.002	TOMM7
obsolete positive regulation of protein targeting to mitochondrion	1	495.6×	0.003	TOMM7
regulation of protein stability	1	125.8×	0.008	TOMM7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TOMM7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	TOMM7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TOMM7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.